ISSN 2959-409X(Print) ISSN 2960-1290(Online) Editor: Shibin Cheng (Brown University) The journal's rigorous process ensures that only high-quality papers are accepted for publication, providing readers with reliable and well-researched articles. This ensures that readers are exposed to the latest and most relevant research in the field of medicine. The journal covers a wide range of topics, from basic medical sciences such as anatomy, physiology, and pharmacology, to clinical specialties such as cardiology, oncology, and pediatrics. This breadth of coverage ensures that readers are exposed to the latest research in various medical fields. MedScien also places a strong emphasis on practical applications of research findings. The journal is committed to promoting research that has real-world applications and can inform clinical practice and healthcare policy-making. As such, readers can expect to find articles that not only contribute to theoretical knowledge but also have practical implications for healthcare professionals.
CAR-T Cell Therapy in Primary Mediastinal B-cell Lymphoma
A specific type of CAR-T cell therapy, the CAR19 therapy has demonstrated notable efficacy for relapsed or refractory (R/R) hematologic cancers, including B-cell lymphomas. After the recent reclassification of the rare subtype Primary Mediastinal B-cell Lymphoma (PMBCL) from general Diffuse Large B-cell Lymphoma (DLBCL), questions have been raised about the application of immunotherapies in this cancer, including the most discussed CAR-T cell therapy. The CAR-T cell therapy, more specifically the CAR19, exerts anti-tumor effects in multiple mechanisms, including different cytotoxic pathways—apoptosis triggering via perforin–granzyme release and Fas/FasL-pathway—driven by calcium-dependent signaling MAPK, PI3K/Akt, and NF-κB. Multiple extant clinical trials have evaluated the response of PMBCL patients to CAR19, specifically the Axi-cel, Liso-cel, and Tisa-cel therapies, focusing the rates of complete response (CR), progression-free survival (PFS), and the overall survival (OS). Studies exclusive to PMBCL patients showed that bridging therapies and other first-line treatments did not influence CAR19 effectiveness, while post-relapse application of Pembrolizumab yielded durable CRs in some patients, and allo-HSCT was associated with high mortality. The CAR-SIE trial in Italy, comparing Axi-cel CAR19 in PMBCL cancer with other B-cell lymphomas, demonstrated a better result in PMBCL patients with higher ORR, CR, and PFS. This paper integrates the underlying mechanisms of CAR19 with clinical trials, aiming to demonstrate both the potential and the limitations of this therapy in PMBCL cancer.
Advances in Nanopore Technology for Single-Nucleotide Polymorphism Detection: From Principles to Translational Precision Medicine
Single-nucleotide polymorphisms (SNPs) are the most common type of variation in the human genome and crucial biomarkers for assessing susceptibility to disease, response to pharmacological intervention. Conventional methods of SNP detection, including Sanger sequencing, polymerase chain reaction (PCR), and microarray analysis, have been widely used; however, these are limited with regards to throughput, scalability, and point-of-care compatibility. Alternatively, nanopore-based sequencing technologies are new platforms, enabling real-time, label-free analysis at the single-molecule level. This review outlines the recent developments in the application of biological, solid-state, and hybrid nanopores as devices for SNP detection, focusing on their fundamental principles, highlights of notable platforms, and technological developments. Key milestones include advancements in sample preparation and translocation control, signal resolution optimization through geometric pore design and the use of ultrathin membranes, and the development of probe engineering strategies targeting allele-specific discrimination as well as minimizing background noise. These advances aim to improve the accuracy and clinical relevance of nanopore-mediated SNP detection, and the translational significance of precision medicine.
Single-Nucleotide Polymorphism Detection
Application of Artificial Intelligence in the Design of Tumor mRNA Vaccines
For many years, scientists have been focused on developing mRNA-based vaccines, an area that has transitioned from theoretical concepts to practical treatments in clinical settings. This remarkable progress highlights the speed at which scientific advancements can occur when collaboration and innovation intersect. mRNA vaccines offer several inherent advantages, such as robust immunogenicity, a lack of gene integration risks, and the potential for cost-effective production. However, challenges related to mRNA stability and degradation continue to pose significant hurdles. To address these challenges and enhance vaccine development, traditional trial-and-error methods are increasingly being complemented and, in some cases, replaced by rational design strategies that leverage artificial intelligence (AI). In this review, we explore the core technologies underpinning mRNA vaccines and discuss how AI-driven design methods are optimizing their development. We also present a case study of trRosettaRNA, a deep learning-based approach for automating the prediction of RNA three-dimensional structures. This method successfully predicts the 3D structure of target RNA, demonstrating the transformative potential of AI in optimizing vaccine design and further advancing mRNA-based therapeutic strategies.
Application of CRISPR in the Treatment of Pancreatic Cancer
As a highly invasive malignant tumor, pancreatic cancer (PC) has an increasing incidence rate and a long-term low 5-year survival rate. At present, CRISPR has been used in the research of PC to analyze the function of oncogenes, explore drug resistance mechanisms and develop treatment strategies. Most of them are in the stage of cell and animal experiments. However, there are still research gaps in tumor microenvironment penetration, low delivery efficiency in vivo, off target effects and treatment limitations caused by tumor heterogeneity. This article systematically reviews the CRISPR foundation, analyzes the pathogenesis of high-frequency mutant genes in PC, elaborates three major treatment strategies based on CRISPR, combs the progress of second-generation CRISPR, clarifies the current technical challenges, and proposes targeted vector development, high fidelity Cas protein application and other corresponding programs. This study provides a comprehensive reference for the clinical transformation of CRISPR in the field of PC, helping to break through the bottleneck of traditional treatment; However, the long-term safety of this technology in the human body still needs to be verified. Future research can rely on the third-generation CRISPR to optimize the targeted delivery system, explore the joint strategy with immunotherapy and chemotherapy, promote the technology to clinical implementation, and provide more accurate treatment schemes for PC patients.
Applications and Future Perspectives of Artificial Intelligence in gRNA Design
The rapid development of CRISPR gene editing has brought revolutionary breakthroughs to the biomedical area, yet the design of gRNA is still facing problems as unstable editing efficiency and the risk of off-target. The introduction of Artificial Intelligence (AI) technology has guided this issue to a brighter future. Studies have shown that deep learning models can predict editing efficiency and assess off-target risk precisely through analyzing information as the sequence features of gRNA, while the introduction of tools like Reinforcement Learning (RL) further enlarges the space of gRNA design. There is still a deficiency in recent studies. This paper analyzes the application of AI in gRNA design, including editing efficiency and off-target risk assessment. The workflow, performance, and limitations of each model are concluded, and the conclusion of AI having a great devotion to gRNA design and the tips for choosing different models in different cases are given. This research provides references about choosing and designing models, but there are still unsolved challenges in aspects of building standard datasets and public databases. In the future, gRNA design can be optimized by reinforcing the use of Federated Learning (FL) and single-cell CRISPR screening technology.
Research Progress on Molecular Mechanisms of Exercise-Regulated Immunity
Physical exercise exerts bidirectional effects on human immune system. This essay is written to demonstrate significant molecular mechanisms of the opposite immune regulations by physical activity. Epidemiologic evidence indicates that regular exercisers experience reduced risk of upper respiratory tract infections (URTIs) and exhibit substantially lower incidence rates of certain cancers. Inversely, athletes who have undergone intense physical training, such as those who have participated in a marathon race. The incidence rate of URTI will increase significantly compared to that of ordinary people who did not participate in the competition during the same period. Through comprehensive literature review and analysis, this review synthesizes current knowledge on exercise-immune interactions. Main findings indicate the J model theory curve relationship between exercise intensity and infection risk of URTIs, demonstrating that moderate activity enhances immunosurveillance while prolonged high-intensity exercises may induce temporary immunosuppression. This article clearly explains the classic cellular pathways of immune regulation, achieving a combination of the macroscopic and the microscopic. Serving as the scientific basis for individualized exercise prescriptions.
Principles and Methods of De Novo Protein Design and Applications
De novo protein design strategy enables to create novel protein sequence that are able to fold in stable and functional structure, while breaking through the limitation of natural evolution. This method, which is based on the idea that the amino acid sequence of a protein dictates its three-dimensional structure, identifies a particular sequence with a low-energy state by combining computational methods, molecular interaction modeling, and thermodynamic optimization. Stabilizing interactions between molecules are precisely engineered to ensure the protein is folded into desired structure, while maintaining conformational stability. Recent advanced methods in de novo protein design includes flexible and fixed backbone modeling and deep learning-guided assembly. These methods have improved accuracy of modeling and broadened available space for protein sequence. De novo protein design can be applied across multiple biomedical domains. De novo protein design achieves notable success in vaccine innovation, where stabilized epitopes are presented to enhance the immune targeting, and in immunotherapy, where synthetic cytokine mimetics achieve high selectivity with reduced toxicity. These developments demonstrate how de novo protein design is transitioning from a conceptual idea to a robust platform for advanced therapeutics.
The Implementation Application of CRISPR Gene-Editing Technology within CAR-T Strategies Targeting Solid Tumors
With impressive clinical results, The management of hematologic malignancies has evolved as a result of CAR-T treatment. However, its application to solid tumors is restricted by immune-suppressive tumor milieus, antigenic heterogeneity, and insufficient persistence and infiltration of engineered T cells. CRISPR-Cas9, a versatile and precise genome-editing platform, offers new strategies to overcome these challenges through targeted modification of its products. This paper describes the mechanical properties and structural layout of CAR-T treatment, together with important obstacles in the context of solid tumors and CRISPR-driven engineering techniques meant to improve therapeutic efficacy. The development of universal CAR-T products for ready-to-use applications, metabolic reprogramming to adapt to nutrient-limited and hypoxic conditions, cytokine gene integration to support persistence and immune communication, and checkpoint receptor disruption to maintain T-cell activity are examples of representative strategies. Collectively, the convergence of CRISPR and CAR-T technologies enhances precision, durability, and broad applicability, positioning this combined strategy as a promising direction for next-generation immunotherapy against solid cancers.
Research on CRISPR-Cas9 Gene Editing Technology in Cancer Treatment
Gene editing technology represents a pioneering biotechnology that leverages molecular tools to achieve efficient and precise modifications of the DNA sequences within a biological genome, enabling the regulation of gene functions or the enhancement of traits. As a component of bacterial adaptive immunity, CRISPR/Cas9 has swiftly emerged as a revolutionary gene editing tool in the life sciences, outperforming traditional zinc finger nucleases and TALEN technologies in terms of editing efficiency and cost-effectiveness. The CRISPR-Cas gene editing tool boasts not only robust functionality but also remarkable specificity and efficiency, facilitating accurate and rapid screening of the entire genome and enabling gene therapy for specific diseases. It has found widespread application in research pertaining to human disease treatment. In the realm of oncology, the CRISPR-Cas system can be employed to edit the genome and delve into the mechanisms underlying tumor initiation, progression, and metastasis. This article provides a comprehensive review of the advancements in CRISPR/Cas9 research pertaining to lung cancer, cervical cancer, pancreatic cancer, and bladder cancer, encompassing key target screening, elucidation of drug resistance mechanisms, development of gene therapy vectors, and clinical trial outcomes. Furthermore, it delves into its potential for clinical application and existing challenges, offering a theoretical foundation for future precision cancer research endeavors.
The Impact of Nanoparticle-Modified Carriers on Drug Entry and Exit in Tumor Cells
In recent years, malignant tumors have posed a severe threat to human health. Currently, most clinically used drug molecules are non-targeted chemical structure drugs with low bioavailability. The halogens or sulfur elements in their structures can easily cause toxic side effects to normal cells. High doses are required to achieve therapeutic concentrations, which may further exacerbate toxic side effects and lead to non-specific adverse reactions. Additionally, the rapid excretion of drugs can easily cause peak and trough phenomena, resulting in poor therapeutic effects. In contrast, nanoparticle carriers wrapped in cell membranes have gained widespread application in cancer treatment due to their high biocompatibility. They can disguise themselves as autologous cells, evade recognition and clearance by the immune system, prolong circulation time in the bloodstream, and enhance targeting to tumors. This is crucial for tumor drug delivery and treatment.
Research on the Epidemiology of Zoonotic Diseases due to Overgrazing - Take Echinococcosis as an Example
Echinococcoccosis is a global zoonotic disease caused by Echinococcus granulosus and Echinococcus multilocularis, posing a serious threat to human health, livestock production and ecological balance. This review examines the epidemiological characteristics of echinococcosis, focusing on the amplifying role of overgrazing in disease transmission. Overgrazing disrupts grassland ecosystems and increases contact between wild canids (foxes, wolves), domestic animals (sheep, cattle) and humans, thereby facilitating the transmission of tapeworm eggs in contaminated environments. Clinical manifestations in humans include pressure organ damage, systemic toxicity and life-threatening anaphylactic reactions, with ruptured cysts and complications leading to high rates of recurrence and mortality. Based on the analyses, this paper proposes corresponding preventive strategies that emphasise comprehensive management of domestic animals in transitional grazing areas, safe handling of infected livestock organs and public health education to interrupt the ‘wildlife-livestock-human’ transmission chain.
Macrophage-mediated Immune Cell Interaction Network and its Synergistic Immune Escape Mechanism in Leishmania Protozoa Infection
Leishmania infection is a highly prevalent cause of parasitic disease in tropical and subtropical regions of the world, causing severe clinical symptoms such as skin ulcers and internal organ damage, posing a long-term threat to public health. Macrophages, as the main host cells of Leishmania invasion, have long been a key blind spot in the study of anti-infection immunity because of their dynamic interactions with T cells, dendritic cells (DCs), natural killer cells (NKs) and other immune cells. In this paper, we systematically analyze the synergistic escape mechanism in the macrophage-mediated immune cell network through cytokine inhibition, antigen presentation blockade, and inflammatory modulation. The article demonstrates that infected macrophages inhibit T cell activation, dendritic cell maturation, and NK cell killing through the secretion of TGF-β and IL-10. By down-regulating the expression of MHC molecules, infected macrophages form an "antigen presentation inhibition-immune cell inactivation" cascade. In addition, the study summarizes the reasons why the remodeling of the inflammatory microenvironment promotes parasite survival. This study provides new perspectives for therapeutic strategies targeting immune checkpoints.
The GLP-1 Revolution: Miracle Drugs, Market Chaos, and the Cost of Slimness
In modern society, unhealthy dietary patterns and sedentary lifestyles have made weight management a pressing challenge for many individuals. Therefore, people are seeking more effective approaches that fit contemporary living. Since 2021, GLP-1 receptor agonists have expanded beyond their original role in diabetes treatment and entered the field of weight control. As novel therapies, they provide effective weight reduction and lower risks of obesity-related diseases such as stroke, hypertension, and heart failure. This article explores the global rise of GLP-1 drugs, considering not only their clinical benefits but also the cultural and economic factors behind their popularity. Cultural norms, beauty standards, and social media have played an important role in fueling public enthusiasm. The trend is especially visible in the United States, China, and Japan, where differences in regulation and pricing strongly shape access. While GLP-1 drugs represent a significant advance, concerns about side effects and access highlight the need to weigh their benefits against potential risks.
Analysis of the effect on immune recognition of the glycosylation of viral envelope based on the analysis of the HIV-1 envelope
This passage firstly presents the global overview of the Human immunodeficiency virus (HIV), then providing a comprehensive review of the difficulties in the development of vaccines against the HIV, focusing on glycosylation modification of the envelope protein. During the infection process of this virus, the glycosylation modification help the virus evade the monitoring of the immune system through a series of immune evasion mechanisms. The glycosylation modifications of the virus are mainly located on the envelope of the virus. During the formation process of the envelope, the core products Group-specific antigen exerts a vital influence and shows positive effects in the maturation of the surface envelope proteins. Also, the components of the viral envelope and the mechanisms of glycosylation are introduced. The envelope protein have a significant impact in the immune evasion. Also, the passage introduces the recent progress in the research on treatment for the virus. An overall review on the impact of glycosylation modifications on immune evasion mechanism of HIV-1 virus is helpful for the future research in this field.
Applications of Electrochemical Biosensors across Medical, Environmental and Food Safety Fields
Traditional laboratory tests remain accurate, but they are slow, costly, and difficult to use outside controlled settings. Electrochemical sensors (including different sensor types and materials) have become indispensable tools nowadays. They offer major advantages, including high sensitivity, strong selectivity, fast response, low cost, simple miniaturization and reliable real-time online monitoring. Recent research have shown the application in three main fields: medical diagnostics, environmental monitoring, and food safety, such as glucose monitoring in diabetes, heavy metal detection in water, and bacterial identification in food, confirming the value of real-time monitoring. They reduce the dependence on complex laboratory equipment. Relevant working mechanisms include signal conversion and biological recognition. As materials and designs improve, they move from experimental trials into daily practice. Meanwhile, limitations still exist. Sensors face problems such as signal interference and short lifespan. Further exploration is needed in the future, in the hope that it can be better applied in clinical practice.
Targeted Therapeutic Strategy for Duchenne Muscular Dystrophy Leveraging RNA Editing
Duchenne muscular dystrophy (DMD) is a devastation X-linked recessive genetic disorder involving progressive muscle tissue degeneration and premature death, primarily occurring in males. Current therapies such as corticosteroids and gene replacement are of limited value and suffer from the problems of enormous side effects and restrictions based on viral vectors. RNA base editing is a new-generation therapeutic strategy for genetic diseases like DMD with advantages of being reversible, less likely to lead to off-target risks than DNA editing, and direct disease-causing mRNA mutation correction. This study reviews the literature for RNA base editing as a therapy for DMD. Major RNA editing technologies, adenosine-to-inosine (A-to-I) editing by engineered ADAR enzymes , are introduced for their potential to edit out premature stop codons in the DMD mRNA to restore functional dystrophin protein expression. Key milestones include the miniaturization of editors suitable for adeno-associated virus (AAV) delivery, demonstration of efficacy in humanized DMD mouse models with dystrophin restoration and functional muscle improvement. The findings reveal the therapeutic utility of RNA base editing for DMD and propose new directions for its future clinical application.
Applications of CRISPR in the Treatment of Autoimmune Diseases
Autoimmune disorders are marked by the immune system’s erroneous recognition and ongoing assault on the body’s own tissues, impacting roughly 5-10% of individuals. Existing interventions, such as immunosuppressive drugs, can ease outward symptoms but cannot eliminate the root cause, while long-term use may bring about risks like heightened infection susceptibility or organ damage due to toxicity. CRISPR gene editing technology, which allows for accurate genomic modifications through Cas9 endonuclease and programmable guide RNA, has exhibited potential in treating monogenic diseases and certain tumors. However, its use in complex autoimmune conditions is still in the early investigative stage, with current approaches centered on editing genes that regulate immune cell activity and reestablishing immune tolerance. Notable research limitations include inefficient cell-type-specific delivery systems, unaddressed off-target modifications, and insufficient verification of long-term safety. This study conducts a comprehensive assessment of CRISPR-based therapeutic strategies for autoimmune diseases, encompassing the identification of disease-related genes (e.g., TLR7 in SLE and PTPN22 in RA), editing techniques (gene knockout, knock-in, and base editing), and the regulation of immune cell functions. Preclinical results show reduced production of autoantibodies, inhibited inflammatory responses, and mitigated tissue harm in models of SLE and RA. These findings offer a scientific foundation for the development of targeted, curative treatments, overcoming the drawbacks of traditional therapies. Future investigations should focus on improving editing accuracy, refining delivery systems, and performing extended safety evaluations to expedite the clinical application of personalized CRISPR-based treatments for autoimmune disorders.
Correlation Study and Treatment of Malignant Tumors with Differentiation Induction in Traditional Chinese Medicine
Traditional Chinese Medicine (TCM) is a holistic approach that emphasizes the importance of strengthening the body's vital energy and eliminating pathogenic factors. It suggests that tumors are linked to qi stagnation, blood stasis, and imbalance between yin and yang. This study explores the correlation between TCM treatment and tumor differentiation, and proposes innovative treatments under TCM theory. By combining clinical observations, research experiments, and collaborative diagnosis and treatment between TCM and Western medicine, the goal is to prevent tumor occurrence and metastasis. Some components of TCM can directly induce tumor cell differentiation and synergize with Western medicine treatment.
A review of studies on the impact of social isolation and loneliness on Alzheimer's disease
Alzheimer's disease (AD), the most common neurodegenerative disease affecting the elderly, is on a continuous global rise in incidence and prevalence, placing a heavy burden on the individual, the family, and society. In recent years, more and more researches have revealed that social isolation and loneliness are important factors of risk for the development of AD. The purpose of this review is to systematically sort out the existing cohort research evidence on the impact of social isolation and loneliness on AD, to deeply explore the underlying neurobiological, psychological, and inflammatory response mechanisms, and to pay special attention to the gender specificity of the effects of social isolation and loneliness on AD, and to analyze the differences in cognitive decline, psychological problems, and disease progression between females and males, as well as their possible causes, with a view to providing new directions for future research and AD early prevention and intervention strategies for AD, with a view to providing new perspectives and theoretical basis for future research directions and early prevention and intervention strategies for AD.
Meniscus injuries are recognized as critical to knee joint function and mobility. This paper examines different diagnostic and treatment strategies for meniscal injuries. Technological advancements such as MRI and arthroscopies, alongside physical diagnostic tests like the Apley test, have significantly improved the accuracy of diagnosis. Treatment depends on severity and individual needs, ranging from conservative management to surgery like meniscectomies or meniscus repairs. Research shows that accelerated rehabilitation may be effective in certain conditions, but standard protocols are being developed. This study uses recent findings and patient outcome data to emphasize the importance of diagnostic and treatment methods in managing meniscus injuries.
Pyroptosis: A New Strategy for Oncolytic Virus Therapy of Cancer
In recent years, pyroptosis, as a form of proinflammatory programmed death, has been found to play a key role in the anti-tumor mechanism of OVs. This article systematically reviews the molecular mechanism of pyroptosis and tumor immune regulation, summarizes novel therapeutic strategies such as genetic engineering of OVs to enhance pyroptosis and combined with immune checkpoint inhibitors (ICIs), and analyzes their effects on tumor microenvironment (TME) immune remodeling. The results showed that OVs mainly induced pyroptosis by activating the caspase-3/GSDME pathway, releasing inflammatory factors (such as IL-18, HMGB1) and damage-associated molecular patterns (DAMPs), recruiting CD8+ T cells and natural killer (NK) cell infiltration, and thus transforming "cold tumors" into "hot tumors". OVs can be transformed to express GSDM proteins, regulate mitochondrial dysfunction, and target tumor immune components to promote the treatment of tumors through pyroptosis. This article provides a theoretical basis for the clinical transformation of OVs and suggests that pyroptosis-based combination therapy may become an important direction for future tumor im-munotherapy.
The Mechanism of Circulating Tumor Cell (CTC) Detection
The high lethality of cancer is mainly attributed to its metastatic ability. Circulating tumor cells (CTCs), as important mediators driving tumor metastasis, have significant research value in tumor progression and prognosis assessment. In recent years, CTC detection methods have been continuously evolving, mainly including detection based on cell surface proteins and detection based on intracellular miRNA molecular markers. Surface protein detection techniques are mature and high-throughput, but prone to missed detections when epithelial-mesenchymal transition (EMT) causes phenotypic changes; miRNA detection, on the other hand, can dynamically reflect the status of tumor cells, with high sensitivity, yet the process is complex and difficult to apply on a large scale. Currently, capturing the phenotypically heterogeneous and rare CTCs accurately remains a challenge in the field of detection. This paper systematically analyzes the principles, methods, current applications, and respective issues of the two major classes of CTC detection technologies: miRNA and surface protein detection. Furthermore, it discusses the positive role of combined detection in enhancing detection sensitivity and accuracy. Studies indicate that multi-marker combined detection can more comprehensively identify CTC heterogeneity, aiding in early tumor diagnosis, dynamic monitoring, and precise treatment. This paper provides a reference for the optimization of subsequent CTC detection technologies and in-depth research on tumor metastasis mechanisms, while pointing out current deficiencies in standardization, automation, and functional status analysis. Future research may focus on directions such as multi-omics integration and intelligent analysis.
TPM-1: A Novel Biomaterial for Cancer Immunotherapy Targeting PD-L1
Immune checkpoint blockade therapy is highly effective for cancer treatment; however, its low response rate limits its clinical application. TPM-1, a novel biomaterial that targets PD-L1, presents a new approach to address this issue. This paper discusses the synthesis, mechanism of action, and drug properties of TPM-1. TPM-1 is a peptide-based self-assembling nanoparticle (TPMI) designed to specifically bind to PD-L1 on the surface of tumor cells, forming a fibrous network in situ. This process promotes the aggregation of PD-L1 and blocks the PD-1/PD-L1 pathway. Compared to traditional inhibitors, TPM-1 offers enhanced targeting and stability, which can help overcome drug resistance and facilitate multi-mechanism synergistic therapy. TPM-1 significantly improves PD-L1 blocking efficiency due to its unique design, demonstrating excellent anti-tumor effects in both in vitro and in vivo experiments. Its self-assembly properties enhance drug retention at tumor sites while minimizing systemic toxicity, providing a promising new strategy for cancer immunotherapy. In the future, the delivery system for TPM-1 can be further optimized, and its potential for combination with other therapies can be explored to promote clinical translation.
Natural Killer Cells Therapy: From in Vitro Amplification to Engineering Modification
In cancer treatment, traditional therapies are limited, and T-cell therapies are faced with challenges such as high costs and toxicity. As a mainstay of innate immunity, natural killer (NK) cells offer distinct advantages, including the ability to kill target cells without antigen sensitization, a low risk of graft-versus-host disease (GVHD), and the potential for "off-the-shelf" application. This review summarizes recent advancements in NK cell-based therapies, focusing on in vitro amplification strategies and genetic engineering modifications. Key findings include: cytokine and feeder layer co-culture systems have been shown to expand NK cells over 500-fold; CD19-targeted chimeric antigen receptor (CAR)-NK cells exhibit a 50%-70% response rate in B-cell lymphoma patients; CRISPR-mediated gene editing enhances cytotoxicity against solid tumors; nanoparticle-based delivery systems improve tumor infiltration of NK cells; and allogeneic NK cell therapy carries a near-zero GVHD risk. Notably, significant challenges persist, such as the immunosuppressive tumor microenvironment, poor in vivo persistence of NK cells, congenital functional defects, potential off-target effects of CAR-NK cells, and the lack of standardized production protocols. While NK cell therapy demonstrates substantial promise in cancer immunotherapy, overcoming these bottlenecks is essential for its broader clinical translation and application.
The Role of m6A Modification in the PD-1/PD-L1 Pathway: from the Inherent Mechanism of Tumor Cells to the Regulation of Immune Microenvironment
The most common epigenome modification in eukaryotic mRNA is N6-methyladenosine modification, which is often referred to as m6A modification. It plays an important role in carcinogenesis, immunological evasion, and drug resistance. The programmed cell death protein 1/programmed death ligand 1(PD-1/PD-L1) pathway is critical for tumor immune evasion. Targeting PD-1/PD-L1 pathway has emerged as a crucial method for treating patients who were diagnosed with advanced tumors. Recent studies have found that: (1) m6A modification acts on this pathway by regulating intrinsic mechanisms of tumor cells, such as affecting the expression of PD-L1 to make it enhanced or decreased or activating the downstream signaling pathway; (2) m6A modification regulates this pathway by modifying the immune environment such as influencing T cell activity and macrophage polarization; (3) m6A modification plays multiple roles in this pathway through the bidirectional regulatory network, suggesting its important clinical translational potential as a possible therapeutic target and prognosis indicator. This article systematically reviewed the mechanism of molecular action of m6A modification in this PD-1/PD-L1 pathway, explored its joint utility and potential intervention strategies, aiming to provide new ideas for overcoming immunotherapy resistance.
Thermalization of Cold Tumor: A Comprehensive Treatment Path for the Transformation of Cold Tumor to Hot Tumor
This article reviews the emerging comprehensive treatment strategies for the transformation of "cold tumor" to "hot tumor", aiming to overcome the limitations of immunotherapy in tumors with low response rates. "Hot tumors" usually have abundant immune cell infiltration and active immune microenvironment, while "cold tumors" respond poorly to immunotherapy due to less immune cell infiltration and strong inhibitory microenvironment. This article focuses on three TME remodeling strategies: Tesla Cell activates innate immunity through metabolic reprogramming (such as inhibition of LDH-A and neutralization of lactate); Near-infrared photoimmunotherapy (NIR- PIT) uses photosensitizers to induce immunogenic death and reverse the immunosuppressive microenvironment. Hyperthermia enhances the activity of immune cells by directly killing tumor cells with high temperature and releasing antigens. In addition, this article analyzes the potential of these strategies in combination with immune checkpoint inhibitors, adoptive cell therapy and tumor vaccines, and compares their intrinsic/exogenous characteristics, safety and clinical transformation prospects. The "hyperthermia" of cold tumors provides a new direction for immunotherapy, which is expected to significantly improve the efficacy of refractory tumors.
Research Progress and Clinical Prospects of Dendritic Cell Vaccines in Breast Cancer Immunotherapy
Dendritic cell (DC) vaccines have shown significant research progress and clinical prospects in breast cancer immunotherapy. This article seeks to explain how dendritic cells (DC) show antigens in the immune environment of breast cancer and discuss the difficulties in creating and preparing DC vaccines to make them more effective. The advantages and disadvantages of DC vaccinations and other therapies were evaluated, combined application strategy of DC vaccines with other therapies such chemotherapy, immune checkpoint inhibitors, and radiotherapy was examined. By improving Presentation of an antigen and reducing T cell immunosuppression, the data demonstrated that DC vaccines can have a synergistic effect when used in conjunction with other treatments, greatly boosting the immune system that combats tumors. response. Compared with CAR-T cell therapy, DC vaccines are less likely to cause serious side effects such as cytokine storms. Compared with PD-L1 inhibitors, DC vaccines can actively activate the immune system, produce immune responses against specific tumor antigens, and have immune memory effects. To further enhance the design and administration of DC vaccines and increase their effectiveness in breast cancer immunotherapy, future research should concentrate on the creation of novel vaccine adjuvants, The discovery of new antigens related to tumors and the development of vaccine delivery methods.
CRISPR-dCas9 in Cancer Epigenetic Therapy Progress
Cancer appears and develops not only related to genes but also takes an important role in epigenetic regulation. In recent years, CRISPR-dCas9 as a new precision gene-editing tool has aroused much attention because it can combine with epigenetic effectors to regulate cancer-related genes specifically. It shows great prospects for treating a wide variety of diseases, particularly for epigenetic modifications of cancer. This article reviews the biochemistry of CRISPR-dCas9 systems and their use in epigenetic modification of cancer, focusing on how DNA methylation, histone modification, etc., affect tumorigenesis. In addition, the recent progress, challenges, and prospects of CRISPR-dCas9 mediated epigenetic editing technology for cancer gene therapy are also presented. By analyzing the current problems encountered in the clinical translation of CRISPR-dCas9 technology, this article has shown that CRISPR-dCas9 technology has the potential to become a targeted cancer treatment, which can also provide references for future medical research.
Acute light deprivation triggers anxiety-like and depressive behaviors in mice
Light exposure plays a critical role in regulating circadian rhythms and mood-related behaviors. While chronic, constant light deprivation has been extensively studied pertaining to anxiety and depression, the impact of acute deprivation of light exposure remains poorly understood. This study investigated the acute light deprivation-induced effects on anxiety and depressive-like behaviors of male C57BL/6 mice. Six behavioral tests were employed to comprehensively assess anxiety-like and depressive-like levels, including the open field test (OFT), elevated zero maze (EZM), light-dark box test (LDT), sucrose splash test (SST), forced swim test (FST), and tail suspension test (TST). The results indicated that there was no significant difference in anxiety-related measures between the control and light-deprived mice. In contrast, depressive-like behaviors were significantly elevated in the light-deprived mice, as evidenced by reduced self-grooming behavior in the SST and increased immobility in stress-inducing environments in the FST and TST. These findings suggest that even short-term and moderate light deprivation can induce depressive phenotypes, emphasizing the sensitivity of mood regulation to environmental changes, especially light exposure, and highlighting the potential mental health risks faced by urban populations with restricted access to natural light. Further studies are warranted to elucidate the underlying neurobiological mechanisms.
Analysis of Research Methods for Heterogeneous Cellular Senescence Biomarkers
Cellular senescence is a fundamental mechanism underlying organismal aging and the development of numerous age-related diseases. Accurate detection of senescent cells is key for understanding and intervening in the aging process. Molecules such as p16INK4a, p21, and SA-β-gal have been widely used in senescence detection. Traditional SA-β-gal staining is popular for its simplicity, but emerging high-throughput spatial omics techniques, such as seqFISH, now enable high-resolution and dynamic multi-marker tracking of senescent cells. Using multi-omics and spatial approaches, researchers are elucidating the distribution and molecular heterogeneity of senescent cells in tissues. However, existing detection methods still lack in specificity, throughput, and clinical utility, and a universal, standardized high-precision detection system remains elusive. This review systematically analyzes the molecular mechanisms and detection methods for p16INK4a, p21, and SA-β-gal, evaluates technological developments from classical biochemical methods to innovative spatial transcriptomics (ST), discusses the potential of single-cell multi-omics and novel biomarkers for improving detection accuracy and understanding senescence heterogeneity, and summarizes limitations and challenges faced by each approach. The results suggest that integrating multi-marker and spatial omics technology can significantly enhance the accuracy and resolution of senescent cell detection, providing a technical basis for developing innovative anti-aging drugs and disease interventions. This study provides reference for optimizing senescent cell detection and biomarker screening, emphasizing the importance of a standardized multi-omics system. Future directions should focus on improving clinical translatability, exploring molecular regulation and cellular heterogeneity within the senescent microenvironment, and advancing disease diagnosis and healthy aging.