Steady-calcium formula (SCF), a functional food mixture with potential of joint care, contains five major ingredients. However, the uncertain cross-reactivity among these included ingredients cannot be excluded. Hence, it is important to ensure the safety of this mixture. In this study, the safety of SCF was evaluated through in vitro genotoxicity assessment and 28-day oral toxicity study in rats. The bacterial reverse mutation test and mammalian chromosome aberration test displayed that SCF did not induce mutagenicity and clastogenicity. The 28-day repeated dose assessment of SCF in rats revealed no mortality and adverse effects in clinical signs, body weight, urinalysis, hematology, organ weight, and histopathology at all treated groups. Although some significant changes were observed in food intake and parameters of serum biochemistry at the highest dose in males, they were not dose-related and considered to be within normal range. These findings indicate that SCF does not possess genotoxic potential and no obvious evidence of subacute toxicity. These results demonstrate for the first time that the genotoxicity and subacute toxicity for SCF are negative under our experimental conditions and the no observed adverse effect level (NOAEL) of SCF may be defined as at least 5470 mg/kg/day.

Stratifying patients according to disease severity has been a major hurdle during the COVID-19 pandemic. This usually requires evaluating the levels of several biomarkers, which may be cumbersome when rapid decisions are required. In this manuscript we show that a single nanoparticle aggregation test can be used to distinguish patients that require intensive care from those that have already been discharged from the intensive care unit (ICU). It consists of diluting a platelet-free plasma sample and then adding gold nanoparticles. The nanoparticles aggregate to a larger extent when the samples are obtained from a patient in the ICU. This changes the color of the colloidal suspension, which can be evaluated by measuring the pixel intensity of a photograph. Although the exact factor or combination of factors behind the different aggregation behavior is unknown, control experiments demonstrate that the presence of proteins in the samples is crucial for the test to work. Principal component analysis demonstrates that the test result is highly correlated to biomarkers of prognosis and inflammation that are commonly used to evaluate the severity of COVID-19 patients. The results shown here pave the way to develop nanoparticle aggregation assays that classify COVID-19 patients according to disease severity, which could be useful to de-escalate care safely and make a better use of hospital resources.

UNASSIGNED: Momordica charantia is popularly used in folk medicine in the management of hyperlipidemia and atherosclerosis.
UNASSIGNED: To evaluate the anti-atherosclerotic potential of M. charantia as well as its haematinic and antioxidant potential.
UNASSIGNED: Seventy-two experimental rats were randomly assigned into 9 groups (I-IX) of 8 rats each. Group I (control), was given 1 ml distilled water; II received 250 mg/kg. M. charantia; III received 500 mg/kg M. charantia; IV was administered 100 mg/kg of Atorvastatin only; V was administered 30 mg/kg of cholesterol dissolved in coconut oil; VI was administered with 250 mg/kg of M. charantia plus 30 mg/kg of cholesterol. VII was treated with 500 mg/kg of M. charantia plus 30 mg/kg of cholesterol solution; VIII was administered 30 mg/kg cholesterol solution plus Atorvastatin at a dose of 100 mg/kg; IX was administered 1 ml of coconut oil only. After 60 days of administration, blood and aorta samples were obtained from the rats. The samples were subjected to biochemical, haematological and histological analysis using standard methods.
UNASSIGNED: Glutathione peroxidase (GPx), Malondialdehyde (MDA) and Catalase (CAT) activities were significantly higher in the treated groups as compared to the control groups. There were significant increases in the monocyte counts of the groups given low dose (250 mg/kg) of the extract (LDMC), high dose (500 mg/kg) of the extract (HDMC), as well as atorvastatin. The mean corpuscular volume (MCV) and mean corpuscular haemoglobin (MCH) of the test groups administered were significantly higher than that of the control group. However, only the group administered with cholesterol plus HDMC showed significantly lower mean corpuscular haemoglobin concentration (MCHC) than that of the control group. Histological sections of the aorta show degeneration of the internal elastic lamina in the group fed with the diet only as well as vascular ulceration and stenosis in the aorta and heavy perivascular infiltrates of inflammatory cells. These alterations were however not visible in the groups administered with the extracts, as well as atorvastatin.
UNASSIGNED: Our findings show the possible anti-atherosclerotic potential of the extract, which could be compared to that of the standard drug (atorvastatin).

This study aimed to investigate the nonclinical safety of lincomycin and spectinomycin hydrochloride (LC-SPH) intramuscular (i.m) doses on target animals (chickens) to provide guidelines for dose level design and side effect monitoring in clinical trials. A total of 80 healthy Arbor Acres plus broiler chicks were completely randomized and blindly divided into four treatment groups (control, one-time dose, three-time dose, and five-time dose) of 20 chicks each (20 chickens per group). At the age of day 15, all chickens (except the control group) were administered LC-SPH intramuscularly (chest muscles) at different doses of 20 mg/kg.bw, 60 mg/kg.bw, and 100 mg/kg.bw respectively for 9 consecutive days recommended by veterinary international cooperation on harmonization (VICH) guidelines. The chickens had ad libitum access to antibiotic-free feed and water. Feeding chickens were observed twice a day throughout the study. The drug safety was evaluated by complete blood count, biochemical parameters, histopathological, clinical signs, body weight gain, and feed conversion ratio (FCR). Hence, considering the minor toxicity of 60 mg/kg, our results reveal that intramuscular injection of at least 20 mg/kg body weight has no effects on growth performance, clinical blood parameters, organ coefficient, and histopathological parameters. Thus, a combination of LC-SPH 20 mg/kg body weight i.m injection investigated safe followed daily administration for nine consecutive days in healthy chickens. It is concluded that the experimental results support the safety of 20 mg/kg body weight in combination for the further clinical research study.

The combination of chemotherapy and immunotherapy motivates a potent immune system by triggering immunogenic cell death (ICD), showing great potential in inhibiting tumor growth and improving the immunosuppressive tumor microenvironment (ITM). However, the therapeutic effectiveness has been restricted by inferior drug bioavailability. Herein, we reported a universal bioresponsive doxorubicin (DOX)-based nanogel to achieve tumor-specific co-delivery of drugs. DOX-based mannose nanogels (DM NGs) was designed and choosed as an example to elucidate the mechanism of combined chemo-immunotherapy. As expected, the DM NGs exhibited prominent micellar stability, selective drug release and prolonged survival time, benefited from the enhanced tumor permeability and prolonged blood circulation. We discovered that the DOX delivered by DM NGs could induce powerful anti-tumor immune response facilitated by promoting ICD. Meanwhile, the released mannose from DM NGs was proved as a powerful and synergetic treatment for breast cancer in vitro and in vivo, via damaging the glucose metabolism in glycolysis and the tricarboxylic acid cycle. Overall, the regulation of tumor microenvironment with DOX-based nanogel is expected to be an effectual candidate strategy to overcome the current limitations of ICD-based immunotherapy, offering a paradigm for the exploitation of immunomodulatory nanomedicines.

Dennettia tripetala G. Baker (Annonaceae), is a plant with nutritional, social economy, and medicinal values. Its rising medicinal profile makes this plant a prospect in drug discovery. However, the reported strong addictive potential among habitual consumers makes the need to establish its safety imperative. In this report, we evaluated the safety profile of the essential oil of the seed of D. tripetala (EODS) in nulliparous female Wistar rats using in vivo single and repeated dose toxicity profiling, as well as in silico toxicity profiling of its known seed oil derived phytoconstituents. Our results showed consistent significant dose-dependent alterations in relative body weights, organ-body and organ-brain weight ratios, haematological and biochemical indices, as well as liver and kidney histoarchitectures, following single and repeated oral administrations. Significant alterations in liver and kidney histoarchitectures were consistent with the observed significant increase in AST/ALT ratio, suggesting deleterious effects of EODS on the kidney and liver. However, the lack of alterations in the histoarchitectures of the hippocampus and hypothalamus suggests that the brain may not have been adversely affected. Also, the in silico analysis suggests that hepatotoxic effects of EODS may be linked to Benzylnitrile, Humulene, Linalool, (Z)-ß-Ocimene. In addition, the failure of ß-Phenylnitroethane, the most abundant phytoconstituent of EODS, to pass phases I and II in silico toxicity screening, and the presence of Caryophyllene oxide, a known toxic compound, coupled with the predicted binding of both to DNA and protein, low LD50 and high percent mortality at 250 mg/kg of repeated doses, further confirmed the potentially toxic nature of EODS. We concluded that based on our in vivo and in silico observations, there is an urgent need for public education to regulate the excessive consumption of the seeds of D. tripetala.

There is little data available for the toxicity of used aircraft engine oils relative to their unused (new) versions. This study was conducted to determine if grade 3 (G3) and 4 (G4) aircraft engine oils in their new states (G3-N and G4-N) and their used versions (G3-U and G4-U) have the potential to induce toxicity via dermal application. Male and female Sprague Dawley rats were dermally exposed to water (control), new and used versions of G3 and G4 oils to determine the oil sub-chronic toxicity potentials. A volume of 300 μL of undiluted oil was applied to the pad of the Hill Top Chamber System©. Then the chamber was attached to a fur-free test site located at the back of the rat for 6 h/day for 5 consecutive days/week for 21 days (15 total exposures). Recovery rats also received similar treatments and were kept for 14 days post-exposure to screen for reversibility, persistence, or delayed occurrence of toxic effects. Both G3 and G4 oils had a significant impact on the weight of male and female reproductive organs: testes weights for recovery rats exposed to G3-N significantly decreased (12%) relative to controls; G3-N and G3-U decreased uterus weights by 23% and 29%, respectively; G4-N decreased uterus weights by 32% but were resolved at the end of the recovery period; G4-N increased the weight of the adrenals and spleen for females by 34% and 27%, respectively, during the recovery period. G3 and G4 induced more changes in female blood indices than in those for males. Of all versions of oils, G4-N induced the most changes in profiles of female blood. G4-N significantly decreased the white blood cells, lymphocytes, neutrophils, eosinophils and increased the mean platelet volumes. Interestingly, males were not affected by exposure to G4-N oil. While G3-N decreased the white blood cells and lymphocytes for females it slightly increased those for males. In summary, G3 and G4 oils impacted the weights for male and reproductive organs. This study highlights the health risks that aircraft maintenance workers may be exposed to if precautions are not taken to minimize exposure to these oils.

The worldwide health crisis caused by the SARS-Cov-2 virus has resulted in>3 million deaths so far. Improving early screening, diagnosis and prognosis of the disease are critical steps in assisting healthcare professionals to save lives during this pandemic. Since WHO declared the COVID-19 outbreak as a pandemic, several studies have been conducted using Artificial Intelligence techniques to optimize these steps on clinical settings in terms of quality, accuracy and most importantly time. The objective of this study is to conduct a systematic literature review on published and preprint reports of Artificial Intelligence models developed and validated for screening, diagnosis and prognosis of the coronavirus disease 2019. We included 101 studies, published from January 1st, 2020 to December 30th, 2020, that developed AI prediction models which can be applied in the clinical setting. We identified in total 14 models for screening, 38 diagnostic models for detecting COVID-19 and 50 prognostic models for predicting ICU need, ventilator need, mortality risk, severity assessment or hospital length stay. Moreover, 43 studies were based on medical imaging and 58 studies on the use of clinical parameters, laboratory results or demographic features. Several heterogeneous predictors derived from multimodal data were identified. Analysis of these multimodal data, captured from various sources, in terms of prominence for each category of the included studies, was performed. Finally, Risk of Bias (RoB) analysis was also conducted to examine the applicability of the included studies in the clinical setting and assist healthcare providers, guideline developers, and policymakers.

BACKGROUND: Thrombotic and inflammatory mechanisms are involved in the pathophysiology of acute coronary syndrome (ACS). The aim of the study was the evaluation of inflammation (white blood cells count/WBC, C-reactive protein/CRP, interleukin-6/IL-6) and platelet (platelet count/PLT, mean platelet volume/MPV, large platelet/LPLT, beta-thromboglobulin/β-TG) biomarkers in the groups of ACS patients depending on the severity of signs and symptoms and compared to controls without coronary artery disease.
METHODS: The study group included 93 patients categorized into 3 subgroups depending on the severity of signs and symptoms of ACS. PLT, MPV, LPLT, and WBC were determined on hematological analyzer, IL-6 and β-TG were measured using the ELISA method.
RESULTS: In the whole group of ACS patients WBC, CRP, IL-6, MPV, and β-TG were significantly higher as compared to controls. Analyzing the inflammation and platelet biomarkers depending on the severity of signs and symptoms in comparison to controls, statistically significant differences for above-mentioned parameters were also found. There were no significant differences between the advancement of coronary artery changes and inflammation as well as platelet parameters, except for CRP concentrations. The AUCs for all inflammation parameters tested were similar, however the highest AUCs showed WBC and CRP. Among platelet parameters the highest AUC revealed β-TG.
CONCLUSIONS: Markers of inflammation and platelet activation may be associated to myocardial ischemia and myocardial injury. WBC, CRP and IL-6 as inflammation parameters and MPV and β-TG as platelet biomarkers may be useful indicators of the presence of coronary artery disease.

Sickle cell disease (SCD) is a life-threatening genetic condition. Patients suffer from chronic systemic and cerebral vascular disease that leads to early and cumulative neurological damage. Few studies have quantified the effects of this disease on brain morphometry and even fewer efforts have been devoted to older patients despite the progressive nature of the disease. This study quantifies global and regional brain volumes in adolescent and young adult patients with SCD and racially matched controls with the aim of distinguishing between age related changes associated with normal brain maturation and damage from sickle cell disease. T1 weighted images were acquired on 33 clinically asymptomatic SCD patients (age = 21.3 ± 7.8; F = 18, M = 15) and 32 racially matched control subjects (age = 24.4 ± 7.5; F = 22, M = 10). Exclusion criteria included pregnancy, previous overt stroke, acute chest, or pain crisis hospitalization within one month. All brain volume comparisons were corrected for age and sex. Globally, grey matter volume was not different but white matter volume was 8.1% lower (p = 0.0056) in the right hemisphere and 6.8% (p = 0.0068) in the left hemisphere in SCD patients compared with controls. Multivariate analysis retained hemoglobin (β = 0.33; p = 0.0036), sex (β = 0.35; p = 0.0017) and mean platelet volume (β = 0.27; p = 0.016) as significant factors in the final prediction model for white matter volume for a combined r2 of 0.37 (p < 0.0001). Lower white matter volume was confined to phylogenetically younger brain regions in the anterior and middle cerebral artery distributions. Our findings suggest that there are diffuse white matter abnormalities in SCD patients, especially in the frontal, parietal and temporal lobes, that are associated with low hemoglobin levels and mean platelet volume. The pattern of brain loss suggests chronic microvascular insufficiency and tissue hypoxia as the causal mechanism. However, longitudinal studies of global and regional brain morphometry can help us give further insights on the pathophysiology of SCD in the brain.