The role of vestibular function tests in nontuberculous mycobacterial otomastoiditis: A case report.

BACKGROUND: Nontuberculous mycobacteria (NTM), an extremely rare pathogen causing cervicofacial infections, may result in permanent hearing impairment or intracranial complications. Due to the lack of specific manifestations during the initial onset of NTM otomastoiditis, physicians may misdiagnose it as cholesteatoma or other common bacterial infections. PATIENT CONCERNS: A 44-year-old male who complained of left-sided aural fullness, otalgia, and dizziness for 2 months. DIAGNOSIS: The initial diagnosis was hypothesized to be cholesteatoma based on a whitish mass with mucoid discharge filling the entire outer ear canal on otoscopy and left-sided mixed hearing loss. However, NTM was identified by microbial culture at the 2-month follow-up after surgery. INTERVENTIONS: The patient underwent a left-sided exploratory tympanotomy. Because NTM otomastoiditis was diagnosed, 3 weeks of starting therapies were administered with azithromycin (500 mg/day, oral administration), cefoxitin (3 g/day, intravenous drip), and amikacin (750 mg/day, intravenous drip). The maintenance therapies were azithromycin (500 mg/day, oral administration) and doxycycline (200 mg/day, oral administration) for 7 months. OUTCOMES: The patient's clinical condition improved initially after surgery, but the otomastoiditis gradually worsened, combined with subtle meningitis, 2 months after surgery. The external auditory canal became swollen and obstructed, making it difficult to monitor the treatment efficacy through otoscopy. Thus, we used regular vestibular function tests, including static posturography, cervical vestibular evoked myogenic potentials, and video Head Impulse Test, to assess recovery outcomes. After antibiotic treatment, the infectious symptoms subsided significantly, and there was no evidence of infection recurrence 7 months after treatment. Improvements in static posturography and cervical vestibular evoked myogenic potentials were compatible with the clinical manifestations, but video Head Impulse Test showed an unremarkable correlation. LESSONS: The clinical condition of NTM otomastoiditis may be evaluated using vestibular tests if patients have symptoms of dizziness.

VisionCoach: Design and Effectiveness Study on VR Vision Training for Basketball Passing.

Vision Training is important for basketball players to effectively search for teammates who has wide-open opportunities to shoot, observe the defenders around the wide-open teammates and quickly choose a proper way to pass the ball to the most suitable one. We develop an immersive virtual reality (VR) system called VisionCoach to simulate the player's viewing perspective and generate three designed systematic vision training tasks to benefit the cultivating procedure. By recording the player's eye gazing and dribbling video sequence, the proposed system can analyze the vision-related behavior to understand the training effectiveness. To demonstrate the proposed VR training system can facilitate the cultivation of vision ability, we recruited 14 experienced players to participate in a 6-week between-subject study, and conducted a study by comparing the most frequently used 2D vision training method called Vision Performance Enhancement (VPE) program with the proposed system. Qualitative experiences and quantitative training results are reported to show that the proposed immersive VR training system can effectively improve player's vision ability in terms of gaze behavior and dribbling stability. Furthermore, training in the VR-VisionCoach Condition can transfer the learned abilities to real scenario more easily than training in the 2D-VPE Condition.

Comparison of computed tomography image features extracted by radiomics, self-supervised learning and end-to-end deep learning for outcome prediction of oropharyngeal cancer.

Background and purpose: To compare the prediction performance of image features of computed tomography (CT) images extracted by radiomics, self-supervised learning and end-to-end deep learning for local control (LC), regional control (RC), locoregional control (LRC), distant metastasis-free survival (DMFS), tumor-specific survival (TSS), overall survival (OS) and disease-free survival (DFS) of oropharyngeal squamous cell carcinoma (OPSCC) patients after (chemo)radiotherapy. Methods and materials: The OPC-Radiomics dataset was used for model development and independent internal testing and the UMCG-OPC set for external testing. Image features were extracted from the Gross Tumor Volume contours of the primary tumor (GTVt) regions in CT scans when using radiomics or a self-supervised learning-based method (autoencoder). Clinical and combined (radiomics, autoencoder or end-to-end) models were built using multivariable Cox proportional-hazard analysis with clinical features only and both clinical and image features for LC, RC, LRC, DMFS, TSS, OS and DFS prediction, respectively. Results: In the internal test set, combined autoencoder models performed better than clinical models and combined radiomics models for LC, RC, LRC, DMFS, TSS and DFS prediction (largest improvements in C-index: 0.91 vs. 0.76 in RC and 0.74 vs. 0.60 in DMFS). In the external test set, combined radiomics models performed better than clinical and combined autoencoder models for all endpoints (largest improvements in LC, 0.82 vs. 0.71). Furthermore, combined models performed better in risk stratification than clinical models and showed good calibration for most endpoints. Conclusions: Image features extracted using self-supervised learning showed best internal prediction performance while radiomics features have better external generalizability.

Clusters of medical specialties around patients with multimorbidity - employing fuzzy c-means clustering to explore multidisciplinary collaboration.

BACKGROUND: Hospital care organization, structured around medical specialties and focused on the separate treatment of individual organ systems, is challenged by the increasing prevalence of multimorbidity. To support the hospitals' realization of multidisciplinary care, we hypothesized that using machine learning on clinical data helps to identify groups of medical specialties who are simultaneously involved in hospital care for patients with multimorbidity. METHODS: We conducted a cross-sectional study of patients in a Dutch general hospital and used a fuzzy c-means clustering algorithm for the analysis. We explored the patients' membership degrees in each cluster to identify subgroups of medical specialties that provide care to the same patients with multimorbidity. We used retrospectively collected electronic health record data from 2017. We extracted data from 22,133 patients aged ≥18 years who had received outpatient clinical care for two or more chronic and/ or oncological diagnoses. RESULTS: We found six clusters of medical specialties and identified 22 subgroups. The clusters were labeled based on the specialties that most characterized them: 1. dermatology/ plastic surgery, 2. six specialties (gynecology/ rheumatology/ orthopedic surgery/ urology/ gastroenterology/ otorhinolaryngology), 3. pulmonology, 4. internal medicine/ cardiology/ geriatrics, 5. neurology/ physiatry (rehabilitation)/ anesthesiology, and 6. internal medicine. Most patients had a full or dominant membership to one of these clusters of medical specialties (11 subgroups), whereas fewer patients had a membership to two clusters. The prevalence of specific diagnosis groups, patient characteristics, and healthcare utilization differed between subgroups. CONCLUSION: Our study shows that clusters and subgroups of medical specialties simultaneously involved in hospital care for patients with multimorbidity can be identified with fuzzy c-means cluster analysis using clinical data. Clusters and subgroups differed regarding the involved medical specialties, diagnoses, patient characteristics, and healthcare utilization. With this strategy, hospitals and medical specialists can further analyze which subgroups are target populations that might benefit from improved multidisciplinary collaboration.

Temporal Lobe Surgery for Epilepsy in a Resource-Limited Vietnamese Cohort.

BACKGROUND: Epilepsy surgery is traditionally difficult to pursue in resource-limited countries but is nevertheless essential in the treatment of medication-refractory, surgically amenable epilepsy. METHODS: With the help of international collaboration, a successful epilepsy program was started in Vietnam. This article comprises a retrospective chart review, combined with prospective longitudinal follow-up of 35 cases of unilateral drug-resistant epilepsy in the temporal lobe who underwent temporal lobectomy, in Viet Duc University Hospital from May 2018 to September 2022. RESULTS: The female/male ratio was 0.6:1, and focal seizures with impaired awareness accounted for 97.14% of patients. Of patients with focal awareness seizures, 51.41% were localized and detected by electroencephalography. Postoperatively, 80% of patients were seizure free (Engel I) at 1 year, and the remaining 20% had worthwhile seizure improvement (Engel II). Postoperative temporal lobe pathology was categorized as follows: mesial temporal sclerosis (48.57%), focal cortical dysplasia (25.71%), and low-grade neoplasms (25.71%). Of patients, 17.14% had postoperative complications (5 infections and 1 transient extremity paresis), and there were no deaths. CONCLUSIONS: Even in low-resource environments, effective and safe surgical care can be provided for drug-resistant epilepsy caused by temporal lobe disease. This study serves as a model of international collaboration and support for future hospitals in low-resource environments to replicate.

A CNN Sound Classification Mechanism Using Data Augmentation.

Sound classification has been widely used in many fields. Unlike traditional signal-processing methods, using deep learning technology for sound classification is one of the most feasible and effective methods. However, limited by the quality of the training dataset, such as cost and resource constraints, data imbalance, and data annotation issues, the classification performance is affected. Therefore, we propose a sound classification mechanism based on convolutional neural networks and use the sound feature extraction method of Mel-Frequency Cepstral Coefficients (MFCCs) to convert sound signals into spectrograms. Spectrograms are suitable as input for CNN models. To provide the function of data augmentation, we can increase the number of spectrograms by setting the number of triangular bandpass filters. The experimental results show that there are 50 semantic categories in the ESC-50 dataset, the types are complex, and the amount of data is insufficient, resulting in a classification accuracy of only 63%. When using the proposed data augmentation method (K = 5), the accuracy is effectively increased to 97%. Furthermore, in the UrbanSound8K dataset, the amount of data is sufficient, so the classification accuracy can reach 90%, and the classification accuracy can be slightly increased to 92% via data augmentation. However, when only 50% of the training dataset is used, along with data augmentation, the establishment of the training model can be accelerated, and the classification accuracy can reach 91%.

Microsurgery for drug resistance epilepsy due to temporal lobe lesions in a resource limited condition: a cross-sectional study.

Epilepsy is a prevalent neurological condition that affects individuals of all ages and genders worldwide. Surgical intervention for drug-resistant epilepsy has been found to improve quality of life, with patient independence being of utmost importance. Methods: The study was a retrospective and prospective cross-sectional study of 35 cases of drug-resistant temporal lobe epilepsy. All patients were operated on by the primary author between May 2018 and September 2022. The study evaluated various factors including clinical characteristics, electroencephalogram, magnetic resonance imaging, surgical outcomes, and histopathology. Results: The success rate of the surgeries (74.3%) is similar to those reported in high-income countries. 51.4% underwent selective amygdalohippocampectomy for cases that localized to the mesial temporal lobe. Lateral/neocortical lesions underwent lesionectomy (48.6%). Our study found a complication rate of 17.1%: meningitis (8.5%), trainset focal paralysis (2.9%), and soft tissue infection (5.7%). There were no mortalities. Conclusions: The article showcases an international collaborative effort that demonstrates the possibility of providing highly effective and safe surgical care for temporal lobe epilepsy even in low-resource environments. The authors hope that this model can be replicated in other areas with similar resource limitations.

User QoS-Based Optimized Handover Algorithm for Wireless Networks.

Due to the development of wireless network technology, various applications relying on good network quality are widely used on mobile devices. Taking the commonly used video streaming service as an example, a network with high throughput and low packet loss rate can meet the service requirements. When the moving distance of the mobile device is greater than the signal coverage of the AP, it will trigger the handover process to connect to another AP, and cause the network to disconnect and reconnect instantaneously. However, frequently triggering the handover procedure will cause a significant drop in network performance and affect the operation of application services. In order to solve this problem, this paper proposes the OHA and OHAQR. The OHA considers whether the signal quality is good or bad, and uses the corresponding HM method to solve the problem of frequent handover procedures. The OHAQR integrates the QoS requirements of the throughput and packet loss rate into the OHA with the Q-handover score, to provide high-performance handover services with QoS. Our experimental results show that the OHA and OHAQR have 13 and 15 handovers in a high-density scenario, respectively, and are better than the other two methods. The actual throughput and packet loss rate of the OHAQR are 123 Mbps and 5%, respectively, and the network performance is better than that of other methods. The proposed method shows excellent performance in ensuring the network QoS requirements and reducing the number of handover procedures.

Malignant cerebral edema after cranioplasty, a rare complication: case series and literature review.

Cranioplasty is standard neurosurgery performed after decompressive craniectomy. Fatal malignant cerebral oedema complications associated with this procedure are rare and clinically distinct, although unpredictable. It is thought that the pressure difference from removing atmospheric pressure had a long-term effect on the brain. This combined with the negative pressure applied by intraoperative pressure drainage may impact the perfusion brain. Here, the authors report four cases of cerebral oedema after cranioplasty and review similar cases in the literature. Case presentation: The authors report on four cases of patients who underwent cranioplasty following decompressive craniotomy and subsequently died after surgery. Three of the patients had undergone craniotomy following trauma, while one patient had skull resorption. All four patients developed cerebral oedema immediately after surgery and exhibited significant craniofacial depression (also known as sunk flap syndrome). A negative pressure drainage system was utilized in all cases. One patient remained intubated, while the remaining three developed postoperative epilepsy and subsequently fell into a coma. Dilated and fixed pupils were observed in all patients, and computed tomography scans revealed diffuse cerebral oedema. Despite intensive resuscitation efforts and attempts at decompression, all four patients ultimately succumbed to their conditions. Conclusion: Fatal post-cranioplasty malignant cerebral oedema is a rare but very dangerous complication. Despite being rare, neurosurgeons should be aware that this fatal complication can occur after cranioplasty.

Intraoperative endoscope view classification of neurovascular compression in hemifacial spasm condition: a single neurosurgeon prospective cross-sectional study.

Hemifacial spasm is a neurological disorder that causes involuntary contractions of facial muscles on one side of the face. This study aims to analyze the intraoperative pattern of neurovascular compression (NVC) and discuss relevant decompression techniques for 29 patients with hemifacial spasm who underwent endoscopy-assisted microvascular decompression (EAMVD). Patients and Methods: This was a prospective, single center, single neurosurgeon, cross-sectional study conducted from November 2020 to August 2022. All patients received EAMVD, and the NVC culprit vessel, compression site, severity, and type were analyzed using a 30-degree endoscope. Results: All 29 patients had successful interposition EAMVD without postoperative symptoms. The most common NVC site was REX (18 in 29 cases), the most common vessel to compress the seventh nerve was AICA (23 in 29 cases), while the most common type of NVC was loop (22 in 29 cases). NVC severity: 17 cases of mild compression, 4 cases of moderate compression, and 8 cases of severe compression. Without an angled telescope, we will miss the NVC in 12 cases (41.3%). Conclusion: EAMVD using an angled endoscope is a promising technique for treating hemifacial spasm. Intraoperative analysis of NVC can lead to a better understanding of the patterns of compression and may help in selecting appropriate decompression techniques.

Chemical investigations and cytotoxic effects of metabolites from Antrodia camphorata against human hepatocellular carcinoma cells.

Antrodia camphorata is used as a medicinal fungus in Taiwan to treat fatigue, food intoxication, and enhance liver function. Here we identified fermented metabolic components from the mycelium of A. camphorata KH37 and explored their anti-hepatoma potentials with study models of human hepatoblastoma cell lines. Bioassay-guided fractionation of the solid fermentation powder of A. camphorata KH37 led to the isolation of one new quinonol, antroquinonol Z (1), and nine known compounds (2-10). Treatment with 10 µM antrocamols LT1 (2) or LT3 (3) reduced cell viability of HepG2 and Huh-7 cells to about 60% in 48 hours. Antroquinonol Z (1) exhibited mild cytotoxicity against Huh-7 cells in 48 and 72 hours. Interestingly, two fractions showed cytotoxicity in HepG2 and Huh-7 cells, even better than compounds isolated from these fractions. The significant cytotoxicity of partially purified samples from A. camphorata KH37 exhibited a potential for developing alternative or complementary therapeutics against hepatoma.

Image-Based OA-Style Paper Pop-Up Design via Mixed-Integer Programming.

Origami architecture (OA) is a fascinating papercraft that involves only a piece of paper with cuts and folds. Interesting geometric structures 'pop up' when the paper is opened. However, manually designing such a physically valid 2D paper pop-up plan is challenging since fold lines must jointly satisfy hard spatial constraints. Existing works on automatic OA-style paper pop-up design all focused on how to generate a pop-up structure that approximates a given target 3D model. This article presents the first OA-style paper pop-up design framework that takes 2D images instead of 3D models as input. Our work is inspired by the fact that artists often use 2D profiles to guide the design process, thus benefited from the high availability of 2D image resources. Due to the lack of 3D geometry information, we perform novel theoretic analysis to ensure the foldability and stability of the resultant design. Based on a novel graph representation of the paper pop-up plan, we further propose a practical optimization algorithm via mixed-integer programming that jointly optimizes the topology and geometry of the 2D plan. We also allow the user to interactively explore the design space by specifying constraints on fold lines. Finally, we evaluate our framework on various images with interesting 2D shapes. Experiments and comparisons exhibit both the efficacy and efficiency of our framework.

The Effect of Homogenization Heat Treatment on 316L Stainless Steel Cast Billet.

This investigation aims to analyze the effect of homogenization heat treatment at 1240 °C for 2 and 6 h on the hardness, distribution, morphology, and chemical composition of the δ-ferrite and sigma phases in 316L stainless steel cast billet. A field emission scanning electron microscope, combined with electron back-scattered diffraction, a field emission electron probe microanalyzer with a wavelength dispersive spectrometer, and a Vickers microhardness tester are applied to identify various phase evolutions in the cast billet. The morphology of the δ-ferrite and sigma phases in the austenite matrix of the 316L cast billet are strongly related to the subsequent hot and cold wire drawings. The homogenization heat treatment is expected to provide a driving force to form spheroid interdendritic δ-ferrite and to minimize the amount of the brittle sigma intermetallic compound in the austenite matrix. The homogenization heat treatment at 1240 °C effectively spheroidized all δ-ferrites into blunt ones in the cast billet. The transformation of δ-ferrite into sigma is dominated by temperature and cooling rate. The fast air cooling after homogenization between 1240 and 850 °C retards the precipitation of the sigma in the δ-ferrite. There are two δ-ferrite transformation mechanisms in this experiment. The direct transformation of the δ-ferrite into sigma is observed in the as-cast 316L stainless steel billet. In contrast, the eutectoid transformation of the δ-ferrite into the sigma and austenite dominates the 316L cast billet homogenized at 1240 °C, with a slow furnace cooling rate.

2,3,5,4'-Tetrahydroxystilbene-2-O-ß-D-Glucoside improves female ovarian aging.

Reduced fertility associated with normal aging may reflect the over-maturity of oocytes. It is increasingly important to reduce aging-induced infertility since recent trends show people marrying at later ages. 2,3,5,4'-Tetrahydroxystilbene-2-O-ß-D-glucoside (THSG), a polyphenol extracted from Polygonum multiflorum, has been reported to have anti-inflammatory and anti-aging properties. To evaluate whether THSG can reduce aging-related ovarian damage in a female mouse model of aging, THSG was administered by gavage at a dose of 10 mg/kg twice weekly, starting at 4 weeks of age in a group of young mice. In addition, the effect of THSG in a group of aged mice was also studied in mice starting at 24 weeks of age. The number of oocytes in the THSG-fed group was higher than in the untreated control group. Although the percentage of secondary polar bodies (PB2) decreased during aging in the THSG-fed group, it decreased much more slowly than in the age-matched control group. THSG administration increased the quality of ovaries in young mice becoming aged. Western blotting analyses also indicated that CYP19, PR-B, and ER-ß expressions were significantly increased in 36-week-old mice. THSG also increased oocyte numbers in aged mice compared to mice without THSG fed. Studies of qPCR and immunohistochemistry (IHC) analyses of ovaries in the aged mice groups were conducted. THSG increased gene expression of anti-Müllerian hormone (AMH), a biomarker of oocyte number, and protein accumulation in 40-week-old mice. THSG increased the expression of pgc1α and atp6, mitochondrial biogenesis-related genes, and their protein expression. THSG also attenuated the fading rate of CYP11a and CYP19 associated with sex hormone synthesis. And THSG maintains a high level of ER-ß expression, thereby enhancing the sensitivity of estrogen. Our findings indicated that THSG increased or extended gene expression involved in ovarian maintenance and rejuvenation in young and aged mice. On the other hand, THSG treatments significantly maintained oocyte quantity and quality in both groups of young and aged mice compared to each age-matched control group. In conclusion, THSG can delay aging-related menopause, and the antioxidant properties of THSG may make it suitable for preventing aging-induced infertility.

COVID-19 and Virtual Nutrition: A Pilot Study of Integrating Digital Food Models for Interactive Portion Size Education.

Background and aims: Digital food viewing is a vital skill for connecting dieticians to e-health. The aim of this study was to integrate a novel pedagogical framework that combines interactive three- (3-D) and two-dimensional (2-D) food models into a formal dietetic training course. The level of agreement between the digital food models (first semester) and the effectiveness of educational integration of digital food models during the school closure due to coronavirus disease 2019 (COVID-19) (second semester) were evaluated. Method: In total, 65 second-year undergraduate dietetic students were enrolled in a nutritional practicum course at the School of Nutrition and Health Sciences, Taipei Medical University (Taipei, Taiwan). A 3-D food model was created using Agisoft Metashape. Students' digital food viewing skills and receptiveness towards integrating digital food models were evaluated. Results: In the first semester, no statistical differences were observed between 2-D and 3-D food viewing skills in food identification (2-D: 89% vs. 3-D: 85%) and quantification (within ±10% difference in total calories) (2-D: 19.4% vs. 3-D: 19.3%). A Spearman correlation analysis showed moderate to strong correlations of estimated total calories (0.69~0.93; all p values < 0.05) between the 3-D and 2-D models. Further analysis showed that students who struggled to master both 2-D and 3-D food viewing skills had lower estimation accuracies than those who did not (equal performers: 28% vs. unequal performers:16%, p = 0.041), and interactive 3-D models may help them perform better than 2-D models. In the second semester, the digital food viewing skills significantly improved (food identification: 91.5% and quantification: 42.9%) even for those students who struggled to perform digital food viewing skills equally in the first semester (equal performers: 44% vs. unequal performers: 40%). Conclusion: Although repeated training greatly enhanced students' digital food viewing skills, a tailored training program may be needed to master 2-D and 3-D digital food viewing skills. Future study is needed to evaluate the effectiveness of digital food models for future "eHealth" care.

Endoscopic assisted microvascular decompression for vertebral artery - Associated hemifacial spasm - A case report.

Introduction: and importance: Vertebral-artery associated hemifacial spasm is rare. Microvascular decompression (MVD) of hemifacial spasm (HFS) associated with the vertebral artery (VA) shows high rates of incomplete cure and complications compared to non-VA-related HFS. Case presentation: A 39-year-old male who presented with a 2-year history of progressive left-sided typical HFS. Endoscopic assisted MVD for VA-associated HFS via a retro-sigmoid keyhole was performed. Neurovascular conflicts by both the VA and the AICA around the root exit zone of the facial nerve in sandwich type were successfully decompressed. Clinical discussion: Vertebral-artery associated hemifacial spasm is challenging. With the assistance of endoscopy, multiple neurovascular conflicts were clearly demonstrated without significant cerebellar retraction. The VA and AICA were safely interposed with preservation of perforators under excellent view. Conclusion: Endoscopic assisted MVD offers reliable decompression with minimum invasiveness in case of VA-associated HFS with multiple compressions.

Role of Integrin αvß3 in Doxycycline-Induced Anti-Proliferation in Breast Cancer Cells.

Doxycycline, an antibiotic, displays the inhibition of different signal transduction pathways, such as anti-inflammation and anti-proliferation, in different types of cancers. However, the anti-cancer mechanisms of doxycycline via integrin αvß3 are incompletely understood. Integrin αvß3 is a cell-surface anchor protein. It is the target for estrogen, androgen, and thyroid hormone and plays a pivotal role in the proliferation, migration, and angiogenic process in cancer cells. In our previous study, thyroxine hormones can interact with integrin αvß3 to activate the extracellular signal-regulated kinase 1/2 (ERK1/2), and upregulate programmed death-ligand 1 (PD-L1) expression. In the current study, we investigated the inhibitory effects of doxycycline on proliferation in two breast cancer cell lines, MCF-7 and MDA-MB-231 cells. Doxycycline induces concentration-dependent anti-proliferation in both breast cancer cell lines. It regulates gene expressions involved in proliferation, pro-apoptosis, and angiogenesis. Doxycycline suppresses cell cyclin D1 (CCND1) and c-Myc which play crucial roles in proliferation. It also inhibits PD-L1 gene expression. Our findings show that modulation on integrin αvß3 binding activities changed both thyroxine- and doxycycline-induced signal transductions by an integrin αvß3 inhibitor (HSDVHK-NH2). Doxycycline activates phosphorylation of focal adhesion kinase (FAK), a downstream of integrin, but inhibits the ERK1/2 phosphorylation. Regardless, doxycycline-induced FAK phosphorylation is blocked by HSDVHK-NH2. In addition, the specific mechanism of action associated with pERK1/2 inhibition via integrin αvß3 is unknown for doxycycline treatment. On the other hand, our findings indicated that inhibiting ERK1/2 activation leads to suppression of PD-L1 expression by doxycycline treatment. Furthermore, doxycycline-induced gene expressions are disturbed by a specific integrin αvß3 inhibitor (HSDVHK-NH2) or a mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinases (ERK) kinase (MAPK/ERK, MEK) inhibitor (PD98059). The results imply that doxycycline may interact with integrin αvß3 and inhibits ERK1/2 activation, thereby regulating cell proliferation and downregulating PD-L1 gene expression in estrogen receptor (ER)-negative breast cancer MDA-MB-231 cells.

Heteronemin and tetrac derivatives suppress non-small cell lung cancer growth via ERK1/2 inhibition.

The most common cancer, lung cancer, causes deaths worldwide. Most lung cancer patients have non-small cell lung carcinomas (NSCLCs) with a poor prognosis. The chemotherapies frequently cause resistance therefore search for new effective drugs for NSCLC patients is an urgent and essential issue. Deaminated thyroxine, tetraiodothyroacetic acid (tetrac), and its nano-analogue (NDAT) exhibit antiproliferative properties in several types of cancers. On the other hand, the most abundant secondary metabolite in the sponge Hippospongia sp., heteronemin, shows effective cytotoxic activity against different types of cancer cells. In the current study, we investigated the anticancer effects of heteronemin against two NSCLC cell lines, A549 and H1299 cells in vitro. Combined treatment with heteronemin and tetrac derivatives synergistically inhibited cancer cell growth and significantly modulated the ERK1/2 and STAT3 pathways in A549 cells but only ERK1/2 in H1299 cells. The combination treatments induce apoptosis via the caspases pathway in A549 cells but promote cell cycle arrest via CCND1 and PCNA inhibition in H1299 cells. In summary, these results suggest that combined treatment with heteronemin and tetrac derivatives could suppress signal transduction pathways essential for NSCLC cell growth. The synergetic effects can be used potentially as a therapeutic procedure for NSCLC patients.