ALOX5 induces EMT and promotes cell metastasis via the LTB4/BLT2/PI3K/AKT pathway in ovarian cancer.

Ovarian cancer represents the most lethal gynecological malignancy with high invasiveness. Epithelial-to-mesenchymal transition (EMT) plays a critical role in cancer metastasis. However, the role of ALOX5 in EMT and cancer metastasis in ovarian cancer (OC) remain unclear. In this study, ALOX5 was significantly upregulated in tumorous and metastatic tissue compared with normal tissue. Furthermore, we found that overexpression of ALOX5 promoted cell migration and invasion, while silencing of ALOX5 suppressed migration and invasion in OC cell lines. Mechanistically, we found that enhanced expression of ALOX5 promoted EMT and cancer metastasis through activation of the PI3K/AKT pathway, whereas SNAIl inhibited the transcription of CDH1 in OC cells. Taken together, our results highlight a role for the ALOX5/PI3K/AKT/ SNAI1 axis in OC, which provides novel strategies for the prevention of metastasis in OC.

Monocyte/Macrophage-Mediated Transport of Dual-Drug ZIF Nanoplatforms Synergized with Programmed Cell Death Protein-1 Inhibitor Against Microsatellite-Stable Colorectal Cancer.

Microsatellite-stable colorectal cancer (MSS-CRC) exhibits resistance to programmed cell death protein-1 (PD-1) therapy. Improving the infiltration and tumor recognition of cytotoxic T-lymphocytes (CTLs) is a promising strategy, but it encounters huge challenges from drug delivery and mechanisms aspects. Here, a zeolitic imidazolate framework (ZIF) coated with apoptotic body membranes derived from MSS-CRC cells is engineered for the co-delivery of ginsenoside Rg1 (Rg1) and atractylenolide-I (Att) to MSS-CRC, named as Ab@Rg1/Att-ZIF. This system is selectively engulfed by Ly-6C+ monocytes during blood circulation and utilizes a "hitchhiking" mechanism to migrate toward the core of MSS-CRC. Ab@Rg1/Att-ZIF undergoes rapid disassembly in the tumor, released Rg1 promotes the processing and transportation of tumor antigens in dendritic cells (DCs), enhancing their maturation. Meanwhile, Att enhances the activity of the 26S proteasome complex in tumor cells, leading to increased expression of major histocompatibility complex class-I (MHC-I). These coordinated actions enhance the infiltration and recognition of CTLs in the center of MSS-CRC, significantly improving the tumor inhibition of PD-1 treatment from ≈5% to ≈69%. This innovative design, involving inflammation-guided precise drug co-delivery and a rational combination, achieves synergistic engineering of the tumor microenvironment, providing a novel strategy for successful PD-1 treatment of MSS-CRC.

Identification and validation of Rab GTPases RAB13 as biomarkers for peritoneal metastasis and immune cell infiltration in colorectal cancer patients.

Background: As one of the most common cancer, colorectal cancer (CRC) is with high morbidity and mortality. Peritoneal metastasis (PM) is a fatal state of CRC, and few patients may benefit from traditional therapies. There is a complex interaction between PM and immune cell infiltration. Therefore, we aimed to determine biomarkers associated with colorectal cancer peritoneal metastasis (CRCPM) and their relationship with immune cell infiltration. Methods: By informatic analysis, differently expressed genes (DEGs) were selected and hub genes were screened out. RAB13, one of the hub genes, was identificated from public databases and validated in CRC tissues. The ESTIMATE, CEBERSORT and TIMER algorithms were applied to analyze the correlation between RAB13 and immune infiltration in CRC. RAB13's expression in different cells were analyzed at the single-cell level in scRNA-Seq. The Gene Set Enrichment Analysis (GSEA) was performed for RAB13 enrichment and further confirmed. Using oncoPredict algorithm, RAB13's impact on drug sensitivity was evaluated. Results: High RAB13 expression was identified in public databases and led to a poor prognosis. RAB13 was found to be positively correlated with the macrophages and other immune cells infiltration and from scRNA-Seq, RAB13 was found to be located in CRC cells and macrophages. GSEA revealed that high RAB13 expression enriched in a various of biological signaling, and oncoPredict algorithm showed that RAB13 expression was correlated with paclitaxel sensitivity. Conclusion: Our study indicated clinical role of RAB13 in CRC-PM, suggesting its potential as a therapeutic target in the future.

Generation of a novel attenuated IBDV vaccine strain by mutation of critical amino acids in IBDV VP5.

Infectious bursal disease virus (IBDV) is an acute and highly infectious RNA virus known for its immunosuppressive capabilities, chiefly inflicting rapid damage to the bursa of Fabricius (BF) of chickens. Current clinical control of IBDV infection relies on vaccination. However, the emergence of novel variant IBDV (nVarIBDV) has posed a threat to the poultry industry across the globe, underscoring the great demand for innovative and effective vaccines. Our previous studies have highlighted the critical role of IBDV VP5 as an apoptosis-inducer in host cells. In this study, we engineered IBDV mutants via a reverse genetic system to introduce amino acid mutations in VP5. We found that the mutant IBDV-VP5/3m strain caused reduced host cell mortality, and that strategic mutations in VP5 reduced IBDV replication early after infection, thereby delaying cell death. Furthermore, inoculation of chickens with IBDV-VP5/3m effectively reduced damage to BF and induced neutralizing antibody production comparable to that of parental IBDV WT strain. Importantly, vaccination with IBDV-VP5/3m protected chickens against challenges with nVarIBDV, an emerging IBDV variant strain in China, reducing nVarIBDV loads in BF while alleviating bursal atrophy and splenomegaly, suggesting that IBDV-VP5/3m might serve as a novel vaccine candidate that could be further developed as an effective vaccine for clinical control of IBD. This study provides a new clue to the development of novel and effective vaccines.

Ferroptosis-related lncRNAs: Distinguishing heterogeneity of the tumour microenvironment and predicting immunotherapy response in bladder cancer.

Ferroptosis, a cell death pathway dependent on iron, has been shown in research to play a role in the development, advancement, and outlook of tumours through ferroptosis-related lncRNAs (FRLRs). However, the value of the FRLRs in bladder cancer (BLCA) has not been thoroughly investigated. This research project involved developing a predictive model using ten specific FRLRs (AC099850.4, AL731567.1, AL133415.1, AC021321.1, SPAG5-AS1, HMGA2-AS1, RBMS3-AS3, AC006160.1, AL583785.1, and AL662844.4) through univariate COX and LASSO regression techniques. The validation of this signature as a standalone predictor was confirmed in a group of 65 patients from the urology bladder tumour database at the First Affiliated Hospital of Wenzhou Medical University in Wenzhou, China. Patients were categorized based on their median risk score into either a low-risk group or a high-risk group. Enrichment analysis identified possible molecular mechanisms that could explain the variations in clinical outcomes observed in high-risk and low-risk groups. Moreover, we explored the correlation between FLPS and immunotherapy-related indicators. The ability of FLPS to forecast the effectiveness of immunotherapy was validated by the elevated levels of immune checkpoint genes (PD-L1, CTLA4, and PD-1) in the group at high risk. We also screened the crucial FRLR (HMGA2-AS1) through congruent expression and prognostic conditions and established a ceRNA network, indicating that HMGA2-AS1 may affect epithelial-mesenchymal transition by modulating the Wnt signalling pathway through the ceRNA mechanism. We identified the top five mRNAs (NFIB, NEGR1, JAZF1, JCAD, and ESM1) based on random forest algorithm and analysed the relationship between HMGA2-AS1, the top five mRNAs, and immunotherapy, and their interactions with drug sensitivities. Our results suggest that patients with BLCA have a greater sensitivity to four drugs (dasatinib, pazopanib, erismodegib and olaparib). Our study provides new insights into the TME, key signalling pathways, genome, and potential therapeutic targets of BLCA, with future guidance for immunotherapy and targeted precision drugs.

[In vivo tumor imaging and therapy based on near-infrared cadmium-free quantum dots].

Near-infrared fluorescence imaging technology, which possesses superior advantages including real-time and fast imaging, high spatial and temporal resolution, and deep tissue penetration, shows great potential for tumor imaging in vivo and therapy. Ⅰ-Ⅲ-Ⅵ quantum dots exhibit high brightness, broad excitation, easily tunable emission wavelength and superior stability, and do not contain highly toxic heavy metal elements such as cadmium or lead. These advantages make Ⅰ-Ⅲ-Ⅵ quantum dots attract widespread attention in biomedical field. This review summarizes the recent advances in the controlled synthesis of Ⅰ-Ⅲ-Ⅵ quantum dots and their applications in tumor imaging in vivo and therapy. Firstly, the organic-phase and aqueous-phase synthesis of Ⅰ-Ⅲ-Ⅵ quantum dots as well as the strategies for regulating the near-infrared photoluminescence are briefly introduced; secondly, representative biomedical applications of near-infrared-emitting cadmium-free quantum dots including early diagnosis of tumor, lymphatic imaging, drug delivery, photothermal and photodynamic therapy are emphatically discussed; lastly, perspectives on the future directions of developing quantum dots for biomedical application and the faced challenges are discussed. This paper may provide guidance and reference for further research and clinical translation of cadmium-free quantum dots in tumor diagnosis and treatment.

Adaptor protein 14-3-3zeta promotes corneal wound healing via regulating cell homeostasis, a potential novel therapy for corneal injury.

Severe corneal injury can lead to blindness even after prompt treatment. 14-3-3zeta, a member of an adaptor protein family, contributes to tissue repair by enhancing cellular viability and inhibiting fibrosis and inflammation in renal disease or arthritis. However, its role in corneal regeneration is less studied. In this study, filter disc of 2-mm diameter soaked in sodium hydroxide with a concentration of 0.5 N was placed at the center of the cornea for 30 s to establish a mouse model of corneal alkali injury. We found that 14-3-3zeta, which is mainly expressed in the epithelial layer, was upregulated following injury. Overexpression of 14-3-3zeta in ocular tissues via adeno-associated virus-mediated subconjunctival delivery promoted corneal wound healing, showing improved corneal structure and transparency. In vitro studies on human corneal epithelial cells showed that 14-3-3zeta was critical for cell proliferation and migration. mRNA-sequencing in conjunction with KEGG analysis and validation experiments revealed that 14-3-3zeta regulated the mRNA levels of ITGB1, PIK3R1, FGF5, PRKAA1 and the phosphorylation level of Akt, suggesting the involvement of the PI3K-Akt pathway in 14-3-3zeta-mediated tissue repair. 14-3-3zeta is a potential novel therapeutic candidate for treating severe corneal injury.

Effective control of postoperative recurrence of pregnancy-related gastric cancer using anti-PD-1 as a monotherapy: a case report.

Pregnancy-related gastric cancer is characterized by a refractory nature and poor prognosis; few gastric cancer cases during pregnancy achieved acceptable outcomes by using anti-PD-1 as a monotherapy. A 32-year-old pregnant female patient was admitted to the emergency department of the obstetrics and gynecology department and eventually diagnosed with gastric cancer. Radical surgery for gastric cancer was conducted after the termination of pregnancy. At 1-year postoperative follow-up, tumor recurrence was revealed. This patient has achieved a decrease in tumor burden after receiving anti-PD-1 as a monotherapy. This case documents tumor response to PD-1 monotherapy in pregnancy-related gastric cancer and highlights the potential for future use in specific clinical scenarios.

Effects of combined microplastic and cadmium pollution on sorghum growth, Cd accumulation, and rhizosphere microbial functions.

The interaction between microplastics (MPs) and cadmium (Cd) poses a threat to agricultural soil environments, and their effects on plant growth and rhizosphere microbial community functions are not yet clear. In this study, energy sorghum was used as a test plant to investigate the effects of two types of MPs, polystyrene (PS) and polyethylene (PE), at different particle sizes (13 µm, 550 µm) and concentrations (0.1%, 1% w/w), and Cd, as well as their interactions, on the growth of sorghum in a soil-cultivation pot experiment. The results showed that the combined effects of MP and Cd pollution on the dry weight and Cd accumulation rate in sorghum varied depending on the type, concentration, and particle size of the MPs, with an overall trend of increasing stress from combined pollution with increasing Cd content and accumulation. High-throughput sequencing analysis revealed that combined MP and Cd pollution increased bacterial diversity, and the most significant increase was observed in the abundance-based coverage estimator (ACE), Shannon, and Sobs indices in the 13 µm 1% PS+Cd treatment group. Metagenomic analysis based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) metabolic pathways revealed that 19 groups of metabolic pathways, including microbial metabolism and methane metabolism, differed significantly under combined MP and Cd pollution. Hierarchical clustering results indicated that Cd treatment and combined MP and Cd treatment affected the abundances of sorghum rhizosphere soil nitrogen (N) and phosphorus (P) cycling genes and that the type of MP present was an important factor affecting N and P cycling genes. The results of this study provide a basis for exploring the toxic effects of combined MP and Cd pollution and for conducting soil environmental risk assessments.

Homologous-magnetic dual-targeted metal-organic framework to improve the Anti-hepatocellular carcinoma efficacy of PD-1 inhibitor.

The insufficient abundance and weak activity of tumour-infiltrating lymphocytes (TILs) are two important reasons for the poor efficacy of PD-1 inhibitors in hepatocellular carcinoma (HCC) treatment. The combined administration of tanshinone IIA (TSA) and astragaloside IV (As) can up-regulate the abundance and activity of TILs by normalising tumour blood vessels and reducing the levels of immunosuppressive factors respectively. For enhancing the efficacy of PD-1 antibody, a magnetic metal-organic framework (MOF) with a homologous tumour cell membrane (Hm) coating (Hm@TSA/As-MOF) is established to co-deliver TSA&As into the HCC microenvironment. Hm@TSA/As-MOF is a spherical nanoparticle and has a high total drug-loading capacity of 16.13 wt%. The Hm coating and magnetic responsiveness of Hm@TSA/As-MOF provide a homologous-magnetic dual-targeting, which enable Hm@TSA/As-MOF to counteract the interference posed by ascites tumour cells and enhance the precision of targeting solid tumours. Hm coating also enable Hm@TSA/As-MOF to evade immune clearance by macrophages. The release of TSA&As from Hm@TSA/As-MOF can be accelerated by HCC microenvironment, thereby up-regulating the abundance and activity of TILs to synergistic PD-1 antibody against HCC. This study presents a nanoplatform to improve the efficacy of PD-1 inhibitors in HCC, providing a novel approach for anti-tumour immunotherapy in clinical practice.

Genome-wide CRISPR screens identify PKMYT1 as a therapeutic target in pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with an overall 5-year survival rate of <12% due to the lack of effective treatments. Novel treatment strategies are urgently needed. Here, PKMYT1 is identified through genome-wide CRISPR screens as a non-mutant, genetic vulnerability of PDAC. Higher PKMYT1 expression levels indicate poor prognosis in PDAC patients. PKMYT1 ablation inhibits tumor growth and proliferation in vitro and in vivo by regulating cell cycle progression and inducing apoptosis. Moreover, pharmacological inhibition of PKMYT1 shows efficacy in multiple PDAC cell models and effectively induces tumor regression without overt toxicity in PDAC cell line-derived xenograft and in more clinically relevant patient-derived xenograft models. Mechanistically, in addition to its canonical function of phosphorylating CDK1, PKMYT1 functions as an oncogene to promote PDAC tumorigenesis by regulating PLK1 expression and phosphorylation. Finally, TP53 function and PRKDC activation are shown to modulate the sensitivity to PKMYT1 inhibition. These results define PKMYT1 dependency in PDAC and identify potential therapeutic strategies for clinical translation.

Nodal staging score for adequacy of nodal staging in cervical cancer.

Background: Cervical cancer remains the fourth most common female malignancy with increasing newly cases around the world. It is of clinical value to precisely evaluate whether false negative nodal existed and develop a nodal staging model in cervical cancer. Materials and methods: Clinical data of cervical cancer patients was retrieved from the Surveillance, Epidemiology, and End Results database. Probability of missing nodal disease and nodal staging score (NSS) was computed to assess the nodal status of each individual.Prognostic value of NSS was assessed. Results: A total of 9056 individuals were in this study, with 5115 squamous cell carcinoma, 2791 adenocarcinoma, 512 adenosquamous carcinoma, and 638 other type individuals. A beta-binomial model was used to compute the probability of nodal disease in four histological types, respectively. False negative probability drastically decreased as more nodes examined. To reach 0.05 of false negative probability, it required at least 17 lymph nodes in squamous cell carcinoma patients,18 in adenocarcinoma, 12 in adenosquamous carcinoma patients and 14 in other types. To reach 0.95 of NSS, it took 10 lymph nodes in squamous cell carcinoma, 6 in adenocarcinoma, 10 in adenosquamous carcinoma and 7 in other types. Significant prognostic values of NSS quartiles subsets were found in all four histological sets. Conclusion: NSS tool enables adequate nodal staging of cervical cancer with significant prognostic value. Exact number of lymph nodes required for surgery in cervical cancer is specified based on histologic type.

Oxidized DJ-1 activates the p-IKK/NF-κB/Beclin1 pathway by binding PTEN to induce autophagy and exacerbate myocardial ischemia-reperfusion injury.

Patients with myocardial infarction have a much worse prognosis when they have myocardial ischemia-reperfusion (I/R) injury. Further research into the molecular basis of myocardial I/R injury is therefore urgently needed, as well as the identification of novel therapeutic targets and linkages to interventions. Three cysteine residues are present in DJ-1 at amino acids 46, 53, and 106 sites, with the cysteine at position 106 being the most oxidation-prone. This study sought to understand how oxidized DJ-1(C106) contributes to myocardial I/R damage. Rats' left anterior descending branches were tied off to establish a myocardial I/R model in vivo. A myocardial I/R model in vitro was established via anoxia/reoxygenation (A/R) of H9c2 cells. The results showed that autophagy increased after I/R, accompanied by the increased expression of oxidized DJ-1 (ox-DJ-1). In contrast, after pretreatment with NAC (N-acetylcysteine, a ROS scavenger) or Comp-23 (Compound-23, a specific antioxidant binding to the C106 site of DJ-1), the levels of ox-DJ-1, autophagy and LDH release decreased, and cell survival rate increased. Furthermore, the inhibition of interaction between ox-DJ-1 and PTEN could increase PTEN phosphatase activity, inhibit the p-IKK/NF-κB/Beclin1 pathway, reduce injurious autophagy, and alleviate A/R injury. However, BA (Betulinic acid, a NF-κB agonist) was able to reverse the protective effects produced by Comp-23 pretreatment. In conclusion, ox-DJ-1 could activate detrimental autophagy through the PTEN/p-IKK/NF-κB/Beclin1 pathway and exacerbate myocardial I/R injury.

Novel methyltransferase G9a inhibitor induces ferroptosis in multiple myeloma through Nrf2/HO-1 pathway.

Multiple myeloma (MM) is a common malignant hematologic neoplasm, and the involvement of epigenetic modifications in its development and drug resistance has received widespread attention. Ferroptosis, a new ferroptosis-dependent programmed death mode, is closely associated with the development of MM. The novel methyltransferase inhibitor DCG066 has higher cell activity, but its mechanism of action in MM has not been clarified. Here, we found that DCG066 (5µM) inhibited the proliferation and induced ferroptosis in MM cells; the intracellular levels of ROS, iron, and MDA were significantly elevated, and the level of GSH was reduced after the treatment of DCG066; The protein expression levels of SLC7A11, GPX4, Nrf2 and HO-1 were significantly reduced, and these phenomena could be reversed by ferroptosis inhibitor Ferrostatin-1 (Fer-1) and Nrf2 activator Tert-butyl hydroquinone (TBHQ). Meanwhile, the protein expression levels of Keap1 was increased, and heat shock proteins (HSP70, HSP90 and HSPB1) were reduced after DCG066 treatment. In conclusion, this study confirmed that DCG066 inhibits MM proliferation and induces ferroptosis via the Nrf2/HO-1 pathway.

Intestinal organoid modeling: bridging the gap from experimental model to clinical translation.

The 3D culture of intestinal organoids entails embedding isolated intestinal crypts and bone marrow mesenchymal stem cells within a growth factor-enriched matrix gel. This process leads to the formation of hollow microspheres with structures resembling intestinal epithelial cells, which are referred to as intestinal organoids. These structures encompass various functional epithelial cell types found in the small intestine and closely mimic the organizational patterns of the small intestine, earning them the name "mini-intestines". Intestinal tumors are prevalent within the digestive system and represent a significant menace to human health. Through the application of 3D culture technology, miniature colorectal organs can be cultivated to retain the genetic characteristics of the primary tumor. This innovation offers novel prospects for individualized treatments among patients with intestinal tumors. Presently established libraries of patient-derived organoids serve as potent tools for conducting comprehensive investigations into tissue functionality, developmental processes, tumorigenesis, and the pathobiology of cancer. This review explores the origins of intestinal organoids, their culturing environments, and their advancements in the realm of precision medicine. It also addresses the current challenges and outlines future prospects for development.

TMED3 stabilizes SMAD2 by counteracting NEDD4-mediated ubiquitination to promote ovarian cancer.

Ovarian cancer is a major cause of death among cancer patients. Recent research has shown that the transmembrane emp24 domain (TMED) protein family plays a role in the progression of various types of cancer. In this study, we investigated the expression of TMED3 in ovarian cancer tumors compared to nontumor tissues using immunohistochemical staining. We found that TMED3 was overexpressed in ovarian cancer tumors, and its high expression was associated with poor disease-free and overall survival. To understand the functional implications of TMED3 overexpression in ovarian cancer, we conducted experiments to knockdown TMED3 using short hairpin RNA (shRNA). We observed that TMED3 knockdown resulted in reduced cell viability and migration, as well as increased cell apoptosis. Additionally, in subcutaneous xenograft models in BALB-c nude mice, TMED3 knockdown inhibited tumor growth. Further investigation revealed that SMAD family member 2 (SMAD2) was a downstream target of TMED3, driving ovarian cancer progression. TMED3 stabilized SMAD2 by inhibiting the E3 ligase NEDD4-mediated ubiquitination of SMAD2. To confirm the importance of SMAD2 in TMED3-mediated ovarian cancer, we performed functional rescue experiments and found that SMAD2 played a critical role in this process. Moreover, we discovered that the PI3K-AKT pathway was involved in the promoting effects of TMED3 overexpression on ovarian cancer cells. Overall, our study identifies TMED3 as a prognostic indicator and tumor promoter in ovarian cancer. Its function is likely mediated through the regulation of the SMAD2 and PI3K-AKT signaling pathway. These findings contribute to our understanding of the molecular mechanisms underlying ovarian cancer progression and provide potential targets for therapeutic intervention.

Synthesis and Properties of Cobalt/Nickel-Iron-Antimony(III, V)-Oxo Tartrate Cluster-Based Compounds.

Two types of isostructural iron-cobalt/nickel-antimony-oxo tartrate cluster-based compounds, namely (H3O)(Me2NH2)[M(H2O)6]2[FeII2SbIII12(µ4-O)3(µ3-O)8(tta)6]·6H2O (M = Co (1); Ni (3)), H5/3[Co2.5FeII4/3FeIII3(H2O)13SbV1/3FeIII2/3(µ4-O)2(µ3-O)4SbIII6(µ3-O)2(tta)6]·2H2O (2) and H2[Ni2.25FeII1.5FeIII3(H2O)14SbV0.25FeIII0.75(µ4-O)2(µ3-O)4SbIII6(µ3-O)2(tta)6]·2H2O (4) (H4tta = tartaric acid) were synthesized via simple solvothermal reactions. All the clusters in the structures adopt sandwich configurations, that is, bilayer sandwich configuration in 1 and 3 and monolayer sandwich configuration in 2 and 4. Interestingly, the monolayer sandwiched compounds 2 and 4 represent rare examples of cluster-based compounds containing mixed-valence Sb(III, V), whose center of the intermediate layer is the co-occupied [FexSbV1-x]. This is different from that of previously reported sandwich-type antimony-oxo clusters in which the center position is either occupied by a transition metal ion or a Sb(V) alone. Thus, the discovery of title compounds 2 and 4 makes the evolution of center metal ion more complete, that is, from M, MxSbV1-x to SbV. All the title compounds were fully characterized, and the photocatalysis, proton conduction and magnetism of compounds 2 and 4 were studied.

Drug-Loaded Biomimetic Carriers for Non-Hodgkin's Lymphoma Therapy: Advances and Perspective.

Chemotherapy remains the mainstay of treatment for the lymphoma patient population, despite its relatively poor therapeutic results, high toxicity, and low specificity. With the advancement of biotechnology, the significance of drug-loading biomimetic materials in the medical field has become increasingly evident, attracting extensive attention from the scientific community and the pharmaceutical industry. Given that they can cater to the particular requirements of lymphoma patients, drug-loading biomimetic materials have recently become a potent and promising delivery approach for various applications. This review mainly reviews the recent advancements in the treatment of tumors with biological drug carrier-loaded drugs, outlines the mechanisms of lymphoma development and the diverse treatment modalities currently available, and discusses the merits and limitations of biological drug carriers. What is more, the practical application of biocarriers in tumors is explored by providing examples, and the possibility of loading such organisms with antilymphoma drugs for the treatment of lymphoma is conceived.

Stomatin-like protein 2 promotes cell proliferation and survival under 5-Fluorouracil stress in hepatocellular carcinoma.

BACKGROUND: The crucial role of STOML2 in tumor progression has been documented recently in various cancers. Previous studies have shown that STOML2 promoted cancer cell proliferation, but the underlying mechanism is not fully illustrated. METHODS AND RESULTS: The expression and clinical relevance of STOML2 in pan-cancer was analyzed by TIMER2 web platform in pan-cancer. The prognostic significance of STOML2 in HCC was evaluated utilizing KM curve and a nomogram model. Signaling pathways associated with STOML2 expression were discovered by GSEA. CCK-8 assay was performed to evaluate the proliferative capacity of HCC cells after manipulating STOML2 expression. Flow cytometry was utilized to analyze cell cycle progression. Results indicated that increased STOML2 expression in HCC linked to unfavorable clinical outcomes. Cell cycle and cell division related terms were enriched under conditions of elevated STOML2 expression via GSEA analysis. A notable decrease in cell proliferation was observed in MHCC97H with STOML2 knocked-down, accompanied by G1-phase arrest, up-regulation of p21, down-regulation of CyclinD1 and its regulatory factor MYC, while STOML2 overexpression in Huh7 showed the opposite results. These results indicated that STOML2 was responsible for HCC proliferation by regulating the expression level of MYC/cyclin D1 and p21. Furthermore, an inverse correlation was found between STOML2 expression and 5-FU sensitivity. CONCLUSIONS: STOML2 promotes cell cycle progression in HCC which is associated with activation of MYC/CyclinD1/p21 pathway, and modulates the response of HCC to 5-FU.

SMYD3 promotes endometrial cancer through epigenetic regulation of LIG4/XRCC4/XLF complex in non-homologous end joining repair.

Endometrial cancer (EC) stands as one of the most prevalent malignancies affecting the female genital tract, witnessing a rapid surge in incidence globally. Despite the well-established association of histone methyltransferase SMYD3 with the development and progression of various cancers, its specific oncogenic role in endometrial cancer remains unexplored. In the present study, we report that the expression level of SMYD3 is significantly upregulated in EC samples and associated with EC progression. Through meticulous in vivo and in vitro experiments, we reveal that depletion of SMYD3 curtails cell proliferation, migration, and invasion capabilities, leading to compromised non-homologous end joining repair (NHEJ) and heightened sensitivity of EC cells to radiation. Furthermore, our pathway enrichment analysis underscores the pivotal involvement of the DNA damage repair pathway in regulating EC progression. Mechanistically, in response to DNA damage, SMYD3 is recruited to these sites in a PARP1-dependent manner, specifically methylating LIG4. This methylation sets off a sequential assembly of the LIG4/XRCC4/XLF complex, actively participating in the NHEJ pathway and thereby fostering EC progression. Notably, our findings highlight the promise of SMYD3 as a crucial player in NHEJ repair and its direct correlation with EC progression. Intriguingly, pharmacological intervention targeting SMYD3 with its specific inhibitor, BCI-121, emerges as a potent strategy, markedly suppressing the tumorigenicity of EC cells and significantly enhancing the efficacy of radiotherapy. Collectively, our comprehensive data position SMYD3 as a central factor in NHEJ repair and underscore its potential as a promising pharmacological target for endometrial cancer therapy, validated through both in vitro and in vivo systems.