BHLHE41/DEC2 Expression Induces Autophagic Cell Death in Lung Cancer Cells and Is Associated with Favorable Prognosis for Patients with Lung Adenocarcinoma.

Lung cancer constitutes a threat to human health. BHLHE41 plays important roles in circadian rhythm and cell differentiation as a negative regulatory transcription factor. This study investigates the role of BHLHE41 in lung cancer progression. We analyzed BHLHE41 function via in silico and immunohistochemical studies of 177 surgically resected non-small cell lung cancer (NSCLC) samples and 18 early lung squamous cell carcinoma (LUSC) cases. We also examined doxycycline (DOX)-inducible BHLHE41-expressing A549 and H2030 adenocarcinoma cells. BHLHE41 expression was higher in normal lung than in lung adenocarcinoma (LUAD) tissues and was associated with better prognosis for the overall survival (OS) of patients. In total, 15 of 132 LUAD tissues expressed BHLHE41 in normal lung epithelial cells. Staining was mainly observed in adenocarcinoma in situ and the lepidic growth part of invasive cancer tissue. BHLHE41 expression constituted a favorable prognostic factor for OS (p = 0.049) and cause-specific survival (p = 0.042) in patients with LUAD. During early LUSC, 7 of 18 cases expressed BHLHE41, and this expression was inversely correlated with the depth of invasion. DOX suppressed cell proliferation and increased the autophagy protein LC3, while chloroquine enhanced LC3 accumulation and suppressed cell death. In a xenograft model, DOX suppressed tumor growth. Our results indicate that BHLHE41 expression prevents early lung tumor malignant progression by inducing autophagic cell death in NSCLC.

Noninvasive molecular diagnosis of craniopharyngioma with MRI-based radiomics approach.

BACKGROUND: Frequent somatic mutations of BRAF and CTNNB1 were identified in both histological subtypes of craniopharyngioma (adamantinomatous and papillary) which shed light on target therapy to cure this oncogenic disease. The aim of this study was to investigate the noninvasive MRI-based radiomics diagnosis to detect BRAF and CTNNB1 mutations in craniopharyngioma patients. METHODS: Forty-four patients pathologically diagnosed as adamantinomatous craniopharyngioma (ACP) or papillary craniopharyngioma (PCP) were retrospectively studied. High-throughput features were extracted from manually segmented tumors in MR images of each case. The modifications-robustness in region of interests and Random Forest-based feature selection methods were adopted to select the most significant features. Random forest classifier with 10-fold cross-validation was applied to build our radiomics model. RESULTS: Four features were selected to make pathological diagnosis between ACP and PCP with area under the receiver operating characteristic curve (AUC) of 0.89, accurancy (ACC) of 0.86, sensitivity (SENS) of 0.89 and specificity (SPEC) of 0.85. The other two features were applied to estimate BRAF V600E mutation with AUC of 0.91, ACC of 0.93, SENS of 0.83 and SPEC of 0.97. Accurate predication of CTNNB1 mutation by three selected features was realized with AUC of 0.93, ACC of 0.86, SENS of 0.86 and SPEC of 0.86. CONCLUSIONS: We developed a reliable MRI-based radiomics approach to perform pathological and molecular diagnosis in craniopharyngioma patients with considerably accurate prediction, which could offer potential guidance for clinical decision-making.

Development and Experimental Validation of a Dry Non-Invasive Multi-Channel Mouse Scalp EEG Sensor through Visual Evoked Potential Recordings.

In this paper, we introduce a dry non-invasive multi-channel sensor for measuring brainwaves on the scalps of mice. The research on laboratory animals provide insights to various practical applications involving human beings and other animals such as working animals, pets, and livestock. An experimental framework targeting the laboratory animals has the potential to lead to successful translational research when it closely resembles the environment of real applications. To serve scalp electroencephalography (EEG) research environments for the laboratory mice, the dry non-invasive scalp EEG sensor with sixteen electrodes is proposed to measure brainwaves over the entire brain area without any surgical procedures. We validated the proposed sensor system with visual evoked potential (VEP) experiments elicited by flash stimulations. The VEP responses obtained from experiments are compared with the existing literature, and analyzed in temporal and spatial perspectives. We further interpret the experimental results using time-frequency distribution (TFD) and distance measurements. The developed sensor guarantees stable operations for in vivo experiments in a non-invasive manner without surgical procedures, therefore exhibiting a high potential to strengthen longitudinal experimental studies and reliable translational research exploiting non-invasive paradigms.

Robotic Pills as Innovative Personalized Medicine Tools: A Mini Review.

The most common route for drug administration is the oral route due to the various advantages offered by this route, such as ease of administration, controlled and sustained drug delivery, convenience, and non-invasiveness. In spite of this, oral drug absorption faces challenges due to various issues related to its stability, permeability and solubility in the GI tract. Biologic drugs generally face problems when administered by oral route as they are readily degradable and thus required to be injected. To overcome these issues in oral absorption, different approaches like novel drug delivery systems and newer pharmaceutical technologies have been adopted. With a combined knowledge of drug delivery and pharmaceutical technology, robotic pills can be designed and used successfully to enhance the adhesion and permeation of drugs through the mucus membrane of the GI tract to achieve drug delivery at the target site. The potential application of robotic pills in diagnosis and drug dispensing is also discussed. The review highlights recent developments in robotic pill drug-device technology and discusses its potential applications to solve the problems and challenges in oral drug delivery.

Association Between Skin Autofluorescence and White Blood Cell Counts in Older Adults.

BACKGROUND/AIM: Advanced glycation end products (AGEs) accumulate in the body with increasing age. However, their excessive accumulation may lead to various inflammatory and chronic diseases. While it is common for older adults to experience various comorbidities, there is a scarcity of published literature documenting the specific impact of ageing and comorbidities on AGEs in this population. The present study aimed to retrospectively evaluate the correlation among AGEs in the skin, calendar age, and comorbidities in older adults. PATIENTS AND METHODS: Accumulated AGEs in the skin were assessed by non-invasive measurement of skin autofluorescence (SAF) inside the forearm. This retrospective study included individuals who underwent SAF measurements at Shujitsu University Community Pharmacy with or without a prescription from October 2019 to October 2021. Subsequently, the associations between SAF, calendar age, comorbidities, and blood test parameters were investigated. RESULTS: SAF showed a positive correlation with calendar age for all enrolled participants; the correlation weakened for participants aged ≥50 years and plateaued for those aged ≥60 years. Furthermore, we observed a significant increase in SAF among all participants with comorbidities compared to those without comorbidities. By contrast, among participants aged ≥50 years, SAF did not show a significant association with comorbidities. However, SAF was significantly positively correlated with white blood cell (WBC) counts in these aged populations. CONCLUSION: The non-invasive assessment of SAF holds promise in evaluating changes in the physical condition associated with WBC counts among older adults.

Emerging Applications of Liquid Biopsies in Ovarian Cancer.

Liquid biopsy is a new diagnostic tool in precision oncology that can be used as a complementary or alternative method to surgical biopsies. It is a cutting-edge sampling technique that examines distinct cancer components, such as exosomes and circulating tumor cells discharged into the peripheral circulation, to identify tumor biomarkers through various methods, including polymerase chain reaction (PCR). Liquid biopsy has several benefits, including its non-invasiveness and practicality, which permit serial sampling and long-term monitoring of dynamic tumor changes. Ovarian cancer (OC), the most lethal gynecologic malignancy in the world, is typically diagnosed at stages II and III, which makes recovery and treatment extremely difficult. Relapsed OC and chemotherapy resistance of ovarian tumor cells are other clinical challenges. Although liquid biopsy is not a routinely used diagnostic test, it should be utilized in the diagnosis and prognosis of OC for early detection and treatment. It is less intrusive than conventional tissue biopsies, allowing for the continuous collection of serial blood samples to track cancer development in real time. Before therapeutic application, more investigation is required to pinpoint the particular release processes, the source tissue, and the biological significance of the bulk of liquid biopsy contents.

Device-Based Therapy for Resistant Hypertension: An Up-to-Date Review.

Hypertension is the major risk factor for cardiovascular morbidity and mortality. Matter of fact, untreated hypertension can worsen the overall health, whereas pharmacotherapy can play an important role in lowering the risk of high blood pressure in hypertensive patients. However, persistent uncontrolled hypertension remains an unsolved condition characterized by non-adherence to medication and increased sympathetic activity. This paper will review the non-pharmacological treatments for resistant hypertension (RH) that have emerged in recent years. In addition, the technologies developed in device-based RH therapy, as well as the clinical trials that support their use, will be discussed. Indeed, the novel device-based approaches that target RH present a promising therapy which has been supported by several studies and clinical trials, whereas drug non-adherence and high sympathetic activity are known to be the main causes of RH. Nevertheless, some additional aspects of these RH systems need to be tested in the near future, with a particular focus on the device's design and availability of randomized controlled trials.

500 Cases of High-intensity Focused Ultrasound (HIFU) Ablated Uterine Fibroids and Adenomyosis.

OBJECTIVE: Clinical outcomes of 500 high-intensity focused ultrasound (HIFU)-treated uterine fibroids and adenomyosis are analyzed and presented. MATERIALS AND METHODS: This is a retrospective cross-sectional analysis from a single tertiary medical center. From April 2015 to October 2018, 546 cases were enrolled for the study. After excluding 46 patients with less than 3 months of follow-up period, there were 404 fibroids, 149 adenomyosis and 53 mixed conditions entered for analysis. The patients' uterine fibroids and adenomyosis were treated by HIFU according to Chongqing Haifu protocol, with 12 cm diameter transducer of focal length 10-16  cm at 0.8 or 1.6 MHz T2-weight MRI imaging was rendered prior to and 3 month post treatment to assess lesion volume change using non-perfusion volume, which was the primary outcome. Secondary outcomes including quality of life, subjective satisfaction, adverse events and pregnancy rate were determined using self-reported questionnaires. The mean follow up period ranged from 3 to 38 months with an average of 21 months. RESULTS: Three months after HIFU-treated uterine fibroids and adenomyosis, the lesion size reduced 40.2% and 46.3%, respectively. Symptoms all improved with better quality of life for the fibroid group, while those with adenomyosis or combined diseases benefit the most from pain control. Serum CA125 decreased significantly for all studied groups, and LDH only showed improvement for fibroids group. Number of adverse events is comparable to Chongqing data (approximately 10.2%), with mostly mild and self-resolving conditions. No permanent sequelae or death was documented. Twelve pregnancies are reported in this cohort. CONCLUSION: HIFU is safe and effective in treating uterine fibroids and adenomyosis. The results are reproducible if standardized treatment schedules are followed. It is a promising treatment alternative with the advantages of precision, non-invasiveness, rapid recovery and readiness for pregnancy.

Detection of Clinical Mesenchymal Cancer Cells from Bladder Wash Urine for Real-Time Detection and Prognosis.

Bladder cancer (BC) is a disease that requires lifelong surveillance due to its high recurrence rate. An efficient method for the non-invasive rapid monitoring of patient prognosis and downstream phenotype characterization is warranted. Here, we develop an integrated procedure to detect aggressive mesenchymal exfoliated bladder cancer cells (EBCCs) from patients in a label-free manner. Using a combination of filtration and inertial focusing principles, the procedure allowed the focusing of EBCCs in a single stream-line for high-throughput separation from other urine components such as large squamous cells and blood cells using a microfluidic sorting device. Characterization of enriched cells can be completed within hours, suggesting a potential utility for real-time detection. We also demonstrate high efficiency of cancer cell recovery (93.3 ± 4.8%) and specific retrieval of various epithelial to mesenchymal transition (EMT) phenotype cell fractions from respective outlets of the microfluidic device. EMT is closely associated with metastasis, drug resistance and tumor-initiating potential. This procedure is validated with clinical samples, and further demonstrate the efficacy of bladder wash procedure to reduce EBCCs counts over time. Overall, the uniqueness of a rapid and non-invasive method permitting the separation of different EMT phenotypes shows high potential for clinical utility. We expect this approach will better facilitate the routine screening procedure in BC and greatly enhance personalized treatment.

The progressive role of acoustic cavitation for non-invasive therapies, contrast imaging and blood-tumor permeability enhancement.

INTRODUCTION: Drug delivery pertaining to acoustic cavitation generated from ultrasonic (US) irradiation is advantageous for devising smarter and more advanced therapeutics. The aim is to showcase microbubbles as drug carriers and robust theranostic for non-invasive therapies across diverse biomedical disciplines, highlighting recent technologies in this field for overcoming the blood-brain barrier (BBB) to treat cancers and neurological disorders. AREAS COVERED: This article reviews work on the optimized tuning of ultrasonic parameters, sonoporation, transdermal and responsive drug delivery, acoustic cavitation in vasculature and oncology, contrast imaging for real-time magnification of cell-microbubble dynamics and biomolecular targeting. Scholarly literature was sought through database search on key terminology, latest topics, reputable experts and established journals over the last five years. EXPERT OPINION: Cavitation offers immense promise in overcoming current diffusion and convection limitations for treating skull/brain/vascular/tissue injuries and ablating tumors to minimize chronic/acute effects. Since stable cavitation facilitates the restoration of US-opened BBB and the modulation of drug concentration, US equipment with programmable imaging modality and sensitivity are envisaged to create safer miniaturized devices for personalized care. Due to differing biomedical protocols with regard to specific medical conditions, quantitative and qualitative controls are mandatory before translation to real-life clinical applications can be accomplished.

DNA Methylation at the Novel CpG Sites in the Promoter of MED15/PCQAP Gene as a Biomarker for Head and Neck Cancers.

Head and neck cancers (HNCs) represent a significant and ever-growing burden to the modern society, mainly due to the lack of early diagnostic methods. A significant number of HNCs is often associated with drinking, smoking, chewing beetle nut, and human papilloma virus (HPV) infections. We have analyzed DNA methylation patterns in tumor and normal tissue samples collected from head and neck squamous cell carcinoma (HNSCC) patients who were smokers. We have identified novel methylation sites in the promoter of the mediator complex subunit 15 (MED15/PCQAP) gene (encoing a co-factor important for regulation of transcription initiation for promoters of many genes), hypermethylated specifically in tumor cells. Two clusters of CpG dinucleotides methylated in tumors, but not in normal tissue from the same patients, were identified. These CpG methylation events in saliva samples were further validated in a separate cohort of HNSCC patients (who developed cancer due to smoking or HPV infections) and healthy controls using methylation-specific PCR (MSP). We used saliva as a biological medium because of its non-invasive nature, close proximity to the tumors, easiness and it is an economically viable option for large-scale screening studies. The methylation levels for the two identified CpG clusters were significantly different between the saliva samples collected from healthy controls and HNSCC individuals (Welch's t-test returning P < 0.05 and Mann-Whitney test P < 0.01 for both). The developed MSP assays also provided a good discriminative ability with AUC values of 0.70 (P < 0.01) and 0.63 (P < 0.05). The identified novel CpG methylation sites may serve as potential non-invasive biomarkers for detecting HNSCC.