Abnormal Cells Research Articles

Abstract PO-019: Ubiquitin E3 ligase OSTM1 regulates the cAMP/PKA/CREB pathway and suppresses B-cell malignancies

Abstract B-cell malignancies (BCM) often arise from genomic alterations introduced during different stages of B-cell development. Here, we performed a whole genome targeting CRISPR/Cas9 screen in the immortalized yet non-transformed IL-3-dependent Ba/F3 murine pro-B cell line to identify genes whose loss confers IL-3 independence, reasoning that these genes may function as tumor suppressor genes (TSGs) in BCM. One of the candidate genes is osteoporosis-associated transmembrane protein 1 (OSTM1), an E3 ubiquitin ligase whose loss-of-function causes autosomal recessive osteoporosis. Informatics analysis of patient data showed that OSTM1 is frequently deleted across BCM, which co-occurs with the deletion of a well-characterized TSG Cdkn2a. Genetic silencing of OSTM1 in Ba/F3 cells conferred IL-3-independent survival and proliferation, as well as splenomegaly, lymphadenopathy, and abnormal peripheral blood cell count, indicative of transformation in vivo. Using mass spectrometry screens, we identified phosphodiesterase 3B (PDE3B) as an interacting partner of OSTM1. OSTM1 ubiquitylates PDE3B and promotes its proteasomal degradation. The OSTM1-PDE3B interaction and PDE3B degradation are negatively regulated by OSTM1 N-glycosylation. As PDE3B catalyzes the conversion of cAMP to AMP, it negatively regulates the cAMP-dependent PKA/CREB/CREBBP tumor suppressive pathway. Indeed, overexpression of PDE3B accelerated cell proliferation while PDE3B silencing in OSTM1 KO cells reversed the transformation phenotype in cell lines and in mouse allograft tumors. Importantly, a strong correlation between OSTM1 disruption, increased PDE3B stability, and decreased PKA/CREB/CEBBP signaling was observed in cell lines and in BCM patient datasets. Finally, CD19-Cre mediated B-cell specific ablation of OSTM1 cooperated with CDKN2A deletion to drive spontaneous immature B-cell lymphomagenesis in mice. Collectively, these results indicate that OSTM1 is a novel TSG which targets PDE3B for proteasomal degradation. Loss of OSTM1 enhances PDE3B stability and abrogates the tumor-suppressive role of cAMP/CREB/CREBBP pathway which promotes BCM. Citation Format: Muhammad Usama Tariq, Julia Shen, Jaeyong Jung, Namratha Sheshadri, Junrong Yan, Rongrong Li, Kevin Lu, Tong Liu, Hong Li, Yue Lynn Wang, Ping Xie, Wei-Xing Zong. Ubiquitin E3 ligase OSTM1 regulates the cAMP/PKA/CREB pathway and suppresses B-cell malignancies [abstract]. In: Proceedings of the Fourth AACR International Meeting on Advances in Malignant Lymphoma: Maximizing the Basic-Translational Interface for Clinical Application; 2024 Jun 19-22; Philadelphia, PA. Philadelphia (PA): AACR; Blood Cancer Discov 2024;5(3_Suppl):Abstract nr PO-019.

Exploring the Role of Clustered Mutations in Carcinogenesis and Their Potential Clinical Implications in Cancer.

Abnormal cell proliferation and growth leading to cancer primarily result from cumulative genome mutations. Single gene mutations alone do not fully explain cancer onset and progression; instead, clustered mutations-simultaneous occurrences of multiple mutations-are considered to be pivotal in cancer development and advancement. These mutations can affect different genes and pathways, resulting in cells undergoing malignant transformation with multiple functional abnormalities. Clustered mutations influence cancer growth rates, metastatic potential, and drug treatment sensitivity. This summary highlights the various types and characteristics of clustered mutations to understand their associations with carcinogenesis and discusses their potential clinical significance in cancer. As a unique mutation type, clustered mutations may involve genomic instability, DNA repair mechanism defects, and environmental exposures, potentially correlating with responsiveness to immunotherapy. Understanding the characteristics and underlying processes of clustered mutations enhances our comprehension of carcinogenesis and cancer progression, providing new diagnostic and therapeutic approaches for cancer.

Leukemic Stem Cells and Hematological Malignancies.

The association between leukemic stem cells (LSCs) and leukemia development has been widely established in the context of genetic alterations, epigenetic pathways, and signaling pathway regulation. Hematopoietic stem cells are at the top of the bone marrow hierarchy and can self-renew and progressively generate blood and immune cells. The microenvironment, niche cells, and complex signaling pathways that regulate them acquire genetic mutations and epigenetic alterations due to aging, a chronic inflammatory environment, stress, and cancer, resulting in hematopoietic stem cell dysregulation and the production of abnormal blood and immune cells, leading to hematological malignancies and blood cancer. Cells that acquire these mutations grow at a faster rate than other cells and induce clone expansion. Excessive growth leads to the development of blood cancers. Standard therapy targets blast cells, which proliferate rapidly; however, LSCs that can induce disease recurrence remain after treatment, leading to recurrence and poor prognosis. To overcome these limitations, researchers have focused on the characteristics and signaling systems of LSCs and therapies that target them to block LSCs. This review aims to provide a comprehensive understanding of the types of hematopoietic malignancies, the characteristics of leukemic stem cells that cause them, the mechanisms by which these cells acquire chemotherapy resistance, and the therapies targeting these mechanisms.

USP22 is required for human endometrial stromal cell proliferation and decidualization by deubiquitinating FoxM1

Despite significant advances in assisted reproductive technology (ART), recurrent implantation failure (RIF) still occurs in some patients. Poor endometrial receptivity and abnormal human endometrial stromal cell (HESC) proliferation and decidualization have been identified as the major causes. Ubiquitin-specific protease 22 (USP22) has been reported to participate in the decidualization of endometrial stromal cells in mice. However, the role of USP22 in HESC function and RIF development remains unknown. In this study, clinical endometrial tissue samples were gathered to investigate the involvement of USP22 in RIF, and HESCs were utilized to examine the molecular mechanisms of USP22 and Forkhead box M1 (FoxM1). The findings indicated a high expression of USP22 in the secretory phase of the endometrium. Knockdown of USP22 led to a notable reduction in the proliferation and decidualization of HESCs, along with a decrease in FoxM1 expression, while overexpression of USP22 yielded opposite results. Furthermore, USP22 was found to deubiquitinate FoxM1 in HESCs. Moreover, both USP22 and FoxM1 were downregulated in the endometria of patients with RIF. In conclusion, these results suggest that USP22 may have a significant impact on HESCs proliferation and decidualization through its interaction with FoxM1, potentially contributing to the underlying mechanisms of RIF pathogenesis.

Confined placental mosaicism: Distribution of chromosomally abnormal cells over the term placenta

ObjectiveNon-invasive prenatal testing (NIPT) investigates placental DNA and may detect confined placental mosaicism (CPM). The aim of this study was to confirm CPM in the term placenta in cases with abnormal NIPT but normal follow-up cytogenetic studies of fetus and mother. Additionally we examined the distribution of abnormal cells over the placenta. MethodsFour chorionic villus (CV) biopsies from four placental quadrants were requested in cases where CPM was assumed. Both cell lineages of the CV, cytotrophoblast (CTB) and mesenchymal core (MC), were analyzed separately with SNP array. ResultsThe chromosome aberration was confirmed in 67 % of the placentas. Three quarters of the CTB and MC biopsies from these mosaic placentas were uniformly normal (57 %) or abnormal (20 %), and a minority showed mosaicism. Among 16 cases of CPM where first trimester CV were examined as well, 11 had chromosomally normal results during pregnancy. DiscussionCytogenetic investigations of term placental biopsies suspected to be affected with CPM did not reveal the chromosome aberration in one third of the placentas. This is caused by the patchy pattern in which chromosomally abnormal cells are distributed over the placenta with the majority of the biopsies being uniformly normal. Further CPM research, including its clinical impact, requires the analysis of more than four biopsies to get insight into the extent of the affected part. Moreover, a subset of CPM type 1 and 3 seems to be only detectable with NIPT and not with first trimester CVS.

Impacts of Acrylamide on testis and spermatozoa.

Acrylamide (ACR) is an industrial chemical used to produce polyacrylamide, a synthetic polymer with a wide range of applications. Depending on the dosage, its presence in occupational and environmental sources poses potential health risks to humans and animals. ACR can be formed in starchy foods cooked at high temperatures. Its effects on human sperm are not well understood. Animal studies indicate that ACR induces toxicity in the male reproductive system through oxidative stress mechanisms. Exposure to ACR alters the normal structure of testicular tubules, leading to congestion, interstitial edema, degeneration of spermatogenic cells, formation of abnormal spermatid giant cells, and necrosis and apoptosis. It also disrupts the balance of important biomarkers such as malondialdehyde, nitric oxide, superoxide dismutase, catalase, and glutathione. ACR has a negative impact on mitochondrial function, antioxidant enzymes, ATP production, and sperm membrane integrity, resulting in decreased sperm quality. Furthermore, it interferes with the expression of steroidogenic genes associated with testosterone biosynthesis. This review explores the detrimental effects of ACR on sperm and testicular function and discusses the potential role of antioxidants in mitigating the adverse effects of ACR on male reproduction.

Multitargeted Docking, DFT-Based Optimisation, Pharmacokinetics, and MD Simulation Reveal 6-Oxidopamine HBr as a Multitargeted Inhibitor of Cervical Cancer Proteins.

Cervical cancer originates in the cervix, the lower part of the uterus, and results from the uncontrolled growth of abnormal cervical cells, forming malignant tumours. It poses a major global health challenge, calling for innovative drug design strategies to enhance treatment outcomes. In this study, we have screened the FDA-approved drug library against four proteins, MCM10, MCM6, DNA polymerase epsilon subunit-2, and TBK1, which are essential for DNA replication, DNA repair, and cellular signalling pathways, which are dysregulated in cervical cancer cells, leading to uncontrolled growth. We have used the multisampling algorithms for screening using HTVS, SP, and XP docking; identified 6- oxidopamine HBr (C8H12BrNO3), which is used to create a model of Parkinson's disease in animals, and obtained the docking score ranging from -5.057 to -8.871 Kcal/mol. The poses were filtered with MM\GBSA score ranging from -21.67 to -27.63 Kcal/mol. We performed QM-based DFT and pharmacokinetics studies and compared them with the standard values, suggesting that the compound can be used in cervical cancer proteins. The P-L complex's interaction fingerprints have resulted in the most interacting residues, 4THR, 4SER, and 4LYS, showing the compound's interaction pattern. Further, the stability of 6-oxidopamine HBr in complex with each protein was evaluated with 100ns MD simulation in the SPC water model in a neutralised state to analyse the deviation, fluctuations, and intermolecular interactions that have proven the compound to have a better inhibitory effect against each protein and that it can be used for cervical cancer; however, experimental validation is suggested before human use.

In Vivo Confocal Microscopy and Anterior Segment Optical Coherence Tomography Findings of Patients with Iridocorneal Endothelial Syndrome

This case report aims to present the findings of in vivo confocal microscopy (IVCM) and anterior segment optical coherence tomography (AS-OCT) in three patients with iridocorneal endothelial (ICE) syndrome. Three female patients 37, 50, and 57 years of age presented with complaints of unilateral visual impairment and elevated intraocular pressure (IOP). Biomicroscopy revealed unilateral pupil irregularities and anterior synechiae, and gonioscopy demonstrated synechiae in the iridocorneal angle. IOP was within normal limits with medical treatment in two patients, while one patient had an IOP of 44 mmHg despite maximal antiglaucomatous treatment. IVCM revealed large, polymorphic, and hyperreflective cells in the corneal endothelial layer of the affected eyes and normal corneal epithelium, stroma, and endothelium in the fellow eyes. AS-OCT findings were normal in healthy eyes, while the affected eye showed synechiae in the iridocorneal angle and a hyperreflective, thickened endothelial layer. The patient with refractory glaucoma underwent trabeculectomy surgery with 5-fluorouracil. In conclusion, IVCM and AS-OCT allow a detailed examination of endothelial cell abnormalities and iridocorneal membranes in ICE syndrome, which is characterized by unilateral pupil and iris irregularities and anterior synechiae mainly in women.

In silico approaches for drug repurposing in oncology: a scoping review.

Introduction: Cancer refers to a group of diseases characterized by the uncontrolled growth and spread of abnormal cells in the body. Due to its complexity, it has been hard to find an ideal medicine to treat all cancer types, although there is an urgent need for it. However, the cost of developing a new drug is high and time-consuming. In this sense, drug repurposing (DR) can hasten drug discovery by giving existing drugs new disease indications. Many computational methods have been applied to achieve DR, but just a few have succeeded. Therefore, this review aims to show in silico DR approaches and the gap between these strategies and their ultimate application in oncology. Methods: The scoping review was conducted according to the Arksey and O'Malley framework and the Joanna Briggs Institute recommendations. Relevant studies were identified through electronic searching of PubMed/MEDLINE, Embase, Scopus, and Web of Science databases, as well as the grey literature. We included peer-reviewed research articles involving in silico strategies applied to drug repurposing in oncology, published between 1 January 2003, and 31 December 2021. Results: We identified 238 studies for inclusion in the review. Most studies revealed that the United States, India, China, South Korea, and Italy are top publishers. Regarding cancer types, breast cancer, lymphomas and leukemias, lung, colorectal, and prostate cancer are the top investigated. Additionally, most studies solely used computational methods, and just a few assessed more complex scientific models. Lastly, molecular modeling, which includes molecular docking and molecular dynamics simulations, was the most frequently used method, followed by signature-, Machine Learning-, and network-based strategies. Discussion: DR is a trending opportunity but still demands extensive testing to ensure its safety and efficacy for the new indications. Finally, implementing DR can be challenging due to various factors, including lack of quality data, patient populations, cost, intellectual property issues, market considerations, and regulatory requirements. Despite all the hurdles, DR remains an exciting strategy for identifying new treatments for numerous diseases, including cancer types, and giving patients faster access to new medications.

Current Evidence on Molecular Mechanisms of Andrographolide in Cancer.

Cancer, a diverse group of diseases characterized by abnormal cell growth and the potential to spread throughout the body, accounts for approximately 10 million deaths globally each year. Current cancer therapies, including chemotherapy, radiation, and various pharmacological treatments, present several challenges and potential side effects. It is important to differentiate these conventional methods, which often involve synthetic drugs, from adjuvant therapies that might be used in conjunction. As a result, there is an increasing interest in alternative therapies, particularly in agents derived from natural sources for cancer treatment. Secondary metabolites have shown promise in promoting the development of new clinical drugs with various anti-cancer mechanisms. This review focuses on the anti-cancer potential of the novel metabolite Andrographolide, extracted mainly from Andrographis paniculata. The chemopreventive properties and the ability to inhibit various signaling pathways across different types of cancers without side effects posit Andrographolide as a promising natural antitumour agent. The review identified that Andrographolide inhibits multiple signaling pathways, contributing to its anti-proliferative, anti-metastatic, and apoptotic effects in various cancers. The compound's natural origin and lack of adverse side effects make it particularly attractive as a therapeutic agent. However, further detailed studies are needed to fully understand its specific mechanisms and potential clinical applications. Andrographolide presents a compelling option as a natural anticancer agent with the potential to overcome some limitations of traditional cancer treatments. Its broad spectrum of anti-cancer activities and absence of side effects highlight its therapeutic potential. The review highlights that continued research and clinical studies are important for confirming the effectiveness and safety of Andrographolide in human use, alongside optimizing dosage and delivery techniques.

Cervical Cancer and Its Association With Pregnancy.

Cancer is a disease in which abnormal cells divide uncontrollably, destroying tissues. A malignant tumor arises from cells in the cervix, the lower portion of the uterus (womb) that links the uterus to the vagina (birth canal), and is known as cervical cancer. One of the most significant global community health problems is cancer, which sees a daily increase in the number of sufferers.Therefore, it is crucial to expand our understanding of the molecular pathophysiology of cervical cancer and to suggest new therapeutic goals as well as new techniques for early detection of the illness. Since early diagnosis of pathologies can dramatically increase a patient's chance of survival, prognosis, and recurrence. This article aims to educate readers about some essential concepts surrounding cervical cancer, including the various types of cervical cancer, the stages of cancer, as well as their etiology, epidemiology, pathogenesis, management, and treatment, and its relationship with pregnancy. All of these concepts are essential for any individual studying medicine or working in the medical industry to understand. We intend to summarize the information that is currently available and the recommended courses of action for treating cervical cancer and its association with pregnancy in this review. Research priorities and controversies are also noted.

Whole transcriptome analysis to identify non-coding RNA regulators and hub genes in sperm of non-obstructive azoospermia by microarray, single-cell RNA sequencing, weighted gene co-expression network analysis, and mRNA-miRNA-lncRNA interaction analysis

BackgroundThe issue of male fertility is becoming increasingly common due to genetic differences inherited over generations. Gene expression and evaluation of non-coding RNA (ncRNA), crucial for sperm development, are significant factors. This gene expression can affect sperm motility and, consequently, fertility. Understanding the intricate protein interactions that play essential roles in sperm differentiation and development is vital. This knowledge could lead to more effective treatments and interventions for male infertility.Materials and methodsOur research aim to identify new and key genes and ncRNA involved in non-obstructive azoospermia (NOA), improving genetic diagnosis and offering more accurate estimates for successful sperm extraction based on an individual’s genotype.ResultsWe analyzed the transcript of three NOA patients who tested negative for genetic sperm issues, employing comprehensive genome-wide analysis of approximately 50,000 transcript sequences using microarray technology. This compared gene expression profiles between NOA sperm and normal sperm. We found significant gene expression differences: 150 genes were up-regulated, and 78 genes were down-regulated, along with 24 ncRNAs up-regulated and 13 ncRNAs down-regulated compared to normal conditions. By cross-referencing our results with a single-cell genomics database, we identified overexpressed biological process terms in differentially expressed genes, such as “protein localization to endosomes” and “xenobiotic transport.” Overrepresented molecular function terms in up-regulated genes included “voltage-gated calcium channel activity,” “growth hormone-releasing hormone receptor activity,” and “sialic acid transmembrane transporter activity.” Analysis revealed nine hub genes associated with NOA sperm: RPL34, CYB5B, GOL6A6, LSM1, ARL4A, DHX57, STARD9, HSP90B1, and VPS36.ConclusionsThese genes and their interacting proteins may play a role in the pathophysiology of germ cell abnormalities and infertility.

Defective mesenchymal Bmpr1a-mediated BMP signaling causes congenital pulmonary cysts.

Abnormal lung development can cause congenital pulmonary cysts, the mechanisms of which remain largely unknown. Although the cystic lesions are believed to result directly from disrupted airway epithelial cell growth, the extent to which developmental defects in lung mesenchymal cells contribute to abnormal airway epithelial cell growth and subsequent cystic lesions has not been thoroughly examined. In the present study using genetic mouse models, we dissected the roles of bone morphogenetic protein (BMP) receptor 1a (Bmpr1a)-mediated BMP signaling in lung mesenchyme during prenatal lung development and discovered that abrogation of mesenchymal Bmpr1a disrupted normal lung branching morphogenesis, leading to the formation of prenatal pulmonary cystic lesions. Severe deficiency of airway smooth muscle cells and subepithelial elastin fibers were found in the cystic airways of the mesenchymal Bmpr1a knockout lungs. In addition, ectopic mesenchymal expression of BMP ligands and airway epithelial perturbation of the Sox2-Sox9 proximal-distal axis were detected in the mesenchymal Bmpr1a knockout lungs. However, deletion of Smad1/5, two major BMP signaling downstream effectors, from the lung mesenchyme did not phenocopy the cystic abnormalities observed in the mesenchymal Bmpr1a knockout lungs, suggesting that a Smad-independent mechanism contributes to prenatal pulmonary cystic lesions. These findings reveal for the first time the role of mesenchymal BMP signaling in lung development and a potential pathogenic mechanism underlying congenital pulmonary cysts.

Defective mesenchymal Bmpr1a-mediated BMP signaling causes congenital pulmonary cysts

Abnormal lung development can cause congenital pulmonary cysts, the mechanisms of which remain largely unknown. Although the cystic lesions are believed to result directly from disrupted airway epithelial cell growth, the extent to which developmental defects in lung mesenchymal cells contribute to abnormal airway epithelial cell growth and subsequent cystic lesions has not been thoroughly examined. In the present study using genetic mouse models, we dissected the roles of bone morphogenetic protein (BMP) receptor 1a (Bmpr1a)-mediated BMP signaling in lung mesenchyme during prenatal lung development and discovered that abrogation of mesenchymal Bmpr1a disrupted normal lung branching morphogenesis, leading to the formation of prenatal pulmonary cystic lesions. Severe deficiency of airway smooth muscle cells and subepithelial elastin fibers were found in the cystic airways of the mesenchymal Bmpr1a knockout lungs. In addition, ectopic mesenchymal expression of BMP ligands and airway epithelial perturbation of the Sox2-Sox9 proximal-distal axis were detected in the mesenchymal Bmpr1a knockout lungs. However, deletion of Smad1/5, two major BMP signaling downstream effectors, from the lung mesenchyme did not phenocopy the cystic abnormalities observed in the mesenchymal Bmpr1a knockout lungs, suggesting that a Smad-independent mechanism contributes to prenatal pulmonary cystic lesions. These findings reveal for the first time the role of mesenchymal BMP signaling in lung development and a potential pathogenic mechanism underlying congenital pulmonary cysts.

Targeting IGF2BP1 alleviated benzene hematotoxicity by reprogramming BCAA metabolism and fatty acid oxidation

Benzene is the main environmental pollutant and risk factor of childhood leukemia and chronic benzene poisoning. Benzene exposure leads to hematopoietic stem and progenitor cell (HSPC) dysfunction and abnormal blood cell counts. However, the key regulatory targets and mechanisms of benzene hematotoxicity are unclear. In this study, we constructed a benzene-induced hematopoietic damage mouse model to explore the underlying mechanisms. We identified that Insulin like growth factor 2 mRNA binding protein 1 (IGF2BP1) was significantly reduced in benzene-exposed mice. Moreover, targeting IGF2BP1 effectively mitigated damages to hematopoietic function and hematopoietic molecule expression caused by benzene in mice. On the mechanics, by metabolomics and transcriptomics, we discovered that branched-chain amino acid (BCAA) metabolism and fatty acid oxidation were key metabolic pathways, and Branched-chain amino acid transaminase 1 (BCAT1) and Carnitine palmitoyltransferase 1a (CPT1A) were critical metabolic enzymes involved in IGF2BP1-mediated hematopoietic injury process. The expression of the above molecules in the benzene exposure population was also examined and consistent with animal experiments. In conclusion, targeting IGF2BP1 alleviated hematopoietic injury caused by benzene exposure, possibly due to the reprogramming of BCAA metabolism and fatty acid oxidation via BCAT1 and CPT1A metabolic enzymes. IGF2BP1 is a potential regulatory and therapeutic target for benzene hematotoxicity.

Molecular Docking and Dynamic Simulation of Erythrina fusca Lour Chemical Compounds Targeting VEGFR-2 Receptor for Anti-Liver Cancer Activity

Liver cancer is a serious health concern characterized by abnormal cell growth, but currently, available treatment options are limited, suggesting the need for a new therapeutic method. Therefore, this research aimed to investigate the potential of chemical compounds obtained from the cangkring plant (Erythrina fusca) as anti-liver cancer agents targeting Vascular Endothelial Growth Factor Receptor 2 (VEGFR-2). The investigation was conducted in silico through molecular docking and dynamic method. Molecular docking was performed using AutoDock Tools, followed by visualization with Biovia Discovery Studio. Additionally, molecular dynamics simulation was conducted using GROMACS software and visualized with Grace. A total of 36 chemical compounds from E. fusca were used as ligands for molecular docking. The results showed that Isobavachalcone (ISB) was the most effective test compound with a binding energy of -11.45 kcal/mol, compared to the positive control Sorafenib with a value of - 11.51 kcal/mol. In this context, hydrogen bonding, as well as hydrophobic, electrostatic, and unfavorable molecular interactions were identified. Moreover, molecular dynamics simulation provided RMSD, RMSF, Radius of Gyration (Rg), and hydrogen bond parameters. Analysis of these parameters further confirmed the superior stability of ISB in binding to VEGFR-2, suggesting the potential to suppress angiogenesis by blocking the receptor.

MobileNet and Streamlit Applications for Classification and Prediction of MRI-Based Types of Brain Tumor

The rapid proliferation of abnormal cells within the cerebrum and its surrounding areas leads to the formation of tumor cells with intricate and challenging patterns. Consequently, relying solely on magnetic resonance imaging (MRI) for brain tumor detection presents complexities due to the need for precise identification amidst normal anatomical structures and potentially anomalous tissues. Recognizing the urgency of early and precise diagnosis in combating brain cancers, this paper proposes a methodology for classifying and predicting MRI based brain tumor types using MobileNet through a Streamlit application. Initially, the input image dataset undergoes preprocessing to enhance image quality, facilitated by a Gaussian filter. Subsequently, the FCM segmentation technique is employed to accurately delineate tumors’ size, location, and morphology. Finally, feature extraction and classification are performed utilizing the MobileNet framework, a deep learning method known for its accuracy and efficiency, particularly in medical image segmentation. Performance evaluation metrics such as precision, recall, and accuracy are computed, culminating in the calculation of the F score to assess the model’s effectiveness. This work leverages the Streamlit environment, a Python platform for developing web based interactive applications, to facilitate seamless user interaction. Ultimately, the predicted output images depicting various brain tumor types glioma, meningioma, pituitary, and absence of tumor are displayed within the Streamlit software interface. By offering a swift and precise means of disease classification, this approach aids healthcare professionals in promptly identifying tumor afflicted patients while streamlining computational overhead. The proposed classifier shows the highest specificity of 94.5 % and sensitivity of 97.6%.

The Biomedical Applications of Biomolecule Integrated Biosensors for Cell Monitoring.

Cell monitoring is essential for understanding the physiological conditions and cell abnormalities induced by various stimuli, such as stress factors, microbial invasion, and diseases. Currently, various techniques for detecting cell abnormalities and metabolites originating from specific cells are employed to obtain information on cells in terms of human health. Although the states of cells have traditionally been accessed using instrument-based analysis, this has been replaced by various sensor systems equipped with new materials and technologies. Various sensor systems have been developed for monitoring cells by recognizing biological markers such as proteins on cell surfaces, components on plasma membranes, secreted metabolites, and DNA sequences. Sensor systems are classified into subclasses, such as chemical sensors and biosensors, based on the components used to recognize the targets. In this review, we aim to outline the fundamental principles of sensor systems used for monitoring cells, encompassing both biosensors and chemical sensors. Specifically, we focus on biosensing systems in terms of the types of sensing and signal-transducing elements and introduce recent advancements and applications of biosensors. Finally, we address the present challenges in biosensor systems and the prospects that should be considered to enhance biosensor performance. Although this review covers the application of biosensors for monitoring cells, we believe that it can provide valuable insights for researchers and general readers interested in the advancements of biosensing and its further applications in biomedical fields.

Characterizing Cellular Physiological States with Three-Dimensional Shape Descriptors for Cell Membranes.

The shape of a cell as defined by its membrane can be closely associated with its physiological state. For example, the irregular shapes of cancerous cells and elongated shapes of neuron cells often reflect specific functions, such as cell motility and cell communication. However, it remains unclear whether and which cell shape descriptors can characterize different cellular physiological states. In this study, 12 geometric shape descriptors for a three-dimensional (3D) object were collected from the previous literature and tested with a public dataset of ~400,000 independent 3D cell regions segmented based on fluorescent labeling of the cell membranes in Caenorhabditis elegans embryos. It is revealed that those shape descriptors can faithfully characterize cellular physiological states, including (1) cell division (cytokinesis), along with an abrupt increase in the elongation ratio; (2) a negative correlation of cell migration speed with cell sphericity; (3) cell lineage specification with symmetrically patterned cell shape changes; and (4) cell fate specification with differential gene expression and differential cell shapes. The descriptors established may be used to identify and predict the diverse physiological states in numerous cells, which could be used for not only studying developmental morphogenesis but also diagnosing human disease (e.g., the rapid detection of abnormal cells).

Nanosphere Precision: Emulsomes Revolutionizing Cancer Targeted Therapy

Abstract: Emulsomes have gained attention because they are a novel lipoidal vesicular system that has an internal solid fat core surrounded by a phospholipid bilayer. Cancer is a complex and broad term that refers to a group of diseases characterized by the uncontrolled growth and spread of abnormal cells in the body. In the context of cancer targeting, emulsomes have shown promising potential due to their ability to improve the solubility, stability, and bioavailability of anticancer drugs, leading to enhanced therapeutic efficacy and reduced systemic toxicity. This article addresses emulsomal composition, preparation techniques, and different kinds of emulsomes loaded with drugs like fluvastatin and raloxifene hydrochloride to target cancer cells. The use of emulsomes in cancer targeting holds great promise for improving the precision, efficacy, and safety of cancer treatments. A comprehensive search of relevant scientific literature was performed. This involved searching databases such as PubMed, Scopus, Web of Science, and others to identify relevant studies, articles, and reviews related to the topic. Emulsomes loaded with specific drugs show promising results in cancer treatment. Examples include piceatannol-loaded emulsomes for colon cancer, raloxifene hydrochloride-loaded emulsomes for breast cancer, and fluvastatin-loaded emulsomes for prostate cancer. Emulsomes represent a cutting-edge approach to cancer drug delivery, offering a versatile and effective solution to address challenges associated with traditional anticancer formulations. Ongoing research holds promise for the continued development of personalized cancer therapy.