Background/Aim
Berberine (BBR) is known to be effective at inhibiting cell proliferation and promoting apoptosis in various cancer cells. However, the effects of BBR on triple‐negative breast cancer ...(TNBC) cells remain unclear. The aim of this study was to investigate the cell inhibition effects of BBR on different subtypes of TNBC cells.
Methods
Using human TNBC cell lines of different subtypes, namely, MDA‐MB‐231, MDA‐MB‐468, MDA‐MB‐453, and BT‐549 as in vitro models, antiproliferative effects of BBR were investigated by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay, trypan blue exclusion assay, and clonogenic assay. Furthermore, cell apoptosis and autophagy were analyzed by flow cytometry, immunofluorescent staining, and LC3 I/II‐targeted Western blotting. Various cell growth‐related signaling pathways (AKT/ERK/p38) and the expression of proteins present in various cell cycle kinase complexes were analyzed by Western blotting.
Results
BBR concentration‐dependently suppressed cell proliferation in MDA‐MB‐468 (0, 3, 6, and 12 μM) and MDA‐MB‐231 (0, 6.25, 12.5, and 25 μM). The inhibitory effect was not brought about by inducing cell apoptosis, necrosis, or autophagy. Cell cycle analysis disclosed an increased S+G2/M fraction among the BBR‐treated MDA‐MB‐231 and MDA‐MB‐453 cells; while with the BBR‐treated MDA‐MB‐468 and BT‐549 lines, an increased G0/G1 fraction was found. In MDA‐MB‐231 and MDA‐MB‐453 cells, by Western blotting, BBR decreased the expression of Cyclin A and CDK1, On the other hand, in BBR‐treated MDA‐MB‐468 and BT‐549 cells, there was a decrease in Cyclin D and CDK4 expression.
Conclusion
Our results demonstrate that the antiproliferation effects of BBR occur via different mechanisms in different subtypes of TNBC cells, which suggests that BBR has potential as a personalized treatment for TNBC patients.
Our results demonstrate that the antiproliferation effects of berberine (BBR) occur via different mechanisms in the four representative triple‐negative breast cancer (TNBC) cell lines, which suggests that BBR has potential as a personalized treatment for TNBC patients
Background and Purpose
Neutrophilic inflammation is a critical pathogenic factor in psoriasis. The therapeutic applicability of palbociclib, a cyclin‐dependent kinase 4 and 6 (CDK4/6) inhibitor ...clinically used to treat cancer, in the treatment of neutrophil‐associated psoriasis remains undefined. In this study, we evaluated the therapeutic potential and pharmacological effect of palbociclib on neutrophil‐associated psoriasiform dermatitis.
Experimental Approach
The anti‐inflammatory effects of palbociclib were determined in activated human neutrophils. The therapeutic feasibility of palbociclib in psoriasis was demonstrated in a mouse model of imiquimod‐induced psoriasiform dermatitis. The in vitro enzymatic assays and in silico analyses were used to identify the underlying pharmacological mechanisms.
Key Results
This study found that palbociclib inhibited neutrophilic inflammation, including superoxide anion generation, reactive oxygen species (ROS) formation, elastase degranulation and chemotactic responses. The mechanistic studies identified that the anti‐inflammatory effects of palbociclib involved the targeting of phosphatidylinositol 3‐kinase (PI3K) but not CDK4/6 in human neutrophils. Palbociclib preferentially targeted the p110δ catalytic subunit of PI3K and thereby blocked signalling via the PI3K/protein kinase B (Akt) pathway. Furthermore, topical application of palbociclib significantly ameliorated imiquimod‐induced psoriasiform dermatitis in mice, including psoriatic symptoms, neutrophil infiltration, Akt activation and cytokine up‐regulation.
Conclusions and Implications
This is the first study to demonstrate that palbociclib can potentially be used to treat neutrophil‐associated psoriasiform dermatitis through the targeting of neutrophilic PI3K activity. Our findings prompt further research to explore the potential of palbociclib and PI3K in psoriasis and other inflammatory diseases.
Traumatic brain injury (TBI) is a major brain injury type commonly caused by traffic accidents, falls, violence, or sports injuries. To obtain mechanistic insights about TBI, experimental animal ...models such as weight-drop-induced TBI in rats have been developed to mimic closed-head injury in humans. However, the relationship between the mechanical impact level and neurological severity following weight-drop-induced TBI remains uncertain. In this study, we comprehensively investigated the relationship between physical impact and graded severity at various weight-drop heights.
The acceleration, impact force, and displacement during the impact were accurately measured using an accelerometer, a pressure sensor, and a high-speed camera, respectively. In addition, the longitudinal changes in neurological deficits and balance function were investigated at 1, 4, and 7 days post TBI lesion. The inflammatory expression markers tested by Western blot analysis, including glial fibrillary acidic protein, beta-amyloid precursor protein, and bone marrow tyrosine kinase gene in chromosome X, in the frontal cortex, hippocampus, and corpus callosum were investigated at 1 and 7 days post-lesion.
Gradations in impact pressure produced progressive degrees of injury severity in the neurological score and balance function. Western blot analysis demonstrated that all inflammatory expression markers were increased at 1 and 7 days post-impact injury when compared to the sham control rats. The severity of neurologic dysfunction and induction in inflammatory markers strongly correlated with the graded mechanical impact levels.
We conclude that the weight-drop-induced TBI model can produce graded brain injury and induction of neurobehavioral deficits and may have translational relevance to developing therapeutic strategies for TBI.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Plants of the genus
are known to possess several medicinal effects. The constituents of the Taiwan endemic plant
have never been studied. Therefore,
was selected for our phytochemical investigation. ...Two new clerodane-type diterpenoids, named callihypolins A (
) and B (
), along with seven known compounds were isolated from the leaves and twigs of the Lamiaceae plant
and then characterized. The structures of compounds
and
were elucidated by spectroscopic data analysis, specifically, two-dimension nuclear magnetic resonance (NMR). The anti-inflammatory activity of compounds
-
based on the suppression of superoxide anion generation and elastase release was evaluated. Among the isolates, compounds
-
showed anti-inflammatory activity (9.52-32.48% inhibition at the concentration 10 μm) by suppressing superoxide anion generation and elastase release. Our findings not only expand the description of the structural diversity of the compounds present in plants of the genus
but also highlight the possibility of developing anti-inflammatory agents from
endemic species.
Aim. The aim of the study was to test the efficacy of sleep care guidelines for controlling night‐time noise and improving sleep quality of patients in a surgical intensive care unit.
Background. ...Poor sleep quality places critically ill patients at greater risk for infection, complications and mortality. Environmental stimuli such as noises, continuous lighting and frequent care‐related activities in an intensive care unit interfere with patients’ sleep.
Design. The study used a quasi‐experimental design.
Method. Sixty surgical patients were recruited from an intensive care unit in Taiwan during December 2007–May 2008. The control group received the usual care, and the experimental group was cared for by nurses who followed the sleep care guidelines for noise and light reduction. Data were collected on noise level and sleep quality using the Sleep in the Intensive Care Unit Questionnaire, the Richards Campbell Sleep Questionnaire and a decibel meter.
Results. The results showed that both the peak sound level (χ2 = 50·1, p < 0·001) and average noise level (χ2 = 46·5, p < 0·001) were reduced significantly, after implementing the guidelines. The perceived noise (t = −2·07, p = 0·046) and sleep interruptions from care‐related activities (t = 5·282, p < 0·001) and noises (t = 4·361, p < 0·001) were all significantly lower in the experimental group than in the control group. The experimental group also reported better sleep quality (t = −2·28, p = 0·027) and sleep efficiency (t = −2·03, p = 0·047) than did the control group.
Conclusions. These results support the efficacy of the guidelines for controlling night‐time noise and care activities to improve patients’ sleep quality.
Relevance to clinical practice. Nurses should try to reduce external environmental stimuli and maintain an almost undisturbed period between midnight and 5:00 a.m. to enhance patients’ sleep in a surgical intensive care unit.
Abstract
Background
Previous studies have assessed note quality and the use of electronic medical record (EMR) as a part of medical training. However, a generalized and user-friendly note quality ...assessment tool is required for quick clinical assessment. We held a medical record writing competition and developed a checklist for assessing the note quality of participants’ medical records. Using the checklist, this study aims to explore note quality between residents of different specialties and offer pedagogical implications.
Methods
The authors created an inpatient checklist that examined fundamental EMR requirements through six note types and twenty items. A total of 149 records created by residents from 32 departments/stations were randomly selected. Seven senior physicians rated the EMRs using a checklist. Medical records were grouped as general medicine, surgery, paediatric, obstetrics and gynaecology, and other departments. The overall and group performances were analysed using analysis of variance (ANOVA).
Results
Overall performance was rated as fair to good. Regarding the six note types, discharge notes (0.81) gained the highest scores, followed by admission notes (0.79), problem list (0.73), overall performance (0.73), progress notes (0.71), and weekly summaries (0.66). Among the five groups, other departments (80.20) had the highest total score, followed by obstetrics and gynaecology (78.02), paediatrics (77.47), general medicine (75.58), and surgery (73.92).
Conclusions
This study suggested that duplication in medical notes and the documentation abilities of residents affect the quality of medical records in different departments. Further research is required to apply the insights obtained in this study to improve the quality of notes and, thereby, the effectiveness of resident training.
•Dipping cut surfaces in acetic acid & ethanol represses lettuce butt discoloration.•Four lettuce phenylalanine ammonia lyase (PAL) genes are wound-inducible.•Acetic acid transcriptionally suppresses ...these four wound-inducible PALs.•Addition of acetic acid inhibits PAL enzyme activity in vitro and in planta.•Ethanol strongly represses microbial growth and moderately inhibits browning.
The enzymatic browning of lettuce (Lactuca sativa L.) is a main cause of postharvest quality loss, and is controlled by the enzyme phenylalanine ammonia lyase (PAL). However, effective browning inhibitors that prevent lettuce butt discoloration have not been commercially developed, so the effects of such inhibitors on PAL are largely unknown. Here, we not only developed an anti-browning treatment, but also explored the mechanisms of the PAL-associated browning of Iceberg lettuce by profiling all homologs of PAL genes at transcript level. The anti-browning treatment used a combination of 0.25 M acetic acid and 200 mL L−1 ethanol and was able to repress enzymatic browning and microbial growth for two weeks. Notably, the lettuce butt discoloration in stem disks was repressed by 0.5 M acetic acid by inhibiting PAL activity, and this inhibition of PAL activity was also observed in vitro using a crude PAL enzyme extract from lettuce stems. To investigate the anti-browning mechanism at the transcriptional level, we identified and cloned six predicted LsPAL genes in the Lettuce Genome Resource, and further found that four of these (LsPAL1 to LsPAL4) were wound-inducible in the lettuce stem. Among these four wound-inducible LsPALs, LsPAL4 showed the highest wound-induced fold-change, suggesting that LsPAL4 has a key role in lettuce browning. Interestingly, wound-induction of LsPAL genes was dramatically downregulated by application of acetic acid. Taken together, acetic acid treatment of lettuce stems repressed butt discoloration by repressing PAL both enzymatically and transcriptionally, and ethanol provided complementary antimicrobial activity. A combination treatment with acetic acid and ethanol therefore has commercial potential in lettuce head processing.
Undertriage of major trauma patients is unavoidable, especially in the trauma system of rural areas. Timely stabilization and transfer of critical trauma patients remains a great challenge for ...hospitals with limited resources. No definitive measure has been proven to improve the outcomes of patients transferred with major trauma. The current study hypothesized that regular feedback on inter-hospital transfer of patients with major trauma can improve quality of care and clinical outcomes.
This retrospective cohort study retrieved data of transferred major trauma patients with an injury severity score (ISS) > 15 between January 2010 and December 2018 from the trauma registry databank of a tertiary medical center. Regular monthly feedback on inter-hospital transfers was initiated in 2014. The patients were divided into a without-feedback group and a with-feedback group. Demographic data, management before transfer, and outcomes after transfer were collected and analyzed.
A total of 178 patients were included: 69 patients in the without-feedback group and 109 in the with-feedback group. The with-feedback group had a higher ISS (25 vs. 27; p = 0.049), more patients requiring massive transfusion (14.49% vs. 29.36%, p = 0.036), and less patients with Glasgow Coma Scale ≤8 (30.43% vs. 23.85%, p < 0.001). After adjusting for confounding factors, the with-feedback group was associated with a higher rate of blood transfusion before transfer (adjusted odds ratio aOR: 2.75; 95% confidence interval CI: 1.01-7.52; p = 0.049), shorter time span before blood transfusion (- 31.80 ± 15.14; p = 0.038), and marginally decreased mortality risk (aOR: 0.43; 95% CI: 0.17-1.09; p = 0.076).
This study revealed that regular feedback on inter-hospital transfer improved the quality of blood transfusion.
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