Several compounds from Cinnamomum kotoense show anticancer activities. However, the detailed mechanisms of most compounds from C. kotoense remain unknown. In this study, we investigated the ...anticancer activity of obtusilactone A (OA) and (−)‐sesamin in lung cancer. Our results show that human Lon is upregulated in non‐small‐cell lung cancer (NSCLC) cell lines, and downregulation of Lon triggers caspase‐3 mediated apoptosis. Through enzyme‐based screening, we identified two small‐molecule compounds, obtusilactone A (OA) and (−)‐sesamin from C. kotoense, as potent Lon protease inhibitors. Obtusilactone A and (−)‐sesamin interact with Ser855 and Lys898 residues in the active site of the Lon protease according to molecular docking analysis. Thus, we suggest that cancer cytotoxicity of the compounds is partly due to the inhibitory effects on Lon protease. In addition, the compounds are able to cause DNA double‐strand breaks and activate checkpoints. Treatment with OA and (−)‐sesamin induced p53‐independent DNA damage responses in NSCLC cells, including G1/S checkpoint activation and apoptosis, as evidenced by phosphorylation of checkpoint proteins (H2AX, Nbs1, and Chk2), caspase‐3 cleavage, and sub‐G1 accumulation. In conclusion, OA and (−)‐sesamin act as both inhibitors of human mitochondrial Lon protease and DNA damage agents to activate the DNA damage checkpoints as well induce apoptosis in NSCLC cells. These dual functions open a bright avenue to develop more selective chemotherapy agents to overcome chemoresistance and sensitize cancer cells to other chemotherapeutics. (Cancer Sci 2010; 101: 2612–2620)
This study extends the research literature by exploring the relations among green organizational identity (GOI), green shared vision (GSV), green product development performance (GPDP), and ...organizational citizenship behavior for the environment (OCBE). Hypotheses were tested through structural equation modeling from a sample of 475 valid questionnaire respondents. The two main findings were as follows: (1) Positive effects for GOI and GSV between OCBE and GPDP and (2) Positive effects of OCBE for GPDP. The results further indicate that the relations among the GOI, GSV, and GPDP were partially mediated by the OCBE; the results point that the OCBE acts as mediator between GOI, GSV, and GPDP. After further examining the collecting data, we found (3) the relationship between GOI and GPDP is completely mediated by OCBE and (4) the relationship between GSV and GPDP is partially mediated by OCBE. These findings indicate that OCBE is critical in the GPDP of companies. Therefore, companies must develop the GOI and GSV to strengthen their OCBE and intensify their GPDP.
Bone marrow stem cell can differentiate to osteoblast by growth factors, pulsed low-intensity ultrasound and electric magnetic field. In the research, bone marrow stem cells were cultured; bone ...marrow stem cells in culture can be stimulated by platelet-rich plasma and electric field.
The culture well of the co-cultivation device has a radius of 7.5 mm and a depth of 7 mm. It is divided into two sub-chambers separated by a 3 mm high and 1 mm wide barrier. The bone marrow stem cells were seeded at a density of 2 × 10
cells and the medium volume was 120μl. Platelet-rich plasma (PRP) or platelet-poor plasma (PPP) was added to the other sub-chamber at a volume of 10μl. The bone marrow stem cells were subjected to different electric fields (0 ~ 1 V/cm) at a frequency of 70 kHz for 60 min.
The highest osteogenic capacity of bone marrow stem cells was achieved by addition of PRP to electric field stimulation (0.25 V/cm) resulted in a proliferation rate of 599.78%. In electric field stimulation (0.75 V/cm) with PPP, the proliferation rate was only 10.46%.
Bone marrow stem cell with PRP in the co-culture device combined with electric field at 0.25 V/cm strength significantly promoted the growth of bone marrow stem cells.
Diabetic nephropathy (DN) is an increasing threat to human health. The impact of hyperglycemia or its metabolites, advanced glycation end-products (AGEs), on glomerular endothelial cells (GECs) and ...their pathophysiologic mechanisms are not well explored. Our results reveal that AGEs increased the expression and secretion of the KIT ligand (KITLG) in GECs. Both AGEs and KITLG promoted endothelial-to-mesenchymal transition (EndoMT) in GECs and further increased the permeability of GECs through the AKT/extracellular-signal-regulated kinase pathway. Inhibition of KITLG’s effects by imatinib prevented AGE-medicated EndoMT in GECs, supporting the belief that KITLG is a critical factor for GEC injury. We found higher KITLG levels in the GECs and urine of db/db mice compared with db/m mice, and urinary KITLG levels were positively correlated with the urinary albumin-to-creatinine ratio (ACR). Furthermore, type 2 diabetic patients had higher urinary KITLG levels than normal individuals, as well as urinary KITLG levels that were positively correlated with urinary ACR and negatively correlated with the estimated glomerular filtration rate. KITLG plays a pathogenic role in GEC injury in DN and might act as a biomarker of DN progression.
The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a public health emergency. The most common symptoms of COVID-19 ...are fever, cough, and fatigue. While most patients with COVID-19 present with mild illness, some patients develop pneumonia, an important risk factor for mortality, at early stage of viral infection, putting these patients at increased risk of death. So far, little has been known about differences in the T cell repertoires between COVID-19 patients with and without pneumonia during SARS-CoV-2 infection. Herein, we aimed to investigate T cell receptor (TCR) repertoire profiles and patient-specific SARS-CoV-2-associated TCR clusters between COVID-19 patients with mild disease (no sign of pneumonia) and pneumonia. The TCR sequencing was conducted to characterize the peripheral TCR repertoire profile and diversity. The TCR clustering and CDR3 annotation were exploited to further discover groups of patient-specific TCR clonotypes with potential SARS-CoV-2 antigen specificities. Our study indicated a slight decrease in the TCR repertoire diversity and a skewed CDR3 length usage in patients with pneumonia compared to those with mild disease. The SARS-CoV-2-associated TCR clusters enriched in patients with mild disease exhibited significantly higher TCR generation probabilities and most of which were highly shared among patients, compared with those from pneumonia patients. Importantly, using similarity network-based clustering followed by the sequence conservation analysis, we found different patterns of CDR3 sequence motifs between mild disease- and pneumonia-specific SARS-CoV-2-associated public TCR clusters. Our results showed that characteristics of overall TCR repertoire and SARS-CoV-2-associated TCR clusters/clonotypes were divergent between COVID-19 patients with mild disease and patients with pneumonia. These findings provide important insights into the correlation between the TCR repertoire and disease severity in COVID-19 patients.
With the rising need for accessible cervical cancer screening, self‐sampling methods offer a promising alternative to traditional physician‐led sampling. This study aims to evaluate the efficacy of ...the HygeiaTouch Self Sampling Kit for Women in detecting human papillomavirus (HPV) types and predicting cervical lesions. We studied the concordance in identifying high‐risk HPV (hrHPV) types between samples collected by physicians and those self‐collected by women using a self‐sampling kit for validation. Women aged 21–65, fitting into specific categories based on their cervical health history were eligible. Cohen's kappa coefficient to gauge concordance between the two specimen types and relative accuracy metrics in identifying cervical intraepithelial neoplasia (CIN) were also calculated, with physician‐sampled specimens serving as a reference. A total of 1210 participants from three institutes were involved. The self‐sampling kit closely matched the physician‐led method in terms of collecting valid specimens (100% vs. 100%), identifying hrHPV types (kappa: 0.75, 95% confidence interval 95% CI: 0.72–0.79; agreement: 87.7%, 95% CI: 85.8–89.6) and predicting CIN grade 2 or worse (CIN2+) (relative sensitivity: 0.949, relative accuracy: 0.959). Kappa values varied between 0.71 and 0.83 for different hrHPV types and combinations, with an overall value 0.75 (95% CI: 0.72–0.79) signifying robust compatibility between the two methods. Our study underscores the potential of the HygeiaTouch Self Sampling Kit as a reliable, efficient, and user‐friendly alternative to traditional sampling methods. This suggests that self‐sampling could be pivotal in expanding cervical cancer screening accessibility and enhancing detection rates.
MicroRNAs offer tools to identify and treat invasive cancers. Using highly invasive isogenic oral squamous cell carcinoma (OSCC) cells, established using in vitro and in vivo selection protocols from ...poorly invasive parental cell populations, we used microarray expression analysis to identify a relative and specific decrease in miR-491-5p in invasive cells. Lower expression of miR-491-5p correlated with poor overall survival of patients with OSCCs. miR-491-5p overexpression in invasive OSCC cells suppressed their migratory behavior in vitro and lung metastatic behavior in vivo. We defined the G-protein-coupled receptor kinase-interacting protein 1 (GIT1)-as a direct target gene for miR-491-5p control. GIT1 overexpression was sufficient to rescue miR-491-5p-mediated inhibition of migration/invasion and lung metastasis. Conversely, GIT1 silencing phenocopied the ability of miR-491-5p to inhibit migration/invasion and metastasis of OSCC cells. Mechanistic investigations indicated that miR-491-5p overexpression or GIT1 attenuation reduced focal adhesions, with a concurrent decrease in steady-state levels of paxillin, phospho-paxillin, phospho-FAK, EGF/EGFR-mediated extracellular signal-regulated kinase (ERK1/2) activation, and MMP2/9 levels and activities. In clinical specimens of OSCCs, GIT1 levels were elevated relative to paired normal tissues and were correlated with lymph node metastasis, with expression levels of miR-491-5p and GIT1 correlated inversely in OSCCs, where they informed tumor grade. Together, our findings identify a functional axis for OSCC invasion that suggests miR-491-5p and GIT1 as biomarkers for prognosis in this cancer.
The determination of resection extent traditionally relies on the microscopic invasiveness of frozen sections (FSs) and is crucial for surgery of early lung cancer with preoperatively unknown ...histology. While previous research has shown the value of optical coherence tomography (OCT) for instant lung cancer diagnosis, tumor grading through OCT remains challenging. Therefore, this study proposes an interactive human–machine interface (HMI) that integrates a mobile OCT system, deep learning algorithms, and attention mechanisms. The system is designed to mark the lesion’s location on the image smartly and perform tumor grading in real time, potentially facilitating clinical decision making. Twelve patients with a preoperatively unknown tumor but a final diagnosis of adenocarcinoma underwent thoracoscopic resection, and the artificial intelligence (AI)-designed system mentioned above was used to measure fresh specimens. Results were compared to FSs benchmarked on permanent pathologic reports. Current results show better differentiating power among minimally invasive adenocarcinoma (MIA), invasive adenocarcinoma (IA), and normal tissue, with an overall accuracy of 84.9%, compared to 20% for FSs. Additionally, the sensitivity and specificity, the sensitivity and specificity were 89% and 82.7% for MIA and 94% and 80.6% for IA, respectively. The results suggest that this AI system can potentially produce rapid and efficient diagnoses and ultimately improve patient outcomes.
Modern technological advancements have led to increase in the development of surgical robots in dentistry, resulting in excellent clinical treatment outcomes.
This study aimed to determine the ...accuracy of automatic robotic implant site preparation for different implant sizes by correlating planned and posttreatment positions, and to compare the performance of robotic and human freehand drilling.
Seventy-six drilling sites on partially edentulous models were used, with three different implant sizes (Ø = 3.5 × 10 mm, 4.0 × 10 mm, 5.0 × 10 mm). The robotic procedure was performed using software for calibration and step-by-step drilling processes. After robotic drilling, deviations in the implant position from the planned position were determined. The angulation, depth, and coronal and apical diameters on the sagittal plane of sockets created by human and robotic drilling were measured.
The deviation of the robotic system was 3.78° ± 1.97° (angulation), 0.58 ± 0.36 mm (entry point), and 0.99 ± 0.56 mm (apical point). Comparison of implant groups showed the largest deviation from the planned position for 5 mm implants. On the sagittal plane, there were no significant differences between robotic and human surgery except for the 5-mm implant angulation, indicating similar quality between human and robotic drilling. Based on standard implant measurements, robotic drilling exhibited comparable performance to freehand human drilling.
A robotic surgical system can provide the greatest accuracy and reliability regarding the preoperative plan for small implant diameters. In addition, the accuracy of robotic drilling for anterior implant surgery can also be comparable to that of human drilling.
This study compared the visual outcomes and complications between sutureless scleral-fixated intraocular lens and iris claw intraocular lens implantation in aphakia without adequate capsule and/or ...zonule support. Studies comparing the clinical outcomes of scleral-fixated intraocular lens and iris claw intraocular lens implantation published until April 2022 were retrieved from the PubMed, EMBASE, Cochrane Library, and Google Scholar databases. The outcomes included postoperative final visual acuity, surgical time, surgery-induced astigmatism, and complications. The weighted mean difference and odds ratio were calculated. Two randomized controlled trials and five cohort studies, including 244 and 290 eyes in the scleral-fixated intraocular lens group and iris claw group, respectively, were included. Scleral-fixated intraocular lens implantation results in a better postoperative final corrected distance visual acuity compared with iris claw intraocular lens implantation; however, it is more time-consuming. Scleral-fixated intraocular lens implantation seems to have lesser incidences of surgery-induced astigmatism. Furthermore, both procedures have a similar complication rate. Therefore, based on current best evidence, these two procedures should be considered according to patient's conditions.
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