deoxygoniopypyrone acetate 9, along with six known styryl lactones (1, 10-15) were also isolated and characterized. 6S-goniothalamin 1 is reported for the first time from a Goniothalamus species. 1, 11 and 12 showed cytotoxic activity against human colon and lung cancer cell lines with IC 50 values ranging from 2.38-7.59 µM.
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Eight new bis-styryllactones, goniolanceolatins A−H (1−8), possessing a rare α,β-unsaturated δ-lactone moiety with a (6S)-configuration, were isolated from the CH 2 Cl 2 extract of the stembark and roots of Goniothalamus lanceolatus Miq., a plant endemic to Malaysia. Absolute structures were established through extensive 1D-and 2D-NMR data analysis, in combination with electronic dichroism (ECD) data. All of the isolates were evaluated for their cytotoxicity against human lung and colorectal cancer cell lines. Compounds 2 and 4 showed cytotoxicity, with IC 50 values ranging from 2.3 to 4.2 μM, and were inactive toward human noncancerous lung and colorectal cells. Compounds 1, 3, 6, 7, and 8 showed moderate to weak cytotoxicity. Docking studies of compounds 2 and 4 showed that they bind with EGFR tyrosine kinase and cyclin-dependent kinase 2 through hydrogen bonding interactions with the important amino acids, including Lys721,
Prostate cancer (PCa) is the second most common malignancy and is the fifth leading cause of cancer mortality among men globally. Docetaxel‐based therapy remains the first‐line treatment for metastatic castration‐resistant prostate cancer. However, dose‐limiting toxicity including neutropenia, myelosuppression and neurotoxicity is the major reason for docetaxel dose reductions and fewer cycles administered, despite a recent study showing a clear survival benefit with increased total number of docetaxel cycles in PCa patients. Although previous studies have attempted to improve the efficacy and reduce docetaxel toxicity through drug combination, no drug has yet demonstrated improved overall survival in clinical trial, highlighting the challenges of improving the activity of docetaxel monotherapy in PCa. Herein, we identified 15 lethality hits for which inhibition could enhance docetaxel sensitivity in PCa cells via a high‐throughput kinome‐wide loss‐of‐function screen. Further drug‐gene interactions analyses identified Janus kinase 1 (JAK1) as a viable druggable target with existing experimental inhibitors and FDA‐approved drugs. We demonstrated that depletion of endogenous JAK1 enhanced docetaxel‐induced apoptosis in PCa cells. Furthermore, inhibition of JAK1/2 by baricitinib and ruxolitinib synergizes docetaxel sensitivity in both androgen receptor (AR)–negative DU145 and PC3 cells, but not in the AR‐positive LNCaP cells. In contrast, no synergistic effects were observed in cells treated with JAK2‐specific inhibitor, fedratinib, suggesting that the synergistic effects are mainly mediated through JAK1 inhibition. In conclusion, the combination therapy with JAK1 inhibitors and docetaxel could be a useful therapeutic strategy in the treatment of prostate cancers.
The potential of superhydrophobic surfaces has gained vast attention in medical settings due to their self‐cleaning effect (including bacterial colonization reduction), minimized cell‐to‐surface interaction, and anti‐biofouling effect. These valuable features allow the vanquishment of some limitations accompanying the blood‐contacting medical devices that are widely used in clinical practice. The extracorporeal circulation used to perform hemodialysis, for instance, as well as the blood collection sets, these essential blood‐contacting medical devices are frequently associated with bacterial infection and hemolysis. Within this study, superhydrophobic surface was substantiated to enhance the biocompatibility. Herein, the graphene (Gr) and titanium dioxide (TiO2) nanoparticles were dip‐coated on poly(lactic acid) (PLA) film to produce a superhydrophobic surface. The uniform distribution of the Gr/TiO2 nanoparticles of the coating enhanced the surface roughness and therefore promoted superhydrophobic properties. Co‐occurrence of the Cassie‐Baxter regime and Wenzel regime was suggested to induce the low surface wettability. The superhydrophobic Gr/TiO2 demonstrated significant inhibition of biofilm formation and antibacterial activity against Staphylococcus aureus, Klebsiella pneumoniae and Pseudomonas aeruginosa. Besides, the in vitro blood compatibility assay showed a hemolysis rate lower than 2%, which was categorized as nonhemolytic. The exposure of human heart cells and kidney cells to the Gr/TiO2‐coated PLA film did not significantly affect the cell viability. The findings herein showed promising results for the superhydrophobic Gr/TiO2‐coated PLA film to act as a potential biomaterial for single‐use blood‐contacting medical devices. This study also provided insight for future medical applications that require superhydrophobic coatings.
Background
Nocturia is widely prevalent condition with detrimental effects on quality of life and general health. In Malaysia, there is a lack of up-to-date prevalence study on nocturia. This study aimed to investigate the prevalence of nocturia and awareness pertaining to nocturia among Malaysian adults.
Methods
A cross-sectional population-based study was conducted among Malaysian adults aged ≥ 18 years old. The data was collected by mixed mode self-administered questionnaire from May 2019 to September 2019. Nocturia was defined as one or more voids at night.
Results
There were a total of 4616 respondents with 74.5% of response rate. The overall prevalence of nocturia among Malaysian adults was found to be 57.3%. In multivariate analysis, respondents aged 31–40 (1.91 [1.52–2.40]) or > 60 years old (2.03 [1.48–2.71]), and those who presented with hypertension (2.84 [2.28–3.53]), diabetes mellitus (1.78 [1.42–2.25]), renal disease (3.58 [1.93–6.63]) or overactive bladder (1.61 [1.10–2.35]) were associated with higher prevalence of nocturia. A significantly lower disease prevalence (p < 0.05) was noted among those aged 41–50 (0.73 [0.59–0.91]), male (0.78 [0.69–0.88]) and Chinese (0.47 [0.30–0.74]) or Indian (0.34 [0.21–0.54]) ethnicities. A total of 37.3% of respondents with nocturia reported that they faced sleeping difficulty about half the time or more after waking up in the middle of night. Those who had ≥ 2 voids per night experienced significantly higher mean bother score than those who had 1 void per night (p < 0.001). Approximately half (56.7%) of all respondents were not aware that night time urination is a medical condition. Only 25.2% of respondents with nocturia had sought medical attention for their nocturia.
Conclusions
The prevalence of nocturia among Malaysian adults is high and strongly influenced by age, sex, race and comorbidities. However, the general awareness pertaining to nocturia being a health issue remains low among Malaysians. The findings also highlighted the impact of nocturia on sleep and the need for nocturia education to better address this disease.
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