Potential Undesirable Side Effects Research Articles

Chem-CRISPR/dCas9FCPF: a platform for chemically induced epigenome editing.

Epigenetic aberration is one of the major driving factors in human cancer, often leading to acquired resistance to chemotherapies. Various small molecule epigenetic modulators have been reported. Nonetheless, outcomes from animal models and clinical trials have underscored the substantial setbacks attributed to pronounced on- and off-target toxicities. To address these challenges, CRISPR/dCas9 technology is emerging as a potent tool for precise modulation of epigenetic mechanism. However, this technology involves co-expressing exogenous epigenetic modulator proteins, which presents technical challenges in preparation and delivery with potential undesirable side effects. Recently, our research demonstrated that Cas9 tagged with the Phe-Cys-Pro-Phe (FCPF)-peptide motif can be specifically targeted by perfluorobiphenyl (PFB) derivatives. Here, we integrated the FCPF-tag into dCas9 and established a chemically inducible platform for epigenome editing, called Chem-CRISPR/dCas9FCPF. We designed a series of chemical inhibitor-PFB conjugates targeting various epigenetic modulator proteins. Focusing on JQ1, a panBET inhibitor, we demonstrate that c-MYC-sgRNA-guided JQ1-PFB specifically inhibits BRD4 in close proximity to the c-MYC promoter/enhancer, thereby effectively repressing the intricate transcription networks orchestrated by c-MYC as compared with JQ1 alone. In conclusion, our Chem-CRISPR/dCas9FCPF platform significantly increased target specificity of chemical epigenetic inhibitors, offering a viable alternative to conventional fusion protein systems for epigenome editing.

A double-edged sword: The complex interplay between engineered nanoparticles and platelets.

Nanoparticles (NP) play a crucial role in nanomedicine, serving as carriers for localized therapeutics to allow for precise drug delivery to specific disease sites and conditions. When injected systemically, NP can directly interact with various blood cell types, most critically with circulating platelets. Hence, the potential activation/inhibition of platelets following NP exposure must be evaluated a priori due to possible debilitating outcomes. In recent years, various studies have helped resolve the physicochemical parameters that influence platelet-NP interactions, and either emphasize nanoparticles' therapeutic role such as to augment hemostasis or to inhibit thrombus formation, or conversely map their potential undesired side effects upon injection. In the present review, we discuss some of the main effects of several key NP types including polymeric, ceramic, silica, dendrimers and metallic NPs on platelets, with a focus on the physicochemical parameters that can dictate these effects and modulate the therapeutic potential of the NP. Despite the scientific and clinical significance of understanding Platelet-NP interactions, there is a significant knowledge gap in the field and a critical need for further investigation. Moreover, improved guidelines and research methodologies need to be developed and implemented. Our outlook includes the use of biomimetic in vitro models to investigate these complex interactions under both healthy physiological and disease conditions.

The effects of social pensions on nutrition-related health outcomes of the poor: Quasi-experimental evidence from Peru.

This paper exploits the discontinuity around a welfare index of eligibility to assess the impact of Peru's social pension program Pension 65 on nutrition-related health outcomes among elderly poor individuals. Overall, we find evidence of how a relatively inexpensive program can produce improvements in anemia and nutrition-related mortality risk markers. The effects appear to be driven by plausible underlying mechanisms, including via improved nutritional quality as well as greater food expenditures and healthcare utilization. These positive effects are only modestly countered by tentative signs of an increased obesity risk among women in the short term (<2years), but not beyond this term. As the program evolves further, policymakers need to confront the challenge of continuing to ensure the health benefits in terms of reducing nutritional deficits while avoiding potential undesirable side effects in terms of over-nutrition in Peru. The findings may serve to highlight the wider benefits of similar pension policies for the poor also in other middle income countries, well beyond the immediate economic welfare effects that the policies have primarily been designed for.

Limitations associated with transcranial direct current stimulation for enhancement: considerations of performance tradeoffs in active-duty Soldiers.

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation method, popular due to its low cost, ease-of-application, and portability. As such, it has gained traction in examining its potential for cognitive enhancement in a diverse range of populations, including active-duty military. However, current literature presents mixed results regarding its efficacy and limited evaluations of possible undesirable side-effects (such as degradation to cognitive processes). To further examine its potential for enhancing cognition, a double-blind, randomized, sham-controlled, within-subjects design, was used to evaluate both online active-anodal and -cathodal on several cognitive tasks administered. Potential undesirable side effects related to mood, sleepiness, and cognitive performance, were also assessed. Active tDCS was applied for 30 min, using 2 mA, to the left dorsolateral prefrontal cortex with an extracephalic reference placed on the contralateral arm of 27 (14 males) active-duty Soldiers. We report mixed results. Specifically, we found improvements in sustained attention (active-anodal) for males in reaction time (p = 0.024, ηp 2 = 0.16) and for sensitivity index in females (p = 0.013, ηp 2 = 0.18). In addition, we found faster reaction time (p = 0.034, ηp 2 = 0.15) and increased accuracy (p = 0.029, ηp 2 = 0.16) associated with executive function (active-anodal and -cathodal), and worsened working memory performance (active-cathodal; p = 0.008, ηp 2 = 0.18). Additionally, we found increased risk-taking with active-anodal (p = 0.001, ηp 2 = 0.33). tDCS may hold promise as a method for cognitive enhancement, as evidenced by our findings related to sustained attention and executive function. However, we caution that further study is required to better understand additional parameters and limitations that may explain results, as our study only focused on anode vs. cathode stimulation. Risk-taking was examined secondary to our main interests which warrants further experimental investigation isolating potential tradeoffs that may be associated with tDCS simulation.

Ingredients in Commercially Available Mouthwashes

Mouthwashes, a cornerstone of oral and dental hygiene, play a pivotal role in combating the formation of dental plaque, a leading cause of periodontal disease and dental caries. This study aimed to review the composition of mouthwashes found on retail shelves in Turkey and evaluate their prevalence and side effects, if any. The mouthwashes examined were sourced from the 5 largest chain stores in each district of Istanbul. A comprehensive list of the constituents was meticulously recorded. The research was supported by an extensive compilation of references from scholarly databases such as Google Scholar, PubMed, and ScienceDirect. Through rigorous analysis, the relative proportions of mouthwash ingredients and components were determined. A total of 45 distinctive variations of mouthwashes, representing 17 prominent brands, were identified. Amongst the 116 ingredients discovered, 70 were evaluated for potential adverse effects and undesirable side effects. The aroma of the mouthwash (n = 45; 100%), as welll as their sodium fluoride (n = 28; 62.22%), sodium saccharin (n = 29; 64.44%), sorbitol (n = 21; 46.6%), and propylene glycol (n = 28; 62.22%) content were the main undesireable features. The limited array of mouthwashes found on store shelves poses a concern for both oral and public health. Furthermore, the intricate composition of these products, consisting of numerous ingredients with the potential for adverse effects, warrants serious attention. Both clinicians and patients should acknowledge the importance and unwarranted side effects of the compnents of the mouthwashes.

Injection of an improperly stored proprotein convertase subtilisin/kexin type 9 monoclonal antibody in a patient with secondary dyslipidemia from nephrotic syndrome: a case report

BackgroundElevated plasma cholesterol and/or plasma triglyceride levels in nephrotic syndrome patients are the result of impaired lipoprotein clearance and a compensatory increase in hepatic lipoprotein synthesis. Plasma proprotein convertase subtilisin/kexin type 9 levels directly correlate to the amount of proteinuria in nephrotic syndrome patients. Proprotein convertase subtilisin/kexin type 9 monoclonal antibody has been used to treat dyslipidemia in some refractory nephrotic syndrome cases. As a therapeutic protein, proprotein convertase subtilisin/kexin type 9 monoclonal antibody simply deteriorates if stored in inappropriate temperatures or conditions.Case presentationIn this article, we present the case of a 16-year-old Thai female with severe combined dyslipidemia secondary to refractory nephrotic syndrome. She received proprotein convertase subtilisin/kexin type 9 monoclonal antibody (alirocumab) treatment. However, the drugs were mistakenly frozen in a freezer for up to 17 hours before being stored at 4 °C. After using two frozen devices, serum total cholesterol, free proprotein convertase subtilisin/kexin type 9, and lipoprotein(a) significantly decreased. Nonetheless, the patient developed a skin rash 2 weeks after the second injection and the lesion spontaneously resolved without any treatment approximately 1 month later.ConclusionsThe effectiveness of proprotein convertase subtilisin/kexin type 9 monoclonal antibody seems to be stable after being stored under freeze–thaw conditions. However, improperly stored drugs should be discarded to avoid any potential undesirable side effects.

Targeted Epigenetic Interventions in Cancer with an Emphasis on Pediatric Malignancies.

Over the past two decades, novel hallmarks of cancer have been described, including the altered epigenetic landscape of malignant diseases. In addition to the methylation and hyd-roxymethylation of DNA, numerous novel forms of histone modifications and nucleosome remodeling have been discovered, giving rise to a wide variety of targeted therapeutic interventions. DNA hypomethylating drugs, histone deacetylase inhibitors and agents targeting histone methylation machinery are of distinguished clinical significance. The major focus of this review is placed on targeted epigenetic interventions in the most common pediatric malignancies, including acute leukemias, brain and kidney tumors, neuroblastoma and soft tissue sarcomas. Upcoming novel challenges include specificity and potential undesirable side effects. Different epigenetic patterns of pediatric and adult cancers should be noted. Biological significance of epigenetic alterations highly depends on the tissue microenvironment and widespread interactions. An individualized treatment approach requires detailed genetic, epigenetic and metabolomic evaluation of cancer. Advances in molecular technologies and clinical translation may contribute to the development of novel pediatric anticancer treatment strategies, aiming for improved survival and better patient quality of life.

Koebner’s phenomena observed in patient receiving adalimumab in psoriasis

Koebner’s phenomena, first described in 1877 as the appearance of psoriatic lesions in the uninvolved skin of psoriatic patients as a consequence of trauma. Koebner phenomena has been associated with the use of biological response modifiers. The development of the anti-TNF therapies is a milestone in the therapy of rheumatic diseases. As in all new treatment opportunities it is of concern whether all potential undesired side effects have been evaluated. We report a case involving a 31-year-old young male patient diagnosed with psoriasis and psoriatic arthritis (PsA) since a year, who received Adalimumab as part of his treatment and developed Koebner’s phenomena.

A pan-tumor-siRNA aptamer chimera to block nonsense-mediated mRNA decay inflames and suppresses tumor progression

Immune-checkpoint blockade (ICB) therapy has changed the clinical outcome of many types of aggressive tumors, but there still remain many cancer patients that do not respond to these treatments. There is an unmet need to develop a feasible clinical therapeutic platform to increase the rate of response to ICB. Here we use a previously described clinically tested aptamer (AS1411) conjugated with SMG1 RNAi (AS1411-SMG1 aptamer-linked siRNA chimeras [AsiCs]) to inhibit the nonsense-mediated RNA decay pathway inducing tumor inflammation and improving response to ICB. The aptamer AS1411 shows binding to numerous mouse and human tumor cell lines tested. AS1411 induces tumor cytotoxicity in long incubation times, which allows for the use of the aptamer as a carrier to target the RNAi inhibition to the tumor. The AS1411-SMG1 AsiCs induce a strong antitumor response in local and systemic treatment in different types of tumors. Finally, AS1411-SMG1 AsiCs are well tolerated with no detected side effects.

Physically Cross-Linked DNA Hydrogel-Based Sustained Cytokine Delivery for In Situ Diabetic Alveolar Bone Rebuilding.

The development of a biodegradable and shape-adaptable bioscaffold that can enhance local cytokine retention and bioactivity is essential for the application of immunotherapy in periodontal diseases. Here, we report a biodegradable, anti-inflammatory, and osteogenic ILGel that uses a physically cross-linked DNA hydrogel as a soft bioscaffold for the long-term sustained release of cytokine interleukin-10 (IL-10) to accelerate diabetic alveolar bone rebuilding. Porous microstructures of ILGel favored the encapsulation of IL-10 and maintained IL-10 bioactivity for at least 7 days. ILGel can be gradually degraded or hydrolyzed under physiological conditions, avoiding the potential undesired side effects on dental tissues. Long-term sustained release of bioactive IL-10 from ILGel not only promoted M2 macrophage polarization and attenuated periodontal inflammation but also triggered osteogenesis of mesenchymal stem cells (MSCs), leading to accelerated alveolar bone formation and healing of alveolar bone defects under diabetic conditions in vivo. ILGel treatment significantly accelerated the defect healing rate of diabetic alveolar injury up to 93.42 ± 4.6% on day 21 post treatment compared to that of free IL-10 treatment (63.30 ± 7.39%), with improved trabecular architectures. Our findings imply the potential application of the DNA hydrogel as the bioscaffold for cytokine-based immunotherapy in diabetic alveolar bone injury and other periodontal diseases.

Preclinical investigations using [177Lu]Lu-Ibu-DAB-PSMA toward its clinical translation for radioligand therapy of prostate cancer

[177Lu]Lu-Ibu-DAB-PSMA was previously characterized with moderate albumin-binding properties enabling high tumor accumulation but reasonably low retention in the blood. The aim of this study was to investigate [177Lu]Lu-Ibu-DAB-PSMA in preclinical in vivo experiments and compare its therapeutic efficacy and potential undesired side effects with those of [177Lu]Lu-PSMA-617 and the previously developed [177Lu]Lu-PSMA-ALB-56. BALB/c nude mice without tumors were investigated on Day 10 and 28 after injection of 10 MBq radioligand. It was revealed that most plasma parameters were in the same range for all groups of mice and histopathological examinations of healthy tissue did not show any alternations in treated mice as compared to untreated controls. Based on these results, a therapy study over twelve weeks was conducted with PC-3 PIP tumor-bearing mice for comparison of the radioligands’s therapeutic efficacy up to an activity of 10 MBq (1 nmol) per mouse. In agreement with the increased mean absorbed tumor dose, [177Lu]Lu-Ibu-DAB-PSMA (~ 6.6 Gy/MBq) was more effective to inhibit tumor growth than [177Lu]Lu-PSMA-617 (~ 4.5 Gy/MBq) and only moderately less potent than [177Lu]Lu-PSMA-ALB-56 (~ 8.1 Gy/MBq). As a result, the survival of mice treated with 2 MBq of an albumin-binding radioligand was significantly increased (p < 0.05) compared to that of mice injected with [177Lu]Lu-PSMA-617 or untreated controls. The majority of mice treated with 5 MBq or 10 MBq [177Lu]Lu-Ibu-DAB-PSMA or [177Lu]Lu-PSMA-ALB-56 were still alive at study end. Hemograms of immunocompetent mice injected with 30 MBq [177Lu]Lu-Ibu-DAB-PSMA or 30 MBq [177Lu]Lu-PSMA-617 showed values in the same range as untreated controls. This was, however, not the case for mice treated with [177Lu]Lu-PSMA-ALB-56 which revealed a drop in lymphocytes and hemoglobin at Day 10 and Day 28 after injection. The data of this study demonstrated a significant therapeutic advantage of [177Lu]Lu-Ibu-DAB-PSMA over [177Lu]Lu-PSMA-617 and a more favorable safety profile as compared to that of [177Lu]Lu-PSMA-ALB-56. Based on these results, [177Lu]Lu-Ibu-DAB-PSMA may has the potential for a clinical translation.

Evaluation of categorical matrix completion algorithms: toward improved active learning for drug discovery.

MotivationHigh throughput and high content screening are extensively used to determine the effect of small molecule compounds and other potential therapeutics upon particular targets as part of the early drug development process. However, screening is typically used to find compounds that have a desired effect but not to identify potential undesirable side effects. This is because the size of the search space precludes measuring the potential effect of all compounds on all targets. Active machine learning has been proposed as a solution to this problem.ResultsIn this article, we describe an improved imputation method, Impute by Committee, for completion of matrices containing categorical values. We compare this method to existing approaches in the context of modeling the effects of many compounds on many targets using latent similarities between compounds and conditions. We also compare these methods for the task of driving active learning in well-characterized settings for synthetic and real datasets. Our new approach performed the best overall both in the accuracy of matrix completion itself and in the number of experiments needed to train an accurate predictive model compared to random selection of experiments. We further improved upon the performance of our new method by developing an adaptive switching strategy for active learning that iteratively chooses between different matrix completion methods.Availability and implementationA Reproducible Research Archive containing all data and code is available at http://murphylab.cbd.cmu.edu/software.Supplementary information Supplementary data are available at Bioinformatics online.

Differentially Private Mobile Crowd Sensing Considering Sensing Errors.

An increasingly popular class of software known as participatory sensing, or mobile crowdsensing, is a means of collecting people’s surrounding information via mobile sensing devices. To avoid potential undesired side effects of this data analysis method, such as privacy violations, considerable research has been conducted over the last decade to develop participatory sensing that looks to preserve privacy while analyzing participants’ surrounding information. To protect privacy, each participant perturbs the sensed data in his or her device, then the perturbed data is reported to the data collector. The data collector estimates the true data distribution from the reported data. As long as the data contains no sensing errors, current methods can accurately evaluate the data distribution. However, there has so far been little analysis of data that contains sensing errors. A more precise analysis that maintains privacy levels can only be achieved when a variety of sensing errors are considered.

Should Antiemetics be Given Prophylactically with Intravenous Opioids While Treating Acute Pain in the Emergency Department?: Clinical Practice Paper Approved by American Academy of Emergency Medicine Clinical Guidelines Committee.

It is common practice for emergency physicians to give parenteral opioids for acute pain, however, some treating physicians have concerns that using parenteral opioids can lead to nausea and vomiting when used alone. Therefore, antiemetics are often given prophylactically with opioids for nausea and vomiting in the emergency department (ED). This systematic review evaluates the use of prophylactic antiemetics with parenteral opioids for the treatment of acute pain in the ED. A 10-year literature search using keywords was performed in PubMed for English-language human studies. Abstracts were screened to identify high-quality studies, which then underwent a more rigorous structured review. The recommendations are made based on the literature review. Eight articles met criteria for structured review and citation in this article. These include one review article, two randomized controlled trials, three prospective observational trials, one retrospective study, and one pre- and post-intervention trial. Based on the literature review, routine use of prophylactic antiemetics are not indicated with administration of parenteral opioids for treatment of acute pain in the ED, as nausea and vomiting are infrequent side effects. The recent literature clearly demonstrates that there are potential undesirable side effects from the use of antiemetics when using opioids. However, one subgroup of patients, those with a known history of nausea and vomiting after opioid use or a history of travel sickness, may benefit from the use of prophylactic antiemetic when being treated with parenteral opioids.

In vivo efficacy of bevacizumab-loaded albumin nanoparticles in the treatment of colorectal cancer.

Bevacizumab (as other monoclonal antibodies) has now become a mainstay in the treatment of several cancers in spite of some limitations, including poor tumour penetration and the development of resistance mechanisms. Its nanoencapsulation may be an adequate strategy to minimize these problems. The aim of this work was to evaluate the efficacy of bevacizumab-loaded nanoparticles (B-NP-PEG) on a xenograft model of human colorectal cancer. For this purpose, human serum albumin nanoparticles were prepared by coacervation, then coated with poly(ethylene glycol) and freeze-dried. B-NP-PEG displayed a mean size of about 300nm and a bevacizumab loading of approximately 145μg/mg. An in vivo study was conducted in the HT-29 xenograft model of colorectal cancer. Both, free and nanoencapsulated bevacizumab, induced a similar reduction in the tumour growth rate of about 50%, when compared to controls. By microPET imaging analysis, B-NP-PEG was found to be a more effective treatment in decreasing the glycolysis and metabolic tumour volume than free bevacizumab, suggesting higher efficacy. These results correlated well with the capability of B-NP-PEG to increase about fourfold the levels of intratumour bevacizumab, compared with the conventional formulation. In parallel, B-NP-PEG displayed six-times lower amounts of bevacizumab in blood than the aqueous formulation of the antibody, suggesting a lower incidence of potential undesirable side effects. In summary, albumin-based nanoparticles may be adequate carriers to promote the delivery of monoclonal antibodies (i.e. bevacizumab) to tumour tissues. Graphical abstract.

Cu, Zn doped borate bioactive glasses: antibacterial efficacy and dose-dependent in vitro modulation of murine dendritic cells.

Among emerging biomaterials, bioactive glasses (BGs) are being widely explored for various applications in tissue engineering. However, the effects of BGs (in particular BG ionic dissolution products) on immune cells and specifically on dendritic cells (DCs), which are the most potent antigen-presenting cells of the immune system, have not been previously investigated in detail. Such interactions between BGs and DCs must be assessed as a novel biocompatibility criterion for biomaterials, since, with the increased application possibilities of BGs, the modulation of the immune system may induce potential complications and undesired side effects. Indeed, the effects of BG exposure on specific immune cells are not well understood. Thus, in this study we investigated, for the first time, the effect of borate BGs doped with biologically active ions on specific immune cells, such as DCs and we further investigated the antibacterial properties of these borate BGs. The compositions of the borate BGs (B3) were based on the well-known 13-93 (silicate) composition by replacing silica with boron trioxide and by adding copper (3 wt%) and/or zinc (1 wt%). By performing an agar diffusion test, the antibacterial effect depending on the compositions of the borate BGs could be proved. Furthermore we found a dose-dependent immune modulation of DCs after treatment with borate BGs, especially when the borate BGs contained Zn and/or Cu. Depending on the ion concentration and the rise in pH, the phenotype and function of DCs were modified. While at low doses B3 and Zn-doped B3 BGs had no impact on DC viability, Cu containing BGs strongly affected cell viability. Furthermore, the surface expression of DC-specific activation markers, such as the major histocompatibility complex (MHC)-II, CD86 and CD80, was modulated. In addition, also DC mediated T-cell proliferation was remarkably reduced when treated with high doses of B3-Cu and B3-Cu-Zn BGs. Interestingly, the release of inflammatory cytokines increased after incubation with B3 and B3-Zn BGs compared to mock-treated DCs. Considering the essential role of DCs in the modulation and regulation of immune responses, these findings provide first evidence of phenotypic and functional consequences regarding the exposure of DCs to BGs in vitro.

Oral administration of the cannabigerol derivative VCE-003.2 promotes subventricular zone neurogenesis and protects against mutant huntingtin-induced neurodegeneration

BackgroundThe administration of certain cannabinoids provides neuroprotection in models of neurodegenerative diseases by acting through various cellular and molecular mechanisms. Many cannabinoid actions in the nervous system are mediated by CB1 receptors, which can elicit psychotropic effects, but other targets devoid of psychotropic activity, including CB2 and nuclear PPARγ receptors, can also be the target of specific cannabinoids.MethodsWe investigated the pro-neurogenic potential of the synthetic cannabigerol derivative, VCE-003.2, in striatal neurodegeneration by using adeno-associated viral expression of mutant huntingtin in vivo and mouse embryonic stem cell differentiation in vitro.ResultsOral administration of VCE-003.2 protected striatal medium spiny neurons from mutant huntingtin-induced damage, attenuated neuroinflammation and improved motor performance. VCE-003.2 bioavailability was characterized and the potential undesired side effects were evaluated by analyzing hepatotoxicity after chronic treatment. VCE-003.2 promoted subventricular zone progenitor mobilization, increased doublecortin-positive migrating neuroblasts towards the injured area, and enhanced effective neurogenesis. Moreover, we demonstrated the proneurogenic activity of VCE-003.2 in embryonic stem cells. VCE-003.2 was able to increase neuroblast formation and striatal-like CTIP2-mediated neurogenesis.ConclusionsThe cannabigerol derivative VCE-003.2 improves subventricular zone-derived neurogenesis in response to mutant huntingtin-induced neurodegeneration, and is neuroprotective by oral administration.

Recent Advances and Applications of Pulsed Electric Fields (PEF) to Improve Polyphenol Extraction and Color Release during Red Winemaking

Pulsed electric fields (PEF) technology is an innovative food processing system and it has been introduced in relatively recent times as a pre-treatment of liquid and semi-solid food. Low cost-equipment and short processing time, coupled to the effectiveness in assisting the extraction of valuable compounds from vegetable tissues, makes PEF a challenging solution for the industrial red winemaking; a tailored PEF-assisted maceration was demonstrated to promote an increase in wine color quality and an improvement in the polyphenolic profile. Despite the application of PEF has been studied and the positive effects in selected wine varieties were demonstrated on batch and pilot-scale systems, there is a need for a more detailed characterization of the impact in different grapes, and for a better understanding of potential undesirable side-effects. This review aims to summarize the state of the art in view of a detailed feasibility study, to promote the introduction of PEF technology in the oenological industry.

REPRESENTATIVENESS OF EUROPEAN BIOCHAR RESEARCH: PART I – FIELD EXPERIMENTS

A representativeness survey of existing European Biochar field experiments within the Biochar COST Action TD1107 was conducted to gather key information for setting up future experiments and collaborations, and to minimise duplication of efforts amongst European researchers. Woody feedstock biochar, applied without organic or inorganic fertiliser appears over-represented compared to other categories, especially considering the availability of crop residues, manures, and other organic waste streams and the efforts towards achieving a zero waste economy. Fertile arable soils were also over-represented while shallow unfertile soils were under-represented. Many of the latter are likely in agroforestry or forest plantation land use. The most studied theme was crop production. However, other themes that can provide evidence of mechanisms, as well as potential undesired side-effects, were relatively well represented. Biochar use for soil contamination remediation was the least represented theme; further work is needed to identify which specific contaminants, or mixtures of contaminants, have the potential for remediation by different biochars.

Tris-base buffer: a promising new inhibitor for cancer progression and metastasis.

Neutralizing tumor external acidity with oral buffers has proven effective for the prevention and inhibition of metastasis in several cancer mouse models. Solid tumors are highly acidic as a result of high glycolysis combined with an inadequate blood supply. Our prior work has shown that sodium bicarbonate, imidazole, and free‐base (but not protonated) lysine are effective in reducing tumor progression and metastasis. However, a concern in translating these results to clinic has been the presence of counter ions and their potential undesirable side effects (e.g., hypernatremia). In this work, we investigate tris(hydroxymethyl)aminomethane, (THAM or Tris), a primary amine with no counter ion, for its effects on metastasis and progression in prostate and pancreatic cancer in vivo models using MRI and bioluminescence imaging. At an ad lib concentration of 200 mmol/L, Tris effectively inhibited metastasis in both models and furthermore led to a decrease in the expression of the major glucose transporter, GLUT‐1. Our results also showed that Tris–base buffer (pH 8.4) had no overt toxicity to C3H mice even at higher doses (400 mmol/L). In conclusion, we have developed a novel therapeutic approach to manipulate tumor extracellular pH (pHe) that could be readily adapted to a clinical trial.