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Background: Advancements in nanoscience have led to a profound paradigm shift in the therapeutic applications of medicinally important natural drugs. The goal of this research is to develop a nano-natural product for efficient cancer treatment. Methods and Results: For this purpose, mesoporous silica nanoparticles (MSNPs) were formulated, characterized, and loaded with caffeine to develop a targeted drug delivery system, i.e., caffeine-coated nanoparticles (CcNPs). In silico docking studies were conducted to examine the binding efficiency of the CcNPs with different apoptotic targets followed by in vitro and in vivo bioassays in respective animal models. Caffeine, administered both as a free drug and in nanomedicine form, along with doxorubicin, was delivered intravenously to a benzene-induced AML model. The anti-leukemic potential was assessed through hematological profiling, enzymatic biomarker analysis, and RT-PCR examination of genetic alterations in leukemia markers. Docking studies show strong inter-molecular interactions between CcNPs and apoptotic markers. In vitro analysis exhibits statistically significant antioxidant activity, whereas in vivo analysis exhibits normalization of the genetic expression of leukemia biomarkers STMN1 and S1009A, accompanied by the restoration of the hematological and morphological traits of leukemic blood cells in nanomedicine-treated rats. Likewise, a substantial improvement in hepatic and renal biomarkers is also observed. In addition to these findings, the nanomedicine successfully normalizes the elevated expression of GAPDH and mTOR induced by exposure to benzene. Further, the nanomedicine downregulates pro-survival components of the NF-kappa B pathway and upregulated P53 expression. Additionally, in the TRAIL pathway, it enhances the expression of pro-apoptotic players TRAIL and DR5 and downregulates the anti-apoptotic protein cFLIP. Conclusions: Our data suggest that MSNPs loaded with caffeine, i.e., CcNP/nanomedicine, can potentially inhibit transformed cell proliferation and induce pro-apoptotic TRAIL machinery to counter benzene-induced leukemia. These results render our nanomedicine as a potentially excellent therapeutic agent against AML. [ABSTRACT FROM AUTHOR]

As Australian lupin cultivars are rich sources of polyphenols, dietary fibers, high-quality proteins, and abundant bioactive compounds with significant antioxidant, antidiabetic, and anticancer activities, this research work is aimed at investigating the colon cancer alleviation activity of nine cultivars of lupin seeds on HCT116 and HT29 colon carcinoma cell lines through anti-proliferation assay, measurement of apoptosis, and identification of the mechanism of apoptosis. Nine cultivars were pre-screened for anti-proliferation of HCT116 and HT29 cells along with consideration of the impact of heat processing on cancer cell viability. Mandelup and Jurien showed significant inhibition of HCT116 cells, whereas the highest inhibition of HT29 cell proliferation was attained by Jurien and Mandelup. Processing decreased the anti-proliferation activity drastically. Lupin cultivars Mandelup, Barlock, and Jurien (dose: 300 μg/mL) induced early and late apoptosis of colon cancer cells in Annexin V-FITC assay. The mechanism of apoptosis was explored, which involves boosting of caspases-3/7 activation and intracellular reactive oxygen species (ROS) generation in HCT116 cells (Mandelup and Barlock) and HT29 cells (Jurien and Mandelup). Thus, the findings showed that lupin cultivars arrest cell cycles by inducing apoptosis of colorectal carcinoma cells triggered by elevated ROS generation and caspases-3/7 activation. [ABSTRACT FROM AUTHOR]

The learner’s own language (commonly referred to as ‘L1’ or ‘first language’) has been neglected as a resource in the learning of another language and, in some contexts, it has been banned altogether. The arguments in favour of own-language exclusion are not supported by research and the policy is not followed by a majority of teachers. A reconsideration of these arguments and an awareness of practical suggestions for drawing on the learners’ own language as a resource for learning may help language teachers to enrich their repertoire of teaching techniques and activities.

Wound care will always be among the main tasks in all surgical specialties. Several medicinal plants have proven efficacy to cure wounds. Ethnobotanical research and ethnopharmacological research have virtually endless potential to find new lead compounds. The aim of this research review is to assess the potential of some Gentiana species as sources of promising active compounds to support wound healing. Gentians are among the most popular medicinal plants used in many countries for a wide spectrum of health conditions. Traditionally, those used to cure wounds are Gentiana lutea, G. punctata, G. asclepiadea, G. cruciata, G. oliverii, G. septemphida, and G. gelida. Candidate compounds with skin regeneration and wound-healing potential isolated from gentians are isogentisin, isoorientin, mangiferin, lupeol, pinoresinol, syringaresinol, eustomoside, and sweroside. Based on the rich source of traditional knowledge on the properties of gentians to cure various skin and soft tissue complications; only very few modern pharmacological studies have been performed to test this potential. Our review demonstrates that this field deserves further investigation. Many gentians are declining in number and have high IUCN conservation status, and cultivation and micropropagation methods are the only solution for the development of new drugs based on gentian extracts. [ABSTRACT FROM AUTHOR]

The presence of p53-pathway dysfunction in chronic lymphocytic leukemia (CLL) can be used to identify patients with chemotherapy-refractory disease. Therapeutic responses are known to vary between patients with chemosensitive CLL and may relate to differences in p53-pathway activity. We hypothesized that the magnitude or type of p53-pathway protein expression is heterogeneous in patients with chemosensitive disease and could associate with white cell responses. In this pilot study, changes in p53 and its transcriptional targets, p21/waf1 and MDM2 were analyzed by immunoblotting and densitometry in CLL cells from 10 patients immediately prior to the start of chemotherapy, and after culture for 24 hours (h) with fludarabine (n=7) or chlorambucil (n=3). The in vitro response was also compared to that in vivo in circulating cells pre-treatment, and at 24h and 96h of chemotherapy. Disease responses were evident in all patients after the first treatment-cycle. Significant p53 induction was observed in CLL cells treated in vitro and in vivo. Greater heterogeneity in the expression-intensity was observed in vivo (σ2=45.15) than in vitro (σ2=1.33) and the results failed to correlate (r2=0.18, p=0.22). p21/waf1 and MDM2 expression-profiles were also dissimilar in vitro and in vivo. Higher in vivo (but not in vitro) responses associated with changes in white cell count (p=0.026). Thus, heterogeneity of p53-pathway activity exists in chemosensitive CLL; in unselected patients, in vivo changes do not correlate with those in vitro, but may associate with post-treatment white cell responses.

This is a summary of some of the issues raised in a recent on-line discussion within the IATEFL Teacher Trainers and Educators Special Interest Group. The IATEFL Teacher Trainers and Educators Special Interest Group periodically organizes on-line fielded discussions on pre-determined topics that are chosen and moderated by volunteers. From time to time, however, vigorous discussions develop in a more informal and less planned way, when a topic strikes a chord with members of the list. Few topics have provoked more response from members of the group than the question of the use of jargon in teacher education.

In response to rising rates of melanoma worldwide, novel noninvasive melanoma detection techniques are emerging to facilitate the early detection of melanoma and decrease unnecessary biopsies of benign pigmented lesions. Because they often report similar study findings, it may be difficult to determine how best to incorporate these technologies into clinical practice based on their supporting studies alone. The first article in this continuing medical education series provides practical advice on how and when to use various noninvasive melanoma detection techniques in clinical practice. [ABSTRACT FROM AUTHOR]

Despite advances in early detection as described in part 1 of this continuing medical education series, melanoma continues to be a large contributor to cutaneous cancer-related mortality. In a subset of patients with unresectable or metastatic disease, surgical clearance is often not possible; therefore, systemic and local therapies are considered. The second article in this series provides dermatologists with an up-to-date working knowledge of the treatment options that may be prescribed by oncologists for patients with unresectable stage III, stage IV, and recurrent melanoma. [ABSTRACT FROM AUTHOR]

Vitamin D is a steroid hormone of importance to the field of dermatology. Skin is unique in that it is the site of vitamin D synthesis upon sun exposure and a target organ for its activity. We explore the physiology and metabolic mechanism of action of vitamin D, as well as its effects on the skin. We also discuss the current evidence of the efficacy and safety of oral and topical vitamin D analogues on skin conditions such as psoriasis, atopic dermatitis, vitiligo, sunburn, actinic keratosis, and fibrosing skin disorders. Based on currently available scientific evidence, the National Academy of Medicine's recommended dietary allowance for vitamin D ranges from 400 IU to 800 IU daily based on age categories. [ABSTRACT FROM AUTHOR]

Temperature can fluctuate widely between different seasons, and this may greatly impact many biological processes. However, little is known about its influence on the functioning of benthic microbial communities. Here we investigated the nutrient accumulation capability of periphytic biofilm under temperature fluctuations (17–35°C). Periphytic biofilm maintained the same nutrient accumulation capacity after experiencing the 'warming-hot-cooling' temperature fluctuation under both lab and outdoor conditions as those without temperature disturbance. In response to temperature increase, both community composition and species richness changed greatly and the increase in biodiversity was identified as being the underlying mechanism boosting the sustainable function in nutrient accumulation, indicating zero net effects of community changes. These findings provide insights into the underlying mechanisms of how benthic microbial communities adapt to temperature fluctuations to maintain nutrient accumulation capacity and elucidate that periphytic biofilm plays important roles in influencing nutrient cycling in aquatic ecosystems under temperature changes such as seasonal fluctuations. [ABSTRACT FROM AUTHOR]