Oral cancer is one of the leading causes of cancer-related deaths worldwide. Chemotherapy is widely used in the treatment of oral cancer, but its clinical efficacy is limited by drug resistance. ...Hence, novel compounds capable of overcoming drug-resistance are urgently needed.
Plumbagin (PG), a natural compound isolated from Plumbago zeylanica L, has been used to treat various cancers. In this study, we investigated the anticancer effects of PG on drug-resistant oral cancer (CR-SAS) cells, as well as the underlying mechanism.
MTT assays were used to evaluate the effect of PG on the viability of CR-SAS cells. Apoptosis and reactive oxygen species (ROS) production by the cells were determined using flow cytometry. Protein expression levels were detected by western blotting.
The results show that PG reduces the viability and causes the apoptosis of CR-SAS cells. PG is able to induce intracellular and mitochondrial ROS generation that leads to mitochondrial dysfunction. Furthermore, endoplasmic reticulum (ER) stress was triggered in PG-treated CR-SAS cells. The inhibition of ROS using N-acetylcysteine (NAC) abrogated the PG-induced ER stress and apoptosis, as well as the reduction in cell viability. Meanwhile, similar results were observed both in zebrafish and in murine models of drug-resistant oral cancer.
Our results indicate that PG induces the apoptosis of CR-SAS cells via the ROS-mediated ER stress pathway and mitochondrial dysfunction. It will be interesting to develop the natural compound PG for the treatment of drug-resistant oral cancer.
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Background
Risk factors associated with a suboptimal response to Gonadotropin-releasing hormone (GnRH) agonists include a high or low body mass index (BMI), prolonged use of oral contraceptive pills, ...and low luteinizing hormone (LH) levels on either the start or trigger days of controlled ovarian stimulation (COS). However, this approach may increase the need for a dual trigger and may also result in a higher incidence of ovarian hyperstimulation syndrome (OHSS) in hyper-responders. We aimed to investigate whether the maximum LH level during stimulation can serve as a predictive factor for achieving an optimal oocyte yield using the GnRH agonist trigger alone.
Methods
We retrospectively reviewed all antagonist protocols or progestin-primed ovarian stimulation (PPOS) protocols triggered with GnRH agonist only between May 2012 and December 2022. Subjects were divided into three groups, depending on basal LH level and LH maximum level. The freeze-all strategy was implemented in all cycles: Group 1, consistently low LH levels throughout COS; Group 2, low basal LH level with high LH max level during COS; Group 3, consistently high LH levels throughout COS. The primary outcome was the oocyte yield rate. The secondary outcome includes the number of collected oocytes, suboptimal response to GnRH agonist trigger, oocyte maturity rate, fertilized rate, clinical pregnancy rate, ongoing pregnancy rate, and live birth rate. The pregnancy outcomes were calculated for the first FET cycle.
Results
Following confounder adjustment, multivariable regression analysis showed that Group 1 (cycles with consistently low LH levels throughout COS) remains an independent predictor of suboptimal response (OR: 6.99; 95% CI 1.035–47.274). Group 1 (b = −12.72; 95% CI −20.9 to −4.55) and BMI (b = −0.25; 95% CI −0.5 to −0.004) were negatively associated with oocyte yield rate. Patients with low basal LH but high LH max levels had similar clinical outcomes compared to those with high LH max levels through COS.
Conclusions
The maximum LH level during COS may serve as an indicator of LH reserve and could be a more reliable predictor of achieving an optimal oocyte yield when compared to relying solely on the basal LH level. In the case of hyper-responders where trigger agents (agonist-only or dual trigger) are being considered, we propose a novel strategy that incorporates the maximum LH level, rather than just the basal or trigger-day LH level, as a reference for assessing LH reserve. This approach aims to minimize the risk of obtaining suboptimal oocyte yield and improve overall treatment outcomes.
Some lichens provide the resources of common traditional medicines and show anticancer effects. However, the anticancer effect of Usnproliea barbata (U. barbata) is rarely investigated, especially ...for oral cancer cells. The aim of this study was to investigate the cell killing function of methanol extracts of U. barbata (MEUB) against oral cancer cells. MEUB shows preferential killing against a number of oral cancer cell lines (Ca9-22, OECM-1, CAL 27, HSC3, and SCC9) but rarely affects normal oral cell lines (HGF-1). Ca9-22 and OECM-1 cells display the highest sensitivity to MEUB and were chosen for concentration effect and time course experiments to address its cytotoxic mechanisms. MEUB induces apoptosis of oral cancer cells in terms of the findings from flow cytometric assays and Western blotting, such as subG1 accumulation, annexin V detection, and pancaspase activation as well as poly (ADP-ribose) polymerase (PARP) cleavage. MEUB induces oxidative stress and DNA damage of oral cancer cells following flow cytometric assays, such as reactive oxygen species (ROS)/mitochondrial superoxide (MitoSOX) production, mitochondrial membrane potential (MMP) depletion as well as overexpression of γH2AX and 8-oxo-2′deoxyguanosine (8-oxodG). All MEUB-induced changes in oral cancer cells were triggered by oxidative stress which was validated by pretreatment with antioxidant N-acetylcysteine (NAC). In conclusion, MEUB causes preferential killing of oral cancer cells and is associated with oxidative stress, apoptosis, and DNA damage.
Presently, natural sources and herbs are being sought for the treatment of human oral squamous cell carcinoma (OSCC) in order to alleviate the side effects of chemotherapy. This study investigates ...the effect of sandensolide, a cembrane isolated from
, to inhibit human OSCC cell growth with the aim of developing a new drug for the treatment of oral cancer. In vitro cultured human OSCC models (Ca9.22, SCC9 and HSC-3 cell lines) and oral normal cells (HGF-1), as well as a zebrafish xenograft model, were used to test the cytotoxicity of sandensolide (MTT assay), as well as to perform cell cycle analysis and Western blotting. Both the in vitro bioassay and the zebrafish xenograft model demonstrated the anti-oral cancer effect of sandensolide. Moreover, sandensolide was able to significantly suppress colony formation and induce apoptosis, as well as cell cycle arrest, in OSCC by regulating multiple key proteins. Induction of reactive oxygen species (ROS) was observed in sandensolide-treated oral cancer cells. However, these apoptotic changes were rescued by NAC pretreatment. These findings contribute to the knowledge of the model of action of sandensolide, which may induce oxidative stress-mediated cell death pathways as a potential agent in oral cancer therapeutics.
Our main goal is to measure stellar masses and ages of these galaxies, which are the most likely sources of the ionizing photons that drive reionization. Accurate knowledge of the star formation ...density and star formation history at this epoch is necessary to determine whether these galaxies indeed reionized the universe. Determination of the stellar masses and ages requires measuring rest-frame optical light, which only Spitzer can probe for sources at z gap 7, for a large enough sample of typical galaxies. To illustrate the survey strategy and characteristics we introduce the sample, present the details of the data reduction and demonstrate that these data are sufficient for in-depth studies of z gap 7 sources (using a z = 9.5 galaxy behind MACS J 1149.5+2223 as an example). For the first cluster of the survey (the Bullet Cluster) we have released all high-level data mosaics and IRAC empirical point-spread function models.
A growing body of literature addresses the possible long-term cognitive effects of anaesthetics, but no study has delineated the normal trajectory of neural recovery attributable to anaesthesia alone ...in adults. We obtained resting-state functional MRI scans on 72 healthy human volunteers between ages 40 and 80 (median: 59) yr before, during, and after general anaesthesia with sevoflurane, in the absence of surgery, as part of a larger study on cognitive function postanaesthesia.
Region-of-interest analysis, independent component analysis, and seed-to-voxel analysis were used to characterise resting-state functional connectivity and to differentiate between correlated and anticorrelated connectivity before, during, and after general anaesthesia.
Whilst positively correlated functional connectivity remained essentially unchanged across these perianaesthetic states, anticorrelated functional connectivity decreased globally by 35% 1 h after emergence from general anaesthesia compared with baseline, as seen by the region-of-interest analysis. This decrease corresponded to a consistent reduction in expression of canonical resting-state networks, as seen by independent component analysis. All measures returned to baseline 1 day later.
The normal perianaesthesia trajectory of resting-state connectivity in healthy adults is characterised by a transient global reduction in anticorrelated activity shortly after emergence from anaesthesia that returns to baseline by the following day.
NCT02275026.
Strong gravitational lensing by galaxy clusters has become a powerful tool for probing the high-redshift universe, magnifying distant and faint background galaxies. Reliable strong-lensing (SL) ...models are crucial for determining the intrinsic properties of distant, magnified sources and for constructing their luminosity function. We present here the first SL analysis of MACS J0308.9+2645 and PLCK G171.9−40.7, two massive galaxy clusters imaged with the Hubble Space Telescope, in the framework of the Reionization Lensing Cluster Survey (RELICS). We use the light-traces-mass modeling technique to uncover sets of multiply imaged galaxies and constrain the mass distribution of the clusters. Our SL analysis reveals that both clusters have particularly large Einstein radii (θE > 30″ for a source redshift of zs = 2), providing fairly large areas with high magnifications, useful for high-redshift galaxy searches (∼2 arcmin2 with > 5 to ∼1 arcmin2 with > 10, similar to a typical Hubble Frontier Fields cluster). We also find that MACS J0308.9+2645 hosts a promising, apparently bright (J ∼ 23.2-24.6 AB), multiply imaged high-redshift candidate at z ∼ 6.4. These images are among the brightest high-redshift candidates found in RELICS. Our mass models, including magnification maps, are made publicly available for the community through the Mikulski Archive for Space Telescopes.
We present a strong lensing analysis of four massive galaxy clusters imaged with the Hubble Space Telescope in the Reionization Lensing Cluster Survey. We use a light-traces-mass technique to uncover ...sets of multiple images and constrain the mass distribution of the clusters. These mass models are the first published for Abell S295 and MACS J0159.8-0849 and are improvements over previous models for Abell 697 and MACS J0025.4-1222. Our analysis for MACS J0025.4-1222 and Abell S295 shows a bimodal mass distribution supporting the merger scenarios proposed for these clusters. The updated model for MACS J0025.4-1222 suggests a substantially smaller critical area than previously estimated. For MACS J0159.8-0849 and Abell 697, we find a single peak and relatively regular morphology revealing fairly relaxed clusters. Despite being less prominent lenses, three of these clusters seem to have lensing strengths, i.e., cumulative area above certain magnification, similar to those of the Hubble Frontier Fields clusters (e.g., A( > 5) ∼ 1-3 arcmin2, A( > 10) ∼ 0.5-1.5 arcmin2), which in part can be attributed to their merging configurations. We make our lens models publicly available through the Mikulski Archive for Space Telescopes. Finally, using Gemini-N/GMOS spectroscopic observations, we detect a single emission line from a high-redshift J125 25.7 galaxy candidate lensed by Abell 697. While we cannot rule out a lower-redshift solution, we interpret the line as Ly at z = 5.800 0.001, in agreement with its photometric redshift and dropout nature. Within this scenario, we measure a Ly rest-frame equivalent width of 52 22 and an observed Gaussian width of 117 15 km s−1.
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