PLoS One. 2023 Aug 28;18(8):e0290316. doi: 10.1371/journal.pone.0290316. eCollection 2023.

ABSTRACT

Wind turbine power curve (WTPC) serves as an important tool for wind turbine condition monitoring and wind power forecasting. Due to complex environmental factors and technical issues of the wind turbines, there are many outliers and inconsistencies present in the recorded data, which cannot be removed through any pre-processing technique. However, the current WTPC models have limited ability to understand such complex relation between wind speed and wind power and have limited non-linear fitting ability, which limit their modelling accuracy. In this paper, the accuracy of the WTPC models is improved in two ways: first is by developing multivariate models and second is by proposing MARS as WTPC modeling technique. MARS is a regression-based flexible modeling technique that automatically models complex the nonlinearities in the data using spline functions. Experimental results show that by incorporating additional inputs the accuracy of the power curve estimation is significantly improved. Also by studying the error distribution it is proved that multivariate models successfully mitigate the adverse effect of hidden outliers, as their distribution has higher peaks and lesser standard deviation, which proves that the errors, are more converged to zero compared to the univariate models. Additionally, MARS with its superior non-linear fitting ability outperforms the compared methods in terms of the error metrics and ranks higher than regression trees and several other popular parametric and non-parametric methods. Finally, an outlier detection method is developed to remove the hidden outliers from the data using the error distribution of the modeled power curves.

PMID:37639426 | PMC:PMC10461849 | DOI:10.1371/journal.pone.0290316

PLoS One. 2023 Aug 28;18(8):e0290578. doi: 10.1371/journal.pone.0290578. eCollection 2023.

ABSTRACT

Organisations rely upon group formation to solve complex tasks, and groups often adapt to the demands of the task they face by changing their composition periodically. Previous research has often employed experimental, survey-based, and fieldwork methods to study the effects of group adaptation on task performance. This paper, by contrast, employs an agent-based approach to study these effects. There are three reasons why we do so. First, agent-based modelling and simulation allows to take into account further factors that might moderate the relationship between group adaptation and task performance, such as individual learning and task complexity. Second, such an approach allows to study large variations in the variables of interest, which contributes to the generalisation of our results. Finally, by employing an agent-based approach, we are able to study the longitudinal effects of group adaptation on task performance. Longitudinal analyses are often missing in prior related research. Our results indicate that reorganising well-performing groups might be beneficial, but only if individual learning is restricted. However, there are also cases in which group adaptation might unfold adverse effects. We provide extensive analyses that shed additional light on and help explain the ambiguous results of previous research.

PMID:37639405 | PMC:PMC10461837 | DOI:10.1371/journal.pone.0290578

Front Immunol. 2023 Aug 10;14:1128754. doi: 10.3389/fimmu.2023.1128754. eCollection 2023.

ABSTRACT

Childhood-onset systemic lupus erythematosus (cSLE) is an autoimmune disease that results in significant damage and often needs more aggressive treatment. Compared to adult-onset SLE, cSLE has a stronger genetic background and more prevalent elevated type I Interferon expression. The management of cSLE is more challenging because the disease itself and treatment can affect physical, psychological and emotional growth and development. High dose oral glucocorticoid (GC) has become the rule for treating moderate to severe cSLE activity. However, GC-related side effects and potential toxicities are problems that cannot be ignored. Recent studies have suggested that GC pulse therapy can achieve disease remission rapidly and reduce GC-related side effects with a reduction in oral prednisone doses. This article reviews characteristics, including pathogenesis and manifestations of cSLE, and summarized the existing evidence on GC therapy, especially on GC pulse therapy in cSLE, followed by our proposal for GC therapy according to the clinical effects and pathogenesis.

PMID:37638017 | PMC:PMC10448525 | DOI:10.3389/fimmu.2023.1128754

Front Endocrinol (Lausanne). 2023 Aug 10;14:1223768. doi: 10.3389/fendo.2023.1223768. eCollection 2023.

ABSTRACT

AIMS: Due to its high heterogenicity and unclear etiology, there is currently no specific treatment for polycystic ovary syndrome (PCOS). Metformin, as an insulin sensitizer, combined with spironolactone, an antiandrogen medication, may exert complementary effects on PCOS. We therefore performed a meta-analysis of trials in which metformin combined with spironolactone was applied to treat PCOS to evaluate the efficacy and safety of the combination therapy.

METHODS: We retrieved the PubMed, Embase, Scopus, Cochrane Library, CNKI, CBM, Wangfang, and VIP databases for literatures published from their inception to December 16, 2022 on the effects of metformin combined with spironolactone in the treatment of PCOS. Inclusion criteria according to P.I.C.O.S criteria were: PCOS patients, metformin combined with spironolactone interventions, metformin alone control group, and randomized controlled trials with the following outcome data: body mass index (BMI), hirsutism score, luteinizing hormone (LH), follicle-stimulating hormone (FSH), total testosterone (TT), fasting blood glucose (FBG), Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), and side effects including nausea, vomiting, diarrhea and drug withdrawal.

RESULTS: Our results revealed that metformin combined with spironolactone significantly reduced BMI and TT, but that it exerted no significant effects on hirsutism score, or on FSH or LH concentrations. Combined treatment also resulted in a significant diminution in FBG and insulin resistance using the HOMA-IR when the interventional time was greater than 6 months. In addition, the combination did not have a higher occurrence of adverse reactions than metformin alone.

CONCLUSION: Compared with metformin alone, metformin combined with spironolactone therapy may be more effective in reducing BMI and serum androgen levels, but the combination showed no significant effect on the hirsutism score or gonadotropin hormone levels, and was not associated with an elevation in side-effects. Moreover, when the treatment course was greater than 6 months, combination therapy reduced FBG and improved insulin resistance more effectively than metformin alone. However, more research is needed to determine the most effective course of treatment.

SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022355515.

PMID:37635987 | PMC:PMC10449574 | DOI:10.3389/fendo.2023.1223768

Int J Nanomedicine. 2023 Aug 22;18:4779-4804. doi: 10.2147/IJN.S413831. eCollection 2023.

ABSTRACT

Tumors are the second-most common disease in the world, killing people at an alarming rate. As issues with drug resistance, lack of targeting, and severe side effects are revealed, there is a growing demand for precision-targeted drug delivery systems. Plant-derived nanovesicles (PDNVs), which arecomposed of proteins, lipids, RNA, and metabolites, are widely distributed and readily accessible. The potential for anti-proliferative, pro-apoptotic, and drug-resistant-reversing effects on tumor cells, as well as the ability to alter the tumor microenvironment (TME) by modulating tumor-specific immune cells, make PDNVs promising anti-tumor therapeutics. With a lipid bilayer structure that allows drug loading and a transmembrane capacity readily endocytosed by cells, PDNVs are also expected to become a new drug delivery platform. Exogenous modifications of PDNVs enhance their circulating stability, tumor targeting ability, high cell endocytosis rate, and controlled-release capacity. In this review, we summarize PDNVs' natural antitumor activity, as well as engineered PDNVs as efficient precision-targeted drug delivery tools that enhance therapeutic effects. Additionally, we discuss critical considerations related to the issues raised in this area, which will encourage researchers to improve PDNVs as better anti-tumor therapeutics for clinic applications.

PMID:37635909 | PMC:PMC10460188 | DOI:10.2147/IJN.S413831

Intest Res. 2023 Aug 29. doi: 10.5217/ir.2023.00019. Online ahead of print.

ABSTRACT

Immune checkpoint inhibitors have dramatically revolutionized the therapeutic landscape for patients with advanced malignancies. Recently, convincing evidence has shown meaningful influence of gut microbiome on human immune system. With the complex link between gut microbiome, host immunity and cancer, the variations in the gut microbiota may influence the efficacy of immune checkpoint inhibitors. Indeed, some bacterial species have been reported to be predictive for cancer outcome in patients treated with immune checkpoint inhibitors. Although immune checkpoint inhibitors are currently proven to be an effective anti-tumor treatment, they can induce a distinct form of toxicity, termed immune-related adverse events. Immune-related colitis is one of the common toxicities from immune checkpoint inhibitors, and it might preclude the cancer therapy in severe or refractory cases. The manipulation of gut microbiome by fecal microbiota transplantation or probiotics administration has been suggested as one of the methods to enhance anti-tumor effects and decrease the risk of immune-related colitis. Here we review the role of gut microbiome on immune checkpoint inhibitor therapy and consequent immune-related colitis to provide a new insight for better anti-cancer therapy.

PMID:37640378 | DOI:10.5217/ir.2023.00019

J Tehran Heart Cent. 2023 Apr;18(2):151-153. doi: 10.18502/jthc.v18i2.13327.

NO ABSTRACT

PMID:37637279 | PMC:PMC10459345 | DOI:10.18502/jthc.v18i2.13327

Sci Rep. 2023 Aug 26;13(1):13989. doi: 10.1038/s41598-023-41095-4.

ABSTRACT

Teicoplanin can cause acute kidney injury, but little is known about the risk of acute kidney injury when teicoplanin is co-administered with loop diuretics (a powerful diuresis), which can alter renal hemodynamics and glomerular filtration rate. We performed a signal detection analysis using a Japanese adverse event database to determine the additive impact of loop diuretics on acute kidney injury associated with teicoplanin. The dataset originated between April 2004 and August 2022. Disproportionality analysis was performed to detect the signals for acute kidney injury (the Standardized MedDRA Query) when co-administered teicoplanin or vancomycin (a positive control) with individual diuretics, including loop diuretics. Multivariate logistic regression analysis was tested to estimate the adjusted reporting odds ratio (aROR) and 95% confidence interval (95% CI). There were 147 and 515 events of acute kidney injury associated with teicoplanin and vancomycin, respectively. A significant positive signal for acute kidney injury when teicoplanin was co-administered with loop diuretics was present (aROR 4.83, 95% CI 3.52-6.61, p < 0.0001). Contrastingly, no significant signals were observed when vancomycin was co-administered with any diuretics. These findings suggest that co-administered loop diuretics may have an unfavorable effect on acute kidney injury while undertaking teicoplanin but not vancomycin.

PMID:37633977 | DOI:10.1038/s41598-023-41095-4

Nutrients. 2023 Aug 18;15(16):3626. doi: 10.3390/nu15163626.

ABSTRACT

Bovine colostrum is considered to provide anti-infective protection. Here, we present the first randomized controlled trial (RCT) aimed at assessing the preventive use of colostrum against upper respiratory tract infections (URTIs) in healthy pre-school children. We analyzed 57 children-35 in the colostrum (COL-dried bovine colostrum) and 22 in the placebo (PBO-dried whey) group, who received these substances as follows: first 15 days 2 × 500 mg and then 30 days 1 × 500 mg. The reporting on the children's health status, specifically on the frequency and gravity of URTI symptoms and abdominal side effects, was performed via an online survey. The influence of colostrum on the frequency of days with URTI symptoms remained significant until the 20th week of observation and reached 31% of median reduction. The median reduction reached 37% when the gravity of symptoms was analyzed. When we grouped symptomatic days into episodes of second gravity level, the reduction in their frequency was even larger (50%) and lasted until the end of the trial (21 weeks). No significant side effects, especially abdominal, were reported during the trial. Colostrum supplementation in pre-school children is well tolerated, safe and provides protection from frequency of URTIs and their gravity.

PMID:37630816 | PMC:PMC10459079 | DOI:10.3390/nu15163626

Molecules. 2023 Aug 8;28(16):5955. doi: 10.3390/molecules28165955.

ABSTRACT

As a therapeutic tool inherited for thousands of years, traditional Chinese medicine (TCM) exhibits superiority in tumor therapy. The antitumor active components of TCM not only have multi-target treatment modes but can also synergistically interfere with tumor growth compared to traditional chemotherapeutics. However, most antitumor active components of TCM have the characteristics of poor solubility, high toxicity, and side effects, which are often limited in clinical application. In recent years, delivering the antitumor active components of TCM by nanosystems has been a promising field. The advantages of nano-delivery systems include improved water solubility, targeting efficiency, enhanced stability in vivo, and controlled release drugs, which can achieve higher drug-delivery efficiency and bioavailability. According to the method of drug loading on nanocarriers, nano-delivery systems can be categorized into two types, including physically encapsulated nanoplatforms and chemically coupled drug-delivery platforms. In this review, two nano-delivery approaches are considered, namely physical encapsulation and chemical coupling, both commonly used to deliver antitumor active components of TCM, and we summarized the advantages and limitations of different types of nano-delivery systems. Meanwhile, the clinical applications and potential toxicity of nano-delivery systems and the future development and challenges of these nano-delivery systems are also discussed, aiming to lay the foundation for the development and practical application of nano-delivery systems of TCM in clinical settings.

PMID:37630208 | PMC:PMC10459615 | DOI:10.3390/molecules28165955

Medicina (Kaunas). 2023 Aug 7;59(8):1429. doi: 10.3390/medicina59081429.

ABSTRACT

Background and Aim: Postoperative pain after scoliosis surgery is severe and usually requires long-term intravenous opioid therapy. Local anesthetic options, such as wound infiltration, are limited and include neuraxial analgesia. However, they are rarely used due to side effects and inconsistent efficacy. We report an opioid-sparing multimodal analgesia regimen with bilateral erector spinae plane blocks. This case series evaluated the analgesic effect of the bilateral bi-level erector spinae plane blocks (ESP) in congenital and neurogenic scoliosis surgery. Patients and Methods: Six pediatric patients with congenital or neurogenic scoliosis underwent posterior spinal fusion involving 5 to 12 vertebral levels. Bilateral single-injection ESPB was performed at one or two levels before incision. Preoperatively, patients received intravenous dexamethasone. General anesthesia with endotracheal intubation and volume-controlled ventilation was performed via TIVA with remifentanil and propofol. During and after the procedure, the basic hemodynamic parameters, opioid consumption, pain scores (numerical rating scale/NRS), and possible block complications were monitored. Results: All the patients experienced minimal postoperative pain levels. In addition, on the first day after surgery, they had low opioid requirements with no side effects. Conclusions: ESPB in patients undergoing congenital and neurogenic scoliosis correction surgery seems to be an essential analgesic technique that may reduce both severities of pain and opioid consumption.

PMID:37629719 | PMC:PMC10456815 | DOI:10.3390/medicina59081429

Medicina (Kaunas). 2023 Jul 31;59(8):1406. doi: 10.3390/medicina59081406.

ABSTRACT

Background: Dermal fillers for soft tissue for the treatment of face sagging, volume loss, and wrinkles have become popular among patients of all ages and ethnicities, and their use is becoming increasingly widespread. Aim: the goal of this study was to evaluate the effectiveness and safety of a micro-pulsed, 1444 nm Nd:YAG laser on dermal filler complications, in particular on granuloma management. Methods: A subcutaneous, 1444 nm Nd:YAG laser was used on five female patients (range age 52-68 years) with hyaluronic filler granulomas located on the face (two on the cheek area and three on the lips); three patients had self-injected the filler, buying it online. Before and after the therapy, the patients received a skin ultrasound to determine the form and location of the granulomas and to determine if there had been a full or partial resolution. During this study, all possible adverse effects at the treatment site were monitored. The 5-point Global Aesthetic Improvement Scale (GAIS) (0 point-no change; 1 point-25%, mild improvement; 2 points-50%, moderate improvement; 3 points-75%, good improvement; 4 points-100%, excellent improvement) was recorded at a 3-month follow-up. Results: good results were obtained in the treatment of filler granulomas with the intralesional 1444 nm laser, even if just a single treatment was performed (one intervention was effective for curing granulomas up to 5 mm in diameter). Three patients were satisfied with excellent improvement, and two patients experienced good improvement. The results are functional and aesthetically satisfying, as shown by photographic assessment. At the last follow-up, the granuloma had reduced or completely disappeared in all cases, and no infections, burns, scarring or fibrosis, episodes of severe bleeding, or other serious adverse effects had been reported. All subjects tolerated the post-treatment period well. Conclusions: Our findings showed that granuloma treatment with an intralesional 1444 nm Nd:YAG laser is a minimally invasive, easy, fast, efficient, and low-risk procedure.

PMID:37629696 | PMC:PMC10456612 | DOI:10.3390/medicina59081406

Int J Mol Sci. 2023 Aug 11;24(16):12694. doi: 10.3390/ijms241612694.

ABSTRACT

Contemporary breast cancer management includes surgical resection combined with a multimodal approach, including chemotherapy, radiotherapy, endocrine therapy, and targeted therapies. Breast cancer treatment is now personalised in accordance with disease and host factors, which has translated to enhanced outcomes for the vast majority of patients. Unfortunately, the treatment of the disease involves patients developing treatment-induced toxicities, with cardiovascular and metabolic side effects having negative implications for long-term quality-of-life metrics. MicroRNAs (miRNAs) are a class of small non-coding ribonucleic acids that are 17 to 25 nucleotides in length, which have utility in modifying genetic expression by working at a post-transcriptional cellular level. miRNAs have involvement in modulating breast cancer development, which is well described, with these biomarkers acting as important regulators of disease, as well as potential diagnostic and therapeutic biomarkers. This review focuses on highlighting the role of miRNAs as regulators and biomarkers of disease, particularly in breast cancer management, with a specific mention of the potential value of miRNAs in predicting treatment-related cardiovascular toxicity.

PMID:37628874 | PMC:PMC10454054 | DOI:10.3390/ijms241612694

Int J Mol Sci. 2023 Aug 9;24(16):12587. doi: 10.3390/ijms241612587.

ABSTRACT

Due to the progressive ageing of the human population, the number of cancer cases is increasing. For this reason, there is an urgent need for new treatments that can prolong the lives of cancer patients or ensure them a good quality of life. Although significant progress has been made in the treatment of cancer in recent years and the survival rate of patients is increasing, limitations in the use of conventional therapies include the frequent occurrence of side effects and the development of resistance to chemotherapeutic agents. These limitations are prompting researchers to investigate whether combining natural agents with conventional drugs could have a positive therapeutic effect in cancer treatment. Several natural bioactive compounds, especially polyphenols, have been shown to be effective against cancer progression and do not exert toxic effects on healthy tissues. Many studies have investigated the possibility of combining polyphenols with conventional drugs as a novel anticancer strategy. Indeed, this combination often has synergistic benefits that increase drug efficacy and reduce adverse side effects. In this review, we provide an overview of the studies describing the synergistic effects of curcumin, a polyphenol that has been shown to have extensive cytotoxic functions against cancer cells, including combined treatment. In particular, we have described the results of recent preclinical and clinical studies exploring the pleiotropic effects of curcumin in combination with standard drugs and the potential to consider it as a promising new tool for cancer therapy.

PMID:37628772 | PMC:PMC10454892 | DOI:10.3390/ijms241612587

Genes (Basel). 2023 Aug 11;14(8):1609. doi: 10.3390/genes14081609.

ABSTRACT

Metformin is a widely used and effective medication in type 2 diabetes (T2DM) as well as in polycystic ovary syndrome (PCOS). Single nucleotide polymorphisms (SNPs) contribute to the occurrence of metformin side effects. The aim of the present study was to identify intronic genetic variants modifying the occurrence of metformin side effects and to replicate them in individuals with T2DM and in women with PCOS. We performed Next Generation Sequencing (Illumina Next Seq) of 115 SNPs in a discovery cohort of 120 metformin users and conducted a systematic literature review. Selected SNPs were analysed in two independent cohorts of individuals with either T2DM or PCOS, using 5'-3'exonucleaseassay. A total of 14 SNPs in the organic cation transporters (OCTs) showed associations with side effects in an unadjusted binary logistic regression model, with eight SNPs remaining significantly associated after appropriate adjustment in the discovery cohort. Five SNPs were confirmed in a combined analysis of both replication cohorts but showed different association patterns in subgroup analyses. In an unweighted polygenic risk score (PRS), the risk for metformin side effects increased with the number of risk alleles. Intronic SNPs in the OCT cluster contribute to the development of metformin side effects in individuals with T2DM and in women with PCOS and are therefore of interest for personalized therapy options.

PMID:37628660 | PMC:PMC10454417 | DOI:10.3390/genes14081609

Biomolecules. 2023 Aug 18;13(8):1264. doi: 10.3390/biom13081264.

ABSTRACT

The number of patients with nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) is increasing globally and is raising serious concerns regarding the increasing medical and economic burden incurred for their treatment. The progression of NASH to more severe conditions such as cirrhosis and hepatocellular carcinoma requires liver transplantation to avoid death. Therefore, therapeutic intervention is required in the NASH stage, although no therapeutic drugs are currently available for this. Several anti-NASH candidate drugs have been developed that enable treatment via the modulation of distinct signaling cascades and include a series of drugs targeting peroxisome proliferator-activated receptor (PPAR) subtypes (PPARα/δ/γ) that are considered to be attractive because they can regulate both systemic lipid metabolism and inflammation. Multiple PPAR dual/pan agonists have been developed but only a few of them have been evaluated in clinical trials for NAFLD/NASH. Herein, we review the current clinical trial status and future prospects of PPAR-targeted drugs for treating NAFLD/NASH. In addition, we summarize our recent findings on the binding modes and the potencies/efficacies of several candidate PPAR dual/pan agonists to estimate their therapeutic potentials against NASH. Considering that the development of numerous PPAR dual/pan agonists has been abandoned because of their serious side effects, we also propose a repositioning of the already approved, safety-proven PPAR-targeted drugs against NAFLD/NASH.

PMID:37627329 | PMC:PMC10452531 | DOI:10.3390/biom13081264

Biomolecules. 2023 Aug 16;13(8):1256. doi: 10.3390/biom13081256.

ABSTRACT

Xenon (Xe) has shown great potential as a stroke treatment due to its exceptional ability to protect brain tissue without inducing side effects. We have previously developed Xe-loaded liposomes for the ultrasound-activated delivery of Xe into the cerebral region and demonstrated their therapeutic efficacy. At present, the sole FDA-approved thrombolytic agent for stroke treatment is recombinant tissue plasminogen activator (rtPA). In this study, we aimed to investigate the potential of combining Xe-liposomes with an intravenous rtPA treatment in a clinically relevant embolic rat stroke model. We evaluated the combinational effect using an in vitro clot lysis model and an in vivo embolic middle cerebral artery occlusion (eMCAO) rat model. The treatment groups received intravenous administration of Xe-liposomes (20 mg/kg) at 2 h post-stroke onset, followed by the administration of rtPA (10 mg/kg) at either 2 or 4 h after the onset. Three days after the stroke, behavioral tests were conducted, and brain sections were collected for triphenyltetrazolium chloride (TTC) and TUNEL staining. Infarct size was determined as normalized infarct volume (%). Both in vitro and in vivo clot lysis experiments demonstrated that Xe-liposomes in combination with rtPA resulted in effective clot lysis comparable to the treatment with free rtPA alone. Animals treated with Xe-liposomes in combination with rtPA showed reduced TUNEL-positive cells and demonstrated improved neurological recovery. Importantly, Xe-liposomes in combination with late rtPA treatment reduced rtPA-induced hemorrhage, attributing to the reduction of MMP9 immunoreactivity. This study demonstrates that the combined therapy of Xe-liposomes and rtPA provides enhanced therapeutic efficacy, leading to decreased neuronal cell death and a potential to mitigate hemorrhagic side effects associated with late rtPA treatment.

PMID:37627321 | PMC:PMC10452377 | DOI:10.3390/biom13081256

Biomolecules. 2023 Aug 11;13(8):1239. doi: 10.3390/biom13081239.

ABSTRACT

Reactive oxygen species (ROS) are highly reactive molecules generated in living organisms and an excessive production of ROS culminates in oxidative stress and cellular damage. Notably, oxidative stress plays a critical role in the pathogenesis of a number of oral mucosal diseases, including oral mucositis, which remains one of cancer treatments' most common side effects. We have shown previously that oral keratinocytes are remarkably sensitive to oxidative stress, and this may hinder the development and reproducibility of epithelial cell-based models of oral disease. Here, we examined the oxidative stress signatures that parallel oral toxicity by reproducing the initial events taking place during cancer treatment-induced oral mucositis. We used three oral epithelial cell lines (an immortalized normal human oral keratinocyte cell line, OKF6, and malignant oral keratinocytes, H357 and H400), as well as a mouse model of mucositis. The cells were subjected to increasing oxidative stress by incubation with hydrogen peroxide (H2O2) at concentrations of 100 μM up to 1200 μM, for up to 24 h, and ROS production and real-time kinetics of oxidative stress were investigated using fluorescent dye-based probes. Cell viability was assessed using a trypan blue exclusion assay, a fluorescence-based live-dead assay, and a fluorometric cytotoxicity assay (FCA), while morphological changes were analyzed by means of a phase-contrast inverted microscope. Static and dynamic real-time detection of the redox changes in keratinocytes showed a time-dependent increase of ROS production during oxidative stress-induced epithelial injury. The survival rates of oral epithelial cells were significantly affected after exposure to oxidative stress in a dose- and cell line-dependent manner. Values of TC50 of 800 μM, 800 μM, and 400 μM were reported for H400 cells (54.21 ± 9.04, p < 0.01), H357 cells (53.48 ± 4.01, p < 0.01), and OKF6 cells (48.64 ± 3.09, p < 0.01), respectively. Oxidative stress markers (MPO and MDA) were also significantly increased in oral tissues in our dual mouse model of chemotherapy-induced mucositis. In summary, we characterized and validated an oxidative stress model in human oral keratinocytes and identified optimal experimental conditions for the study of oxidative stress-induced oral epithelial toxicity.

PMID:37627304 | PMC:PMC10452318 | DOI:10.3390/biom13081239

Pharmaceuticals (Basel). 2023 Aug 15;16(8):1161. doi: 10.3390/ph16081161.

ABSTRACT

This study aimed to determine the type of drugs reported as suspected of causing severe supraventricular arrhythmias from the Spanish Human Pharmacovigilance System database. A total of 1053 reports were analysed, of which 526 (50%) were on men and 516 (49%) were on women. The most affected age group was the over-65s, with 593 reports (56%). Of the 1613 drugs, those belonging to the cardiovascular system (ATC Group C) were the most numerous (414 reports, 26%), with digoxin being the most frequent drug (49 reports, 12%). Other common groups were antiinfectives for systemic use (ATC Group J; 306 reports, 19%), antineoplastic and immunomodulating agents (ATC Group L; 198 reports, 12%), and nervous system drugs (ATC Group N; 185 reports, 11%). The most common supraventricular arrhythmia was atrial fibrillation (561 reports, 51%). Regarding outcomes, 730 (66%) patients recovered, 76 (7%) did not recover, 25 (3%) recovered but with sequelae, and 23 (2%) resulted in death. This study revealed that certain drugs have reported to be associated more frequently to supraventricular arrhythmias as serious adverse reactions, especially in the older population. Proper clinical management and effective strategies to ensure medication appropriateness should always be considered to improve patient safety when prescribing drugs.

PMID:37631076 | DOI:10.3390/ph16081161

Pharmaceuticals (Basel). 2023 Aug 10;16(8):1137. doi: 10.3390/ph16081137.

ABSTRACT

Phytoestrogens (PEs) are plant-based compounds that can interact with estrogen receptors and are mainly used to treat menopausal complaints. However, the safety of products with assumed phytoestrogenic activity is not fully understood. This study aimed to identify plant species with assumed phytoestrogenic activity, review existing literature on their use and safety, and critically evaluate adverse reaction (AR) reports of single-herb, multi-herb, and mixed-multiple products, as submitted to the Netherlands Pharmacovigilance Centre Lareb and to VigiBase of the World Health Organization (WHO). In the Lareb database, the most commonly reported plant species to cause ARs (total of 67 reports) were Actaea racemosa L. (black cohosh) (47.8%), Humulus lupulus L. (hops) (32.8%), and Glycine max (L.) Merr. (soybean) (22.4%). In the VigiBase database (total of 21,944 reports), the top three consisted of Glycine max (L.) Merr. (71.4%), Actaea racemosa L. (11.6%), and Vitex agnus-castus L. (chaste tree) (6.4%). In the scoping review (total of 73 articles), Actaea racemosa L. (30.1%), Glycine max (L.) Merr. (28.8%), and Trifolium pratense L. (13.7%) were the most frequently mentioned plant species. ARs were most frequently reported in the system organ classes "gastrointestinal disorders", "skin and subcutaneous tissue disorders", "reproductive system and breast disorders", and "general disorders and administration site conditions". Furthermore, from the scoping review, it appeared that the use of products with assumed phytoestrogenic activity was associated with postmenopausal bleeding. It was concluded that, while the potential benefits of products with assumed phytoestrogenic activity have been extensively pursued, the potential occurrence of ARs after using these products is less well understood. This study highlights the need for further investigation and careful monitoring of these products to better understand their effects and ensure the safety and well-being of individuals using them.

PMID:37631050 | DOI:10.3390/ph16081137