Bergenin inhibits growth of human cervical cancer cells by decreasing Galectin-3 and MMP-9 expression.

Cervical cancer is still the leading cause of cancer mortality worldwide even after introduction of vaccine against Human papillomavirus (HPV), due to low vaccine coverage, especially in the developing world. Cervical cancer is primarily treated by Chemo/Radiotherapy, depending on the disease stage, with Carboplatin/Cisplatin-based drug regime. These drugs being non-specific, target rapidly dividing cells, including normal cells, so safer options are needed for lower off-target toxicity. Natural products offer an attractive option compared to synthetic drugs due to their well-established safety profile and capacity to target multiple oncogenic hallmarks of cancer like inflammation, angiogenesis, etc. In the current study, we investigated the effect of Bergenin (C-glycoside of 4-O-methylgallic acid), a natural polyphenol compound that is isolated from medicinal plants such as Bergenia crassifolia, Caesalpinia digyna, and Flueggea leucopyrus. Bergenin has been shown to have anti-inflammatory, anti-ulcerogenic, and wound healing properties but its anticancer potential has been realized only recently. We performed a proteomic analysis of cervical carcinoma cells treated with bergenin and found it to influence multiple hallmarks of cancers, including apoptosis, angiogenesis, and tumor suppressor proteins. It was also involved in many different cellular processes unrelated to cancer, as shown by our proteomic analysis. Further analysis showed bergenin to be a potent-angiogenic agent by reducing key angiogenic proteins like Galectin 3 and MMP-9 (Matrix Metalloprotease 9) in cervical carcinoma cells. Further understanding of this interaction was carried out using molecular docking analysis, which indicated MMP-9 has more affinity for bergenin as compared to Galectin-3. Cumulatively, our data provide novel insight into the anti-angiogenic mechanism of bergenin in cervical carcinoma cells by modulation of multiple angiogenic proteins like Galectin-3 and MMP-9 which warrant its further development as an anticancer agent in cervical cancer.

Silicomolybdic Acid Cluster as Biocompatible Catalyst for One-Pot Tandem Synthesis of Orthogonally Protected Glycosides.

The present paper describes a new and practical approach for the one-pot preparation of O-isopropylidene derivatives and also orthogonally protected S- and O-glycosides from the corresponding unprotected saccharides by employing 2 mol % of a silicomolybdic acid (SMA) cluster as a versatile and biocompatible catalyst. The present protocol is applicable to two-step one-pot tandem transformations, which include the O-isopropylidation, spiroketal functionalization, 4,6-O-arylidene acetalations, and arylidene acetylation processes under relatively mild reaction conditions. One-pot sequential transformations, low catalyst loading, rapid transformation, high to excellent reaction yields, mild reaction conditions, and a nontoxic biocompatible workup procedure are the notable advantages of devised protocol.

Therapeutic implications of signaling pathways and tumor microenvironment interactions in esophageal cancer.

Esophageal cancer (EC) is significantly influenced by the tumor microenvironment (TME) and altered signaling pathways. Downregulating these pathways in EC is essential for suppressing tumor development, preventing metastasis, and enhancing therapeutic outcomes. This approach can increase tumor sensitivity to treatments, enhance patient outcomes, and inhibit cancer cell proliferation and spread. The TME, comprising cellular and non-cellular elements surrounding the tumor, significantly influences EC's development, course, and treatment responsiveness. Understanding the complex relationships within the TME is crucial for developing successful EC treatments. Immunotherapy is a vital TME treatment for EC. However, the heterogeneity within the TME limits the application of anticancer drugs outside clinical settings. Therefore, identifying reliable microenvironmental biomarkers that can detect therapeutic responses before initiating therapy is crucial. Combining approaches focusing on EC signaling pathways with TME can enhance treatment outcomes. This integrated strategy aims to interfere with essential signaling pathways promoting cancer spread while disrupting factors encouraging tumor development. Unraveling aberrant signaling pathways and TME components can lead to more focused and efficient treatment approaches, identifying specific cellular targets for treatments. Targeting the TME and signaling pathways may reduce metastasis risk by interfering with mechanisms facilitating cancer cell invasion and dissemination. In conclusion, this integrative strategy has significant potential for improving patient outcomes and advancing EC research and therapy. This review discusses the altered signaling pathways and TME in EC, focusing on potential future therapeutics.

Guidelines for dental implants in the times of COVID-19.

Since the first reported case in December 2019, COVID-19 has become a worldwide pandemic. Although primarily a zoonotic infection, human-to-human transmission is well reported now and the mode of spread is mainly via respiratory droplets during direct contact or via surfaces contaminated with the virus as it remains viable on the surfaces for a long time. Direct communication and consistent exposure to body fluids such as blood and saliva and the fact that routinely done dental procedures generate aerosols predisposing dental professionals to serious risk for COVID-19 infection. Hence, to ensure the smooth working and safety of dental professionals as well as the patients, a set of directives are of paramount importance. Various guidelines have been released for the efficient operation of dental professionals; however, no such recommendations/directives have been laid out pertaining to dental implants in particular. Here, we are presenting a set of recommendations for managing urgent implant-related treatment procedures.

Effectiveness of IMPUTE ADT-1 mobile application in children with autism spectrum disorder: An interim analysis of an ongoing randomized controlled trial.

Objectives: IMPUTE Inc., a software firm dedicated to healthcare technology, has developed a mobile medical application known as IMPUTE ADT-1 for children with autism spectrum disorder (ASD) based on the principle of applied behavior analysis. Materials and Methods: The primary objective of this trial was to compare the efficacy of add-on treatment with IMPUTE ADT-1 in children with ASD aged two to six years as compared to standard care alone for 12 weeks (in terms of change in Autism Diagnostic Observation Schedule [ADOS-2] scores). The secondary objective of the study was to assess the compliance with IMPUTE ADT-1 among participants and also to evaluate the feedback of parents regarding IMPUTE ADT-1 at the end of 12 weeks. The application provides personalized programs tailored to each user's needs, and the program evolves based on the user's progress. It also utilizes face tracking, eye tracking, and body tracking to gather behavior-related information for each child and apply it in reinforcement learning employing artificial intelligence-based algorithms. Results: Till the time of interim analysis, 37 and 33 children had completed 12-week follow-up in IMPUTE ADT-1 and control arm. At 12 weeks, as compared to baseline, change in social affect domain, repetitive ritualistic behavior domain, total ADOS-2 score, and ADOS-2 comparison score was better in the intervention group as compared to the control group (P < 0.001 for all). A total of 30 (81%), 28 (75%), and 29 (78%) caregivers in the IMPUTE ADT-1 group believed that the ADT-1 app improved their child's verbal skills, social skills, and reduced repetitive behavior, respectively. Conclusion: IMPUTE ADT-1 mobile application has the efficacy to improve the severity of autism symptoms in children. Parents of these children also feel that the application is beneficial for improving the socialization and verbal communication of their children.

Depression among currently married ever pregnant adolescents in Uttar Pradesh and Bihar: Evidence from understanding the lives of adolescents and young adults (UDAYA) survey, India.

Background: Depression is a major public health concern among Indian adolescents. Pre- and post-natal depression can often alter fetal development and have negative consequences on the physical and mental health of the mother. This paper aims to draw attention to the prevalence of depression and its correlates among currently married, ever-pregnant adolescents from two Indian States, i.e. Uttar Pradesh and Bihar. Methods: This study utilizes data from a subsample (n = 3116) of the prospective cohort study Understanding the Lives of Adolescents and Young Adults (UDAYA) among 10 to 19 year-old adolescents. Bivariate analysis was performed to assess the prevalence of depression by sociodemographic and behavioral characteristics. To further access the predictors associated with depression a logistic regression model was applied. Results: Around one-tenth (9%) of pregnant adolescents had depression. Regression analysis indicated that substance use, religion, autonomy, considering attempting suicide, premarital relationship, violence, dowry, adverse pregnancy outcome, menstrual problem, and parental pressure for the child immediately after marriage were significantly associated with depression. Conclusions: This study confirms the pre-existing annotation that teen pregnancy is linked with depression. Findings indicate that Adolescent mothers experiencing violence, and a history of adverse pregnancy outcomes are at increased risk of developing depression. These study findings call for an urgent need to address depression among adolescent mothers.

Comparative Evaluation of Surgical Operability with and without Induction Chemotherapy in Locally Advanced Head and Neck Squamous Cell Carcinoma.

To compare and evaluation of surgical operability with and without induction chemotherapy in locally advanced head and neck squamous cell carcinoma. Head and neck malignancy grossly refers to squamous cell carcinomas of head and neck (HNSCC) have multiple treatment modalities and strategies, when opted in an appropriate manner renders tumours curable. The aim of this study is to compare and evaluation of surgical operability with and without induction chemotherapy in locally advanced head and neck squamous cell carcinoma. A prospective observational study involving 50 patients of histologically proven squamous cell carcinoma of head and neck region. Patients were categorized into two major groups, group-1 patients included resectable tumour stage and group-2 included unresectable tumour stage. Both groups were compared after appropriate chemotherapy and surgical intervention. There were a total of 78% males and 22% females with majority of patients in age group of 41-60 years. 54% patients had ulcerative type of growth pattern and most patients had primary site of lesion in oral cavity. 50% patients had moderately differentiated squamous cell carcinoma. Induction chemotherapy was considered in 70% of patients, while majority of patients were belonging to T4N2M0 stage. In this study, we recommend that the borderline category of patients who are initially in an unresectable tumour stage can undergo induction chemotherapy to downstage and shrink the tumour to a resectable stage following which the appropriate surgical intervention should be done with a close monitoring and sustained follow up to prevent recurrence.

Stereotactic biopsy for brain lesions: Doing more with less.

Objectives: Stereotactic biopsy (STB) is a potential diagnostic tool considering its minimal invasiveness, high diagnostic yield, and minimal associated complications. Over the years, various frame-based instrument systems and frameless stereotactic biopsy systems have emerged to be employed in clinical use. With this study, we intend to get more by doing less in the form of STB for the patients of doubtful intracranial lesions treated over the past 5 years. We also want to highlight the technique of performing the procedure under scalp block, which can be used as a versatile tool in many clinical scenarios. Stereotactic biopsies may be planned even in rural district-level health facilities. One-time investment to procure instruments and avail existing imaging can lead to establishing definitive diagnoses in many doubtful cases. This will result in lesser cost and early establishment of treatment. Independent risk factors determining the outcome, such as deep-seated lesions, associated edema, and intraoperative hypertension, were studied. Establishing the diagnosis helped in prognosticating the disease, explaining the natural progression of symptoms, and starting adjuvant therapy. This tissue biopsy would also help secure samples for research and molecular analysis. Materials and Methods: Twenty patients underwent STBs at our institution between January 2018 and December 2022. We retrospectively analyzed patient characteristics, tumor pathology, surgical procedures, and outcomes, including the diagnostic value and surgery-related complications. These patients were followed up, and their progression-free and overall survival were analyzed. The need for adjuvant treatment was noted and analyzed. All procedures were performed using Cosman Roberts Wells® stereotactic frame. Pre-procedure magnetic resonance scans were performed at the time of admission. Contrast-enhanced computerized tomography (CT) scan after frame application was performed to identify targets and calculate the coordinates. A post-procedure CT scan was done to confirm the accessibility of the targeted lesion. Results: The most common location of the tumor was a deep-seated thalamic lesion. A definitive diagnosis was established in 19 patients (95%) at the first STB. The diagnoses were glioma in 55% of cases, primary central nervous system lymphoma, tuberculosis, and demyelinating disorders in 10% of each, and a metastatic brain tumor in 1 (5%). The post-operative complications were all transient except in one patient with deterioration of motor weakness. The follow-up was noted, and modes of adjuvant treatment needed in these patients were recorded. Conclusion: Stereotactic biopsy is a useful and effective method for achieving a definitive diagnosis and aiding in treating multifocal or small deep-seated lesions in or around eloquent regions.

Ubiquitin specific peptidase (USP37) mediated effects in microscaffold-encapsulated cells: a comprehensive study on growth, proliferation and EMT.

Though significant advances have been made in developing therapeutic strategies for cancer, suitable in vitro models for mechanistically identifying relevant drug targets and understanding disease progression are still lacking. Most studies are generally performed using two-dimensional (2D) models, since these models can be readily established and allow high throughput assays. However, these models have also been reported as the reason for unreliable pre-clinical information. To avoid this discrepancy, three-dimensional (3D) cell culture models have been established and have demonstrated the potential to provide alternative ways to study tissue behavior. However, most of these models first require optimization and cell cultures with a certain density, thus adding a prepping step in the platform before it can be used for any studies. This limits their use in studies where the fundamental understanding of biological processes must be carried out in a short time frame. In this study, we developed a 3D cell culture system that tests a less explored cancer therapeutic target-the deubiquitinating enzyme ubiquitin specific peptidase 37 (USP37)-in different cancer cell lines using sensitive carbon dot pH nanosensors, which provides a rapid model for studies compared to the parallel model available commercially. This enzyme is found to be elevated in different cancers and has been reported to play a role in cell cycle regulation, oncogenesis and metastasis. However, the confirmation of the role of USP37 downregulation in cellular proliferation via appropriate in vitro 3D models has not been demonstrated. To establish the applicability of the developed 3D platform in studying such oncogenes, classical 2D models have been used in this study for identifying the role of USP37 in tumor progression and metastasis. The data clearly suggests that this ingeniously developed 3D cell culture system is a better alternative to 2D models to study the growth and migration of different cancer cell lines on depletion of oncogenic proteins like USP37 and its effect on epithelial-mesenchymal transition (EMT) markers, and it can further be targeted as a viable therapeutic option.

Unveiling HPV's hidden link: Cardiovascular diseases and the viral intrigue.

Cardiovascular diseases (CVD) remain a major global health challenge, with an escalating impact on mortality despite advancements in managing conventional risk factors. This review investigates the intricate relationship between human papillomavirus (HPV) and CVD, shedding light on a novel aspect of cardiovascular health. Despite significant progress in understanding and managing traditional CVD risk factors, a substantial proportion of CVD cases lack these conventional markers. Recent research has unveiled HPV, a prevalent sexually transmitted infection, as a potential unconventional risk factor for CVD. This review delves into the underlying mechanisms linking HPV to CVD pathogenesis. HPV's influence on vascular endothelium and induction of systemic inflammation are key contributors. Additionally, HPV disrupts host lipid metabolism, further exacerbating the development of atherosclerosis. The link between HPV and CAD is not merely correlative; it encompasses a complex interplay of virological, immunological, and metabolic factors. Understanding the connection between HPV and CVD holds transformative potential. Insights from this review not only underscore the significance of considering HPV as a crucial risk factor but also advocate for targeted HPV screening and vaccination strategies to mitigate CVD risks. This multidisciplinary exploration bridges the gap between infectious diseases and cardiovascular health, emphasizing the need for a comprehensive approach to combating the global burden of cardiovascular disease. Further research and clinical guidelines in this realm are essential to harness the full scope of preventive and therapeutic interventions, ultimately shaping a healthier cardiovascular landscape.

Cancer cell plasticity: from cellular, molecular, and genetic mechanisms to tumor heterogeneity and drug resistance.

Cancer is a complex disease displaying a variety of cell states and phenotypes. This diversity, known as cancer cell plasticity, confers cancer cells the ability to change in response to their environment, leading to increased tumor diversity and drug resistance. This review explores the intricate landscape of cancer cell plasticity, offering a deep dive into the cellular, molecular, and genetic mechanisms that underlie this phenomenon. Cancer cell plasticity is intertwined with processes such as epithelial-mesenchymal transition and the acquisition of stem cell-like features. These processes are pivotal in the development and progression of tumors, contributing to the multifaceted nature of cancer and the challenges associated with its treatment. Despite significant advancements in targeted therapies, cancer cell adaptability and subsequent therapy-induced resistance remain persistent obstacles in achieving consistent, successful cancer treatment outcomes. Our review delves into the array of mechanisms cancer cells exploit to maintain plasticity, including epigenetic modifications, alterations in signaling pathways, and environmental interactions. We discuss strategies to counteract cancer cell plasticity, such as targeting specific cellular pathways and employing combination therapies. These strategies promise to enhance the efficacy of cancer treatments and mitigate therapy resistance. In conclusion, this review offers a holistic, detailed exploration of cancer cell plasticity, aiming to bolster the understanding and approach toward tackling the challenges posed by tumor heterogeneity and drug resistance. As articulated in this review, the delineation of cellular, molecular, and genetic mechanisms underlying tumor heterogeneity and drug resistance seeks to contribute substantially to the progress in cancer therapeutics and the advancement of precision medicine, ultimately enhancing the prospects for effective cancer treatment and patient outcomes.

Understanding trimester-specific miscarriage risk in Indian women: insights from the calendar data of National Family Health Survey (NFHS-5) 2019-21.

BACKGROUND: The primary public health issue, especially in low- and middle-income countries, is early pregnancy loss driven by miscarriage. Understanding early pregnancy losses and the characteristics of mothers who have miscarriages is essential to creating effective reproductive health strategies. Thus, this study's primary goal is to delve into the factors which impact miscarriages that take place prior to and following the first 12 weeks of gestation. METHODS: The bivariate analysis was employed to determine the frequency of miscarriages. The factors associated with miscarriages in the first (≤12 weeks) and second & above (> 12 weeks) trimesters of pregnancy were then examined using a generalised linear regression model, with 95% confidence intervals. Finally, we use ArcGIS to illustrate the prevalence of miscarriage in the districts of India. RESULTS: Our result shows that miscarriages occur often in India (4.9%), with 23% of cases occurring in the first trimester (≤12 weeks). In our bivariate analysis, we identified several factors associated with a higher prevalence of miscarriages in India. It was found that mothers aged thirty years or older, residing in urban areas, with less than ten years of education, belonging to the richest wealth quantile, expressing a desire for more children, having no demand for contraception, and possessing no parity experienced a higher prevalence of miscarriage in total pregnancies in India. On the other hand, the generalised linear model's findings show that mothers who are thirty years of age or older, practise other religions, live in urban areas, are members of other castes, want more children, marry before the age of eighteen, and meet their contraceptive needs are more likely to have miscarriages in total pregnancy. However, there is a larger likelihood of miscarriage in the first trimester (≤12 weeks) for mothers who follow other religions, live in urban areas, are from Other Backward Class (OBC), get married before the age of eighteen, and fall into the middle and upper wealth quantiles. A mother is more likely to miscarriage in the second & above (> 12 weeks) trimesters if she is older than thirty, from other castes, wants more children, has moderate media exposure, marries before turning eighteen, meets her contraceptive needs, and does not feel the need for contraception. After accounting for socioeconomic characteristics, all results were statistically significant. CONCLUSIONS: Given the substantial number of miscarriages in India, police need to improve planning and guidance in order to lower pregnancy loss due to miscarriage. Miscarriage rates may be significantly decreased by enhancing the availability and quality of reproductive health care infrastructure, particularly in rural areas.

CAR-T cell therapy: a game-changer in cancer treatment and beyond.

In recent years, cancer has become one of the primary causes of mortality, approximately 10 million deaths worldwide each year. The most advanced, chimeric antigen receptor (CAR) T cell immunotherapy has turned out as a promising treatment for cancer. CAR-T cell therapy involves the genetic modification of T cells obtained from the patient's blood, and infusion back to the patients. CAR-T cell immunotherapy has led to a significant improvement in the remission rates of hematological cancers. CAR-T cell therapy presently limited to hematological cancers, there are ongoing efforts to develop additional CAR constructs such as bispecific CAR, tandem CAR, inhibitory CAR, combined antigens, CRISPR gene-editing, and nanoparticle delivery. With these advancements, CAR-T cell therapy holds promise concerning potential to improve upon traditional cancer treatments such as chemotherapy and radiation while reducing associated toxicities. This review covers recent advances and advantages of CAR-T cell immunotherapy.

YouTube as a Patient Information Source for Gastrointestinal Reflux Disease.

Introduction Gastroesophageal reflux disease (GERD) affects a substantial portion of the global population, resulting in significant morbidity and impacting the quality of life. YouTube (YouTube, San Bruno, California) serves as a platform where medical professionals, individuals with personal experiences, and educational channels share their insights on GERD. However, with the vast amount of information available on YouTube, the question of credibility and reliability is a concern and, thus, is crucial to evaluate. This research paper aims to explore the impact of YouTube as a source of information on GERD. The aim of this study is to assess the quality and reliability of the information on YouTube about GERD. Methodology This cross-sectional observational study was conducted in June 2023. A questionnaire was designed using Google Forms (Google, Mountain View, California) with predetermined criteria such as characteristics of YouTube videos (time since uploaded, uploader, number of likes and comments); information about GERD (symptoms, investigations, treatment); and quality and reliability of information on YouTube about GERD using Global Quality Scale (GQS) and Reliability score. The Kruskal-Wallis Test was used to evaluate the difference in quality and reliability of information about GERD on YouTube based on the type of uploader.  Results Out of 90 videos analyzed, 68 YouTube videos on GERD that met inclusion criteria were included in the study. The number of videos uploaded by hospitals was 28 (41.2%), those by doctors was 12 (17.6%), and the remaining by others (like pharmacists, patients, and non-medical personnel) was 28 (41.2%). A significant proportion of videos (88.24%) shared information pertaining to disease symptoms and cause/etiology. The videos uploaded by "others" had significantly higher (p<0.05) reach as assessed by the Video Power Index (VPI) compared to those uploaded by doctors and hospitals. However, there was no significant difference (>0.05) in the quality and reliability of videos uploaded by doctors, hospitals, and other sources.  Conclusion Although the YouTube videos uploaded by doctors and hospitals had less reach among viewers compared to other uploaders (patients, news agencies, pharmaceutical companies, and others unrelated to healthcare), the quality and reliability of videos uploaded by doctors, hospitals, and other uploaders were of good quality and reliability and with no significant difference based on type of uploader. Healthcare organizations and government agencies should ensure that viewers have access to accurate and reliable information from social media like YouTube, which is crucial in their health decision-making.

CAR-T-Cell Therapy in Multiple Myeloma: B-Cell Maturation Antigen (BCMA) and Beyond.

Significant progress has been achieved in the realm of therapeutic interventions for multiple myeloma (MM), leading to transformative shifts in its clinical management. While conventional modalities such as surgery, radiotherapy, and chemotherapy have improved the clinical outcomes, the overarching challenge of effecting a comprehensive cure for patients afflicted with relapsed and refractory MM (RRMM) endures. Notably, adoptive cellular therapy, especially chimeric antigen receptor T-cell (CAR-T) therapy, has exhibited efficacy in patients with refractory or resistant B-cell malignancies and is now also being tested in patients with MM. Within this context, the B-cell maturation antigen (BCMA) has emerged as a promising candidate for CAR-T-cell antigen targeting in MM. Alternative targets include SLAMF7, CD38, CD19, the signaling lymphocyte activation molecule CS1, NKG2D, and CD138. Numerous clinical studies have demonstrated the clinical efficacy of these CAR-T-cell therapies, although longitudinal follow-up reveals some degree of antigenic escape. The widespread implementation of CAR-T-cell therapy is encumbered by several barriers, including antigenic evasion, uneven intratumoral infiltration in solid cancers, cytokine release syndrome, neurotoxicity, logistical implementation, and financial burden. This article provides an overview of CAR-T-cell therapy in MM and the utilization of BCMA as the target antigen, as well as an overview of other potential target moieties.

Epigenetic inhibitors and their role in cancer therapy.

Epigenetic modifications to DNA are crucial for normal cellular and biological functioning. DNA methylation, histone modifications, and chromatin remodeling are the most common epigenetic mechanisms. These changes are heritable but still reversible. The aberrant epigenetic alterations, such as DNA methylation, histone modification, and non-coding RNA (ncRNA)-mediated gene regulation, play an essential role in developing various human diseases, including cancer. Recent studies show that synthetic and dietary epigenetic inhibitors attenuate the abnormal epigenetic modifications in cancer cells and therefore have strong potential for cancer treatment. In this chapter, we have highlighted various types of epigenetic modifications, their mechanism, and as drug targets for epigenetic therapy.

Selection and ranking of dental restorative composite materials using hybrid Entropy-VIKOR method: An application of MCDM technique.

The objective of this investigation was to design the selection and ranking of dental restorative composite materials using hybrid Entropy-VIKOR as the MCDM method. Eleven performance defining attributes (PDAs) of dental composites were considered to investigate the best formulation among the dental composites. The weight criteria of various PDAs of the dental composite were calculated by the Entropy method: PDA-1(0.0527), PDA-2 (0.0113), PDA-3(0.1692), PDA-4(0.1291), PDA-5(0.0207), etc. The VIKOR method was employed to demonstrate the rank of dental composites. As per the VIKOR method, the first rank was obtained by DHZ6, the second rank was by DHZ8, the third rank was by DHZ4, the fourth rank was by DHZ2, and the lowest rank was by DHZ0. The Hybrid Entropy-VIKOR method holds significance in the biomedical realm due to its capability to effectively address complex decision-making scenarios. Its ability to account for multiple criteria, uncertainties, and compromise solutions makes it particularly useful for enhancing decision-making processes in the biomedical field, where selecting the most suitable options is critical for patient outcomes and healthcare advancements.

Ubiquitination and deubiquitination: Implications on cancer therapy.

The ubiquitin proteasomal system (UPS) represents a highly regulated protein degradation pathway essential for maintaining cellular homeostasis. This system plays a critical role in several cellular processes, which include DNA damage repair, cell cycle checkpoint control, and immune response regulation. Recently, the UPS has emerged as a promising target for cancer therapeutics due to its involvement in oncogenesis and tumor progression. Here we aim to summarize the key aspects of the UPS and its significance in cancer therapeutics. We begin by elucidating the fundamental components of the UPS, highlighting the role of ubiquitin, E1-E3 ligases, and the proteasome in protein degradation. Furthermore, we discuss the intricate process of ubiquitination and proteasomal degradation, emphasizing the specificity and selectivity achieved through various signaling pathways. The dysregulation of the UPS has been implicated in cancer development and progression. Aberrant ubiquitin-mediated degradation of key regulatory proteins, such as tumor suppressors and oncoproteins, can lead to uncontrolled cell proliferation, evasion of apoptosis, and metastasis. We outline the pivotal role of the UPS in modulating crucial oncogenic pathways, including the regulation of cyclins, transcription factors, Replication stress components and DNA damage response. The increasing recognition of the UPS as a target for cancer therapeutics has spurred the development of small molecules, peptides, and proteasome inhibitors with the potential to restore cellular balance and disrupt tumor growth. We provide an overview of current therapeutic strategies aimed at exploiting the UPS, including the use of proteasome inhibitors, deubiquitinating enzyme inhibitors, and novel E3 ligase modulators. We further discuss novel emerging strategies for the development of next-generation drugs that target proteasome inhibitors. Exploiting the UPS for cancer therapeutics offers promising avenues for developing innovative and effective treatment strategies, providing hope for improved patient outcomes in the fight against cancer.

Harnessing the potential of CAR-T cell therapy: progress, challenges, and future directions in hematological and solid tumor treatments.

Traditional cancer treatments use nonspecific drugs and monoclonal antibodies to target tumor cells. Chimeric antigen receptor (CAR)-T cell therapy, however, leverages the immune system's T-cells to recognize and attack tumor cells. T-cells are isolated from patients and modified to target tumor-associated antigens. CAR-T therapy has achieved FDA approval for treating blood cancers like B-cell acute lymphoblastic leukemia, large B-cell lymphoma, and multiple myeloma by targeting CD-19 and B-cell maturation antigens. Bi-specific chimeric antigen receptors may contribute to mitigating tumor antigen escape, but their efficacy could be limited in cases where certain tumor cells do not express the targeted antigens. Despite success in blood cancers, CAR-T technology faces challenges in solid tumors, including lack of reliable tumor-associated antigens, hypoxic cores, immunosuppressive tumor environments, enhanced reactive oxygen species, and decreased T-cell infiltration. To overcome these challenges, current research aims to identify reliable tumor-associated antigens and develop cost-effective, tumor microenvironment-specific CAR-T cells. This review covers the evolution of CAR-T therapy against various tumors, including hematological and solid tumors, highlights challenges faced by CAR-T cell therapy, and suggests strategies to overcome these obstacles, such as utilizing single-cell RNA sequencing and artificial intelligence to optimize clinical-grade CAR-T cells.