Curcuminoids as cell signaling pathway modulators: A potential strategy for cancer prevention.

Despite substantial advancements in curative modern medicine in the last few decades, cancer risk and casualty rates have continued to mount globally. The exact reason for cancer's onset and progression is still unknown. However, skeletal and functional abnormalities in the genetic code are assumed to be the primary cause of cancer. Many lines of evidences reported that some medicinal plants can be utilized to curb cancer cell proliferation with a safe, fruitful, and cost-efficient perspective. Curcuminoids, isolated from Curcuma longa, have gotten a lot of focus due to their anticancer potential as they reduce tumor progression, invasion, and dissemination. Further, they modulated signal transduction routes like MAPK, PI3K/Akt/mTOR, JAK/STAT, and Wnt/ß-catenin, etc., and triggered apoptosis as well as actuated autophagy in malignant cells without altering the normal cells, thus preventing cancer progression. Besides, Curcuminoids also regulate the function and expression of anti-tumor and carcinogenic miRNAs. Clinical studies also reported the therapeutic effect of Curcuminoids against various cancer through decreasing specific biomarkers like TNF-α, Bcl-2, COX-2, PGE2, VEGF, IκKß, and various cytokines like IL-12p70, IL-10, IL-2, IFN-γ levels and increasing in p53 and Bax levels. Thus, in the present review, we abridged the modulation of several signal transduction routes by Curcuminoids in various malignancies, and its modulatory role in the initiation of tumor-suppressive miRNAs and suppression of the oncogenic miRNAs are explored. Additionally, various pharmacokinetic approaches have been projected to address the Curcuminoids bioavailability like the use of piperine as an adjuvant; nanotechnology-based Curcuminoids preparations utilizing Curcuminoids analogues are also discussed.

Novel insights on perils and promises of miRNA in understanding colon cancer metastasis and progression.

Colorectal cancer (CRC) is the third highest frequent malignancy and ultimate critical source of cancer-associated mortality around the world. Regardless of latest advances in molecular and surgical targeted medicines that have increased remedial effects in CRC patients, the 5-year mortality rate for CRC patients remains dismally low. Evidence suggests that microRNAs (miRNAs) execute an essential part in the development and spread of CRC. The miRNAs are a type of short non-coding RNA that exhibited to control the appearance of tumor suppressor genes and oncogenes. miRNA expression profiling is already being utilized in clinical practice as analytical and prognostic biomarkers to evaluate cancer patients' tumor genesis, advancement, and counteraction to drugs. By modulating their target genes, dysregulated miRNAs are linked to malignant characteristics (e.g., improved proliferative and invasive capabilities, cell cycle aberration, evasion of apoptosis, and promotion of angiogenesis). This review presents an updated summary of circulatory miRNAs, tumor-suppressive and oncogenic miRNAs, and the potential reasons for dysregulated miRNAs in CRC. Further we will explore the critical role of miRNAs in CRC drug resistance.

TGF-ß signaling pathway: Therapeutic targeting and potential for anti-cancer immunity.

Transforming growth factor-ß (TGFß) is a pleiotropic secretory cytokine exhibiting both cancer-inhibitory and promoting properties. It transmits its signals via Suppressor of Mother against Decapentaplegic (SMAD) and non-SMAD pathways and regulates cell proliferation, differentiation, invasion, migration, and apoptosis. In non-cancer and early-stage cancer cells, TGFß signaling suppresses cancer progression via inducing apoptosis, cell cycle arrest, or anti-proliferation, and promoting cell differentiation. On the other hand, TGFß may also act as an oncogene in advanced stages of tumors, wherein it develops immune-suppressive tumor microenvironments and induces the proliferation of cancer cells, invasion, angiogenesis, tumorigenesis, and metastasis. Higher TGFß expression leads to the instigation and development of cancer. Therefore, suppressing TGFß signals may present a potential treatment option for inhibiting tumorigenesis and metastasis. Different inhibitory molecules, including ligand traps, anti-sense oligo-nucleotides, small molecule receptor-kinase inhibitors, small molecule inhibitors, and vaccines, have been developed and clinically trialed for blocking the TGFß signaling pathway. These molecules are not pro-oncogenic response-specific but block all signaling effects induced by TGFß. Nonetheless, targeting the activation of TGFß signaling with maximized specificity and minimized toxicity can enhance the efficacy of therapeutic approaches against this signaling pathway. The molecules that are used to target TGFß are non-cytotoxic to cancer cells but designed to curtail the over-activation of invasion and metastasis driving TGFß signaling in stromal and cancer cells. Here, we discussed the critical role of TGFß in tumorigenesis, and metastasis, as well as the outcome and the promising achievement of TGFß inhibitory molecules in the treatment of cancer.

The Future of Precision Medicine in the Cure of Alzheimer's Disease.

This decade has seen the beginning of ground-breaking conceptual shifts in the research of Alzheimer's disease (AD), which acknowledges risk elements and the evolving wide spectrum of complicated underlying pathophysiology among the range of diverse neurodegenerative diseases. Significant improvements in diagnosis, treatments, and mitigation of AD are likely to result from the development and application of a comprehensive approach to precision medicine (PM), as is the case with several other diseases. This strategy will probably be based on the achievements made in more sophisticated research areas, including cancer. PM will require the direct integration of neurology, neuroscience, and psychiatry into a paradigm of the healthcare field that turns away from the isolated method. PM is biomarker-guided treatment at a systems level that incorporates findings of the thorough pathophysiology of neurodegenerative disorders as well as methodological developments. Comprehensive examination and categorization of interrelated and convergent disease processes, an explanation of the genomic and epigenetic drivers, a description of the spatial and temporal paths of natural history, biological markers, and risk markers, as well as aspects about the regulation, and the ethical, governmental, and sociocultural repercussions of findings at a subclinical level all require clarification and realistic execution. Advances toward a comprehensive systems-based approach to PM may finally usher in a new era of scientific and technical achievement that will help to end the complications of AD.

Treatment of Autism Spectrum Disorders by Mitochondrial-targeted Drug: Future of Neurological Diseases Therapeutics.

Autism is a neurodevelopmental disorder with a complex etiology that might involve environmental and genetic variables. Recently, some epidemiological studies conducted in various parts of the world have estimated a significant increase in the prevalence of autism, with 1 in every 59 children having some degree of autism. Since autism has been associated with other clinical abnormalities, there is every possibility that a sub-cellular component may be involved in the progression of autism. The organelle remains a focus based on mitochondria's functionality and metabolic role in cells. Furthermore, the mitochondrial genome is inherited maternally and has its DNA and organelle that remain actively involved during embryonic development; these characteristics have linked mitochondrial dysfunction to autism. Although rapid stride has been made in autism research, there are limited studies that have made particular emphasis on mitochondrial dysfunction and autism. Accumulating evidence from studies conducted at cellular and sub-cellular levels has indicated that mitochondrial dysfunction's role in autism is more than expected. The present review has attempted to describe the risk factors of autism, the role of mitochondria in the progression of the disease, oxidative damage as a trigger point to initiate mitochondrial damage, genetic determinants of the disease, possible pathogenic pathways and therapeutic regimen in vogue and the developmental stage. Furthermore, in the present review, an attempt has been made to include the novel therapeutic regimens under investigation at different clinical trial stages and their potential possibility to emerge as promising drugs against ASD.

In Silico molecular docking and dynamic analysis of natural compounds against major non-structural proteins of SARS-COV-2.

COVID-19 has infected millions and significantly affected the global economy and healthcare systems. Despite continuous lockdowns, symptomatic management with currently available medications, and numerous vaccination drives, it is still far more difficult to control. Against COVID-19 infection, the pressure to develop vaccines and drugs has led to using some currently available medications like remdesivir, azithromycin, hydroxychloroquine and ritonavir. Understanding the importance and potential of harmless molecules to tackle SARS-COV-2, we designed the present study to identify potential natural phytocompounds. In the present study, we docked natural compounds and standard drugs against SARS-COV-2 proteins: papain-like protease, main protease and helicase. ADME/T and ProTox-II analyses were used to determine the toxicity of phytocompounds and drugs. The docking analysis revealed that podophyllotoxin gave the highest binding affinity scores of -8.1, -7.1 and -7.4 kcal/mol against PLpro, Mpro and helicase, respectively. Among the control drugs, doxycycline hydrochloride showed the highest binding affinity of -10.5, -8.4 and -8.8 kcal/mol against PLpro, Mpro and helicase. The results of this study revealed that podophyllotoxin and doxycycline hydrochloride could be promising inhibitors against SARS-Cov-2. Molecular dynamic simulations were executed for the best docked (PLpro-podophyllotoxin) complex, and the results displayed stable conformation and convergence. Energy plot results predicted a global minima average energy of -95 kcal/mol and indicated podophyllotoxin's role in stabilizing protein and making it compact and complex. FarPPI server used MM/GBSA approach to determine free binding affinity, and helicase-gallic acid complex showed the highest affinity, respectively. Therefore, it can be concluded that there is still a need for in vitro and in vivo studies to support further and validate these findings and validate these findings.Communicated by Ramaswamy H. Sarma.

Mitochondrial dysfunctions, oxidative stress and neuroinflammation as therapeutic targets for neurodegenerative diseases: An update on current advances and impediments.

Neurodegenerative diseases (NDs) such as Alzheimer disease (AD), Parkinson disease (PD), and Huntington disease (HD) represent a major socio-economic challenge in view of their high prevalence yet poor treatment outcomes affecting quality of life. The major challenge in drug development for these NDs is insufficient clarity about the mechanisms involved in pathogenesis and pathophysiology. Mitochondrial dysfunction, oxidative stress and inflammation are common pathways that are linked to neuronal abnormalities and initiation of these diseases. Thus, elucidating the shared initial molecular and cellular mechanisms is crucial for recognizing novel remedial targets, and developing therapeutics to impede or stop disease progression. In this context, use of multifunctional compounds at early stages of disease development unclogs new avenues as it acts on act on multiple targets in comparison to single target concept. In this review, we summarize overview of the major findings and advancements in recent years focusing on shared mechanisms for better understanding might become beneficial in searching more potent pharmacological interventions thereby reducing the onset or severity of various NDs.

Multiomics technologies: role in disease biomarker discoveries and therapeutics.

Medical research has been revolutionized after the publication of the full human genome. This was the major landmark that paved the way for understanding the biological functions of different macro and micro molecules. With the advent of different high-throughput technologies, biomedical research was further revolutionized. These technologies constitute genomics, transcriptomics, proteomics, metabolomics, etc. Collectively, these high-throughputs are referred to as multi-omics technologies. In the biomedical field, these omics technologies act as efficient and effective tools for disease diagnosis, management, monitoring, treatment and discovery of certain novel disease biomarkers. Genotyping arrays and other transcriptomic studies have helped us to elucidate the gene expression patterns in different biological states, i.e. healthy and diseased states. Further omics technologies such as proteomics and metabolomics have an important role in predicting the role of different biological molecules in an organism. It is because of these high throughput omics technologies that we have been able to fully understand the role of different genes, proteins, metabolites and biological pathways in a diseased condition. To understand a complex biological process, it is important to apply an integrative approach that analyses the multi-omics data in order to highlight the possible interrelationships of the involved biomolecules and their functions. Furthermore, these omics technologies offer an important opportunity to understand the information that underlies disease. In the current review, we will discuss the importance of omics technologies as promising tools to understand the role of different biomolecules in diseases such as cancer, cardiovascular diseases, neurodegenerative diseases and diabetes.

Nanogel-based Transdermal Drug Delivery System: A Therapeutic Strategy with Under Discussed Potential.

The application of nanoparticles in medication delivery has revolutionized the field of therapeutic biology. To improve medical efficacy, currently, drug nanocarriers are employed to control the release and stability, expand its circulation time, or protect it from cell clearance or premature breakdown. A crosslinked polymeric framework is used to crosslink the hydrogel nanoparticle dispersions for safer and stable delivery on target sites. Nanogels have developed in the last two decades as potential biomaterials with a wide variety of applications. Later attributes of nanogels are mainly due to large surface areas, retention of molecules, size flexibility, and water-based formulations that have made them popular as drug delivery vehicles, as seen by several in vivo uses. The gel matrix containing the nanoparticle drug demonstrated a considerable increase in drug penetration in transdermal drug and topical delivery methods. This review aims to understand why and how nanogels are considered so innovative as a drug delivery method. It also examines their preparation methods and applications in the pharmaceutical and biomedical fields and discusses the benefits of nanogels, including swelling capacity and stimulus stimuli sensitivity. Nanogels, on the other hand, have recently been investigated for applications outside the field of biomedicine. Since there are many possible uses for nanogels, we have comprehensively reviewed the current state of the art for all feasible nanogel applications and manufacturing methods.

Perception of pharmacy students toward numeracy: An observational study from King Saud University, Riyadh Saudi Arabia.

Background and objective: Numeracy is the branch of mathematics involved in understanding basic calculations, quantitation, estimation, reasoning, and execution of multistep operations. It is very imperative that pharmacists understand and apply numeracy skills in their routine work in the interest of their profession and patient care. This observational study was designed to assess the pharmacy student's perceptions of numeracy. Methods: A prospective observational study was conducted by the Department of Pharmacy, King Saud University, Kingdom of Saudi Arabia, between December 2021 and February 2022. All the enrolled subjects pursued a 5-year Pharma degree course at the university using a 9-item instrument, which accessed the perception of students toward numeracy. The data were analyzed using the statistical software statistical package for social science (SPSS) version 26.0 (SPSS Inc., Chicago, IL, USA). Chi-square and Fisher's exact test were used to derive an association between various parameters of the study subjects. A P-value of < 0.05 was taken as statistically significant. Results: A total of 550 pharmacy students were approached in this study, out of which 21 (3.8%) students were excluded due to incompleteness of the responses; thereupon, 529 students were included in the study. We learned that almost 90.0% of students had excellent and/or good mathematical ability, but at the same time, they were frequent users of calculators. Most of the students endorsed the importance of numeracy and showed their interest in attaining more knowledge of numeracy. Similarly rating the perceptions of mathematical ability is significantly associated with the frequency of use of a calculator for calculations (p = 0.0001). Conclusion: Pharmacy students showed interest in numeracy and correspondingly showed excellent perceptions toward mathematical ability. Although the role of numeracy has been well accepted, inciting changes in teaching-learning practices through mathematically focused teaching approaches throughout the pharmacy program will increase its applicability in healthcare.

Job Motivation and Satisfaction Among Female Pharmacists Working in Private Pharmacy Professional Sectors in Saudi Arabia.

Background: Pharmacists' job satisfaction has been of interest for many years and is of great importance in several respects, such as productivity and ultimately organizational performance. Objective: This study aimed to investigate the perceived motivational factors and levels of job satisfaction of female pharmacists working in private pharmaceutical sectors. Methods: This was a cross-sectional study using a web-based survey of randomly selected female pharmacists working in different private settings including community pharmacies, pharmaceutical companies, private hospitals, and other private sectors using a pre-validated satisfaction scale (Warr-Cook-Wall scale). Results: A total of 232 female pharmacists participated in the study with a mean age of 26.1±2.4 years. Of the total respondents, more than half (58%) worked for pharmaceutical companies, 25% worked in community pharmacies, and 16.8% were from hospital pharmacies. The most attractive motivating factors that encourage female pharmacists toward better performance were having the opportunity to learn new skills, being in contact with people both locally and internationally, gaining a sense of achievement, and being recognized, appreciated, and rewarded. The participants of this study were shown to have a moderate job satisfaction level. Conclusion: This study revealed that the non-Saudi, part-time pharmacists who never expected a promotion were less satisfied than the Saudi, full-time employees who expected a promotion within a year.

Mechanisms of Mitochondrial Malfunction in Alzheimer's Disease: New Therapeutic Hope.

Mitochondria play a critical role in neuron viability or death as it regulates energy metabolism and cell death pathways. They are essential for cellular energy metabolism, reactive oxygen species production, apoptosis, Ca++ homeostasis, aging, and regeneration. Mitophagy and mitochondrial dynamics are thus essential processes in the quality control of mitochondria. Improvements in several fundamental features of mitochondrial biology in susceptible neurons of AD brains and the putative underlying mechanisms of such changes have made significant progress. AD's etiology has been reported by mitochondrial malfunction and oxidative damage. According to several recent articles, a continual fusion and fission balance of mitochondria is vital in their normal function maintenance. As a result, the shape and function of mitochondria are inextricably linked. This study examines evidence suggesting that mitochondrial dysfunction plays a significant early impact on AD pathology. Furthermore, the dynamics and roles of mitochondria are discussed with the link between mitochondrial malfunction and autophagy in AD has also been explored. In addition, recent research on mitochondrial dynamics and mitophagy in AD is also discussed in this review. It also goes into how these flaws affect mitochondrial quality control. Furthermore, advanced therapy techniques and lifestyle adjustments that lead to improved management of the dynamics have been demonstrated, hence improving the conditions that contribute to mitochondrial dysfunction in AD.

Chemical Composition Analysis, Cytotoxic, Antimicrobial and Antioxidant Activities of Physalis angulata L.: A Comparative Study of Leaves and Fruit.

Physalis angulata L. belongs to the family Solanaceae and is distributed throughout the tropical and subtropical regions. Physalis angulata leaf and fruit extracts were assessed for in vitro anticancer, antioxidant activity, and total phenolic and flavonoid content. The GC-MS technique investigated the chemical composition and structure of bioactive chemicals reported in extracts. The anticancer activity results revealed a decrease in the percentage of anticancer cells' viability in a concentration- and time-dependent way. We also noticed morphological alterations in the cells, which we believe are related to Physalis angulata extracts. Under light microscopy, we observed that as the concentration of ethanolic extract (fruit and leaves) treated HeLa cells increased, the number of cells began to decrease.

Myricetin (3,3',4',5,5',7-Hexahydroxyflavone) Prevents 5-Fluorouracil-Induced Cardiotoxicity.

5-Fluorouracil (5-FU) is a strong anti-cancer drug used to manage numerous cancers. Cardiotoxicity, renal toxicity, and liver toxicity are some of the adverse effects which confine its clinical use to some extent. 5-FU-induced organ injuries are associated with redox imbalance, inflammation, and damage to heart functioning, particularly in the present study. Myricetin is an abundant flavonoid, commonly extracted from berries and herbs having anti-oxidative and anti-cancer activities. We planned the current work to explore the beneficial effects of myricetin against 5-FU-induced cardiac injury in Wistar rats through a biochemical and histological approach. Prophylactic myricetin treatment at two doses (25 and 50 mg/kg) was given to rats orally for 21 days against cardiac injury induced by a single injection of 5-FU (150 mg/kg b.wt.) given on the 20th day intraperitoneally. The 5-FU injection induced oxidative stress, inflammation, and extensive cardiac damage. Nevertheless, myricetin alleviated markers of inflammation, apoptosis, cardiac toxicity, oxidative stress, and upregulated anti-oxidative machinery. The histology of heart further supports our biochemical findings mitigated by the prophylactic treatment of myricetin. Henceforth, myricetin mitigates 5-FU-induced cardiac damage by modulating oxidative stress, inflammation, and cardiac-specific markers, as found in the present study.

Current nano-therapeutic approaches ameliorating inflammation in cancer progression.

Cancer is one of the biggest causes of mortality in the world. The advances in cancer research have taken us to distance in understanding the disease, which helps develop therapeutic strategies. Surgery and chemotherapy are the two main chosen routes of combat for cancer. These chemotherapeutic agents are good at targeting cancer, but many lack the specificity to make the distinction between healthy cells. Also, the toxicity of these chemotherapeutic agents is very high. This gap makes it quintessential to either look for better and safe agents or makes it possible for existing agents to meet these needs. Nanotechnology has the potential to deal with these unmet needs. Nanotechnology has been a hot topic recently due to its applications, one of these being nanomedicine. Studies have proven that cancer nanomedicine has a scope of being revolutionary. With the help of nanoparticles, we can make drugs specific for the cancer tissue; it can also help in increasing the bioavailability of the drug. A nanoparticle can be modified as such that it can carry the drug load that is required and deliver it to the specific target. In this review article, we have discussed the advances in nanomedicine and the current clinical status of various nanomedicines. We have extensively explored various strategies used to develop cancer nanomedicine while also discussing their mechanism of action.

Knowledge, Attitude and Perception of Pharmacy Students towards Pharmacogenomics and Genetics: An Observational Study from King Saud University.

Pharmacists are considered among the most accessible healthcare workers in fundamental positions to implement new clinical initiatives, such as pharmacogenomics services. The scope of pharmacogenomics in improving health outcomes and the quality of health care is well-known. Implementation of such initiatives requires adequate knowledge, perception, and positive attitudes among pharmacists. A study was conducted on pharmacy students at King Saud University in Riyadh to analyze their attitudes, knowledge, and perceptions concerning pharmacogenomics to explore the feasibility of establishing full-time pharmacogenomics instruction and services. A cross-sectional study was carried out in one of the significant pharmacy schools of Saudi Arabia, using a simple questionnaire-based survey in pharmacy students pursuing Bpharm and PharmD courses to obtain preliminary information about pharmacogenomics among the surveyed population. The study's secondary objective was to determine the perceived belief about pharmacogenomics implementation in clinical practice. Out of the total of 552 participants, 41.8% correctly defined pharmacogenomics and 81.3% understood that genetic change could lead to adverse reactions. More than half of the participants agreed that the FDA recommends pharmacogenomics testing for certain drugs. The knowledge about a year of use of pharmacogenomics in clinical practice was found to be very low; only 15.2% could correctly answer. Only 60% of students agreed on pharmacogenomics testing for selecting the therapy with the most negligible adverse effects. Due to the limited knowledge about and understanding of pharmacogenomics, there is a lack of interest among pharmacy students in implementing pharmacogenomics testing in clinical practice. Our study highlights the need for improving pharmacy students' knowledge about pharmacogenomics and pharmacogenetics so that the implementation of pharmacogenomics testing in clinical practice will become easier. There is a need to introduce an up-to-date curriculum for pharmacy courses other pharmacogenomics-based health education programs in Saudi Arabia.

Prevalence and Self-Medication for Acne among Students of Health-Related Science Colleges at King Saud University in Riyadh Region Saudi Arabia.

Background and Objectives: In Saudi Arabia, Acne vulgaris is a very predominant ailment among adolescents, especially female university students, and self-medication has become a trend to manage this condition. To determine the prevalence of Acne vulgaris among health care students and to access the scenario of its self-medication in light of students' knowledge, attitude, and practice towards it. Materials and Methods: This was an observational study conducted at King Saud University, Riyadh, Kingdom of Saudi Arabia, from January 2022 to March 2022. The study was undertaken using a pre-structured questionnaire. Results: A total of 550 university students were recruited and the incidence of acne was observed to be 78.5% (432 out of 550) with a female predominance. A total of 56.0% (244 of 432) students used self-medications for acne without a prescription and the most used prescription drugs were topical and oral antibiotics (38.1%), followed by Isotretinoin (22.55), and topical adaplene (20.9%). Female students (n = 181, 63.5%) were significantly more likely to self-medicate compared to male students (n = 63, 42.9%, p ≤ 0.001). Almost 60% of medical students had proper knowledge of medication for acne. Conclusion: Acne vulgaris is a highly prevalent condition among university students of Saudi Arabia and use of self-medication among acne sufferers is high. Education programs should be made to raise awareness about acne and its treatment.

The Characteristics of Clinical Studies Submitted to the Saudi Food and Drug Authority from 2009 until 2020.

BACKGROUND: Clinical trials are crucial in contemporary evidence-based medicine for discovering new treatments for diseases. Their registration in a registry increases the transparency in the dissemination of knowledge about clinical research. It is essential to understand the activity of clinical trials in a country, thus identifying research gaps. OBJECTIVE: This study, therefore, aims to describe the clinical trial activity since the inception of clinical trials' administration and national clinical trials' registry within the Kingdom of Saudi Arabia (KSA). METHOD: A descriptive study was conducted by reviewing all clinical studies that have been registered during 2009 and June 2020. The inclusion criterion was all phases of the clinical trials registered in the national registry during that period. Data analysis was done using descriptive statistics. RESULTS: Since 2009, 352 studies have been registered. However, a total of 333 studies with complete data was included in the analysis. A total of 80 sponsors funded the clinical studies in the KSA. The majority of the clinical studies are funded by multinational pharmaceutical companies. Oncology (13.81%) and diabetes (11.71%) were the most common therapeutic areas and constituted the largest proportion of the overall studies. 44% were phase 4 and 40% were phase 3 studies. CONCLUSION: With a population approaching 34 million, the number of clinical trials in the KSA is not sufficient. Since the inception of the clinical trial's administration and SCTR, the emphasis has been on phase 3 and phase 4 clinical studies. The most studied therapeutic areas were oncology and diabetes. Many clinical studies in the KSA were sponsored by multinational pharmaceutical companies.

Fate of arsenic in living systems: Implications for sustainable and safe food chains.

Arsenic, a group 1 carcinogen for humans, is abundant as compared to other trace elements in the environment and is present mainly in the Earth's crust and soil. The arsenic distributions in different geographical regions are dependent on their geological histories. Anthropogenic activities also contribute significantly to arsenic release into the environment. Arsenic presents several complications to humans, animals, and plants. The physiology of plants and their growth and development are affected by arsenic. Arsenic is known to cause cancer and several types of organ toxicity, such as cardiotoxicity, nephrotoxicity, and hepatotoxicity. In the environment, arsenic exists in variable forms both as inorganic and organic species. From arsenic containing compartments, plants can absorb and accumulate arsenic. Crops grown on these contaminated soils pose several-fold higher toxicity to humans compared with drinking water if arsenic enters the food chain. Information regarding arsenic transfer at different trophic levels in food chains has not been summarized until now. The present review focuses on the food chain perspective of arsenic, which affects all components of the food chain during its course. The circumstances that facilitate arsenic accumulation in flora and fauna, as components of the food chain, are outlined in this review.

Dietary Phytochemicals in Cancer Signalling Pathways: Role of miRNA Targeting.

Cancer is a multi-factorial health condition involving uncontrolled cell divisions. The disease has its roots in genetic mutation. This disease affects men, women, and even children. Chemotherapy, photodynamic, photothermal, and hormonal therapies have been used to treat this deadliest disease, but a huge percentage of patients have chances of disease recurrence or resistance. Nowadays, dysregulation in miRNAs is considered one of the key factors for the development and progression of different types of cancers as they control the expression of genes responsible for cell proliferation, growth, differentiation, and apoptosis. Dietary phytochemicals with anticancer properties have been gaining focus for cancer treatment since they have been found more effective in targeting cancer via regulating miRNAs expression. These phytochemicals have no side effects and are readily available at a low cost. Several dietary phytochemicals with regulatory effects on the expression of miRNAs have been reported, including curcumin, diallyl disulfide, 3, 30-diindolylmethane, ellagic acid, genistein, indole-3-carbinol, quercetin, resveratrol, and sulforaphane. They exert their regulatory effects against different cancers either by upregulating or downregulating different cancer signalling pathways and inhibiting their progression. Curcumin down-regulates SHH pathways, epigallocatechin-3-gallate regulates the Notch pathway and inhibits TGFß1/SMAD signalling, and resveratrol regulates the Wnt/ß-catenin pathway and carnosic acid-induced apoptosis in colon cancer cell via JAK2/STAT3 signalling pathway. The miRNAs are used for the treatment of cancer as essential modulators in cellular pathways. Therefore, identifying the miRNAs and their targets and countering them with specific phytochemicals provide a safe and effective mechanism for the treatment of cancer.