The striking gender disparity observed in the incidence of hepatocellular carcinoma (HCC) suggests an important role of sex hormones in HCC pathogenesis. Though the studies began as early as in 1980s, the precise role of sex hormones and the significance of their receptors in HCC still remain poorly understood and perhaps contribute to current controversies about the potential use of hormonal therapy in HCC. A comprehensive review of the existing literature revealed several shortcomings associated with the studies on estrogen receptor (ER) and androgen receptor (AR) in normal liver and HCC. These shortcomings include the use of less sensitive receptor ligand binding assays and immunohistochemistry studies for ERα alone until 1996 when ERβ isoform was identified. The animal models of HCC utilized for studies were primarily based on chemical-induced hepatocarcinogenesis with less similarity to virus-induced HCC pathogenesis. However, recent in vitro studies in hepatoma cells provide newer insights for hormonal regulation of key cellular processes including interaction of ER and AR with viral proteins. In light of the above facts, there is an urgent need for a detailed investigation of sex hormones and their receptors in normal liver and HCC. In this review, we systematically present the information currently available on androgens, estrogens and their receptors in normal liver and HCC obtained from in vitro , in vivo experimental models and clinical studies. This information will direct future basic and clinical research to bridge the gap in knowledge to explore the therapeutic potential of hormonal therapy in HCC.
Candida albicansis the most importantCandidaspecies causing vulvovaginal candidiasis (VVC). VVC has significant medical and economical impact on women’s health and wellbeing. While current antifungal treatment is reasonably effective, supportive and preventive measures such as application of probiotics are required to reduce the incidence of VVC. We investigated the potential of the probioticsLactobacillus rhamnosusGR-1 andLactobacillus reuteriRC-14 towards control ofC. albicans.In vitroexperiments demonstrated that lactic acid at low pH plays a major role in suppressing fungal growth. Viability staining following cocultures with lactobacilli revealed thatC. albicanscells lost metabolic activity and eventually were killed. Transcriptome analyses showed increased expression of stress-related genes and lower expression of genes involved in fluconazole resistance, which might explain the increased eradication ofCandidain a previous clinical study on conjoint probiotic therapy. Our results provide insights on the impact of probiotics onC. albicanssurvival.
A new composition of gelatin/bioactive-glass/silver nanoparticle was synthesized and employed to prepare antibacterial macroporous scaffolds with potential applications in bone tissue engineering. A set of macroporous nanocomposite scaffolds were developed from an aqueous solution of gelatin by freeze-drying and crosslinking using genipin at ambient temperature. Silver nanoparticles were successfully synthesized in situ in gelatin solution by heat treatment reduction as a simple and "green" method in which gelatin acted as a natural reducing and stabilizing agent. The effect of the incorporation of the bioactive-glass and the silver nanoparticle concentration on the physicochemical properties of the scaffolds, such as the gel fraction, porosity, in vitro enzyme degradation, morphology, and swelling behavior was studied. Furthermore, the in vitro viability of human mesenchymal stem cells (hMSC) and the antibacterial activity against gram-negative Escherichia coli and gram-positive Staphylococcus aureus were tested on the scaffolds. It was found that upon the addition of silver nanoparticles the porosity, pore size, swelling, and antibacterial properties were enhanced. The silver nanoparticles increased the in vitro enzyme degradation in samples without bioactive-glass; however, the degradation was remarkably reduced by addition of bioactive-glass. In addition, formation of apatite particles, the main inorganic constituent of the bone, on the surface of the bioactive-glass containing scaffolds were confirmed after immersion in simulated body fluid (SBF). The viability of hMSC on the scaffold suggested that gelatin/bioactive-glass/nanosilver scaffolds can be used as an antibacterial scaffolds.
The human gut microbiome is considered critical for establishing and maintaining intestinal function and homeostasis throughout life. Evidence for bidirectional communication with the immune and nervous systems has spawned interest in the microbiome as a key factor for human and animal health. Consequently, appreciation of the microbiome as a target of xenobiotics, including environmental pollutants such as heavy metals, has risen steadily because disruption of a healthy microbiome (dysbiosis) has been linked to unfavorable health outcomes. Thus, toxicology must consider toxicant effects on the host's microbiome as an integral part of the holobiont. We discuss current findings on the impact of toxic metals on the composition, diversity, and function of the gut microbiome as well as the modulation of metal toxicity by the microbiome. Present limitations and future needs in elucidating microbiome-metal interactions and the potential of harnessing beneficial traits of the microbiota to counteract metal toxicity are also considered.
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