The correlation between echinoderms diversity and physicochemical parameters in marine pollution: A case study of the Persian Gulf coastline.

This study was conducted with the aim of investigating the correlation between echinoderms diversity and physicochemical parameters in the Persian Gulf coastline in Bushehr province in 4 seasons from March to December 2017. The physicochemical parameters including water temperature, dissolved oxygen (DO), electrical conductivity (EC), salinity, pH and turbidity were measured at each sampling location. The results showed a significant correlation between echinoderms diversity and physicochemical parameters. The correlation coefficient of the Astropecten polyacanthus species with the parameters of temperature, DO, EC, salinity and turbidity was reported as -0.41, 0.64, -0.25, -0.44 and 0.60 respectively. This coefficient for the Ophiothrix fragilis species was reported as -0.68, 0.70, -0.21, -0.36 and -0.55 respectively. The results demonstrated that the most sensitive species were Astropecten polyacanthus and Ophiothrix fragilis respectively. The different species of echinoderms can be used as biological indicators of pollution in evaluating the physicochemical quality of marine environments.

Glucosinolates in cancer prevention and treatment: experimental and clinical evidence.

Glucosinolates are naturally occurring ß-d-thioglucosides that mainly exist in the Brassicaceae family. The enzyme myrosinase hydrolyzes glucosinolates to form isothiocyanates, which are chemical protectors. Phenethyl isothiocyanate, sulforaphane, and benzyl isothiocyanate are potential isothiocyanate with efficient anti-cancer effects as a protective or treatment agent. Glucosinolate metabolites exert the cancer-preventive activity through different mechanisms, including induction of the Nrf2 transcription factor, inhibition of expression of tumor necrosis factor-α (TNFα) and interleukin-1ß (IL-1ß), induction of apoptosis through inhibiting phase I enzymes and inducting phase II enzymes, interruption of caspase pathways, STAT1/STAT2, inhibition of sulfotransferases. Moreover, glucosinolates and their metabolites are effective in cancer treatment by inhibiting angiogenesis, upregulating natural killers, increasing expression of p53, p21, caspase 3 and 9, and modulating NF-κB. Despite the mentioned cancer-preventing effects, some isothiocyanates can increase the risk of tumors. So, further studies are needed to obtain an accurate and effective dose for each glucosinolates to treat different types of tumors.

Targeted protein modification as a paradigm shift in drug discovery.

Targeted Protein Modification (TPM) is an umbrella term encompassing numerous tools and approaches that use bifunctional agents to induce a desired modification over the POI. The most well-known TPM mechanism is PROTAC-directed protein ubiquitination. PROTAC-based targeted degradation offers several advantages over conventional small-molecule inhibitors, has shifted the drug discovery paradigm, and is acquiring increasing interest as over ten PROTACs have entered clinical trials in the past few years. Targeting the protein of interest for proteasomal degradation by PROTACS was the pioneer of various toolboxes for selective protein degradation. Nowadays, the ever-increasing number of tools and strategies for modulating and modifying the POI has expanded far beyond protein degradation, which phosphorylation and de-phosphorylation of the protein of interest, targeted acetylation, and selective modification of protein O-GlcNAcylation are among them. These novel strategies have opened new avenues for achieving more precise outcomes while remaining feasible and minimizing side effects. This field, however, is still in its infancy and has a long way to precede widespread use and translation into clinical practice. Herein, we investigate the pros and cons of these novel strategies by exploring the latest advancements in this field. Ultimately, we briefly discuss the emerging potential applications of these innovations in cancer therapy, neurodegeneration, viral infections, and autoimmune and inflammatory diseases.

Curcumin-loaded mesoporous silica nanoparticles for drug delivery: synthesis, biological assays and therapeutic potential - a review.

Curcumin-loaded mesoporous silica nanoparticles (MSNs) have shown promise as drug delivery systems to address the limited pharmacokinetic characteristics of curcumin. Functionalization with folic acid and PEGylation enhance anticancer activity, biocompatibility, stability, and permeability. Co-delivery with other drugs results in synergistically enhanced cytotoxic activity. Environment-responsive MSNs prevent undesirable drug leakage and increase selectivity towards target tissues. This review summarizes the methods of Cur-loaded MSN synthesis and functionalization and their application in various diseases, and also highlights the potential of Cur-loaded MSNs as a promising drug delivery system.

New perspective on DNA response pathway (DDR) in glioblastoma, focus on classic biomarkers and emerging roles of ncRNAs.

BACKGROUND: Glioblastoma (GBM) is the most frequent type of primary brain cancer, having a median survival of only 15 months. The current standard of care includes a combination of surgery, radiotherapy (RT) and chemotherapy with temozolomide, but with limited results. Moreover, multiple studies have shown that tumour relapse and resistance to classic therapeutic approaches are common events that occur in the majority of patients, and eventually leading to death. New approaches to better understand the intricated tumour biology involved in GBM are needed in order to develop personalised treatment approaches. Advances in cancer biology have widen our understanding over the GBM genome and allowing a better classification of these tumours based on their molecular profile. METHODS: A new targeted therapeutic approach that is currently investigated in multiple clinical trials in GBM is represented by molecules that target various defects in the DNA damage repair (DDR) pathway, a mechanism activated by endogenous and exogenous factors that induce alteration of DNA, and is involved for the development of chemotherapy and RT resistance. This intricate pathway is regulated by p53, two important kinases ATR and ATM and non-coding RNAs including microRNAs, long-non-coding RNAs and circular RNAs that regulate the expression of all the proteins involved in the pathway. RESULTS: Currently, the most studied DDR inhibitors are represented by PARP inhibitors (PARPi) with important results in ovarian and breast cancer. PARPi are a class of tumour agnostic drugs that showed their efficacy also in other localisations such as colon and prostate tumours that have a molecular signature associated with genomic instability. These inhibitors induce the accumulation of intracellular DNA damage, cell cycle arrest, mitotic catastrophe and apoptosis. CONCLUSIONS: This study aims to provide an integrated image of the DDR pathway in glioblastoma under physiological and treatment pressure with a focus of the regulatory roles of ncRNAs. The DDR inhibitors are emerging as an important new therapeutic approach for tumours with genomic instability and alterations in DDR pathways. The first clinical trials with PARPi in GBM are currently ongoing and will be presented in the article. Moreover, we consider that by incorporating the regulatory network in the DDR pathway in GBM we can fill the missing gaps that limited previous attempts to effectively target it in brain tumours. An overview of the importance of ncRNAs in GBM and DDR physiology and how they are interconnected is presented.

Short interfering RNA in colorectal cancer: is it wise to shoot the messenger?

Colorectal cancer (CRC) is the third most common cancer and the leading cause of gastrointestinal cancer death. 90% of people diagnosed with colorectal cancer are over the age of 50; nevertheless, the illness is more aggressive among those detected at a younger age. Chemotherapy-based treatment has several adverse effects on both normal and malignant cells. The primary signaling pathways implicated in the advancement of CRC include hedgehog (Hh), janus kinase and signal transducer and activator of transcription (JAK/STAT), Wingless-related integration site (Wnt)/ß-catenin, transforming growth factor-ß (TNF-ß), epidermal growth factor receptor (EGFR)/Mitogen-activated protein kinases (MAPK), phosphoinositide 3-kinase (PI3K), nuclear factor kappa B (NF-κB), and Notch. Loss of heterozygosity in tumor suppressor genes like adenomatous polyposis coli, as well as mutation or deletion of genes like p53 and Kirsten rat sarcoma viral oncogene (KRAS), are all responsible for the occurrence of CRC. Novel therapeutic targets linked to these signal-transduction cascades have been identified as a consequence of advances in small interfering RNA (siRNA) treatments. This study focuses on many innovative siRNA therapies and methodologies for delivering siRNA therapeutics to the malignant site safely and effectively for the treatment of CRC. Treatment of CRC using siRNA-associated nanoparticles (NPs) may inhibit the activity of oncogenes and MDR-related genes by targeting a range of signaling mechanisms. This study summarizes several siRNAs targeting signaling molecules, as well as the therapeutic approaches that might be employed to treat CRC in the future.

Production of high molecular-ordered stilbene oligomers for the study of their biological activity: total synthesis, bio-catalyzed synthesis and production by plant systems.

Though the iconic stilbene resveratrol and its related dimers constitute a top storyline in the field of natural product research, resveratrol oligomers (condensation >2) have been left aside despite their higher biological activity compared to that of the monomers. This situation largely results from the difficulty of getting them in sufficient quantities to enable evaluation of their biological properties in vivo. We present here a synthetic and critical analysis of the methods used for the production of high molecular-ordered stilbene oligomers of potential biomedical interest, gathering the most salient data regarding the approaches employed to prepare them by total synthesis, use of biomimetic approaches or through plant systems.

DihydrofolateReductase (DHFR) Inhibitors: A Comprehensive Review.

BACKGROUND: Dihydrofolate reductase (DHFR) is an indispensable enzyme required for the survival of most prokaryotic and eukaryotic cells as it is involved in the biosynthesis of essential cellular components. DHFR has attracted a lot of attention as a molecular target for various diseases like cancer, bacterial infection, malaria, tuberculosis, dental caries, trypanosomiasis, leishmaniasis, fungal infection, influenza, Buruli ulcer, and respiratory illness. Various teams of researchers have reported different DHFR inhibitors to explore their therapeutic efficacy. Despite all the progress made, there is a strong need to find more novel leading structures, which may be used as better and safe DHFR inhibitors, especially against the microorganisms which are resistant to the developed drug candidates. OBJECTIVE: This review aims to pay attention to recent development, particularly made in the past two decades and published in this field, and pay particular attention to promising DHFR inhibitors. Hence, an attempt has been made in this article to highlight the structure of dihydrofolate reductase, the mechanism of action of DHFR inhibitors, most recently reported DHFR inhibitors, diverse pharmacological applications of DHFR inhibitors, reported in-silico study data and recent patents based on DHFR inhibitors to comprehensively portray the current scenery for researchers interested in designing novel DHFR inhibitors. CONCLUSION: A critical review of recent studies revealed that most novel DHFR inhibitor compounds either synthetically or naturally derived are characterized by the presence of heterocyclic moieties in their structure. Non-classical antifolates like trimethoprim, pyrimethamine, and proguanil are considered excellent templates to design novel DHFR inhibitors, and most of them have substituted 2,4-diamino pyrimidine motifs. Targeting DHFR has massive potential to be investigated for newer therapeutic possibilities to treat various diseases of clinical importance.

The Progress and Research Trends of Statin Medications: Advanced Epidemiological and Bibliometrical Assessment.

Statin medications are considered as important lipid lowering agents to prevent subsequent cardiovascular events. However, there was limited evidence regarding the bibliometric analysis on preclinical and clinical studies. In January, 2021, the data was retrieved from Scopus and Dimensions database. For detail analysis, we focused on Scopus. Thirty-three thousand two hundred forty-seven research documents were found in the database which contained the word "Statin" either in titles, abstracts and/or keywords of the research documents. They mostly comprised of research articles (n = 22586/67.93%), reviews (n = 6366/19.15%). Scopus classified these documents in various subject categorized like medicine, biochemistry, genetics and molecular biology, pharmacology, toxicology and pharmaceutics, nursing, neuroscience, biological sciences, immunology, and microbiology to name a few. The highest documents are published in 2016 (n = 540/7.16%), followed by 2015 (n = 534/7.08%), 2017 (n = 527/6.99%), 2014 (n = 514/6.81%), and 2020 (n = 504/6.68%). The top sources as well as total number of authors, institutes, and countries involved in publications are described. For detail analysis, we designed the publication and citation clubs. Based on Vosviewer analysis we also provided details about co-authorship network for authors, institutes, and countries. In order to understanding the research focus of the publications, we performed the co-words analysis. The present study may provide details and research trends about statin publications.

Persistent organic pollutants influence the marine benthic macroinvertebrate assemblages in surface sediments of Nayband National Park and Bay, Northern Persian Gulf, Iran.

Macroinvertebrate communities have been influenced by chemical substances, originated from petrochemical developments, that caused many problems in the marine biota. This study investigated the surface sediments of Nayband National Park and Bay (northern Persian Gulf) for polycyclic aromatic hydrocarbons (PAHs) and total petroleum hydrocarbons (TPHs) in terms of their distribution, source, and impacts on benthic macroinvertebrate assemblages. To this end, a total of 180 surface sediment samples from 20 stations were collected using Van-Veen grab sampler during winter 2018. The concentration of PAHs, TPHs, total organic carbon (TOC). and total organic matter (TOM) were evaluated, and grain size measurements were conducted on sediment samples in this study. Benthic macroinvertebrates were then identified in terms of presence and distribution. The results indicated that coarse granulometric fractions of sands were prevalence in all samples stations. The total concentration of PAHs ranged from 47.57 to 657.68 ng/g and TPHs 5.72 to 42.16 µg/g dw. The risk of ΣPAHs and TPHs in the sediments was relatively low to moderate according to the sediment quality guidelines. Analysis of the results revealed a significant negative correlation between ΣPAHs (R-value = - 0.917; P < 0.01), TPHs (R-value = - 0.849; P < 0.01) and macrofaunal abundance. Findings demonstrated that the species richness and abundance were at the lowest levels in stations where concentrations of PAHs, TPHs, TOC, and TOM were in the highest values, suggesting that these contaminants could negatively influence the benthic organisms in Nayband National Park and Bay. The results of correspondence analysis (CA) and principal component analysis (PCA) analysis showed that sedimentary habitats in Nayband National Park and Bay are being negatively affected by PAHs and TPHs, released from Pars Special Economic Energy Zone (PSEEZ). Moreover, the marine biotic index (AMBI) and Shannon-Weiner Diversity (H') results suggest that Nayband National Park and Bay can be classified as slightly to moderate polluted area. In conclusion, Northern Persian Gulf is significantly affected by oil industry developments and petrochemical activities. The unique ecosystem like Nayband National Park and Bay has been in a cautious status in terms of the PSEEZ pollutants and the levels of PAHs and TPHs concentration, warning that urgent environmental programs should be considered to protect the diversity and ecology of this valuable marine systems.

Harnessing polyphenol power by targeting eNOS for vascular diseases.

Vascular diseases arise due to vascular endothelium dysfunction in response to several pro-inflammatory stimuli and invading pathogens. Thickening of the vessel wall, formation of atherosclerotic plaques consisting of proliferating smooth muscle cells, macrophages and lymphocytes are the major consequences of impaired endothelium resulting in atherosclerosis, hypercholesterolemia, hypertension, type 2 diabetes mellitus, chronic renal failure and many others. Decreased nitric oxide (NO) bioavailability was found to be associated with anomalous endothelial function because of either its reduced production level by endothelial NO synthase (eNOS) which synthesize this potent endogenous vasodilator from L-arginine or its enhanced breakdown due to severe oxidative stress and eNOS uncoupling. Polyphenols are a group of bioactive compounds having more than 7000 chemical entities present in different cereals, fruits and vegetables. These natural compounds possess many OH groups which are largely responsible for their strong antioxidative, anti-inflammatory antithrombotic and anti-hypersensitive properties. Several flavonoid-derived polyphenols like flavones, isoflavones, flavanones, flavonols and anthocyanidins and non-flavonoid polyphenols like tannins, curcumins and resveratrol have attracted scientific interest for their beneficial effects in preventing endothelial dysfunction. This article will focus on in vitro as well as in vivo and clinical studies evidences of the polyphenols with eNOS modulating activity against vascular disease condition while their molecular mechanism will also be discussed.

Putative Therapeutic Impact of Inflammasome Inhibitors against COVID-19-Induced ARDS.

Given the importance of COVID-19-induced ARDS, recently, researchers have strived to determine underlying mechanisms involved in the inflammatory responses. In this regard, inflammasomes possess a distinct priority for cytokine storm occurrence and, subsequently, ARDS progression in ill patients with SARS-CoV-2 infection. In this minireview, the characteristics of known inflammasome inhibitors and designed research in this field were concretely deciphered.

Oral microbiota in cancer: could the bad guy turn good with application of polyphenols?

The human oral cavity is comprised of dynamic and polynomial microbes which uniquely reside in the microenvironments of oral cavities. The cumulative functions of the symbiotic microbial communities maintain normal homeostasis; however, a shifted microbiota yields a dysbiosis state, which produces local and systemic diseases including dental caries, periodontitis, cancer, obesity and diabetes. Recent research reports claim that an association occurs between oral dysbiosis and the progression of different types of cancers including oral, gastric and pancreatic ones. Different mechanisms are proposed for the development of cancer, such as induction of inflammatory reactions, production of carcinogenic materials and alteration of the immune system. Medications are available to treat these associated diseases; however, the current strategies may further worsen the disease by unwanted side effects. Natural-derived polyphenol molecules significantly inhibit a wide range of systemic diseases with fewer side effects. In this review, we have displayed the functions of the oral microbes and we have extended the report regarding the role of polyphenols in oral microbiota to maintain healthy conditions and prevention of diseases with emphasis on the treatment of oral microbiota-associated cancer.

New Visions on Natural Products and Cancer Therapy: Autophagy and Related Regulatory Pathways.

Macroautophagy (autophagy) has been a highly conserved process throughout evolution and allows cells to degrade aggregated/misfolded proteins, dysfunctional or superfluous organelles and damaged macromolecules, in order to recycle them for biosynthetic and/or energetic purposes to preserve cellular homeostasis and health. Changes in autophagy are indeed correlated with several pathological disorders such as neurodegenerative and cardiovascular diseases, infections, cancer and inflammatory diseases. Conversely, autophagy controls both apoptosis and the unfolded protein response (UPR) in the cells. Therefore, any changes in the autophagy pathway will affect both the UPR and apoptosis. Recent evidence has shown that several natural products can modulate (induce or inhibit) the autophagy pathway. Natural products may target different regulatory components of the autophagy pathway, including specific kinases or phosphatases. In this review, we evaluated ~100 natural compounds and plant species and their impact on different types of cancers via the autophagy pathway. We also discuss the impact of these compounds on the UPR and apoptosis via the autophagy pathway. A multitude of preclinical findings have shown the function of botanicals in regulating cell autophagy and its potential impact on cancer therapy; however, the number of related clinical trials to date remains low. In this regard, further pre-clinical and clinical studies are warranted to better clarify the utility of natural compounds and their modulatory effects on autophagy, as fine-tuning of autophagy could be translated into therapeutic applications for several cancers.

Plant based food bioactives: A boon or bane for neurological disorders.

Neurological disorders are the foremost occurring diseases across the globe resulting in progressive dysfunction, loss of neuronal structure ultimately cell death. Therefore, attention has been drawn toward the natural resources for the search of neuroprotective agents. Plant-based food bioactives have emerged as potential neuroprotective agents for the treatment of neurodegenerative disorders. This comprehensive review primarily focuses on various plant food bioactive, mechanisms, therapeutic targets, in vitro and in vivo studies in the treatment of neurological disorders to explore whether they are boon or bane for neurological disorders. In addition, the clinical perspective of plant food bioactives in neurological disorders are also highlighted. Scientific evidences point toward the enormous therapeutic efficacy of plant food bioactives in the prevention or treatment of neurological disorders. Nevertheless, identification of food bioactive components accountable for the neuroprotective effects, mechanism, clinical trials, and consolidation of information flow are warranted. Plant food bioactives primarily act by mediating through various pathways including oxidative stress, neuroinflammation, apoptosis, excitotoxicity, specific proteins, mitochondrial dysfunction, and reversing neurodegeneration and can be used for the prevention and therapy of neurodegenerative disorders. In conclusion, the plant based food bioactives are boon for neurological disorders.

The potential of pumpkin seed oil as a functional food-A comprehensive review of chemical composition, health benefits, and safety.

The growing interest in foods that can be beneficial to human health is bringing into focus some products that have been used locally for centuries but have recently gained worldwide attention. One of these foods is pumpkin seed oil, which has been used in culinary and traditional medicine, but recent data also show its use in the pharmaceutical and cosmetic industries. In addition, some sources refer to it as a potential functional food, mainly because it is obtained from pumpkin seeds, which contain many functional components. However, the production process of the oil may affect the content of these components and consequently the biological activity of the oil. In this review, we have focused on summarizing scientific data that explore the potential of pumpkin seed oil as a functional food ingredient. We provide a comprehensive overview of pumpkin seed oil chemical composition, phytochemical content, biological activity, and safety, as well as the overview of production processes and contemporary use. The main phytochemicals in pumpkin seed oil with health-related properties are polyphenols, phytoestrogens, and fatty acids, but carotenoids, squalene, tocopherols, and minerals may also contribute to health benefits. Most studies have been conducted in vitro and support the claim that pumpkin seed oil has antioxidant and antimicrobial activities. Clinical studies have shown that pumpkin seed oil may be beneficial in the treatment of cardiovascular problems of menopausal women and ailments associated with imbalance of sex hormones.

Psychological Interventions in a Pandemic Emergency: A Systematic Review and Meta-Analysis of SARS-CoV-2 Studies.

Background: The study aim was to review the evidence and effectiveness of psychological interventions applied during Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic. Methods: A literature search was run from April 2020 to April 2021. The inclusion criteria were: (1) RCTs or observational studies; (2) professional health carers and patients who had contracted coronavirus during the pandemic; (3) adults and elderly people with a viral infection diagnosis; (4) suitable measures to assess intervention effectiveness on clinical status and psychological and behavioral aspects. An internal validity assessment was planned using robvis. Data were synthesized according to PICO criteria. Results: A total of 12 studies were selected. Studies measuring mental health outcomes demonstrated the greatest reduction in symptoms, with eight out of the twelve studies demonstrating a reduction in symptoms that reached statistical significance (p < 0.05) and four of the studies reaching a higher significance level of p < 0.01. The type of psychological intervention was predominantly cognitive behavioral therapy (CBT). All studies except one was run online. Conclusion: Psychological interventions have a benefit on mental health outcomes, even if performed online. In particular, CBT seems to be the psychological intervention that is used more and also seems to have a larger effect size on the mitigation of mental health symptoms and increasing resilience.