Resistance to Diet Induced Visceral Fat Accumulation in C57BL/6NTac Mice Is Associated with an Enriched Lactococcus in the Gut Microbiota and the Phenotype of Immune B Cells in Intestine and Adipose Tissue.

Humans and rodents exhibit a divergent obesity phenotype where not all individuals exposed to a high calorie diet become obese. We hypothesized that in C57BL/6NTac mice, despite a shared genetic background and diet, variations in individual gut microbiota function, immune cell phenotype in the intestine and adipose determine predisposition to obesity. From a larger colony fed a high-fat (HF) diet (60% fat), we obtained twenty-four 18-22-week-old C57BL/6NTac mice. Twelve had responded to the diet, had higher body weight and were termed obese prone (OP). The other 12 had retained a lean frame and were termed obese resistant (OR). We singly housed them for three weeks, monitored food intake and determined insulin resistance, fat accumulation, and small intestinal and fecal gut microbial community membership and structure. From the lamina propria and adipose tissue, we determined the population of total and specific subsets of T and B cells. The OP mice with higher fat accumulation and insulin resistance harbored microbial communities with enhanced capacity for processing dietary sugars, lower alpha diversity, greater abundance of Lactobacilli and low abundance of Clostridia and Desulfobacterota. The OR with less fat accumulation retained insulin sensitivity and harbored microbial communities with enhanced capacity for processing and synthesizing amino acids and higher diversity and greater abundance of Lactococcus, Desulfobacterota and class Clostridia. The B cell phenotype in the lamina propria and mesenteric adipose tissue of OR mice was characterized by a higher population of IgA+ cells and B1b IgM+ cells, respectively, compared to the OP. We conclude that variable responses to the HF diet are associated with the function of individuals' gut microbiota and immune responses in the lamina propria and adipose tissue.

The Vegetable 'Kale' Protects against Dextran-Sulfate-Sodium-Induced Acute Inflammation through Moderating the Ratio of Proinflammatory and Anti-Inflammatory LPS-Producing Bacterial Taxa and Augmenting the Gut Barrier in C57BL6 Mice.

Kale (Brassica oleracea var. acephala), a food rich in bioactive phytochemicals, prevents diet-induced inflammation and gut dysbiosis. We hypothesized that the phytochemicals protect against the lipopolysaccharide (LPS)-induced acute inflammation which results from gut dysbiosis and loss of gut barrier integrity. We designed this study to test the protective effects of the whole vegetable by feeding C57BL/6J mice a rodent high-fat diet supplemented with or without 4.5% kale (0.12 g per 30 g mouse) for 2 weeks before administering 3% dextran sulfate sodium (DSS) via drinking water. After one week, DSS increased the representation of proinflammatory LPS (P-LPS)-producing genera Enterobacter and Klebsiella in colon contents, reduced the representation of anti-inflammatory LPS (A-LPS)-producing taxa from Bacteroidales, reduced the expression of tight junction proteins, increased serum LPS binding protein, upregulated molecular and histopathological markers of inflammation in the colon and shortened the colons. Mice fed kale for 2 weeks before the DSS regime had a significantly reduced representation of Enterobacter and Klebsiella and instead had increased Bacteroidales and Gram-positive taxa and enhanced expression of tight junction proteins. Downstream positive effects of dietary kale were lack of granuloma in colon samples, no shortening of the colon and prevention of inflammation; the expression of F4/80, TLR4 and cytokines 1L-1b, IL-6, TNF-a and iNOS was not different from that of the control group. We conclude that through reducing the proliferation of P-LPS-producing bacteria and augmenting the integrity of the gut barrier, kale protects against DSS-induced inflammation.

Sakuranetin and its therapeutic potentials - a comprehensive review.

Sakuranetin (SKN), a naturally derived 7-O-methylated flavonoid, was first identified in the bark of the cherry tree (Prunus spp.) as an aglycone of sakuranin and then purified from the bark of Prunus puddum. It was later reported in many other plants including Artemisia campestris, Boesenbergia pandurata, Baccharis spp., Betula spp., Juglans spp., and Rhus spp. In plants, it functions as a phytoalexin synthesized from its precursor naringenin and is the only known phenolic phytoalexin in rice, which is released in response to different abiotic and biotic stresses such as UV-irradiation, jasmonic acid, cupric chloride, L-methionine, and the phytotoxin coronatine. Till date, SKN has been widely reported for its diverse pharmacological benefits including antioxidant, anti-inflammatory, antimycobacterial, antiviral, antifungal, antileishmanial, antitrypanosomal, glucose uptake stimulation, neuroprotective, antimelanogenic, and antitumor properties. Its pharmacokinetics and toxicological properties have been poorly understood, thus warranting further evaluation together with exploring other pharmacological properties such as antidiabetic, neuroprotective, and antinociceptive effects. Besides, in vivo studies or clinical investigations can be done for proving its effects as antioxidant and anti-inflammatory, antimelanogenic, and antitumor agent. This review summarizes all the reported investigations with SKN for its health-beneficial roles and can be used as a guideline for future studies.

Ethnobotany, Phytochemistry, Biological Activities, and Health-Promoting Effects of the Genus Bulbophyllum.

The genus Bulbophyllum is of scientific interest due to the phytochemical components and diverse biological activities found across species of the genus. Most Bulbophyllum species are epiphytic and located in habitats that range from subtropical dry forests to wet montane cloud forests. In many cultures, the genus Bulbophyllum has a religious, protective, ornamenting, cosmetic, and medicinal role. Detailed investigations into the molecular pharmacological mechanisms and numerous biological effects of Bulbophyllum spp. remain ambiguous. The review focuses on an in-depth discussion of studies containing data on phytochemistry and preclinical pharmacology. Thus, the purpose of this review was to summarize the therapeutic potential of Bulbophyllum spp. biocompounds. Data were collected from several scientific databases such as PubMed and ScienceDirect, other professional websites, and traditional medicine books to obtain the necessary information. Evidence from pharmacological studies has shown that various phytoconstituents in some Bulbophyllum species have different biological health-promoting activities such as antimicrobial, antifungal, antioxidant, anti-inflammatory, anticancer, and neuroprotective. No toxicological effects have been reported to date. Future clinical trials are needed for the clinical confirmation of biological activities proven in preclinical studies. Although orchid species are cultivated for ornamental purposes and have a wide traditional use, the novelty of this review is a summary of biological actions from preclinical studies, thus supporting ethnopharmacological data.

Molecular modelling approaches predicted 1,2,3-triazolyl ester of ketorolac (15K) to be a novel allosteric modulator of the oncogenic kinase PAK1.

P21-activated kinases (PAKs) are serine/threonine protein kinase which have six different isoforms (PAK1-6). Of those, PAK1 is overexpressed in many cancers and considered to be a major chemotherapeutic target. Most of the developed PAK1 inhibitor drugs work as pan-PAK inhibitors and show undesirable toxicity due to having untargeted kinase inhibition activities. Selective PAK1 inhibitors are therefore highly desired and oncogenic drug hunters are trying to develop allosteric PAK1 inhibitors. We previously synthesized 1,2,3-triazolyl ester of ketorolac (15K) through click chemistry technique, which exhibits significant anti-cancer effects via inhibiting PAK1. Based on the selective anticancer effects of 15K against PAK1-dependent cancer cells, we hypothesize that it may act as an allosteric PAK1 inhibitor. In this study, computational analysis was done with 15K to explore its quantum chemical and thermodynamic properties, molecular interactions and binding stability with PAK1, physicochemical properties, ADMET, bioactivities, and druglikeness features. Molecular docking analysis demonstrates 15K as a potent allosteric ligand that strongly binds to a novel allosteric site of PAK1 (binding energy ranges - 8.6 to - 9.2 kcal/mol) and does not target other PAK isoforms; even 15K shows better interactions than another synthesized PAK1 inhibitor. Molecular dynamics simulation clearly supports the stable binding properties of 15K with PAK1 crystal. Density functional theory-based calculations reveal that it can be an active drug with high softness and moderate polarity, and ADMET predictions categorize it as a non-toxic drug as evidenced by in vitro studies with brine shrimp and fibroblast cells. Structure-activity relationship clarifies the role of ester bond and triazol moiety of 15K in establishing novel allosteric interactions. Our results summarize that 15K selectively inhibits PAK1 as an allosteric inhibitor and in turn shows anticancer effects without toxicity.

Kale supplementation during high fat feeding improves metabolic health in a mouse model of obesity and insulin resistance.

Cruciferous vegetables have been widely studied for cancer prevention and cardiovascular health. Broccoli is the cruciferous vegetable whose phytochemistry and physiological effects have been most extensively studied. Kale (Brassica oleracea var. acephala) appears on lists of 'healthiest, nutrient dense foods' but, there is paucity of data on kale as a functional food. In a 12-week study, we tested the effect of curly green kale on high fat diet (HFD) induced obesity and insulin resistance, lipid metabolism, endotoxemia and inflammation in C57BL/6J mice fed isocaloric diets. Kale supplementation did not attenuate HFD diet induced fat accumulation and insulin resistance (P = ns; n = 9) but, it lowered serum triglycerides, low density lipoprotein (LPL) cholesterol and prevented HFD induced increases in systemic endotoxemia and inflammation (serum LPS and Ccl2) (P<0.01; n = 9). In adipose tissue, kale enhanced the expression of genes involved in adipogenesis (P<0.01; n = 9), reduced the appearance of histologic markers of inflammation, downregulated both the gene expression and protein expression of the adipose tissue specific inflammation markers CD11c and F4/80 (P<0.001; n = 9) and reduced the gene expression of a battery of chemokine C-C motif ligands (Ccl2, Ccl6, Ccl7, Ccl8, Ccl9) and chemokine C-C motif receptors (Ccr2, Ccr3, Ccr5). We conclude that kale vegetable protects against HFD diet induced dysfunction through mechanisms involving lipid metabolism, endotoxemia and inflammation.

Previously published ethno-pharmacological reports reveal the potentiality of plants and plant-derived products used as traditional home remedies by Bangladeshi COVID-19 patients to combat SARS-CoV-2.

Several plants have traditionally been used since antiquity to treat various gastroenteritis and respiratory symptoms similar to COVID-19 outcomes. The common symptoms of COVID-19 include fever or chills, cold, cough, flu, headache, diarrhoea, tiredness/fatigue, sore throat, loss of taste or smell, asthma, shortness of breath, or difficulty breathing, etc. This study aims to find out the plants and plant-derived products which are being used by the COVID-19 infected patients in Bangladesh and how those plants are being used for the management of COVID-19 symptoms. In this study, online and partially in-person survey interviews were carried out among Bangladeshi respondents. We selected Bangladeshi COVID-19 patients who were detected Coronavirus positive (+) by RT-PCR nucleic acid test and later recovered. Furthermore, identified plant species from the surveys were thoroughly investigated for safety and efficacy based on the previous ethnomedicinal usage reports. Based on the published data, they were also reviewed for their significant potentialities as antiviral, anti-inflammatory, and immunomodulatory agents. We explored comprehensive information about a total of 26 plant species, belonging to 23 genera and 17 different botanical families, used in COVID-19 treatment as home remedies by the respondents. Most of the plants and plant-derived products were collected directly from the local marketplace. According to our survey results, greatly top 5 cited plant species measured as per the highest RFC value are Camellia sinensis (1.0) > Allium sativum (0.984) > Azadirachta indica (0.966) > Zingiber officinale (0.966) > Syzygium aromaticum (0.943). Previously published ethnomedicinal usage reports, antiviral, anti-inflammatory, and immunomodulatory activity of the concerned plant species also support our results. Thus, the survey and review analysis simultaneously reveals that these reported plants and plant-derived products might be promising candidates for the treatment of COVID-19. Moreover, this study clarifies the reported plants for their safety during COVID-19 management and thereby supporting them to include in any future pre-clinical and clinical investigation for developing herbal COVID-19 therapeutics.

A review on chemistry, source and therapeutic potential of lambertianic acid.

Lambertianic acid (LA) is a diterpene bioactive compound mainly purified from different species of Pinus. It is an optical isomer of another natural compound daniellic acid and was firstly purified from Pinus lambertiana. LA can be synthesized in laboratory from podocarpic acid. It has been reported to have potential health benefits in attenuating obesity, allergies and different cancers including breast, liver, lung and prostate cancer. It exhibits anticancer properties through inhibiting cancer cell proliferation and survival, and inducing apoptosis, targeting major signalling components including AKT, AMPK, NFkB, COX-2, STAT3, etc. Most of the studies with LA were done using in vitro models, thus warranting future investigations with animal models to evaluate its pharmacological effects such as antidiabetic, anti-inflammatory and neuroprotective effects as well as to explore the underlying molecular mechanisms and toxicological profile. This review describes the chemistry, source, purification and therapeutic potentials of LA and it can therefore be a suitable guideline for any future study with LA.

Long non-coding RNAs in the doxorubicin resistance of cancer cells.

Chemotherapy is the main treatment used for cancer patients failing surgery. Doxorubicin (DOX) is a well-known chemotherapeutic agent capable of suppressing proliferation in cancer cells and triggering apoptosis via inhibiting topoisomerase II activity and producing DNA breaks. This activity of DOX restrains mitosis and cell cycle progression. However, frequent application of DOX results in the emergence of resistance in the cancer cells. It seems that genetic and epigenetic factors can provide DOX resistance of cancer cells. Long non-coding RNAs (lncRNAs) are a subcategory of non-coding RNAs with role in the regulation of several cellular processes such as proliferation, migration, differentiation and apoptosis. LncRNA dysregulation has been associated with chemoresistance, and this profile occurs upon DOX treatment of cancer. In the present review, we focus on the role of lncRNAs in mediating DOX resistance and discuss the molecular pathways and mechanisms. LncRNAs can drive DOX resistance via activating pathways such as NF-κB, PI3K/Akt, Wnt, and FOXC2. Some lncRNAs can activate protective autophagy in response to the stress caused by DOX, which mediates resistance. In contrast, there are other lncRNAs involved in the sensitivity of cancer cells to DOX, such as GAS5, PTCSC3 and FENDRR. Some anti-tumor agents such as polydatin can regulate the expression of lncRNAs, enhancing DOX sensitivity. Overall, lncRNAs are potential players in DOX resistance, and their identification and targeting are of importance in chemosensitivity. Furthermore, these findings can be translated into clinical for treatment of cancer patients.

Crosstalk of Long Non-coding RNAs and EMT: Searching the Missing Pieces of an Incomplete Puzzle for Lung Cancer Therapy.

BACKGROUND: Lung cancer has the first place among cancer-related deaths worldwide and demands novel strategies in the treatment of this life-threatening disorder. The aim of this review is to explore the regulation of epithelial-to-mesenchymal transition (EMT) by long non-coding RNAs (lncRNAs) in lung cancer. INTRODUCTION: LncRNAs can be considered as potential factors for targeting in cancer therapy, since they regulate a bunch of biological processes, e.g. cell proliferation, differentiation and apoptosis. The abnormal expression of lncRNAs occurs in different cancer cells. On the other hand, epithelial-to-mesenchymal transition (EMT) is a critical mechanism participating in migration and metastasis of cancer cells. METHODS: Different databases, including Google Scholar, Pubmed and Science direct, were searched for collecting articles using keywords such as "LncRNA", "EMT", and "Lung cancer". RESULTS: There are tumor-suppressing lncRNAs that can suppress EMT and metastasis of lung cancer cells. Expression of such lncRNAs undergoes down-regulation in lung cancer progression and restoring their expression is of importance in suppressing lung cancer migration. There are tumor- promoting lncRNAs triggering EMT in lung cancer and enhancing their migration. CONCLUSION: LncRNAs are potential regulators of EMT in lung cancer, and targeting them, both pharmacologically and genetically, can be of importance in controlling the migration of lung cancer cells.

Metagenomic insights into the effects of Urtica dioica vegetable on the gut microbiota of C57BL/6J obese mice, particularly the composition of Clostridia.

Urtica dioica (UT) vegetable attenuates diet induced weight gain and insulin resistance. We hypothesized that UT imparts metabolic health by impacting the gut microbiota composition. We examined effects of UT on the cecal bacterial taxonomic signature of C57BL/6J mice fed isocaloric diets: a low-fat diet (LFD) with 10% fat, a high fat diet (HFD) with 45% fat or the HFD supplemented with 9% UT (HFUT). Among Firmicutes, the HFD had no significant impact on Clostridia, but increased Bacilli particularly genus Lactococcus and Lactobacillus. HFUT lowered Lactococcus but not Lactobacillus to levels of the LFD (P<.01; n=9). Further examination of Clostridia showed that HFUT increased genus Clostridium by over 2-fold particularly the species C. vincentii and C. disporicum and increased genus Turicibacter by three-fold (P<.05; n=9). Abundance of Clostridium and Turicibacter negatively correlated with body weight (P<.05; R2=0.42) and HOMA-IR (P<.05; R2=0.45). Turicibacter and Clostridium have been shown to be more abundant in lean phenotypes compared to obese. Clostridium impacts host phenotype by inducing intestinal T cell responses. The HFUT diet had no effect on members of Actinobacteria. Among Bacteroidetes, HFUT mainly increased proliferation of Bacteroides thetaiotaomicron (P<.05; n=9) with no significant impact on other groups. Functional analysis showed that HFUT enhanced bacterial beta-alanine and D-arginine metabolism both of which are associated with a lean phenotype and enhanced insulin sensitivity. We conclude that increasing the proliferation of Clostridium and Turicibacter and altering amino acid metabolism may be contributing mechanism(s) by which Urtica dioica impacts metabolic health.

Kale Attenuates Inflammation and Modulates Gut Microbial Composition and Function in C57BL/6J Mice with Diet-Induced Obesity.

Kale (Brassica oleracea var. acephala) is a vegetable common in most cultures but is less studied as a functional food compared to other cruciferous vegetables, such as broccoli. We investigated the effect of supplementing a high-fat diet (HFD) with kale (HFKV) in C57BL/6J mice. We particularly explored its role in metabolic parameters, gut bacterial composition and diversity using 16S rRNA sequencing, systematically compared changes under each phylum and predicted the functional potential of the altered bacterial community using PICRUSt2. Like other cruciferous vegetables, kale attenuated HFD-induced inflammation. In addition, kale modulated HFD-induced changes in cecal microbiota composition. The HFD lowered bacterial diversity, increased the Firmicutes: Bacteroidetes (F/B) ratio and altered composition. Specifically, it lowered Actinobacteria and Bacteroidetes (Bacteroidia, Rikenellaceae and Prevotellaceae) but increased Firmicutes (mainly class Bacilli). Kale supplementation lowered the F/B ratio, increased both alpha and beta diversity and reduced class Bacilli and Erysipelotrichi but had no effect on Clostridia. Within Actinobacteria, HFKV particularly increased Coriobacteriales/Coriobacteriaceae about four-fold compared to the HFD (p < 0.05). Among Bacteroidia, HFKV increased the species Bacteroides thetaiotaomicron by over two-fold (p = 0.05) compared to the HFD. This species produces plant polysaccharide digesting enzymes. Compared to the HFD, kale supplementation enhanced several bacterial metabolic functions, including glycan degradation, thiamine metabolism and xenobiotic metabolism. Our findings provide evidence that kale is a functional food that modulates the microbiota and changes in inflammation phenotype.

Quercetin in Attenuation of Ischemic/Reperfusion Injury: A Review.

Ischemia/reperfusion (I/R) injury is a serious pathologic event that occurs due to restriction in blood supply to an organ, followed by hypoxia. This condition leads to enhanced levels of pro-inflammatory cytokines such as IL-6 and TNF-α, and stimulation of oxidative stress via enhancing reactive oxygen species (ROS) levels. Upon reperfusion, blood supply incz reases, but it deteriorates condition and leads to the generation of ROS, cell membrane disruption and finally, cell death. Plant derived-natural compounds are well-known due to their excellent antioxidant and anti-inflammatory activities. Quercetin is a flavonoid exclusively found in different vegetables, herbs, and fruits. This naturally occurring compound possesses different pharmacological activities making it an appropriate option in disease therapy. Quercetin can also demonstrate therapeutic effects via affecting molecular pathways such as NF-κB, PI3K/Akt and so on. In the present review, we demonstrate that quercetin administration is beneficial in ameliorating I/R injury via reducing ROS levels, inhibition of inflammation, and affecting molecular pathways such as TLR4/NF-κB, MAPK and so on. Quercetin can improve cell membrane integrity via decreasing lipid peroxidation. Apoptotic cell death is inhibited by quercetin via downregulation of Bax, and caspases, and upregulation of Bcl-2. Quercetin is able to modulate autophagy (inhibition/induction) in decreasing I/R injury. Nanoparticles have been applied for the delivery of quercetin, enhancing its bioavailability and efficacy in the alleviation of I/R injury. Noteworthy, clinical trials have also confirmed the capability of quercetin in reducing I/R injury.

Virtual screening, molecular dynamics, density functional theory and quantitative structure activity relationship studies to design peroxisome proliferator-activated receptor-γ agonists as anti-diabetic drugs.

Type 2 diabetes (T2D) is generally characterized by elevated blood glucose levels, insulin resistance, and relative lack of insulin; however, insulin resistance is the predominant risk factor. Hence, the use of insulin sensitizer drugs to increase insulin sensitivity has gained immense interest as an attractive treatment option for T2D and their major target is a nuclear receptor PPAR-γ (peroxisome proliferator-activated receptor-γ). A wide range of synthetic insulin sensitizers such as thiazolidinedione act as PPAR-γ agonists thereby enhancing insulin action and improving hyperglycemia in patients. Nonetheless, they pose severe adverse effects for human, necessitating an emergent need to develop effective insulin sensitizer drugs. Herein, virtual screening of 10,000 ligands is performed and the best five ligands are identified. MET364, ILE341, CYS285, ALA292, PHE282, and LEU330 residues are found to play an important role in ligand binding. It is shown from the molecular dynamics simulations results of the top-ranked ligands that increased numbers of hydrogen bonds are formed with PPAR-γ catalytic residues. Quantum chemical calculations reveal that all the best ligands can demonstrate good thermodynamic stability and pharmacokinetic properties. Partial-least-square (PLS) regression of quantitative structural activity relationship (QSAR) is utilized to model and predict the binding energy for ligands. Principal component analysis is further explored for the best ligands' QSAR pattern recognition. Importantly, the predicted values of the binding energy of the potential ligands by the PLS regression is favourably compared with the values of binding energy obtained from molecular docking with incredible high accuracy of 98%.

Chemical composition and pharmacological properties of Macaranga-type Pacific propolis: A review.

Propolis, a resinous substance, is collected from plants and processed by honeybees to seal holes and cracks in beehives, protecting them from microbial infection. Based on the plant source and geographical location, propolis is categorized into seven groups. Of these, Pacific propolis, found in the Pacific islands, originates from Macaranga spp. and is, therefore, known as Macaranga-type Pacific propolis. Okinawa propolis and Taiwanese propolis, which are both Macaranga-type propolis, are rich in prenylated flavonoids from the same botanical source, Macaranga tanarius, and are used locally as traditional remedies. They are reported to have a wide range of pharmacological benefits, including antioxidant, anti-inflammation, antimicrobial, anticancer, antidiabetic, anti-Alzheimer's, anti-melanogenic, and longevity-extending effects. However, not much is known about their mode of action, and recently, the extract of Okinawa propolis and its major prenylated flavonoids were found to selectively inhibit the oncogenic kinase, p21-activated kinase 1 (PAK1). PAK1 enables cross-talking among several signaling pathways, causing many diseases/disorders. The existing results reviewed here support the use of Macaranga-type Pacific propolis for the effective development of safe herbal drugs and functional foods. Furthermore, its mode of action by modulating PAK1 can be explored, and the geographical and seasonal effects on its chemistry and biology, and its pharmacokinetics and toxicology should be studied as well.

Artepillin C: A comprehensive review of its chemistry, bioavailability, and pharmacological properties.

Artepillin C (ARC), a prenylated derivative of p-coumaric acid, is one of the major phenolic compounds found in Brazilian green propolis (BGP) and its botanical source Baccharis dracunculifolia. Numerous studies on ARC show that its beneficial health effects correlate with the health effects of both BGP and B. dracunculifolia. Its wide range of pharmacological benefits include antioxidant, antimicrobial, anti-inflammatory, anti-diabetic, neuroprotective, gastroprotective, immunomodulatory, and anti-cancer effects. Most studies have focused on anti-oxidation, inflammation, diabetic, and cancers using both in vitro and in vivo approaches. Mechanisms underlying anti-cancer properties of ARC are apoptosis induction, cell cycle arrest, and the inhibition of p21-activated kinase 1 (PAK1), a protein characterized in many human diseases/disorders including COVID-19 infection. Therefore, further pre-clinical and clinical studies with ARC are necessary to explore its potential as intervention for a wide variety of diseases including the recent pandemic coronaviral infection. This review summarizes the comprehensive data on the pharmacological effects of ARC and could be a guideline for its future study and therapeutic usage.

Sensing the scent of death: Modulation of microRNAs by Curcumin in gastrointestinal cancers.

Gastrointestinal (GI) cancers with a high incidence rate and adverse complications are related to severe morbidity and mortality around the world. MicroRNAs (miRs) are potential regulators of cellular events, and their aberrant expression occurs in gastrointestinal (GI) cancers. Increasing evidence demonstrates that plant derived-natural compounds are capable of regulation of miRs in cancer therapy. Curcumin is a naturally occurring nutraceutical compound isolated from curcuma longa and possesses valuable pharmacological activities in which anti-tumor activity is of importance, since in suppressing cancer malignancy, curcumin can target various molecular pathways such as STAT3, PTEN, PI3K/Akt, Wnt, and so on. In the present review, our aim is to shed some light on regulation of miRs by curcumin in GI cancers, and demonstrate how regulation of miRs by curcumin can affect proliferation and metastasis of GI cancers. Noteworthy, curcumin affects down-stream targets such as PTEN, VEGFA, PI3K/Akt and so on that are responsible for growth and migration of GI cancers via regulation of miRs. Affected miRs, and their down-stream targets are discussed in this review in a mechanistic way. Besides, challenges for clinical translation of current studies are described.

Cancer and SOX proteins: New insight into their role in ovarian cancer progression/inhibition.

Transcription factors are potential targets in disease therapy, particularly in cancer. This is due to the fact that transcription factors regulate a variety of cellular events, and their modulation has opened a new window in cancer therapy. Sex-determining region Y (SRY)-related high-mobility group (HMG) box (SOX) proteins are potential transcription factors that are involved in developmental processes such as embryogenesis. It has been reported that abnormal expression of SOX proteins is associated with development of different cancers, particularly ovarian cancer (OC). In the present review, our aim is to provide a mechanistic review of involvement of SOX members in OC. SOX members may suppress and/or promote aggressiveness and proliferation of OC cells. Clinical studies have also confirmed the potential of transcription factors as diagnostic and prognostic factors in OC. Notably, studies have demonstrated the relationship between SOX members and other molecular pathways such as ST6Ga1-I, PI3K, ERK and so on, leading to more complexity. Furthermore, SOX members can be affected by upstream mediators such as microRNAs, long non-coding RNAs, and so on. It is worth mentioning that the expression of each member of SOX proteins is corelated with different stages of OC. Furthermore, their expression determines the response of OC cells to chemotherapy. These topics are discussed in this review to shed some light on role of SOX transcription factors in OC.

Role of microRNA/Epithelial-to-Mesenchymal Transition Axis in the Metastasis of Bladder Cancer.

Bladder cancer (BC) is the 11th most common diagnosed cancer, and a number of factors including environmental and genetic ones participate in BC development. Metastasis of BC cells into neighboring and distant tissues significantly reduces overall survival of patients with this life-threatening disorder. Recently, studies have focused on revealing molecular pathways involved in metastasis of BC cells, and in this review, we focus on microRNAs (miRNAs) and their regulatory effect on epithelial-to-mesenchymal transition (EMT) mechanisms that can regulate metastasis. EMT is a vital process for migration of BC cells, and inhibition of this mechanism restricts invasion of BC cells. MiRNAs are endogenous non-coding RNAs with 19-24 nucleotides capable of regulating different cellular events, and EMT is one of them. In BC cells, miRNAs are able to both induce and/or inhibit EMT. For regulation of EMT, miRNAs affect different molecular pathways such as transforming growth factor-beta (TGF-ß), Snail, Slug, ZEB1/2, CD44, NSBP1, which are, discussed in detail this review. Besides, miRNA/EMT axis can also be regulated by upstream mediators such as lncRNAs, circRNAs and targeted by diverse anti-tumor agents. These topics are also discussed here to reveal diverse molecular pathways involved in migration of BC cells and strategies to target them to develop effective therapeutics.

Biological activities and health-promoting effects of Pyracantha genus: a key approach to the phytochemical's potential.

Pyracantha spp. are commonly called firethorn, and attract human attention due to their colorful berries. These berries are eaten globally as a traditional remedy for treating different stomach abnormalities, and as a cooking ingredient for folk diets. The present review aims to provide an overview on Pyracantha genus' geographical distribution and botanical description, traditional uses, phytochemical composition, biological activities and safety issues. Several biological activities have been reported to Pyracantha species, namely antioxidant, anti-inflammatory, antimicrobial, larvicidal and cytotoxic properties, most of them attributed to the use of their fruits. Pyracantha species phytochemical composition reveal the presence of interesting bioactive molecules, such as pyracrenic acid and fortuneanosides. The currently reported biological activities to these plants derive from in vitro and in vivo studies, so that clinical trials are needed to confirm these preclinical results. Nonetheless, Pyracantha species can be suggested as a safe herb useful to develop future drug formulations and functional foods.