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Background: Comorbidities and risk factors likely to complicate treatment are common in elderly cancer patients. Anthracyclines remain the cornerstone of first-line therapy for non-Hodgkin’s lymphoma (NHL) and metastatic and early breast cancer but can cause congestive heart failure. Elderly patients are at increased risk of this event and measures to reduce it should be considered.Methods: A committee of experts in breast cancer and NHL met under the auspices of the International Society for Geriatric Oncology to review the literature and make recommendations, based on level of evidence, for the assessment, treatment and monitoring of elderly patients requiring anthracyclines.Results and recommendations: Use of anthracycline-based chemotherapy illustrates many of the dilemmas facing elderly cancer patients. Age in itself should not prevent access to potentially curative treatment or treatment that prolongs life or improves its quality. The risk of cardiotoxicity with conventional anthracyclines is increased by the following factors: an existing or history of heart failure or cardiac dysfunction; hypertension, diabetes and coronary artery disease; older age (independent of comorbidities and performance status); prior treatment with anthracyclines; higher cumulative dose of anthracyclines and short infusion duration. The fact that cumulative and irreversible cardiotoxicity is likely to be greater in this population than among younger patients calls for effective pretreatment screening for risk factors, rigorous monitoring of cardiac function and early intervention. Use of liposomal anthracycline formulations, prolonging the infusion time for conventional anthracyclines and cardioprotective measures should be considered. However, when treatment is being given with curative intent, care should be taken to ensure reduced cardiotoxicity is not achieved at the expense of efficacy. [ABSTRACT FROM AUTHOR]

In recent years, Chinese herbal medicine has gained more and more recognition in disease prevention and control due to its low toxicity and comprehensive treatment. C. morifolium (Chrysanthemum morifolium Ramat.), as the medicine food homology plant with the bioactivity of anti-oxidation, anti-inflammatory, neuroprotection and cardiovascular protection, has important therapeutic effects and health benefits for colds, inflammation, cardiovascular diseases and various chronic diseases. By reviewing the historical development, classification and distribution of germplasm resources, phytochemistry, pharmacology, and modern application of C. morifolium , the paper provides a reliable basis for the further research and application of chrysanthemum as therapeutic agents and functional additives. The literature and information about C. morifolium published in the last ten years were collected from various platforms, including Google Scholar, PubMed, ScienceDirect, Web of Science and China Knowledge Network. A comprehensive analysis confirmed that C. morifolium originated in China, and it went through the development process from food and tea to medicine for more than 3000 years. During this period, different cultivars emerged through several breeding techniques and were distributed throughout the world. Moreover, A variety of chemical components such as flavonoids, phenolic acids, volatile oils, and terpenes in chrysanthemum have been proven they possess various pharmacology of anti-inflammatory, anti-oxidant, and prevention of chronic diseases by regulating inflammatory cytokines, oxidative stress responses and signaling pathways, which are the essential conditions to play a role in TCM, nutraceuticals and diet. This paper provides a comprehensive review of historical development, classification, phytochemistry, pharmacology, and modern application of C. morifolium. However, future studies should continue to focus on the bioactive compounds and the synergistic mechanism of the "multi-component, multi-target, and multi-pathway" of chrysanthemum, and it is necessary to develop more innovative products with therapeutic effects. [Display omitted] [ABSTRACT FROM AUTHOR]

Dual programmed cell death-1 and vascular endothelial growth factor pathway inhibition is the novel standard of care for patients with unresectable hepatocellular carcinoma. Direct comparisons between first-line treatments are lacking. We conducted a literature search in MEDLINE (https://pubmed.ncbi.nlm.nih.gov), the Cochrane library (https://www.cochranelibrary.com) and Embase (www.embase.com) between January 2007 and February 2022. We included phase III randomised controlled trials that tested immune-checkpoint inhibitors or tyrosine kinase inhibitors, including sorafenib, lenvatinib and donafenib, and evaluated as primary end-point overall survival (OS) or progression-free survival (PFS). Studies testing loco-regional therapies were excluded. The primary end-point was to compare the efficacy of first-line options in terms of OS and PFS. We extracted Hazard ratios (HR) and 95% confidence intervals (95% CI) for OS and PFS and performed a frequentist network meta-analysis with fixed effect multivariable meta-regression models. The research protocol was registered in PROSPERO, an international prospective register of systematic reviews (registration code CRD42022312489). Literature review yielded 13709 results, after duplicates removal and exclusion of not relevant studies, 70 papers were available for screening. After full-text review, 9 studies were eligible for analysis. Atezolizumab plus bevacizumab reduced the risk of death compared to placebo (HR 0·40; 95% CI 0·28-0·57), sorafenib (HR 0·58; 95% CI 0·42-0·80), lenvatinib (HR 0·63; 95% CI 0·44-0·89), atezolizumab plus cabozantinib (HR 0·64; 95% CI 0·43-0·97), nivolumab (HR 0·68; 95% CI 0·48-0·98) and donafenib (HR 0·69; 95% CI 0·48-0·99). Atezolizumab plus bevacizumab was not statistically superior to durvalumab plus tremelimumab (HR 0·74; 95% CI 0·52-1·06) and sintilimab plus IBI305 (HR 1·02; 95% CI 0·67-1·55) in reducing the risk of death. Efficacy was associated with a higher risk of grade 3 adverse events. • Immune-checkpoint inhibitor plus anti-vascular endothelial growth factor agent provide the highest reduction in the risk of death in hepatocellular carcinoma. • The efficacy of immune-checkpoint inhibitor plus anti-vascular endothelial growth factor is similar to that of dual checkpoint inhibition. • The efficacy of combination strategies comes at the expense of higher toxicity. • Nivolumab is associated with the lowest risk of adverse events. [ABSTRACT FROM AUTHOR]

Liposarcoma (LPS) is a rare soft tissue sarcoma that develops from the differentiation of fat cells, typically occurring in the lower extremities and retroperitoneal space. Depending on its histological morphology and molecular changes, LPS can be divided into various subtypes, each exhibiting distinct biological behaviors. During treatment, especially for LPS arising in the retroperitoneum, the extent and quality of the initial surgery are critically important. Treatment strategies must be tailored to the specific type of LPS. Over the past few decades, the treatment of LPS has undergone numerous advancements, with new therapeutic approaches such as targeted drugs and immunotherapies continually emerging. This paper reviews the biological characteristics, molecular alterations, as well as surgical and pharmacological treatments of various LPS subtypes, with the aim of enhancing clinicians' understanding and emphasizing the importance of individualized precision therapy. With a deeper understanding of the biological characteristics and molecular alterations of LPS, future treatment trends are likely to focus more on developing personalized treatment plans to better address the various types of LPS. [Display omitted] • Due to the heterogeneity of liposarcoma, the available treatment options are limited. • Expanding the scope of surgery with the aim of achieving radical cure is gradually becoming a trend in the surgical treatment of liposarcoma. • Combination drug therapy can enhance efficacy, but potential drug toxicity should also be noted. • A multidisciplinary diagnostic and therapeutic approach holds great potential for the treatment of liposarcoma. [ABSTRACT FROM AUTHOR]

Normal tissue complication probability (NTCP) models can guide clinical decision making in radiotherapy. In recent years, they have been used for patient selection for proton beam therapy (PBT) for some anatomical tumour sites. This review synthesizes the published evidence regarding the use of NTCP models to predict the toxicity of PBT, for different end points in patients with brain tumours. A search of Medline and Embase using the Patients, Intervention, Comparison, Outcome (PICO) criteria was undertaken. In total, 37 articles were deemed relevant and were reviewed in detail. Nineteen articles on NTCP modelling of toxicity end points were included. Of these, 11 were comparative NTCP studies of PBT versus conventional photon radiotherapy (XRT), which evaluated differences in plan dosimetry and then assumed that XRT-derived literature estimates of NTCP would be applicable to both. Seven papers derived NTCP models based on PBT outcome data, two of which provided model parameters. Among analysed end points, the reduced risk of secondary tumours with PBT as compared with XRT is estimated – through modelling studies – to be considerable and was highlighted by most authors. For other analysed end points, the clinical benefit of PBT mainly depends on tumour location in relation to organs at risk as well as prescription doses. NTCP models can be useful tools for treatment plan comparison. However, most published toxicity data were derived from XRT cohorts; this review has highlighted the need for further studies relating dose-volume parameters to observed toxicity in PBT-treated patients. Specifically, there is a need for PBT-specific NTCP models that can be implemented in the clinical practice. NTCP models built on robust clinical data for the most common radiotherapy toxicities in the brain would potentially redefine the current indications for PBT. [ABSTRACT FROM AUTHOR]

Cervical cancer (CC) is a potentially lethal disorder that can have serious consequences for a woman's health. Because early symptoms are typically only present in the middle to late stages of the disease, clinical diagnosis and treatment can be challenging. Traditional Chinese medicine (TCM) has been shown to have unique benefits in terms of alleviating cancer clinical symptoms, lowering the risk of recurrence after surgery, and reducing toxic side effects and medication resistance after radiation therapy. It has also been shown to improve the quality of life for patients. Because of its improved anti-tumor effectiveness and biosafety, it could be considered an alternative therapy option. This study examines how TCM causes apoptosis in CC cells via signal transduction, including the active components and medicinal tonics. It also intends to provide a reliable clinical basis and protocol selection for the TCM therapy of CC. The following search terms were employed in PubMed, Web of Science, Embase, CNKI, Wanfang, VIP, SinoMed, and other scientific databases to retrieve pertinent literature on "cervical cancer," "apoptosis," "signaling pathway," "traditional Chinese medicine," "herbal monomers," "herbal components," "herbal extracts," and "herbal formulas." It has been demonstrated that herbal medicines can induce apoptosis in cells of the cervix, a type of cancer, by influencing the signaling pathways involved. A comprehensive literature search was conducted, and 148 papers from the period between January 2017 and December 2023 were identified as eligible for inclusion. After a meticulous process of screening, elimination and summary, generalization, and analysis, it was found that TCM can regulate multiple intracellular signaling pathways and related molecular targets, such as STAT3, PI3K/AKT, Wnt/β-catenin, MAPK, NF-κB, p53, HIF-1α, Fas/FasL and so forth. This regulatory capacity was observed to induce apoptosis in cervical cancer cells. The study of the mechanism of TCM against cervical cancer and the screening of new drug targets is of great significance for future research in this field. The results of this study will provide ideas and references for the future development of Chinese medicine in the diagnosis and treatment of cervical cancer. [ABSTRACT FROM AUTHOR]

Monitoring aspartate aminotransferase (AST) has been demonstrated to be a sensitive sign of liver dysfunction and an essential method for determining the health status of the living body. The quantitative analysis of AST in vivo/vitro is still challenged by complicated processes, expensive equipment, and/or limited sensitivity. A colorimetric assay using multicolored fluorescent nanomaterials holds great promise in vivo/vitro sensing for visual and highly sensitive disease diagnosis. However, achieving a one-step synthesis of multicolored fluorescence (FL) GQDs probe presents challenges. Herein, we successfully designed novel multicolored GQDs with a high quantum yield (QY) of 60.7 % via a simple nitrogen-induced intramolecular charge transfer (ICT) approach. Leveraging the non-toxic and color-tunable properties of N-GQDs, we developed an innovative N-GQDs-based FL test paper for sensitive colorimetric on-site detection of AST, employing the FL colorimetric method based on the transamination reaction. The FL quenching intensity demonstrated an excellent linear relationship with the concentration of AST within the range of 2.0−60.0 U/L, achieving an impressively low limit of detection (LOD) as low as 0.065 U/L. Moreover, the N-GQDs were utilized for AST in vivo detection and FL imaging in living zebrafish, further showcasing their potential in various applications such as liver disease diagnosis, assessment of myocardial damage, and monitoring of drug and toxic poisonings. • Multicolor N-GQDs with high QY were successfully fabricated via one-step method. • The color-tunable property of N-GQDs was demonstrated by the ICT mechanism. • The N-GQDs-based test strip was developed for AST in vitro ultrasensitive sensing. • The N-GQDs were utilized for in vivo FL sensing of AST in zebrafish. [ABSTRACT FROM AUTHOR]

The dried and mature seeds of Strychnons pierriana A.W.Hill. have been called Strychnine Semen (S. Semen). It have been used in traditional Chinese medicine for nearly 400 years. In recent decades, scholars at home and abroad have widely used S. Semen in the treatment of tumor diseases, showing good anti-tumor effects. In this paper, the modern research achievements of S. Semen are reviewed, including traditional uses, phytochemistry, pharmacology, and toxicology. In recent years, the research on S. Semen has increased gradually, especially the research on its anti-tumor. This paper not only reviewed the traditional uses, chemical constituents and pharmacological activities of S. Semen , but also comprehensively listed the mechanisms of Strychnos in the treatment of different tumors, providing a review for further research and development of Strychnos resources. A systematic review of the literature on Fuzi was performed using several resources, namely classic books on Chinese herbal medicine and various scientific databases, such as PubMed, the Web of Science, and the China Knowledge Resource Integrated databases. The main constituents of S. Semen include alkaloids, terpenoids, steroids, and their glycosides. Modern studies have proved that S. Semen has a wide range of pharmacological effects, including anti-inflammatory and analgesic, anti-thrombotic, myocardial cell protection, immune regulation, nerve excitation, and anti-tumor effects. Among them, the anti-tumor effect has been the focus of research in recent years. S. Semen have a certain therapeutic effect on many kinds of tumors, such as liver cancer, colon cancer, and stomach cancer in the digestive system, breast, cervical, and ovarian cancer in the reproductive system, myeloma and leukemia in the blood system, and those in the nervous system and the immune system. Strychnine has an inhibitory effect on a variety of tumors. However, modern studies of strychnine are incomplete, and more in-depth studies are needed on its stronger bioactive constituents and potential pharmacological effects. The antitumor effect of Strychnine is worth further exploration. [Display omitted] [ABSTRACT FROM AUTHOR]

Highlights • Novel Neutrosophic Rule-based Classification System (NRCS) models are proposed. • Our dataset has 553 drugs that were bio-transformed into liver. • Three rough set-based algorithms are used for features selection. • Three sampling algorithms are used to obtain balanced data. • The proposed model obtained promising results. Abstract Measuring toxicity is an important step in drug development. However, the current experimental methods which are used to estimate the drug toxicity are expensive and need high computational efforts. Therefore, these methods are not suitable for large-scale evaluation of drug toxicity. As a consequence, there is a high demand to implement computational models that can predict drug toxicity risks. In this paper, we used a dataset that consists of 553 drugs that biotransformed in the liver. In this data, there are four toxic effects, namely, mutagenic, tumorigenic, irritant and reproductive effects. Each drug is represented by 31 chemical descriptors. This paper proposes two models for predicting drug toxicity risks. The proposed models consist of three phases. In the first phase, the most discriminative features are selected using rough set-based methods to reduce the classification time and improve the classification performance. In the second phase, three different sampling algorithms, namely, Random Under-Sampling, Random Over-Sampling, and Synthetic Minority Oversampling Technique (SMOTE) are used to obtain balanced data. In the third phase, the first proposed model employs the Neutrosophic Rule-based Classification System (NRCS), and the second model uses Genetic NRCS (GNRCS) to classify an unknown drug into toxic or non-toxic. The experimental results proved that the proposed models obtained high sensitivity (89–93%), specificity (91–97%), and GM (90–94%) for all toxic effects. Overall, the results of the proposed models indicate that it could be utilized for the prediction of drug toxicity in the early stages of drug development. [ABSTRACT FROM AUTHOR]

Plants from the Thymelaeaceae family are widely distributed in tropical and temperate regions, with approximately 113 species used as Traditional Herbals. There are numerous applications for them, such as treating leukemia, AIDS, and liver cancer. It should be noted that around 20% of these plants have shown harmful side effects when used in clinical applications, including solid irritations to the skin and mucous membranes, carcinogenic effects, organ damage, vomiting, and diarrhea. This paper aims to review the toxic side effects, toxic compounds, toxic mechanisms, and detoxification methods of Traditional Herbals in Thymelaeaceae, guiding their safe clinical uses. This review employed the keywords "Thymelaeaceae," 48 different "genus," 966 "species," and the combination of "toxicity" to identify the medicinal value and toxicity of plants from Thymelaeaceae in scientific databases (Pubmed, SciFinder Scholar, Elsevier, Web of Science, and CNKI). Information relevant to the toxicity of Traditional Herbals from Thymelaeaceae up to June 2023 has been summarized. The plant names have been checked with "World Flora Online" (www.worldfloraonline.org). 28 toxic Traditional Herbals from 13 genera within the Thymelaeaceae family were categorized. Toxicities were summarized at the cellular, animal, and clinical levels. The toxic substances are primarily concentrated in the Daphne L. and Wikstroemia Endl. genera, with terpenes being the main toxic components. The toxicity mechanism is primarily associated with the mitochondrial pathways. Detoxification and enhanced efficacy can be achieved through processing methods such as vinegar-processing and sweat-soaking. Medicinal plants in the Thymelaeaceae exhibit significant pharmacological activities, such as anti-HIV and anti-tumor effects, indicating a broad potential for application. However, their clinical uses are hindered by their inherent toxicity. Researching the toxic components and mechanisms of these Traditional Herbals and exploring more effective detoxification methods can contribute to unveiling the latent value of these medicinal plants from Thymelaeaceae. [Display omitted] • Summarize the toxicity of Traditional Herbals from Thymelaeaceae for the first time. • 28 herbals from Thymelaeaceae are toxic at cellular, animal, and clinical levels. • Terpenes and flavonoids are the main toxic components. • The toxicity mechanism is primarily associated with the mitochondrial pathway. [ABSTRACT FROM AUTHOR]

Pre-therapeutic UGT1A1 genotyping is not yet routinely performed in most hospitals in patients starting irinotecan chemotherapy. The aim of this position paper was to evaluate the available evidence and to assess the potential value of genotyping of UGT1A1 ∗ 2 8 and UGT1A1*6 in patients before starting treatment with irinotecan to reduce the risk of severe toxicity. The literature was selected and assessed based on five pre-specified criteria: 1) the level of evidence for associations between UGT1A1 polymorphisms and irinotecan-induced severe toxicity, 2) clinical validity and utility of pre-therapeutic genotyping of UGT1A1 , 3) safety and tolerability of irinotecan in carriers of UGT1A1 polymorphisms, 4) availability of specific dose recommendations for irinotecan in carriers of UGT1A1 polymorphisms, 5) evidence of cost benefits of pre-therapeutic genotyping of UGT1A1. On all five criteria, study results were favourable for pre-therapeutic genotyping of UGT1A1. A high level of evidence (level I) was found for a higher incidence of irinotecan-induced severe toxicity in homozygous carriers of UGT1A1*28 or UGT1A1*6. The clinical validity and utility of this genetic test proved to be acceptable. Dose-finding studies showed a lower maximum tolerated dose in homozygous variant allele carriers, and most of the drug labels and guidelines recommend a dose reduction of 25–30% in these patients. In addition, pre-therapeutic genotyping of UGT1A1 is likely to save costs. Pre-therapeutic genotyping of UGT1A1 in patients initiating treatment with irinotecan improves patient safety, is likely to be cost-saving, and should, therefore, become standard of care. • Pre-therapeutic UGT1A1 genotyping improves patient safety. • Pre-therapeutic UGT1A1 genotyping is likely cost-saving. • UGT1A1 genotyping before starting irinotecan treatment should be standard of care. [ABSTRACT FROM AUTHOR]

The 2019 Nîmes International Symposium in Antibiotic Therapy Optimisation aimed at determining the best approaches of a number of the antibiotic management strategies for critically ill patients. Experts reviewed the latest literature relating to requirements for an optimal antibiotic stewardship program, risks of sub-therapeutic dosing of antibiotics in critically ill patients, persisting issues about efficiency of combination therapy and the value of de-escalation, new perspectives of pharmacokinetics, drug toxicities including collateral damages-associated with antibiotics, the place of nebulisation of antibiotics, management of patients receiving extracorporeal therapies and the place of new antibiotics. In this paper, each of these issues is discussed with key messages presented after a brief review of evidence. [ABSTRACT FROM AUTHOR]

This paper presents a methodology for synthesizing concentration gradient generators (CGGs) with arbitrary concentration profiles. The synthesized CGGs employ the design of a one-step-dilution microfluidic network, and utilize inexpensive multi-barrel syringe pumps for reducing the complexity of the flow manifold. The proposed design potentially exhibits high throughput with a wide range of input flowrates. The core of the proposed methodology is a CGG-synthesizing algorithm and a set of parametrized standard microfluidic components. The algorithm calculates the equivalent channel flow resistances, which control the volumetric mixing ratios of the CGG mixing channels to generate predefined concentration gradient profiles. Using a computational fluid dynamics (CFD) solver, the synthesized CGG microfluidic networks, including the linear, Gaussian, and logarithmic concentration profiles, were simulated and validated. The logarithmic profiles include profiles over 2-fold and 10-fold concentration increases. The maximum discrepancies between the simulated concentration profiles and the target profiles for these cases were less than 5 %. These synthesized CGGs were fabricated and implemented. The performance of the concentration profile generation was measured by dye visualization. The results show that the CGGs produce precise concentration gradients for the designs of the linear, Gaussian, and logarithmic profiles. The maximum discrepancy between the measurement results and the target profiles is approximately 1–8 %, which indicates that the diluted solution of the given concentration profiles can be generated consistently. The CGGs synthesized by the proposed algorithm are ready for applications such as drug screening and toxicity evaluation. In addition, by using a simple microfluidic outlet chip, the outputs of a linear CGG can be combined into a single flow with a monotonic concentration profile, which is suitable for the applications of chemotaxis studies. [Display omitted] • An algorithm for synthesizing customized concentration gradient generators (CGGs). • One-step-dilution design with high throughput, easy scale-up and small footprint. • Automatic generation of simple CGG layouts with standard microfluidic components. • Performance validation conducted for the CGGs with huge concentration variations. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Aconitum has been used as local and traditional medicines in many asian regions for the treatment of various diseases such as collapse, syncope, painful joints, oedema, bronchial asthma et al. Higenamine, a plant-based alkaloid, was initially isolated from Aconitum and identified as the active cardiotonic component of Aconitum . It has been tested as a candidate of pharmacologic stress agent in the detection of coronary artery diseases (CADs) and now researchers have just accomplished the phase III clinical studies successfully in China. Besides, a large number of studies have revealed the various pharmacological properties and potentially multi-spectral medical applications of higenamine. However, to date, no comprehensive review on higenamine has been published. Aim of the review This present paper aims to compile a comprehensive update regarding the biochemistry, pharmacokinetic features, pharmacological activities, clinical and potential clinical uses and toxicities on higenamine with the ultimate objective of providing a guide for future research on this drug. Materials and methods The selection of relevant data was made through a search using the keyword “higenamine” in “Web of science”, “Pubmed”, and “China Knowledge Resource Integrated (CNKI)”. Information was also acquired from local classic herbal literature, government reports and conference papers. Results In addition to Aconitum , higenamine also exists in many other plants including Tinospora crispa , Nandina domestica T HUNBERG , Gnetum Parvifolium C.Y. Cheng, sarum Heterotropoides , Nelumbo nucifera , N.nucifera . The pharmacokinetic studies conducted in animals and humans showed that higenamine conformed to a two-compartment pharmacokinetic model. Studies over the last four decades on higenamine have revealed its various pharmacological properties such as positive inotropic and chronotropic effect, activating slow channel effect, vascular and tracheal relaxation effect, anti-thrombotic, anti-apoptotic and anti-oxidative effect, anti-inflammatory and immunomodulatory effect. This phytochemical constituent has shown its potential therapeutic effects for diseases like heart failure, disseminated intravascular coagulation (DIC), shock, arthritis, asthma, ischemia/reperfusion (I/R) injuries and erectile dysfunction. Conclusions Extensive basic and clinical studies on higenamine showed valuable therapeutic effects on different disorders. However, the underlying mechanisms of higenamine have not been established. Therefore, the safety, tolerability and efficacy of higenamine are as yet, not fully understood. Additionally, some of the studies were small sample-sized and unreliable. To sum up, there is a need for deeper investigation in the mechanisms of higenamine action, as well as well-designed preclinical and clinical trials studies to test the safety and clinical value of the drug. [ABSTRACT FROM AUTHOR]

In this paper, we studied the electrochemical oxidation mechanisms of three typical fluoroquinolone antibiotics (FQs), and investigated residual antibacterial activity and toxicity changes after oxidation processes. Electrochemistry coupled to mass spectrometry (EC-MS) was used to study the oxidation processes of ciprofloxacin (CIP), norfloxacin (NOR) and ofloxacin (OFL). Eight oxidation products for each parent compound were identified and their chemical structures were elucidated. The transformation trend of each product, with the continuous increase of voltage from 0 to 3000 mV, was recorded by online EC-MS. The oxidation pathways were proposed based on the structural information and transformation trends of oxidation products. We found the oxidation mechanisms of FQs consisted of the hydroxylation and cleavage of piperazinyl ring via reactions with hydroxyl radicals, while the fluoroquinolone core remained intact. The antibacterial activity of the parent compounds and their oxidation mixtures was estimated using zone inhibition tests for gram-negative bacteria Salmonella typhimurium . It was found that the oxidation mixtures of CIP and NOR retained the antibacterial properties with lower activity compared to their parent compounds, while the antibacterial activity of OFL was almost eliminated after oxidation. Furthermore, the toxicity of the three FQs and their oxidation mixtures were evaluated using algal growth inhibition test ( Desmodesmus subspicatus ). The median effective concentration (EC 50 ) values for the algal inhibition tests were calculated for the end point of growth rate. The toxicity of CIP and NOR to green algae after electrochemical oxidation, remained unchanged, while that of OFL significantly increased. The results presented in this paper contribute to an understanding of the electrochemical oxidation mechanisms of FQs, and highlight the potential environmental risks of FQs after electrochemical oxidation processes. [ABSTRACT FROM AUTHOR]

The emerging dual threats of underaged drinking (UAD) and prescription drug misuse (PDM) require sustained prevention efforts across multiple levels of interventions. In response to the continuing proliferation of UAD and PDM among youth and young adults, the Substance Abuse and Mental Health Services Administration (SAMHSA) developed the Partnerships for Success (PFS) program. Across five cohorts funded from 2012 to 2016, PFS created linkages between health care providers, treatment and prevention services providers, government agencies, and nonprofit organizations for the delivery of multiple sets of services (e.g., prevention education, community activities, screening) targeted toward UAD and PDM. This paper reports on the impact of the PFS program on reductions in ethanol and prescription drug poisoning exposures as reported from data in the National Poisoning Data System (NPDS). Across 35 States, communities targeted by PFS interventions were compared to non-targeted communities using a non-equivalent comparison groups design and propensity score weighting. Using propensity-weighted, multilevel latent growth modeling, steeper reductions in ethanol and prescription drug poisoning exposure call rates were observed in States which had a higher proportion of communities participating in PFS. Grantee-level longitudinal analogs to Cohen's d effect sizes ranged from -0.24 to -0.97, whereas PFS' effects on individual communities (net of Statewide effects) were negligible. The study serves as a unique exemplar of using the NPDS to extract community-level intervention effects that might otherwise be "hidden" within epidemiological data while underscoring the cumulative effects of PFS' community-level efforts in stemming the tide on underaged drinking and prescription drug misuse. [ABSTRACT FROM AUTHOR]

• Malaria, a protozoal infection caused by Plasmodium parasites leading to more than one million deaths each year. • The malaria parasites turn to acquire resistance against most of the existing drugs. • The intracellular nature and scattered location of the parasites produce a great challenge for developing a new molecule. • Nanotechnology based malaria therapy could be one of the approaches to target a drug directly into the infected host cells. Malaria, one of the major infectious disease-causing sizeable morbidity, mortality and economic loss worldwide. The main drawback for the failure to eradicate malaria is the spread of multiple drug resistance to the majority of currently available chemotherapy. At present nanotechnology offers an advanced opportunity in the delivery of drugs and vaccines to the desired targeted site in the body following oral and systemic administration. It confers the major advantages like improving drug pharmacokinetic profiles, reduce dose frequency and reduction in drug toxicity. Hence, Nano-based drug delivery system can provide a promising prospect in the way of malaria treatment. This paper is a review of recent researches highlighting includes nanocarriers loaded antimalarial drugs for better therapeutic efficacy and future perspective in the treatment of malaria. [ABSTRACT FROM AUTHOR]

Abstract The intention of this paper is to review actual developments in target therapy in SLE. Target therapy includes both the objective of intervention and the aim of treatment. The objective should be linked to the pathophysiologic process of SLE; the aim has to be in any case an improved outcome. The current therapeutic in SLE is guided mostly by secondary prevention. In SLE, besides a BASIC concept with antimalarials, bone and sun protection, vaccination and cardiovascular risk minimising, treatment waits for new manifestations to be started to prevent secondarily damage. With the new treatment target remission, treatment should aim at ensuring long-term survival, preventing organ damage and optimizing health-related quality-of-life by controlling disease activity and minimising comorbidities and drug toxicity. First examples show that some patients are in remission and that those patients have a better outcome. But for treat-to-target a strategy needs to be developed that needs to be evaluated. [ABSTRACT FROM AUTHOR]

Abstract Introduction The evaluation of drug's cytotoxicity is a crucial step in the development of new pharmacological compounds. 31P NMR can be a tool for toxicological screening, as it enables the study of drugs' cytotoxicity and their effect on cell energy metabolism in a real-time, in a non- invasive and non-destructive way. This paper details a step-by-step protocol to implement a bioreactor system able to maintain cell viability during NMR acquisitions, at high cell densities and for several hours, enabling toxicological evaluation of pharmacological compounds in living cells. Method HeLa cells were immobilized in agarose gel threads and continuously perfused with oxygenated medium inside a 5 mm NMR tube. Signals corresponding to intracellular high-energy phosphorous compounds were continuously monitored by 31P NMR to assess cell energy levels, intracellular pH and intracellular free Mg2+ concentrations ([Mg2+] f) under control and in the presence of two different cytotoxic drugs, calix-NH 2 or 5-fluorouracil (5-FU). Results The bioreactor system was effective in maintaining cell energy levels as well as intracellular pH and [Mg2+] f along time, with a good 31P NMR signal to noise ratio. Calix-NH 2 and 5-FU decreased cell energy levels by 35% and 39%, respectively, with a negligible increase in intracellular [Mg2+] f , and without affecting intracellular pH. Discussion The immobilization and perfusion system here detailed, along with 31P NMR, is useful in toxicological evaluation of new pharmacological compounds, enabling the continuous assessment of drugs' effect on energy levels, intracellular pH and [Mg2+] f in intact cells, for several hours without compromising cell viability. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Securidaca longipedunculata Fresen (Polygalaceae) is a multi-purpose plant with a long history of use in African traditional medicine to treat various sexually transmitted infections, hernias, coughs, fever, ascariasis, constipation, headaches, rheumatism, stomach ache, malaria, tuberculosis, pain, epilepsy, pneumonia, skin infections, and it is also used as an aphrodisiac for men. The current paper provides an overview of the present phytochemistry, toxicology, ethnomedicinal uses and pharmacological properties of S. longipedunculata . Materials and methods The information reported in this paper was collected from a literature search using various computerised databases including ScienceDirect, Scopus, Scielo, PubMed and Google Scholar. The extra information was sourced from various academic dissertations, theses and botanical books. Results Phytochemically, extracts from various parts of S. longipedunculata , especially the root bark, contain numerous valuable compounds including xanthones, some benzyl benzoates and triterpene saponins amongst others. Toxicity studies, both in vivo and in vitro , revealed that extracts are only toxic at relatively high concentrations. Furthermore, extracts have antimicrobial, antioxidant, antiparasitic, anti-diabetic, anti-inflammatory, antimalarial, insecticidal, pesticidal, and anticonvulsant properties. Conclusions S. longipedunculata is an important plant species with potential benefits in the treatment of transmissible and infectious diseases, including malaria, tuberculosis, and those caused by community acquired microorganisms. Although extracts from this species generally have little toxicity at low concentrations, further efforts are required to investigate the potential toxicity of S. longipedunculata . The antimicrobial properties of extracts and purified compounds against microorganisms causing sexually transmitted infections are also deserving of further research. Moreover, the pharmacokinetic properties of extracts and compounds of the species need to be explored as there is insufficient data available on these aspects. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Areca catechu L. (Arecaceae), widely distributed in South and Southeast Asia, is a popular traditional herbal medicine that can be chewed for the purpose of dispersing accumulated fluid in the abdominal cavity and killing worms. The present paper aims to provide an up-to-date review on the traditional uses and advances in the botany, phytochemistry, pharmacology and toxicology of this plant. Furthermore, the possible trends and a perspective for future research of this plant are also discussed. Materials and methods A literature search was performed on A. catechu based on classic books of herbal medicine, PhD. and MSc. dissertations, government reports, the state and local drug standards, scientific databases including Pubmed, SciFinder, Scopus, the Web of Science, Google Scholar, and others. Various types of information regarding this plant are discussed in corresponding parts of this paper. In addition, perspectives for possible future studies of A. catechu are discussed. Results The seeds of A. catechu (areca nut) have been widely used in clinical practice in China, India and other South and Southeast Asian Countries. Currently, over 59 compounds have been isolated and identified from A. catechu , including alkaloids, tannins, flavones, triterpenes, steroids, and fatty acids. The extracts and compounds isolated from A. catechu have many pharmacological activities. These include antiparasitic effects, anti-depressive effects, anti-fatigue effects, antioxidant effects, antibacterial and antifungal effects, antihypertensive effects, anti-inflammatory and analgesic effects, anti-allergic effects, the promotion of digestive functions, suppression of platelet aggregation, regulatory effects on blood glucose and lipids, etc . Although arecoline is the primary active constituent of A. catechu , it is also the primary toxic compound. The main toxicities of arecoline are the promotion of oral submucosal fibrosis (OSF) and cytotoxic effects on normal human cells, which involve inducing apoptosis. Conclusion As an important herbal medicine, A. catechu has potential for the treatment of many diseases, especially parasitic diseases, digestive function disorders, and depression. Many traditional uses of A. catechu have now been validated by current investigations. However, further research should be undertaken to investigate the clinical effects, toxic constituents, target organs, and pharmacokinetics and to establish criteria for quality control for A. catechu- derived medications. In addition, it will be interesting to investigate the active macromolecular compounds and active constituents other than alkaloids in both raw and processed products of A. catechu . [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Rhizoma alismatis (simplified as RA, “Zexie” in Chinese, 泽泻) is a well-known natural medicine with long history in Chinese medicine. As a traditional medicine in China, RA is an important part of many prescriptions and has been commonly used for treating a wide range of ailments related to dysuria, edema, nephropathy, hyperlipidaemia, diabetes, inflammation as well as tumor in clinical applications. Based on scientific literatures, the present paper aims to provide comprehensive and up-to date information about the traditional uses, phytochemistry, pharmacology, toxicology and quality control of RA as well as critical analysis of the research. The review will provide a new foundation and direction for the further studies of RA. Materials and methods All available information about RA was supplied by library database and electronic search (ScienceDirect, Web of Science, Pubmed, Google Scholar, etc .). The different types of useful information were collected and arranged in corresponding part of the paper. Results Phytochemical studies showed that the main chemical composition of RA was the terpenoid including sesquiterpene, diterpene and triterpene. The crude extracts and isolated compounds from RA showed diverse pharmacological activities including diuretic, nephroprotective, anti-hyperlipidemic, anti-atherosclerotic, anti-cancer, anti-inflammatory and anti-oxidative activities. However, high-dose or long-term use of RA can lead to water-electrolyte imbalance, bloody urine, acidosis and even hepatotoxicity or nephrotoxicity, which have been proven by several studies. Conclusions Pharmacological researches show RA possessing various bioactivities including diuresis, nephroprotective effect, anti-hyperlipidemia, etc . However, more bioactive components especially diuretic and nephroprotective compounds need to be isolated and identified, and more rigorous researches on action mechanisms are required. More experiments in vitro or in vivo and clinical studies are encouraged to clarify correlation between traditional uses and modern applications, and the toxicity need to be further and precisely explored. In addition, a standardized fingerprint for RA is indispensable and emergent. These achievements will further expand to therapeutic potential and usage of RA and provide a powerful support for clinical use. [ABSTRACT FROM AUTHOR]

Quantitative structure-activity relationship (QSAR) is an in silico technique which can be used in drug discovery, environmental fate modeling, property and toxicity prediction of chemical entities and regulatory toxicology. The predictive potential of a QSAR model is judged from various validation metrics in order to evaluate how well it is capable to predict endpoint values of new untested compounds. The rm² group of metrics is one of the stringent validation metrics currently used by the QSAR fraternity in different reports. We scrutinized a recently published paper which raised an issue that the constructed criteria based on regression through origin (RTO) are not optimal and there is a significant difference in the rm² metrics values computed from different statistical software packages. According to our point of view, the conclusion drawn in this paper appears to be misleading. Any inconsistency in the software algorithms has nothing to do with the calculation of rm² metrics, as such computation is not limited by the use of any specific software, rather it depends only on fundamental mathematical formulae that are well established. However, it is a concern to the QSAR users that Excel and SPSS can return different results for the metrics using the RTO method. Thus, a proper validation of the software tool is required before its use for computation of any validation metric. [ABSTRACT FROM AUTHOR]

Background and objective Drug-drug interaction (DDI) is one of the main causes of toxicity and treatment inefficacy. This work focuses on non-communicable diseases (NCDs), the non-transmissible and long-lasting diseases since they are the leading cause of death globally. Drugs that are used in NCDs increase the probability of DDIs as a result of long time usage. This work proposes an Integrated Action Crossing (IAC) method that is effective in predicting the NCDs DDIs based on pharmacokinetic (PK) mechanism. Methods Drug-Enzyme (CYP450) and Drug-Transporter actions including substrate, inhibitor and inducer affect the PK mechanism of other drugs. Hence, this paper proposes an enzyme and transporter protein integrated action crossing method for DDIs prediction in NCDs. The NCDs Drugs information was retrieved from the DrugBank database and the actions of enzymes and transporter proteins that were crossed and integrated. The datasets were generated for machine training. Results Three machine learning approaches: Support Vector Machine, k-Nearest Neighbors, and Neural Networks were used for the assessment of the method. Performance evaluation was performed through five-fold cross validation and the different datasets and learning methods were compared. Two layers NNs achieved the best performance at the accuracy of 83.15% (F-Measure 85.23% and AUC 0.901). Conclusions The IAC method delivers better performance compared to the conventional method for the identification of NCDs DDIs. [ABSTRACT FROM AUTHOR]

Introduction The sensitivity of a given test to detect a treatment-induced effect in a variable of interest is intrinsically related to the variability of that variable observed without treatment and the number of observations made in the study (i.e. number of animals). To evaluate test sensitivity to detect drug-induced changes in myocardial contractility using the variable LVdP/dt max , a HESI-supported consortium designed and conducted studies in chronically instrumented, conscious dogs using telemetry. This paper evaluated the inherent variability of the primary endpoint, LVdP/dt max , over time in individual animals as well as the variability between animals for a given laboratory. An approach is described to evaluate test system variability and thereby test sensitivity which may be used to support the selection of the number of animals for a given study, based on the desired test sensitivity. Methods A double 4 × 4 Latin square study design where eight animals each received a vehicle control and three dose levels of a test compound was conducted at six independent laboratories. LVdP/dt max was assessed via implanted telemetry systems in Beagle dogs ( N  = 8) using the same protocol and each of the six laboratories conducted between two and four studies. Vehicle data from each study was used to evaluate the between-animal and within-animal variability in different time averaging windows. Simulations were conducted to evaluate statistical power and type I error for LVdP/dt max based on the estimated variability and assumed treatment effects in hourly-interval, bi-hourly interval, or drug-specific super interval. Results We observe that the within-animal variability can be reduced by as much as 30% through the use of a larger time averaging window. Laboratory is a significant source of animal-to-animal variability as between-animal variability is laboratory-dependent and is less impacted by the use of different time averaging windows. The statistical power analysis shows that with N  = 8, the double Latin square design has over 90% power to detect a minimal time profile with a maximum change of up to 15% or approximately 450 mm Hg/s in LVdP/dt max . With N  = 4, the single Latin square design has over 80% power to detect a minimal time profile with a maximum change of up to 20% or approximately 600 mm Hg/s in LVdP/dt max . Discussion We describe a statistical procedure to quantitatively evaluate the acute cardiac effects from studies conducted across six sites and objectively examine the variability and sensitivity that were difficult or impossible to calculate consistently based on previous works. Although this report focuses on the evaluation on LVdP/dt max , this approach is appropriate for other variables such as heart rate, arterial blood pressure, or variables derived from the ECG. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Dioscorea zingiberensis C. H. Wright ( D. zingiberensis ), Dioscoreaceae, is used extensively in traditional Chinese medicines. The aim of the current review paper is to give a comprehensive overview of the traditional usage and phytochemistry of the plant. Clinical studies performed and products prepared from the plant and active principles will be mentioned. In addition a review of the taxonomy of the genus Dioscorea is given. Materials and methods A systematic search on literature has been performed in databases like Google Scholar, Science Direct, Scifinder, Web of Science, and in Chinese databases (China Knowledge Resource Integrated, i.e., CNKI and Wanfang) including Ph.D. and M.Sc. dissertations. These from the period 1983–2016 have been searched. Results D. zingiberensis is an endemic plant in China widely distributed in some provinces, especially Hubei and Shaanxi. The rhizomes are the medicinal part in Dun-Ye-Guan-Xin-Ning tablets and are used for isolation of diosgenin. Steroidal saponins are believed to be the active principles. More than 70 compounds have been identified. Several of these have been tested in preclinical assays and clinical trials. A wide spectrum of biological effects including cardiovascular, anti-thrombosis, hyperlipidemia, neuroprotection, anti-inflammatory, and anthelmintic effect has been verified. Conclusions Because of the promising results from the investigations on the plant material of D. zingiberensis , further in depth analyses ought to be performed to evaluate its potential as either a traditional drug or a source of bioactive principle. The presently performed studies do not explain mechanism of action, pharmacokinetics (ADME properties), or toxicity. All of these topics need more elaborate investigations. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Species of the genus Codonopsis are perennial herbs mainly distributed throughout East, Southeast and Central Asia. As recorded, they have been used as traditional Chinese medicines since the Qing Dynasty, where they were claimed for strengthening the spleen and tonifying the lung, as well as nourishing blood and engendering liquid. Some species are also used as food materials in southern China and Southeast Asia, such as tea, wine, soup, plaster, and porridge. Aim of the review The review aims to assess the ethnopharmacological uses, explicit the material basis and pharmacological action, promote the safety of medical use, and suggest the future research potentials of Codonopsis . Materials and methods Information on the studies of Codonopsis was collected from scientific journals, books, and reports via library and electronic data search (PubMed, Elsevier, Scopus, Google Scholar, Springer, Science Direct, Wiley, Researchgate, ACS, EMBASE, Web of Science and CNKI). Meanwhile, it was also obtained from published works of material medica, folk records, ethnopharmacological literatures, Ph.D. and Masters Dissertation. Plant taxonomy was confirmed to the database “The Plant List” ( www.theplantlist.org ). Results Codonopsis has been used for medicinal purposes all around the world. Some species are also used as food materials in southern China and Southeast Asia. The chemical constituents of Codonopsis mainly are polyacetylenes, polyenes, flavonoids, lignans, alkaloids, coumarins, terpenoids, steroids, organic acids, saccharides, and so on. Extract of Codonopsis exhibit extensive pharmacological activities, including immune function regulation, hematopoiesis improvement, cardiovascular protection, neuroprotection, gastrointestinal function regulation, endocrine function regulation, cytotoxic and antibacterial effects, anti-aging and anti-oxidation, etc. Almost no obvious toxicity or side effect are observed and recorded for Codonopsis . Conclusions The traditional uses, phytochemistry, pharmacology and toxicology of Codonopsis are reviewed in this paper. Species of the genus have long been used as traditional medicines and food materials, they are reported with a large number of chemical constituents with different structures, extensive pharmacological activities in immune system, blood system, digestive system, etc. and almost no toxicity. More profound studies on less popular species, pharmacodynamic material basis and pharmacological mechanism, and quality assurance are suggested to be carried out to fulfil the research on the long-term clinical use and new drug research of Codonopsis . [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance The genus Polygonatum (Asparagaceae) comprises 71 species distributed throughout the temperate Northern Hemisphere. The medicinal plants of Polygonatum have been traditionally used as tonics in China, India, Pakistan, Iran and Japan, and have been demonstrated to be highly effective in clinical practice for treating age-related diseases, diabetes, lung diseases, fatigue, feebleness and indigestion. Aim of the review This paper aims to provide the links among traditional uses, chemical constituents, pharmacological effects and toxicity to support their therapeutic potential and uncover opportunities for future research. Materials and methods The relevant information on the genus Polygonatum was gathered from scientific databases (Google Scholar, Web of Science, SciFinder, ScienceDirect, ACS Publications, PubMed, Wiley Online Library, CNKI). Information was also obtained from online databases, books, Ph.D. dissertations and M.Sc. theses. The literature cited in this review dates from 1917 to June 2017. Results At least 37 species and 1 variety of Polygonatum plants have been used as traditional medicine and functional food. The major chemical constituents of Polygonatum plants are steroidal saponins, triterpenoid saponins, homoisoflavanones, polysaccharides and lectins. A putative biosynthetic pathway of steroidal saponins and triterpenoid saponins has been established based on the compounds isolated from Polygonatum plants. The crude extracts and certain pure compounds from Polygonatum plants have shown a wide range of pharmacological effects such as anti-aging, anti-diabetic, anti-fatigue, and anticancer effects. The rhizomes of Polygonatum plants have a low degree of toxicity after processing. Conclusions Based on this review, some traditional uses of Polygonatum species have been confirmed by pharmacological studies, such as its anti-osteoporosis, neuroprotective, immunomodulatory, anti-diabetic and anti-fatigue effects. Most of the pharmacological effects of this genus can be attributed to its polysaccharides, saponins and lectins. However, to clarify the chemical differences that lead to the different traditional uses between “Huangjing” (derived from P. sibiricum , P. kingianum , P. cyrtonema ) and “Yuzhu” (derived from P. odoratum ), a systematic comparison of the small molecule compositions and polysaccharides of these four species is needed. In addition to these four species, other locally used medicinal Polygonatum species should be the subject of research, and the chemical and pharmacological relationships of these species should be investigated to expand the medicinal resources and standardize the use of Polygonatum species. [ABSTRACT FROM AUTHOR]

Anti-inflammatory enzymes promote the dissolution and excretion of sticky phlegm, clean the wound surface and accelerate drug diffusion to the lesion. They play important roles in treating different types of inflammation and pain. Currently, various formulations of anti-inflammatory enzymes are successfully prepared to improve the enzymatic characteristics, pharmacokinetic properties and anti-inflammatory efficacies. The work was performed by systematically searching all available literature. An overall summary of current research about various anti-inflammatory enzymes and their novel formulations is presented. The original and improved enzymatic characteristics, pharmacokinetic properties, action mechanisms, clinical information, storage and shelf life, treatment efficacies of anti-inflammatory enzymes and their different formulations are summarized. The influencing factors such as enzyme type, source, excipient, pharmaceutical technique, administration route and dosage are analyzed. The combined application of enzymes and other drugs are included in this paper. Anti-inflammatory enzymes were widely applied in treating different types of inflammation and diseases with accompanying edema. Their novel formulations increased enzymatic stabilities, improved pharmacokinetic properties, provided different administration routes, and enhanced anti-inflammatory efficacies of anti-inflammatory enzymes but decreased side effects and toxicity. Novel enzyme formulations improve and expand the usage of anti-inflammatory enzymes. [ABSTRACT FROM AUTHOR]

The breast cancer affects women with high mortality and morbidity worldwide. The risk is highest in the most developed world but also is markedly rising in the developing countries. It is well documented that melatonin has a significant anti-tumor activities demonstrated on various cancer types in a plethora of preclinical studies. In breast cancer, melatonin is capable to disrupt estrogen-dependent cell signaling, resulting in a reduction of estrogen-stimulated cells, moreover, it’s obvious neuro-immunomodulatory effect in organism was described. Several prospective studies have demonstrated the inverse correlation between melatonin metabolites and the risk of breast cancer. This correlation was confirmed by observational studies that found lower melatonin levels in breast cancer patients. Moreover, clinical studies have showed that circadian disruption of melatonin synthesis, specifically night shift work, is linked to increased breast cancer risk. In this regard, proper light/dark exposure with more selective use of light at night along with oral supplementation of melatonin may have benefits for high-risk women. The results of current preclinical studies, the mechanism of action, and clinical efficacy of melatonin in breast cancer are reviewed in this paper. Melatonin alone or in combined administration seems to be appropriate drug for the treatment of early stages of breast cancer with documented low toxicity over a wide range of doses. These and other issues are also discussed. [ABSTRACT FROM AUTHOR]

Hepatic cell cultures are exploited for different applications in liver disease studies, drug toxicity testing and bioartificial liver (BAL) devices. Despite the development of various 3D cell culture systems, mass transfer properties and limitations, especially oxygen supply, still remain a controversial topic. In this paper, oxygen transport in a convection-enhanced, crossed-configuration hollow fibre membrane bioreactor hosting hepatocyte spheroids has been investigated through coupled free/porous media flow hydrodynamics and mass transfer modelling using finite-element simulations. Starting from experimental measurements of the oxygen concentration in the bioreactor, a systematic parametric study was performed to evaluate the effect of different parameters – oxygen partial pressure, perfusion rate, hollow fibre spacing, spheroid size, Michaelis-Menten kinetics for oxygen uptake and porosities of the spheroid and the membrane – on dissolved oxygen concentration profile. These parameters were studied in relation to dimensionless groups and variables. Among the operational conditions, oxygen concentration was much more influential than perfusion rate. As for the Michaelis-Menten parameters, oxygen concentration profile inside the spheroids was strongly affected by the maximum consumption rate (V max ) and weakly dependent on the constant K M . Culturing smaller spheroids minimized the exposure of cells to hypoxic conditions, owing to the short diffusive penetration depth of oxygen especially at low porosities (0.2). An in vivo-like microenvironment in terms of physiological oxygen concentration range was achieved in large spheroids (400 µm diameter) at spheroid porosity of 0.47. Membrane porosity also affected the intra-spheroid oxygen concentration and an improvement in oxygen supply to the spheroids could be achieved by reducing the corresponding transfer resistances. The mechanical stress on the spheroid surfaces was found to be within the tolerated ranges. Overall, the most important parameters for optimization of the bioreactor were identified. [ABSTRACT FROM AUTHOR]

A supercritical chromatographic method for the separation of a drug and its impurities has been developed and optimized applying an experimental design approach and chromatogram simulations. Stationary phase screening was followed by optimization of the modifier and injection solvent composition. A design-of-experiment (DoE) approach was then used to optimize column temperature, back-pressure and the gradient slope simultaneously. Regression models for the retention times and peak widths of all mixture components were built. The factor levels for different grid points were then used to predict the retention times and peak widths of the mixture components using the regression models and the best separation for the worst separated peak pair in the experimental domain was identified. A plot of the minimal resolutions was used to help identifying the factor levels leading to the highest resolution between consecutive peaks. The effects of the DoE factors were visualized in a way that is familiar to the analytical chemist, i.e. by simulating the resulting chromatogram. The mixture of an active ingredient and seven impurities was separated in less than eight minutes. The approach discussed in this paper demonstrates how SFC methods can be developed and optimized efficiently using simple concepts and tools. [ABSTRACT FROM AUTHOR]

Death due to mechanical or chemical intoxication of heroin body packers, thanks to the continuous improvement in packaging techniques, are increasingly rare, and almost all the cases reported in the literature refer to drug swallowers. A case of fatal acute heroin intoxication in a body pusher with an unreported packaging technique is presented, and previous deaths due to heroin body packing are reviewed, taking into consideration imaging techniques performed, cause of death, toxicological analysis on biological and non-biological samples, as well as number, position and type of drug packages identified at the dissection of the body. The innovative packaging technique found in the present case, constituted by an external multilayer cellophane casing containing 16 smaller packages of hardened heroin powder, each one covered with cigarette paper and multiple layers of heat-sealed cellophane, was probably used to avoid both chemical complications of package rupture and to create a package with morphological and radiological features different from those reported by previous studies. Drug dealers, in fact, are continually looking for packaging methods that, besides being safer, minimize the risk of detection at the radiological examinations performed, thus increasing the number of false negative findings. The identification of new types of package is therefore important, in order to identify packages that do not have the typical radiological signs, both in order to protect the patient's health and to avoid the non-recognition of a drug carrier. Despite the presence of multilayer composition of both the smaller and the bigger external coverage, these new types of package did not guarantee the greater safety of the drug dealer. [ABSTRACT FROM AUTHOR]

Integration of a dynamic signal transduction pathway into the tissue dosimetry model is a major advancement in the area of computational toxicology. This paper illustrates the ways to incorporate the use of existing system biological model in the field of toxicology via its coupling to the Physiological based Pharmacokinetics and Pharmacodynamics (PBPK/PD) model. This expansion framework of integrated PBPK/PD coupled mechanistic system pathway model can be called as system toxicology that describes the kinetics of both – the chemicals and – biomolecules, help us to understand the dynamic and steady-state behaviors of molecular pathways under perturbed condition. The objective of this article is to illustrate a system toxicology based approach by developing an integrated PBPK/PD coupled miRNA-BDNF pathway model and to demonstrate its application by taking a case study of the PFOS mediated neurotoxicity. System dynamic involves miRNA-mediated BDNF regulation, which plays an important role in the control of neuronal cell proliferation, differentiation, and survivability. [ABSTRACT FROM AUTHOR]

Celastrol, triptolide and triptonide are the most significant active ingredients of Tripterygium wilfordii Hook F (TWHF). In 2007, the 'Cell' journal ranked celastrol, triptolide, artemisinin, capsaicin and curcumin as the five natural drugs that can be developed into modern medicinal compounds. In this review, we collected relevant data from the Web of Science, PubMed and China Knowledge Resource Integrated databases. Some information was also acquired from government reports and conference papers. Celastrol, triptolide and triptonide have potent pharmacological activity and evident anti-cancer, anti-tumor, anti-obesity and anti-diabetes effects. Because these compounds have demonstrated unique therapeutic potential for acute and chronic inflammation, brain injury, vascular diseases, immune diseases, renal system diseases, bone diseases and cardiac diseases, they can be used as effective drugs in clinical practice in the future. However, celastrol, triptolide and triptonide have certain toxic effects on the liver, kidney, cholangiocyte heart, ear and reproductive system. These shortcomings limit their clinical application. Suitable combination therapy, new dosage forms and new routes of administration can effectively reduce toxicity and increase the effect. In recent years, the development of different targeted drug delivery formulations and administration routes of celastrol and triptolide to overcome their toxic effects and maximise their efficacy has become a major focus of research. However, in-depth investigation is required to elucidate the mechanisms of action of celastrol, triptolide and triptonide, and more clinical trials are required to assess the safety and clinical value of these compounds. [ABSTRACT FROM AUTHOR]

The current review emphasizes on the herbal bioenhancers which themselves do not possess inherent pharmacological activity of their own but when co-administered with Active Pharmaceutical Ingredients (API), enhances their bioavailability and efficacy. Herbal bioenhancers play a crucial role in enhancing the bioavailability and bioefficacy of different classes of drugs, such as antihypertensives, anticancer, antiviral, antitubercular and antifungal drugs at low doses. This paper highlights various natural compounds that can be utilized as an efficient bioenhancer. Several herbal compounds including piperine, quercetin, genistein, naringin, sinomenine, curcumin, and glycyrrhizin have demonstrated capability to improve the pharmacokinetic parameters of several potent API. This article also focuses on various United States patents on herbal bioenhancers, which has proved to be beneficial in improving oral absorption of nutraceuticals like vitamins, minerals, amino acids and certain herbal compounds. The present paper also describes proposed mechanism of action, which mainly includes absorption process, drug metabolism, and action on drug target. The herbal bioenhancers are easily available, safe, free from side effects, minimizes drug toxicity, shortens the duration of treatment, lowers the drug resistance problems and minimizes the cost of treatment. Inspite of the fact that herbal bioenhancers provide an innovative concept for enhancing the bioavailability of several potent drugs, there are numerous bioenhancers of herbal origin that are yet to be explored in several vital areas. These bioenhancers must also be implied to enhance the bioavailability and bioefficacy through routes other than the oral route of drug delivery. There is a vast array of unexploited plants which can be investigated for their drug bioenhancing potency. The toxicity profiles of these herbal bioenhancers must not be overlooked. Researches must be carried out to solve these issues and to deliver a safe and effective dose of drugs to attain desired pharmacological response. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: Though inflammatory response is beneficial to body damage repair, if it is out of control, it can produce adverse effects on the body. Although purely western anti-inflammatory drugs, orthodox medicines, can control inflammation occurrence and development, it is not enough. The clinical efficacy of anti-inflammation therapies is unsatisfactory, thus the search for new anti-inflammation continues. Chinese Material Medica (CMM) remains a promising source of new therapeutic agents. CMM and herbal formulae from Traditional Chinese Medicine (TCM), unorthodox medicines, play an improtant anti-inflammatory role in multi-targets, multi-levels, and multi-ways in treating inflammation diseases in a long history in China, based on their multi-active ingredient characteristics. Due to these reasons, recently, CMM has been commercialized as an anti-inflammation agent which has become increasingly popular in the world health drug markets. Major research contributions in ethnopharmacology have generated vast amount of data associated with CMM in anti-inflammtion aspect. Therefore, a systematic introduction of CMM anti-inflammatory research progress is of great importance and necessity. Aim of the study: This paper strives to describe the progress of CMM in the treatment of inflammatory diseases from different aspects, and provide the essential theoretical support and scientific evidence for the further development and utilization of CMM resources as a potential anti-inflammation drug through a variety of databases. Material and methods: Literature survey was performed via electronic search (SciFinder®, Pubmed®, Google Scholar and Web of Science) on papers and patents and by systematic research in ethnopharmacological literature at various university libraries. Results: This review mainly introduced the current research on the anti-inflammatory active ingredient, anti-inflammatory effects of CMM, their mechanism, anti-inflammatory drug development of CMM, and toxicological information. Conclusion: CMM is used clinically to treat inflammation symptoms in TCM, and its effect is mediated by multiple targets through multiple active ingredients. Although scholars around the world have made studies on the anti-inflammatory studies of CMM from different pathways and aspects and have made substantial progress, further studies are warranted to delineate the inflammation actions in more cogency models, establish the toxicological profiles and quality standards, assess the potentials of CMM in clinical applications, and make more convenient preparations easy to administrate for patients. Development of the clinically anti-inflammatory drugs are also warranted. [Copyright &y& Elsevier]

Amphotericin B is an antifungal drug widely used in Intensive Care Units. Therapeutic drug monitoring (TDM) of amphotericin B is recommended for the assessment of toxicity surveillance and treatment optimization. In this paper we described the development and validation of a new Ultra High Performance Liquid Chromatography coupled to Diode Array Detection (UHPLC-DAD) method for the quantification of Amphotericin B in 200 μL human plasma over a wide range of concentrations (0.125–10 mg/L). The new method has been validated following international guidelines on bioanalytical method validation and showed high selectivity, high accuracy and precision and high process efficiency. The new UHPLC-DAD method that we describe is robust, rapid, cost effective and suitable for application to the routine TDM analyses. [ABSTRACT FROM AUTHOR]

According to the current European legislation, the safety assessment of each individual cosmetic ingredient of any formulation is the basis for the safety evaluation of a cosmetic product. Also, animal testing in the European Union is prohibited for cosmetic ingredients and products since 2004 and 2009, respectively. Additionally, the commercialization of any cosmetic products containing ingredients tested on animal models was forbidden in 2009. In consequence of these boundaries, the European Centre for the Validation of Alternative Methods (ECVAM) proposes a list of validated cell-based in vitro models for predicting the safety and toxicity of cosmetic ingredients. These models have been demonstrated as valuable and effective tools to overcome the limitations of animal in vivo studies. Although the use of in vitro cell-based models for the evaluation of absorption and permeability of cosmetic ingredients is widespread, a detailed study on the properties of these platforms and the in vitro-in vivo correlation compared with human data are required. Moreover, additional efforts must be taken to develop in vitro models to predict carcinogenicity, repeat dose toxicity and reproductive toxicity, for which no alternative in vitro methods are currently available. This review paper summarizes and characterizes the most relevant in vitro models validated by ECVAM employed to predict the safety and toxicology of cosmetic ingredients. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Bletilla striata (Thunb.) Reichb. f. (Orchidaceae), also known as Hyacinth Orchid and Baiji (Simplified Chinese: 白及), not only has been widely used for the treatment of hematemesis, hemoptysis, and traumatic bleeding due to the efficacy of arresting bleeding with astringent action, but also has been applied topically to overcome ulcers, sores, swellings, and chapped skin due to the efficacy of dispersing swelling and promoting tissue regeneration. Additional medical applications include the treatment of tuberculosis, malignant ulcers, hemorrhoids, anthrax, eye diseases, and silicosis. Aim of this review This review aims to provide up-to-date information on the botanical characterization, medicinal uses, chemical constituents, pharmacological activities, and toxicity of B. striata . In addition, this paper also focuses on the possible exploitation of this plant for the treatment of different diseases, and uncovers opportunities for future research. Materials and methods The relevant information on B. striata was gathered from worldwide accepted scientific databases via an electronic search (Google Scholar, Web of Science, ScienceDirect, ACS Publications, PubMed, Wiley Online Library, SciFinder, CNKI). Information was also obtained from The Plant List, Chinese pharmacopoeia, Chinese herbal classics books, PhD and MSc dissertations, etc. Results A comprehensive analysis of the literature obtained through the above-mentioned sources confirmed that the ethnomedical usages of B. striata have been recorded in Mongolia, Korea, Japan, and China. Phytochemical investigations revealed that the major chemical constituents of B. striata are polysaccharides, bibenzyls, phenanthrenes, triterpenoids and its saponins, steroids and its saponins, which also have been proven to be the main bioactive substances capable of exhibiting numerous pharmacological activities including wound healing, antiulcer, hemostasis, cytotoxicity, antimicrobial, anti-inflammation, anti-oxidation, immunomodulation, anti-fibrosis, antiaging, anti-allergy, and anti-itch. Conclusions Preliminary investigations on pharmacological properties of B. striata have shown that B. striata is an outstanding astringent hemostatic medicinal, B. striata polysaccharides (BSP) as the major bioactive components not only capable of promoting wound healing, but also show good performance as a kind of promising natural biomaterial. More importantly, BSP are also reported to be excellent embolic material. However, further investigations need to be carried out to fully clarify its efficacy of dispersing swelling and promoting tissue regeneration. Moreover, this plant also needs a lot more investigations to clarify the pathways of absorption, distribution, metabolism and excretion, and to evaluate its long-term in vivo chronic toxicity before proceeding to the development of pharmaceutical formulation. [ABSTRACT FROM AUTHOR]

Characterizing the U-shaped exposure response relationship for manganese (Mn) is necessary for estimating the risk of adverse health from Mn toxicity due to excess or deficiency. Categorical regression has emerged as a powerful tool for exposure-response analysis because of its ability to synthesize relevant information across multiple studies and species into a single integrated analysis of all relevant data. This paper documents the development of a database on Mn toxicity designed to support the application of categorical regression techniques. Specifically, we describe (i) the conduct of a systematic search of the literature on Mn toxicity to gather data appropriate for dose-response assessment; (ii) the establishment of inclusion/exclusion criteria for data to be included in the categorical regression modeling database; (iii) the development of a categorical severity scoring matrix for Mn health effects to permit the inclusion of diverse health outcomes in a single categorical regression analysis using the severity score as the outcome variable; and (iv) the convening of an international expert panel to both review the severity scoring matrix and assign severity scores to health outcomes observed in studies (including case reports, epidemiological investigations, and in vivo experimental studies) selected for inclusion in the categorical regression database. Exposure information including route, concentration, duration, health endpoint(s), and characteristics of the exposed population was abstracted from included studies and stored in a computerized manganese database ( MnDB ), providing a comprehensive repository of exposure-response information with the ability to support categorical regression modeling of oral exposure data. [ABSTRACT FROM AUTHOR]

Emodin is the main pharmacodynamic components of rhubarb, with significant pharmacological effects and clinical efficacy.Emodin has a variety of therapy effects, such as anti-cancer, anti-fibrosis effects, and is widely used to treat encephalitis, diabetic cataract and organ fibrosis. Several studies have shown that emodin has a good treatment effect on organ fibrosis, but the mechanism is complex. Moreover, the evidence of some studies is conflicting and confusing. This paper reviewed the mechanism, pharmacokinetics and toxicology of emodin in fibrosis treatment, and briefly discussed relevant cutting-edge new formulations to improve the efficacy, the result can provide some reference for future study. [Display omitted] [ABSTRACT FROM AUTHOR]

Pulmonary fibrosis (PF) is a chronic and irreversible pulmonary disease, and can lead to decreased lung function, respiratory failure and even death. The pathogenesis research and treatment strategy of PF significantly lag behind the medical progress and clinical needs. The treatment of this disease remains a thorny clinical problem, and the effective therapeutic drugs are still limited. Monomeric compounds from traditional Chinese medicine own various biological activities and high safety. They play a broad part in treating diseases and is also a candidate drug for preventing and treating PF. In this paper, we reviewed the mechanism of action and potential value of various anti-PF monomeric compounds from traditional Chinese medicine. These monomeric compounds can attenuate inflammatory response, oxidative stress, epithelial mesenchymal transformation and other processes of lung through many signaling pathways, and inhibit the activation and differentiation of fibroblasts, thus contributing to the treatment of PF. This review can provide new ideas for the development of anti-PF drugs in high efficiency with low toxicity. [Display omitted] [ABSTRACT FROM AUTHOR]

Ethnopharmacological reference The use of medicinal plants in the treatment of infections is ancient. A wide variety of ethnotherapeutic properties and pharmacological actions has been attributed to Terminalia sericea . Studies by various groups of investigators reveal that it is a multipurpose medicinal plant used mostly in the treatment of diarrhoea, sexually transmitted infections, skin rashes, tuberculosis and other infections. The current paper is aimed at providing an overview of the ethnomedicinal uses, toxicology, pharmacology and the phytochemistry of Terminalia sericea . Materials and methods Information was retrieved using various search engines, including Pubmed, Science Direct, Google Scholar, Scielo, SciFinder and Scopus. The key words used included Terminalia sericea , secondary metabolites, phytochemistry, biological activity, pharmacology, ethnobotanical survey, medicinal uses, safety, toxicology and other related words. Results Terminalia sericea is an important medicinal plant which possesses anti-HIV, anti-fungal, anti-bacterial, anticancer, lipolytic, wound healing, antiparasitic, anti-inflammatory and anti-oxidant activity, as the most valuable biological activities, thus lending pharmacological support to the plant's folkloric uses in indigenous medicine. Toxicologically, the extracts and isolated compounds from the plant species may have mild toxic effects. Phytochemically, the plant species possesses valuable compounds including triterpenes, alkaloids and flavonoids which may well contribute to its biological activity. Conclusions Terminalia sericea contains secondary metabolites which are valuable in the treatment of a variety of human infections, including community acquired infections which may be prevalent in developing countries. The degree of toxicity reported in various extracts warrants further exploration of the cytotoxicity of the plant species, both against normal human cell lines and in vivo . Moreover, the acetylcholinesterase inhibitory and anti-inflammatory effects also need to be further investigated as there are only a few reports from the literature on these aspects. There is also a need to further understand the mode of action of the extracts against various enzymes relating to inflammation. Antioxidant activity of the plant extracts against various forms of free radicals needs to be investigated. Although T. sericea is reported to be used for ethnoveterinary infections, there are no scientific reports on the anti-parasitic activity of the plant species against common animal parasites. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Cecropia pachystachya is a medicinal plant native to South and Central Americas used to treat asthma and diabetes. Aim of the study In this study, we evaluated the genotoxic, mutagenic and antigenotoxic effects of crude aqueous extract of C. pachystachya (CAE- Cp ) leaves. Material and methods CAE- Cp was analyzed by the Folin–Ciocalteu method to determine total phenolic and tannin contents. High performance liquid chromatography (HPLC) was used to identify major compounds. Distinct tissues from female and male adult mice were treated with 500−2000 mg/kg of CAE- Cp by gavage for the comet assay and micronucleus test analyses. In addition, peripheral blood slides of the group treated with 2000 mg/kg CAE- Cp were analyzed 3, 6, and 24 h after treatment and were exposed to hydrogen peroxide ( ex vivo ) to evaluate the genotoxic effect using the comet assay. The Salmonella /microsome assay was carried out against to TA100, TA98, TA97a, TA102, and TA1535 strains in presence and absence of the S9 mix. Results HPLC showed the presence of chlorogenic acid, isoorientin, orientin, and isovitexin as major compounds. Total phenolic and tannin contents were, respectively, 305.6±0.80 and 144.6±19.04 mg of gallic acid equivalent/g of extract. Brain DNA damage was observed in all groups treated with CAE- Cp . The H 2 O 2 challenge indicated genotoxic effect only 6 h after the administration of the extract. No increase was detected in micronucleus frequency for any group treated with the extract. Mutagenic effects were detected by Salmonella /microsome assay only in TA102 strain without S9 mix at higher doses. Conclusion The results obtained indicate that CAE- Cp was genotoxic to brain tissue. This result is supported by other papers, showing that compounds present in this extract can cross the blood-brain barrier and act on central nervous system. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance The genus Bupleurum includes approximately 200 species that are widely distributed in the Northern Hemisphere, Eurasia and North Africa. Certain species of this genus have long been used as antiphlogistic, antipyretic and analgesic agents in traditional folk medicine. As described in the Chinese Pharmacopoeia, the roots of Bupleurum chinense DC. and B. scorzonerifolium Willd. are the herbal materials that compose Chaihu ( Radix Bupleuri ), a well-known TCM herb. Aim of the review This review aims to provide up-to-date and comprehensive information regarding the distribution, toxicity, molecular mechanism and relatively new methods for the qualitative and quantitative determination of polyacetylenes in different Bupleurum species. Method The information needed for this paper were sourced from publishing sites such as Elsevier, science Direct, PubMed; electronic search engines such as Scopus and Web of Science, Google scholar; other scientific database sites for chemicals such as ChemSpider, PubChem, SciFinder, and also from on line books. Results Polyacetylenes, which are widely distributed in genus Bupleurum of the Apiaceae family, have high toxicity. Among polyacetylenes, bupleurotoxin, acetylbupleurotoxin and oenanthotoxin have strong neurotoxicity. Through previous research, it was found that the toxicity of Bupleurum polyacetylenes manifested as epileptic seizures, with the target of toxicity being the brain. The neurotoxicity of polyacetylenes exhibits a relationship with the γ-aminobutyric acid (GABA) receptor pathway, and polyacetylenes have been shown to inhibit GABA-induced currents ( I GABA ) in a competitive manner. Conclusions The plants of genus Bupleurum have been used in traditional medicine for thousands of years. However, certain species of this genus are poisonous, and it was attributed to the high content of polyacetylenes. The present review indicates that certain polyacetylenes in the genus Bupleurum have highly neurotoxic effects. The major challenge with regard to toxic polyacetylenes is to test their neurotoxic effects in vivo as well as in further preclinical studies, which will require large amounts of purified polyacetylenes. More reference substances should be prepared, and sophisticated analytical technologies should be developed to comprehensively assess the quality of Radix Bupleuri herbs. These investigations will be helpful for further utilization of the plants of genus Bupleurum . [ABSTRACT FROM AUTHOR]

Abstract: The metabolome is the set of small molecular mass organic compounds found in a given biological media. It includes all organic substances naturally occurring from the metabolism of the studied living organism, except biological polymers, but also xenobiotics and their biotransformation products. The metabolic fingerprints of biofluids obtained by mass spectrometry (MS) or nuclear magnetic resonance (NMR)-based methods contain a few hundreds to thousands of signals related to both genetic and environmental contributions. Metabolomics, which refers to the untargeted quantitative or semi-quantitative analysis of the metabolome, is a promising tool for biomarker discovery. Although proof-of-concept studies by metabolomics-based approaches in the field of toxicology and clinical chemistry have initially been performed using NMR, the use of liquid chromatography hyphenated to mass spectrometry (LC/MS) has increased over the recent years, providing complementary results to those obtained with other approaches. This paper reviews and comments the input of LC/MS in this field. We describe here the overall process of analysis, review some seminal papers in the field and discuss the perspectives of metabolomics for the biomonitoring of exposure and diagnosis of diseases. [ABSTRACT FROM AUTHOR]

Abstract: We investigated the efficacy of data capture of patient-reported toxicity following radiotherapy by comparing electronic and paper formats. Patient-reported toxicity questionnaires based on items from the NCI Common Terminology Criteria for Adverse Events (CTCAE) were created for patients receiving radiotherapy. Electronic and paper questionnaires had identical questions. Thirty seven gynaecological cancer and 40 prostate cancer patients completed questionnaires. Both questionnaire formats (electronic and paper) were completed by each patient at time points before and after radiotherapy. The average questionnaire and subsection scores for each format were compared directly and by using intra-class correlation (ICC) coefficients. The internal consistency/reliability was assessed by determining Cronbach’s α coefficient. Patient preference for questionnaire format including clarity and ease-of-use was recorded. 324 questionnaires were collected as part of this study. A similar pattern of average subsection scores was found for the electronic and paper questionnaires. ICC coefficients for the mean overall questionnaire scores and subsection scores were high (>0.8). Cronbach’s α was generally greater than 0.6, indicating that the reliability was high. Of the patients that responded, 27.3% preferred the electronic format, 25.7% preferred the paper format and 47% had no preference. The average time taken to complete a questionnaire was about 9 minutes for each format. The different questionnaire formats measured toxicity effects consistently and were reliable for both gynaecological cancer and prostate cancer patients. The survey indicated that patients found the questionnaires clear, easy to understand and straightforward to complete. Electronic data capture of patient-reported toxicity for CTCAE is feasible and acceptable. [Copyright &y& Elsevier]

Ilex rotunda Thunb. (I. rotunda) is an Ilex species of Aquifoliaceae, widely distributed in East Asia. Its dried bark is commonly used as a medicinal part in the field of traditional Chinese medicine (TCM), named Ilicis Rotundae Cortex. This medicinal plant is commonly used for clearing heat and removing toxin, draining dampness and relieving pain in TCM to treat tonsillitis, acute gastroenteritis, gastric and duodenal ulcer, rheumatism, traumatic injury, and so on. It also has significant development value on lipid-lowering, hepatoprotection and anti-inflammation, but the potential mechanism needs to be further explored. More and more medicinal substances are being discovered in I. rotunda with multiple biological activities, which help to advance the ethno-pharmacological research in I. rotunda. However, to date there is a lack of a systematic summary of research progress on I. rotunda. This review aims to provide a critical summary of the current studies on I. rotunda. The progress in research on botany, phytochemistry, traditional uses, pharmacology, toxicology, quality control and pharmacokinetics of the plant is discussed. It hopes to provide useful references and guidance for the future directions of research on I. rotunda. Studies of I. rotunda were collected via Google Scholar and Baidu Scholar, PubMed, ScienceDirect, SciFinder, Web of Science, China National Knowledge Infrastructure (CNKI), WANFANG DATA and libraries. Some local books, official websites, PhD or MS's dissertations were also included. The literature cited in this review covered the period from 1956 to January 2022. Analysis of the literature indicates that I. rotunda is a potentially valuable herbal medicine for the therapeutic of various diseases. To date, 120 compounds were found and identified in I. rotunda , mainly including triterpenoids, phenylpropanoids, etc. Modern pharmacological studies also found that the plant has the activities of protecting the cardiovascular system, lowering lipids and protecting the liver, as well as being an anti-inflammatory, anti-tumor and antibacterial. This review summarizes the results from current studies of I. rotunda. However, the current explanation seems insufficient and unsatisfactory, in terms of the relationships between the traditional uses and the modern pharmacological activities, the mechanisms and the material basis. Thus, a critical and comprehensive evaluation is necessary to explore its future research prospects and development direction. [Display omitted] • The highlights of the paper are: • Anti-inflammatory and TCM efficacy are linked in Ilicis Rotundae Cortex (IRC). • Anti-lipid metabolism disorders and TCM efficacy are linked in IRC. • Rotundic acid, pedunculoside and syringin could be key medicinal substances. • This is the first systematic critical review of studies on Ilex rotunda Thunb. [ABSTRACT FROM AUTHOR]