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•Comprehensive and critical review focused on human studies.•Focus on adverse effects of phthalates and their metabolites in humans.•Major clinical studies are covered.•Illustrations ...are given in 8 Figures and 7 Tables.•Plausible molecular signalling mechanism of phthalates depicted.
Disregarding the rising alarm on the hazardous nature of various phthalates and their metabolites, ruthless usage of phthalates as plasticizer in plastics and as additives in innumerable consumer products continues due low their cost, attractive properties, and lack of suitable alternatives. Globally, in silico computational, in vitro mechanistic, in vivo preclinical and limited clinical or epidemiological human studies showed that over a dozen phthalates and their metabolites ingested passively by man from the general environment, foods, drinks, breathing air, and routine household products cause various dysfunctions. Thus, this review addresses the health hazards posed by phthalates on children and adolescents, epigenetic modulation, reproductive toxicity in women and men; insulin resistance and type II diabetes; overweight and obesity, skeletal anomalies, allergy and asthma, cancer, etc., coupled with the description of major phthalates and their general uses, phthalate exposure routes, biomonitoring and risk assessment, special account on endocrine disruption; and finally, a plausible molecular cross-talk with a unique mechanism of action. This clinically focused comprehensive review on the hazards of phthalates would benefit the general population, academia, scientists, clinicians, environmentalists, and law or policy makers to decide upon whether usage of phthalates to be continued swiftly without sufficient deceleration or regulated by law or to be phased out from earth forever.
Curcumin is a polyphenol that is commonly used for its perceived health benefits. However, the absorption efficacy of curcumin is too low to exhibit beneficial effects. We have successfully developed ...a highly absorptive curcumin dispersed with colloidal nano-particles, and named it THERACURMIN. The absorption efficacy of THERACURMIN was investigated and compared with that of curcumin powder. The area under the blood concentration–time curve (AUC) after the oral administration of THERACURMIN was found to be more than 40-fold higher than that of curcumin powder in rats. Then, healthy human volunteers were administered orally 30 mg of THERACURMIN or curcumin powder. The AUC of THERACURMIN was 27-fold higher than that of curcumin powder. In addition, THERACURMIN exhibited an inhibitory action against alcohol intoxication after drinking in humans, as evidenced by the reduced acetaldehyde concentration of the blood. These findings demonstrate that THERACURMIN shows a much higher bioavailability than currently available preparations. Thus, THERACURMIN may be useful to exert clinical benefits in humans at a lower dosage.
Ionic liquids (ILs) are the only media that can allow the homogeneous organocatalytic reactions of lignocellulosic biomass (lignocellulose), since the designability of their cations and anions offers ...the dual functions of solubility and catalytic activity. This review provides an account of our recent achievements in the organocatalytic approaches for converting lignocellulose into polymer materials based on the principles of IL design that we have originally established. These methodologies include the simple and mild chemical modification of cellulose and lignin under high conversions, with high selectivity, and/or with efficient atom economy. Similar reactions and subsequent fractionation processes are applied to lignocellulose, and a highly productive reaction system is developed using a twin‐screw extruder that is specific to the IL media.
Ionic liquids (ILs) are distinctive organic salts that can dissolve lignocellulosic biomass and can also act as organocatalysts for homogeneous chemical modification reactions. IL catalysis varies depending on the designable structures of the cation and the anion, while the non‐distillable nature and viscosity of ILs can be exploited as ingenious synthetic strategy for the sustainable and scalable production of lignocellulosic materials. The recent advances in our group are summarized in this Personal Account.
The role of long noncoding RNAs (lncRNAs) in the epithelial‐mesenchymal transition (EMT) in pancreatic ductal adenocarcinoma (PDAC) is unclear. Some lncRNAs can be transferred by extracellular ...vesicles (EVs) and have potential as biomarkers. Here, we identify an lncRNA that could serve as a biomarker for PDAC and show the functional roles of the lncRNA. Expression profiling of lncRNAs revealed that highly upregulated in liver cancer (HULC) was highly expressed, and induced, by transforming growth factor‐β in PDAC cells and their EVs. Knockdown of HULC decreased PDAC cell invasion and migration by inhibiting the EMT. Thus, HULC could be transferred by EVs, and promote EMT, invasion, and migration in recipient PDAC cells. To assess the roles of HULC, PDAC cell xenografts in nude mice were established. Knockdown of HULC in PDAC cells implanted in mice inhibited tumor growth. Moreover, microRNA‐133b suppressed PDAC cell invasion and migration by inhibiting the EMT through targeting HULC. Furthermore, serum samples were obtained from 20 PDAC and 22 intraductal papillary mucinous neoplasm (IPMN) patients, as well as 21 healthy individuals. Analysis of serum EV HULC expression by digital PCR showed that HULC expression was significantly increased in PDAC patients compared to healthy individuals or IPMN patients. Additionally, HULC showed good predictive performance for discriminating PDAC, suggesting that the analysis of EV‐encapsulated HULC would contribute to the diagnosis for human PDAC. Extracellular vesicle‐transported HULC promotes cell invasion and migration by inducing the EMT, and microRNA‐133b suppresses the EMT by targeting HULC. Extracellular vesicle‐encapsulated HULC could be a potential circulating biomarker for human PDAC.
Extracellular vesicle HULC can regulate cell invasion and migration through induction of epithelial‐mesenchymal transition. Extracellular vesicle HULC could compare favorably with CA19‐9 as a novel biomarker in liquid biopsy for human pancreatic ductal adenocarcinoma.
Shaping cellulose into functional materials entered a new era with the introduction of ionic liquids as novel, green solvents about 20 years ago. As non-volatile solvents with high thermal and ...chemical stability, ionic liquids can provide an environmentally more benign tunable platform for cellulose processing, compared to existing technologies. The past decades have seen fruitful efforts devoted to the development of materials based on ionic liquid/cellulose processing systems. In this review we discuss the experiences gained, and highlight the emerging applications. In particular,
coatings and thin film
applications for structural materials (
e.g.
, for packaging),
thin film filtration membranes
,
immobilisation of enzymes
, and
catalytically active nanoparticles
, s
eparator membranes and conductive composites for energy storage and other electronics applications
,
cellulose
/
biopolymer green biocomposites
, cellulose-based
ionogels, hydrogels and aerogels
, and
cellulose-based or composite fibres
will be discussed in detail. We will also take a critical look at the perspectives of this field. The use of a certain grade of technical cellulose, and the purity of the prepared materials should be more carefully justified in the future, as they have an influence not only on the properties of the fabricated material, but also on the economics of the process. Furthermore, to make ionic liquids truly green solvents, and competitive alternatives to existing technologies, more studies are needed on
recyclability
after material fabrication, and on ways to minimise the
energy consumption
of such processes, among other issues.
The past two decades have seen fruitful efforts in shaping cellulose into functional materials using ionic liquids. This Tutorial Review aims at providing guidance from a materials science perspective to stimulate more research in this field.
Hepatocellular cancer (HCC) is a highly treatment-refractory cancer and is also highly resistant to adverse cellular stress. Although cell behavior can be modulated by noncoding RNAs (ncRNA) within ...extracellular vesicles (EV), the contributions of long noncoding RNAs (lncRNAs) are largely unknown. To this end, the involvement and functional roles of lncRNAs contained within EVs during chemotherapeutic stress in human HCC were determined. Expression profiling identified a subset of lncRNAs that were enriched in tumor cell-derived vesicles released from two different cell lines. Of these, lincRNA-VLDLR (linc-VLDLR) was significantly upregulated in malignant hepatocytes. Exposure of HCC cells to diverse anticancer agents such as sorafenib, camptothecin, and doxorubicin increased linc-VLDLR expression in cells as well as within EVs released from these cells. Incubation with EVs reduced chemotherapy-induced cell death and also increased linc-VLDLR expression in recipient cells. RNAi-mediated knockdown of linc-VLDLR decreased cell viability and abrogated cell-cycle progression. Moreover, knockdown of VLDLR reduced expression of ABCG2 (ATP-binding cassette, subfamily G member 2), whereas overexpression of this protein reduced the effects of VLDLR knockdown on sorafenib-induced cell death. Here, linc-VLDLR is identified as an EV-enriched lncRNA that contributes to cellular stress responses.
These findings provide new insight into the role of EVs and demonstrate the capacity of lncRNAs to mediate chemotherapeutic stress response in HCC.
Summary
Lignin is the most abundant phenolic polymer; thus, its decomposition by microorganisms is fundamental to carbon cycling on earth. Lignin breakdown is initiated by depolymerization catalysed ...by extracellular oxidoreductases secreted by white‐rot basidiomycetous fungi. On the other hand, bacteria play a predominant role in the mineralization of lignin‐derived heterogeneous low‐molecular‐weight aromatic compounds. The outline of bacterial catabolic pathways for lignin‐derived bi‐ and monoaryls are typically composed of the following sequential steps: (i) funnelling of a wide variety of lignin‐derived aromatics into vanillate and syringate, (ii) O demethylation of vanillate and syringate to form catecholic derivatives and (iii) aromatic ring‐cleavage of the catecholic derivatives to produce tricarboxylic acid cycle intermediates. Knowledge regarding bacterial catabolic systems for lignin‐derived aromatic compounds is not only important for understanding the terrestrial carbon cycle but also valuable for promoting the shift to a low‐carbon economy via biological lignin valorisation. This review summarizes recent progress in bacterial catabolic systems for lignin‐derived aromatic compounds, including newly identified catabolic pathways and genes for decomposition of lignin‐derived biaryls, transcriptional regulation and substrate uptake systems. Recent omics approaches on catabolism of lignin‐derived aromatic compounds are also described.
The
Vārṣṇeyādhyātma
, which is comprised of chapters 203–210 of the 12th Book of the
Mahābhārata
, is an early exposition of the practice of Yoga centered on the
manas
(mind) and the bodily channel ...called
manovahā
(mind-conveying). The importance of the
Vārṣṇeyādhyātma
’s doctrine for the history of Yoga has not been appropriately acknowledged in previous research and its systematic description of the practice of Yoga has never been studied in its entirety. A careful reading of the text suggests that the
Vārṣṇeyādhyātma
touches upon the physiological as well as psychological aspects of a human being in the context of the practice of Yoga. This paper attempts to reconstruct the
Vārṣṇeyādhyātma
’s understanding of the
manas
and the
manovahā
channel on the basis of a critical reading of
Mahābhārata
12.207.16–29.
MicroRNAs (miRNAs) are single-stranded short-chain RNAs that are endogenously expressed in vertebrates; they are considered the fine-tuners of cellular protein expression that act by modifying mRNA ...translation. miRNAs control tissue development and differentiation, cell growth, and apoptosis in cancer and non-cancer cells. Aberrant regulation of miRNAs is involved in the pathogenesis of various diseases including cancer. Numerous investigations have shown that the changes in cellular miRNA expression in cancerous tissues and extracellular miRNAs enclosed in exosomes are correlated with cancer prognosis. Therefore, miRNAs can be used as cancer biomarkers and therapeutic targets for cancer in clinical applications. In the previous decade, miRNAs have been shown to regulate cellular functions by directly binding to proteins and mRNAs, thereby controlling cancer progression. This regulatory system implies that cancer-associated miRNAs can be applied as molecular-targeted therapy. This review discusses the roles of miRNA-protein systems in cancer progression and its future applications in cancer treatment.
Stem cell‐based therapies have potential for treatment of liver injury by contributing to regenerative responses, through functional tissue replacement or paracrine effects. The release of ...extracellular vesicles (EV) from cells has been implicated in intercellular communication, and may contribute to beneficial paracrine effects of stem cell‐based therapies. Therapeutic effects of bone‐marrow derived mesenchymal stem cells (MSC) and vesicles released by these cells were examined in a lethal murine model of hepatic failure induced by d‐galactosamine/tumor necrosis factor‐α (TNF‐α). Systemically administered EV derived from MSC accumulated within the injured liver following systemic administration, reduced hepatic injury, and modulated cytokine expression. Moreover, survival was dramatically increased by EV derived from either murine or human MSC. Similar results were observed with the use of cryopreserved mMSC‐EV after 3 months. Y‐RNA‐1 was identified as a highly enriched noncoding RNA within hMSC‐EV compared to cells of origin. Moreover, siRNA mediated knockdown of Y‐RNA‐1 reduced the protective effects of MSC‐EV on TNF‐α/ActD‐mediated hepatocyte apoptosis in vitro. These data support a critical role for MSC‐derived EV in mediating reparative responses following hepatic injury, and provide compelling evidence to support the therapeutic use of MSC‐derived EV in fulminant hepatic failure. Stem Cells Translational Medicine 2017;6:1262–1272
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