Dietary molecules and experimental evidence of epigenetic influence in cancer chemoprevention: An insight.

The world-wide rate of incidence of cancer disease has been only modestly contested by the past and current preventive and interventional strategies. Hence, the global effort towards novel ideas to contain the disease still continues. Constituents of human diets have in recent years emerged as key regulators of carcinogenesis, with studies reporting their inhibitory potential against all the three stages vis-a-vis initiation, promotion and progression. Unlike drugs which usually act on single targets, these dietary factors have an advantage of multi-targeted effects and pleiotropic action mechanisms, which are effective against cancer that manifest as a micro-evolutionary and multi-factorial disease. Since most of the cellular targets have been identified and their consumption considered relatively safe, these diet-derived agents often appear as molecules of interest in repurposing strategies. Currently, many of these molecules are being investigated for their ability to influence the aberrant alterations in cell's epigenome for epigenetic therapy against cancer. Targeting the epigenetic regulators is a new paradigm in cancer chemoprevention which acts to reverse the warped-up epigenetic alterations in a cancer cell, thereby directing it towards a normal phenotype. In this review, we discuss the significance of dietary factors and natural products as chemopreventive agents. Further, we corroborate the experimental evidence from existing literature, reflecting the ability of a series of such molecules to act as epigenetic modifiers in cancer cells, by interfering with molecular events that map the epigenetic imprints such as DNA methylation, histone acetylation and non-coding RNA mediated gene regulation.

A panoramic view on phytochemical, nutritional, and therapeutic attributes of Ziziphus mauritiana Lam.: A comprehensive review.

Ziziphus mauritiana (Rhamnaceae), commonly known as Indian jujube, is a pharmacologically diverse medicinal plant. A plethora of active phytochemical constituents of this plant has been revealed so far, namely, berberine, quercetin, kaempferol, sitosterol, stigmasterol, lanosterol, diosgenin, and so forth. Several studies demonstrated the exploration of pharmacological potential of various parts such as fruits, leaves, and stems of the plant as antioxidant, cytotoxic, antimicrobial, anti-diarrhoeal, antidepressant, immunomodulator, and hepatoprotective. This review gives a unique summary including phytochemistry, nutritional value, and significant pharmacological importance of Z. mauritiana. The literature search was carried out via search engine PubMed, Science Direct, and so on. The data were heterogeneous in terms of leaves, stem, roots, and fruits which were used for different experimental findings, which made the comparison a lengthy task. Study findings suggested that the extracts from this plant may possess numerous types of pharmacological activities. As the search for novel drugs from botanical sources continues, there is need for future investigations to isolate and characterize pharmacologically active agents that confer medicinal properties on Z. mauritiana, as well as to elucidate the structures of these agents by which they exert their healing properties and to scientifically validate the existing traditional practices concerning its health benefits.

Dermaceutical Utilization of Nigella sativa Seeds: Applications and Opportunities.

Skin diseases have recently become a major concern among people of all ages due to their highly visible symptoms and persistent and difficult treatment, which significantly impact their quality of life. Nigella sativa seeds, also known as "black seeds" or "kalonji," are one of the most commonly used herbal medicines due to their wide range of biological and pharmacological activities. It contains a wide range of bioactive constituents found in both fixed and essential oils. It has been used for hundreds of years as an alternative ethnomedicine to treat a wide range of skin conditions. N. sativa's dermatological applications in skin diseases are attributed to its potent antioxidant, anti-inflammatory, antimicrobial, and immunomodulatory properties, making it an intriguing skincare candidate. Several studies unravelled positive results associated with N. sativa on skin diseases. As N. sativa is the most studied medicinal plant, several preclinical and clinical studies have been conducted to establish its use in the treatment of various skin diseases. Thymoquinone has anti-inflammatory, antioxidant, and antibacterial properties, which mainly contributed to the treatment of skin diseases. In this context, the present review explores all the available studies on the association of N. sativa and its effect on treating skin diseases in light of recent studies and patents supporting its therapeutic applications.

Transfersome, an ultra-deformable lipid-based drug nanocarrier: an updated review with therapeutic applications.

The application of nanotechnology with integration of chemical sciences is increasing continuously in the management of diseases. The drug's physicochemical and pharmacological characteristics are enhanced by application of nanotechnological principles. Several nanotechnology-based formulations are being investigated to improve patient compliance. One such novel nanocarrier system is transfersome (TFS) and is composed of natural biocompatible phospholipids and edge activators. Morphologically, TFS are similar to liposomes but functionally, these are ultra-deformable vesicles which can travel through pores smaller than their size. Because of their amphipathic nature, TFS have the potential to deliver the drugs through sensitive biological membranes, especially the blood-brain barrier, skin layers, and nasal epithelium. Different molecular weight drugs can be transferred inside the cell by encapsulation into the TFS. Knowing the tremendous potentiality of TFS, the present work provides an in-depth and detailed account (pharmaceutical and preclinical characteristics) of TFS incorporating different categories of therapeutic moieties (anti-diabetic, anti-inflammatory, anti-cancer, anti-viral, anti-fungal, anti-oxidant, cardiovascular drugs, CNS acting drugs, vaccine delivery, and miscellaneous applications). It also includes information about the methods of preparation employed, significance of excipients used in the preparation, summary of clinical investigations performed, patent details, latest investigations, routes of administration, challenges, and future progresses related to TFS.

Nanocarrier-Based Delivery Approaches of Mangiferin: An Updated Review on Leveraging Biopharmaceutical Characteristics of the Bioactive.

In recent years, bioactive constituents from plants have been investigated as an alternative to synthetic approaches of therapeutics. Mangiferin (MGF) is a xanthone glycoside extracted from Mangifera indica and has shown numerous medicinal properties, such as antimicrobial, anti-diarrhoeal, antiviral, anti-inflammatory, antihypertensive, anti-tumours, and anti-diabetic effects. However, there are numerous challenges to its effective therapeutic usage, including its low water solubility, limited absorption, and poor bioavailability. Nano formulation approaches in recent years exhibited potential for the delivery of phytoconstituents with key benefits of high entrapment, sustained release, enhanced solubility, stability, improved pharmacokinetics, and site-specific drug delivery. Numerous techniques have been employed for the fabrication of MGF-loaded Nano formulations, and each technique has its advantages and limitations. The nanocarriers that have been employed to fabricate MGF nanoformulations for various therapeutic purposes include; polymeric nanoparticles, nanostructure, lipid carriers, polymeric micelles, Nano emulsions, microemulsion & self-microemulsifying drug delivery system, solid lipid nanoparticles, gold nanoparticles, carbon nanotubes, transfersomes, nanoliposomes, ethosomes & transethosomes, and glycethosomes. Different biopharmaceutical characteristics (size, shape, entrapment efficiency, zeta potential, in vitro drug release, ex vivo drug permeation,, and in vivo studies) of the mentioned MGF-loaded nanocarriers have been methodically discussed. Patent reports are also included to further strengthen the potential of MGF in the management of diseases.

LSTM based stock prediction using weighted and categorized financial news.

A significant correlation between financial news with stock market trends has been explored extensively. However, very little research has been conducted for stock prediction models that utilize news categories, weighted according to their relevance with the target stock. In this paper, we show that prediction accuracy can be enhanced by incorporating weighted news categories simultaneously into the prediction model. We suggest utilizing news categories associated with the structural hierarchy of the stock market: that is, news categories for the market, sector, and stock-related news. In this context, Long Short-Term Memory (LSTM) based Weighted and Categorized News Stock prediction model (WCN-LSTM) is proposed. The model incorporates news categories with their learned weights simultaneously. To enhance the effectiveness, sophisticated features are integrated into WCN-LSTM. These include, hybrid input, lexicon-based sentiment analysis, and deep learning to impose sequential learning. Experiments have been performed for the case of the Pakistan Stock Exchange (PSX) using different sentiment dictionaries and time steps. Accuracy and F1-score are used to evaluate the prediction model. We have analyzed the WCN-LSTM results thoroughly and identified that WCN-LSTM performs better than the baseline model. Moreover, the sentiment lexicon HIV4 along with time steps 3 and 7, optimized the prediction accuracy. We have conducted statistical analysis to quantitatively assess our findings. A qualitative comparison of WCN-LSTM with existing prediction models is also presented to highlight its superiority and novelty over its counterparts.

Exploring the potential of nanocarriers in antipsoriatic therapeutics.

Psoriasis is an autoimmune disease characterized by erythematous, scaly patches on the skin. It can be effectively managed with topical therapies since they deliver drugs to target sites of disease efficiently and can minimize systemic side-effects while ensuring high patient compliance. However, conventional topical formulations are ineffective in treating psoriasis due to their poor percutaneous penetration and inability to reach deeper layers of the skin. Thus, it is important to explore new approaches for managing psoriasis safely and effectively while also maintaining patient compliance without compromising safety. Over the last few decades, a variety of nanocarriers have been extensively investigated as a new approach to delivering drugs to the skin that are effective against psoriasis. These nanocarriers are notable for their therapeutic effectiveness, increased localization of medication in the skin, and reduced side-effects. The purpose of this review is to explore the recent advances in polymer-based, lipid-based, metallic, and microneedle-based novel nanoformulations of antipsoriatic drugs. There have been detailed discussions about several nanocarrier systems including nanoemulsions, liposomes, nanostructured lipid carriers, ethosomes, solid lipid nanoparticles, micelles, gold nanoparticles, silver nanoparticles, and microneedles. In a nutshell, nanoformulations are considered a promising avenue for psoriasis treatment since they offer better penetration, targeted delivery, and enhanced safety and efficacy.

Diet-derived small molecules (nutraceuticals) inhibit cellular proliferation by interfering with key oncogenic pathways: an overview of experimental evidence in cancer chemoprevention.

Discouraging statistics of cancer disease has projected an increase in the global cancer burden from 19.3 to 28.4 million incidences annually within the next two decades. Currently, there has been a revival of interest in nutraceuticals with evidence of pharmacological properties against human diseases including cancer. Diet is an integral part of lifestyle, and it has been proposed that an estimated one-third of human cancers can be prevented through appropriate lifestyle modification including dietary habits; hence, it is considered significant to explore the pharmacological benefits of these agents, which are easily accessible and have higher safety index. Accordingly, an impressive embodiment of evidence supports the concept that the dietary factors are critical modulators to prevent, retard, block, or reverse carcinogenesis. Such an action reflects the ability of these molecules to interfere with multitude of pathways to subdue and neutralize several oncogenic factors and thereby keep a restraint on neoplastic transformations. This review provides a series of experimental evidence based on the current literature to highlight the translational potential of nutraceuticals for the prevention of the disease through consumption of enriched diets and its efficacious management by means of novel interventions. Specifically, this review provides the current understanding of the chemopreventive pharmacology of nutraceuticals such as cucurbitacins, morin, fisetin, curcumin, luteolin and garcinol toward their potential as anticancer agents.

Pharmacological Efficacy and Safety of Glycyrrhiza glabra in the Treatment of Respiratory Tract Infections.

Respiratory tract infections are underestimated because they are mild and disabling, but in clinical medicine, these are the most prevalent problems. According to the World Health Organization third-most comprehensive cause of death in the world till 2030 would be Chronic Obstructive Pulmonary Disease (COPD). Dominating viruses of respiratory infections are influenza, respiratory syncytial virus, rhinoviruses, and human coronaviruses. Antibiotics are mostly used to treat bacterial infections, and they do not effectively manage viral infections like sinusitis, sore throats, bronchitis, influenza, and common respiratory infections. Presently no medication is available only symptomatic interventions is an option in our hand. However, a lot of research is going on the vaccine and drugs-based approaches against respiratory viruses worldwide. Traditional medicines are getting the attraction to treat many diseases. It is vital to screen the medicinal plants to find the potential of new compounds for treatment against antiviral and antimicrobial activities. Glycyrrhiza glabra L. (Licorice) pharmacological actions modulate the immune system, inhibit virus growth, produce anti-inflammatory activity, and inactivate viruses. This comprehensive review mainly focuses on the role of licorice in managing respiratory infections caused by viruses and bacteria, including complications associated with its excess intake. There has been limited human research's exhibited licorice effectiveness in respiratory infections; therefore, there is a need for uncompromising and long-term research. This paper will be a valuable reference for biologists and physicians looking for a medication for respiratory infections. Glycyrrhiza glabra could open the door to novel agents in drug discovery and development.

Anticancer Potential of Naringenin, Biosynthesis, Molecular Target, and Structural Perspectives.

Numerous novel medicinal agents isolated from plant sources were used as indigenous remedies for the management and treatment of various types of cancer diseases. Naringenin is a naturally occurring flavanone glycoside, and aglycone (genin) moiety of naringin, predominantly found in citrus and grapefruits, has emerged as a potential therapeutic agent for the management of a variety of diseases. A number of scientific papers have been published on naringenin describing its detailed studies and its therapeutic application in different diseases. The current study highlights a comprehensive study on naringenin concerning its biosynthesis, molecular targets/pathways involved in carcinogenesis, mechanism of actions (MOAs), and structure-activity relationships (SARs), and patents granted have been highlighted. Naringenin and its derivatives have great anti-cancer activity due to their inhibitory potential against diverse targets, namely ABCG2/P-gp/BCRP, 5a-reductase, 17- bhydroxysteroid dehydrogenase, aromatase, proteasome, HDAC/Situin-1, VEGF, VEGFR-2 kinase, MMP-2/9, JAK/STAT signaling pathways, CDC25B, tubulin, topoisomerase-II, cathepsin-K, Wnt, NF-kB, B-Raf and mTOR, etc. With the in-depth knowledge of molecular targets, structural intuition, and SARs, the current study may be beneficial to design more potent, safe, effective, and economic anti-cancer naringenin. This has been concluded that naringenin is a promising natural product for the management and therapy of cancer. Further evolution for pharmacological importance, clinical research, and trials are required to manifest its therapeutic action on metabolic syndrome in the human community.

Effectual Endeavors of Silk Protein Sericin against Isoproterenol Induced Cardiac Toxicity and Hypertrophy in Wistar Rats.

The silkworm cocoon has been used in the treatment of various ailments in different Asian countries. This research was designed to evaluate the effect of sericin on myocardial necrosis and hypertrophy in isoproterenol-challenged rats. The rats were administered with sericin (500 and 1000 mg/kg, p.o.) for 28 days, followed by administration of isoprenaline (85 mg/kg, s.c.) on the 29th and 30th days. The cardioprotective activity was assessed by various physical, enzymatic, and histopathological parameters along with apoptotic marker expression. The cardioprotective effect showed that pre-treatment of rats with sericin significantly increased the non-enzymatic antioxidants marker in serum and heart tissue (glutathione, vitamin E, and vitamin C). The results were the same in enzymatic antioxidant marker, mitochondrial enzymes, and protein. The grading of heart, heart/body weight ratio, gross morphology, cardiac markers, oxidative stress markers in serum and heart tissue, glucose, serum lipid profiling and Lysosomal hydrolases, heart apoptotic markers such as MHC expression by western blot, apoptosis by flow cytometry, total myocardial collagen content, fibrosis estimation, myocyte size were significantly decreased when compared with isoproterenol (ISG) group however histopathological studies showed normal architecture of heart in both control and treated rats. The pharmacological study reflects that sericin on both doses i.e., 500 mg/kg and 1000 mg/kg have potent cardioprotective action against the experimental model which was confirmed by various physical, biochemical, and histopathological parameters evaluated further research is required to examine the molecular mechanism of cardioprotective effect of sericin.

Pharmacological Efficacy of Probiotics in Respiratory Viral Infections: A Comprehensive Review.

Mortality and morbidity from influenza and other respiratory viruses are significant causes of concern worldwide. Infections in the respiratory tract are often underappreciated because they tend to be mild and incapacitated. On the other hand, these infections are regarded as a common concern in clinical practice. Antibiotics are used to treat bacterial infections, albeit this is becoming more challenging since many of the more prevalent infection causes have acquired a wide range of antimicrobial resistance. Resistance to frontline treatment medications is constantly rising, necessitating the development of new antiviral agents. Probiotics are one of several medications explored to treat respiratory viral infection (RVI). As a result, certain probiotics effectively prevent gastrointestinal dysbiosis and decrease the likelihood of secondary infections. Various probiotic bacterias and their metabolites have shown immunomodulating and antiviral properties. Unfortunately, the mechanisms by which probiotics are effective in the fight against viral infections are sometimes unclear. This comprehensive review has addressed probiotic strains, dosage regimens, production procedures, delivery systems, and pre-clinical and clinical research. In particular, novel probiotics' fight against RVIs is the impetus for this study. Finally, this review may explore the potential of probiotic bacterias and their metabolites to treat RVIs. It is expected that probiotic-based antiviral research would be benefitted from this review's findings.

News sensitive stock market prediction: literature review and suggestions.

Stock market prediction is a challenging task as it requires deep insights for extraction of news events, analysis of historic data, and impact of news events on stock price trends. The challenge is further exacerbated due to the high volatility of stock price trends. However, a detailed overview that discusses the overall context of stock prediction is elusive in literature. To address this research gap, this paper presents a detailed survey. All key terms and phases of generic stock prediction methodology along with challenges, are described. A detailed literature review that covers data preprocessing techniques, feature extraction techniques, prediction techniques, and future directions is presented for news sensitive stock prediction. This work investigates the significance of using structured text features rather than unstructured and shallow text features. It also discusses the use of opinion extraction techniques. In addition, it emphasizes the use of domain knowledge with both approaches of textual feature extraction. Furthermore, it highlights the significance of deep neural network based prediction techniques to capture the hidden relationship between textual and numerical data. This survey is significant and novel as it elaborates a comprehensive framework for stock market prediction and highlights the strengths and weaknesses of existing approaches. It presents a wide range of open issues and research directions that are beneficial for the research community.

Efficacy of Dexamethasone for the Treatment of COVID-19 Infection: A Perspective Review.

The current COVID-19 pandemic has provoked the urgent requirement to search for effective treatments since the implications are so huge globally as compared to the earlier pandemics. Momentarily, there has been no effective medicine for SARS-CoV-2 infection, and supportive care tends to be the most effective approach to treat COVID-19 patients. The rapidly growing awareness of SARS-CoV-2 virology offers a large number of possible drug targets. The World Health Organisation (WHO) is steadily updating the treatment protocol for COVID-19 based on the recent clinical trials. In the present review, we have summarised the possible mode of action, clinical evidence, consequences of dexamethasone as the therapeutic agent against Covid-19. Currently, many corticosteroids are being tested in ongoing randomised trials. Dexamethasone could come as the life-saving drug. Dexamethasone drug looks useful only in those patients who are already in a critical state. We might allow dexamethasone as a fascinating shot, if the drug proves to be clinically favourable for long-term health effects of Covid-19 recovered patients. It is commonly accepted to reinforce approved drugs in the fight against newly emerging diseases such as COVID-19 as these drugs have established pharmacokinetic profiles and protection. The current focus should be on the development of novel proven therapeutics along with vaccines. There is a need for high quality, more extensive, rapid and collaborative randomized controlled trials with more control groups.

Effectiveness of Azithromycin as Add-on Therapy in COVID-19 Management.

As winter is approaching us, the possibility of respiratory tract infection is rising in the current scenario due to the lack of Covid-19 prophylaxis. So no one could be safe until everyone is safe. Researchers are looking for the vaccine to remove the need for social distancing, mask-wearing, and social gathering worldwide. We cannot say about the vaccine's effectiveness if the vaccine is available. Several drugs are being tested to save people's life from the pandemic; azithromycin is one of them. This work is a review article with the updated findings of azithromycin in the context of COVID-19. The option of azithromycin regarding COVID-19 is justified by its anti-inflammatory, immunomodulatory, and anti-fibrotic effects and their pharmacokinetic properties, leading to effective concentrations in the target tissue. Azithromycin tends to be an effective candidate for SARS-CoV-2 replication inhibition that blocks the initial stage of the viral life cycle. Clinical trials at a preliminary scale and final stage show the significant results of azithromycin in supportive care therapy. Azithromycin was an early candidate for the medication of Covid-19 with or without hydroxychloroquine. It is exercised mainly as an outpatient antibiotic in COVID-19. In summing up, any primary anti-viral and antibiotic treatment is not the only possibility of fighting COVID-19 pharmacologically. It will be an injustice to those who require broader spectrum antibiotics if we do not use azithromycin. So significant research priority is needed to determine whether azithromycin is useful in the treatment of COVID-19.

Withdrawal Notice: A Panoramic View on the Phytochemical, Nutritional and Therapeutic value of Ziziphus mauritiana Lam.: A Comprehensive Review

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Diligent profiling of preclinical safety of the silk protein sericin.

BACKGROUND: Sericin is a widely used protein in the pharmaceutical industry derived from the silkworm, Bombyx mori, and used for the treatment of various diseases and pathological conditions. It is the main ingredient of the Unani preparation khameera abresham. The study was conducted to evaluate the preclinical toxicity of the silk protein sericin in mice. METHODS: In the acute toxicity study, sericin was administered once orally to different groups of animals at doses of 500, 1000, and 2000 mg/kg. Animals were observed for 14 days. In the sub-acute toxicity study, sericin was administered in mice for 4 weeks in the toxic group at doses of 500, 1000, and 2000 mg/kg, while in the recovery group it was administered for 4 weeks at doses of 500 and 2000 mg/kg followed by 2 weeks of distilled water administration. RESULTS: In the acute toxicity study, the observed parameters showed no significant difference, and no mortality was reported. In the sub-acute toxicity study, there were no toxicological effects in any of the estimated parameters, while histopathological analysis showed inflammation in vital organs at the dose of 2000 mg/kg. CONCLUSIONS: Results of our acute toxicity study suggest that sericin is safe at all administered doses, while the sub-acute study suggests that the NOAEL (no-observed-adverse-effect level) of sericin is below 2000 mg/kg, at which it can be considered safe.

An Insight on Silk Protein Sericin: From Processing to Biomedical Application.

Silks are naturally occurring polymers that have been used clinically as sutures for hundreds of years. It's so for obtained from insects or worms, silk consists of a filament core protein, termed fibroin, and a glue-like coating made up of sericin proteins. An important component of silk has an extended history of being discarded as a waste in the course of silk processing. The cost of sericin for tissue engineering is underestimated and its capability in using as regenerative remedy has simply began to be explored. Its variable amino acid composition and various functional groups confer upon it attractive bioactive proteins, which are particularly interesting for biomedical programs. Because of its antioxidant properties, moisturizing ability, and mitogenic effect on mammalian cells, sericin is beneficial in cell regeneration and tissue engineering. Research shows that keratinocytes and fibroblasts have brought about the improvement of sericin-primarily based biomaterials for skin tissue repair, in particular as wound dressings. Moreover, sericin may be used for bone tissue engineering due to its ability to set off nucleation of bone-like hydroxyapatite. Stable silk sericin biomaterials, as films, sponges, and hydrogels, are obtained by means of cross-linking, ethanol precipitation, or mixing with different polymers. Now a day, sericin may also be used for delivery of drugs due to its chemical reactivity and pH-responsiveness which facilitate the fabrication of nano and microparticles, hydrogels, and conjugated molecules, enhancing the bioactivity of drugs. In this review, we outlined the current headways from extraction of sericin till its physical properties and biomedical applications.

A conglomeration of preclinical models related to myocardial infarction

Cardiovascular diseases are the main source of death and morbidity in developed and developing nations. Animal models are required to propel our understanding of the pathogenesis, increase our knowledge, disease progress, and mechanism behind cardiovascular disorder, providing new approaches focused to improve the diagnostic and the treatment of these pathological conditions and additionally to test various therapeutic ways to deal with tissue regeneration and re-establish heart working following damage. A perfect model framework ought to be reasonable, effectively controlled, reproducible, and physiologically illustrative of human disease, show cardinal signs and pathology that resembles after the human ailment and ethically stable. The decision of selection of animal model should be considered precisely since it influences exploratory results and whether results of the research can be sensibly matched with the human. In this way, no specific technique splendidly reproduces the human disease, and relying upon the model, extra cost burden, resources, infrastructure and the necessity for technical hands, should also be kept under consideration. Here we have discussed and compiled various methods of inducing myocardial infarction in animals, basically by surgery, chemicals and through genetic modification, this may benefit the researchers in getting a complied data regarding various methods through which they can induce myocardial infarction in animals.