RESUMEN
Renal cell carcinoma (RCC) is one of the most common tumors that afflicts the urinary system, accounting for 90-95% of kidney cancer cases. Although its incidence has increased over the past decades, its pathogenesis is still unclear. Tumor-associated macrophages (TAMs) are the most prominent immune cells in the tumor microenvironment (TME), comprising more than 50% of the tumor volume. By interacting with cancer cells, TAMs can be polarized into two distinct phenotypes, M1-type and M2-type TAMs. In the TME, M2-type TAMs, which are known to promote tumorigenesis, are more abundant than M1-type TAMs, which are known to suppress tumor growth. This ratio of M1 to M2 TAMs can create an immunosuppressive environment that contributes to tumor cell progression and survival. This review focused on the role of TAMs in RCC, including their polarization, impacts on tumor proliferation, angiogenesis, invasion, migration, drug resistance, and immunosuppression. In addition, we discussed the potential of targeting TAMs for clinical therapy in RCC. A deeper understanding of the molecular biology of TAMs is essential for exploring innovative therapeutic strategies for the treatment of RCC.
Asunto(s)
Carcinoma de Células Renales , Inmunoterapia , Neoplasias Renales , Macrófagos Asociados a Tumores , Humanos , Carcinoma de Células Renales/terapia , Carcinoma de Células Renales/inmunología , Carcinoma de Células Renales/patología , Macrófagos Asociados a Tumores/inmunología , Macrófagos Asociados a Tumores/metabolismo , Inmunoterapia/métodos , Neoplasias Renales/inmunología , Neoplasias Renales/terapia , Neoplasias Renales/patología , Microambiente Tumoral/inmunologíaRESUMEN
Biomaterials with osteoinductivity are widely used for bone defect repair due to their unique structures and functions. Machine learning (ML) is pivotal in analyzing osteoinductivity and accelerating new material design. However, challenges include creating a comprehensive database of osteoinductive materials and dealing with low-quality, disparate data. As a standard for evaluating the osteoinductivity of biomaterials, ectopic ossification has been used. This paper compiles research findings from the past thirty years, resulting in a robust database validated by experts. To tackle issues of limited data samples, missing data, and high-dimensional sparsity, a data enhancement strategy is developed. This approach achieved an area under the curve (AUC) of 0.921, a precision of 0.839, and a recall of 0.833. Model interpretation identified key factors such as porosity, bone morphogenetic protein-2 (BMP-2), and hydroxyapatite (HA) proportion as crucial determinants of outcomes. Optimizing pore structure and material composition through partial dependence plot (PDP) analysis led to a new bone area ratio of 14.7±7% in animal experiments, surpassing the database average of 10.97%. This highlights the significant potential of ML in the development and design of osteoinductive materials. STATEMENT OF SIGNIFICANCE: This study leverages machine learning to analyze osteoinductive biomaterials, addressing challenges in database creation and data quality. Our data enhancement strategy significantly improved model performance. By optimizing pore structure and material composition, we increased new bone formation rates, showcasing the vast potential of machine learning in biomaterial design.
RESUMEN
Currently, titanium and its alloys have emerged as the predominant metallic biomaterials for orthopedic implants. Nonetheless, the relatively high post-operative infection rate (2-5%) exacerbates patient discomfort and imposes significant economic costs on society. Hence, urgent measures are needed to enhance the antibacterial properties of titanium and titanium alloy implants. The titanium dioxide nanotube array (TNTA) is gaining increasing attention due to its topographical and photocatalytic antibacterial properties. Moreover, the pores within TNTA serve as excellent carriers for chemical ion doping and drug loading. The fabrication of TNTA on the surface of titanium and its alloys can be achieved through various methods. Studies have demonstrated that the electrochemical anodization method offers numerous significant advantages, such as simplicity, cost-effectiveness, and controllability. This review presents the development process of the electrochemical anodization method and its applications in synthesizing TNTA. Additionally, this article systematically discusses topographical, chemical, drug delivery, and combined antibacterial strategies. It is widely acknowledged that implants should possess a range of favorable biological characteristics. Clearly, addressing multiple needs with a single antibacterial strategy is challenging. Hence, this review proposes systematic research into combined antibacterial strategies to further mitigate post-operative infection risks and enhance implant success rates in the future.
RESUMEN
With the high incidence of urogenital tumors worldwide, urinary system tumors are among the top 10 most common tumors in men, with prostate cancer ranking first and bladder cancer fourth. Patients with resistant urogenital tumors often have poor prognosis. In recent years, researchers have discovered numerous specific cancer antigens, which has led to the development of several new anti-cancer drugs. Using protein analysis techniques, researchers developed immune checkpoint inhibitors (ICIs) and antibody-conjugated drugs (ADCs) for the treatment of advanced urogenital tumors. However, tumor resistance often leads to the failure of monotherapy. Therefore, clinical trials of the combination of ICIs and ADCs have been carried out in numerous centers around the world. This article reviewed phase 2 and 3 clinical studies of ICIs, ADCs, and their combination in the treatment of urogenital tumors to highlight safe and effective methods for selecting individualized therapeutic strategies for patients. ICIs activate the immune system, whereas ADCs link monoclonal antibodies to toxins, which can achieve a synergistic effect when the two drugs are combined. This synergistic effect provides multiple advantages for the treatment of urogenital tumors.
Asunto(s)
Ensayos Clínicos Fase II como Asunto , Inhibidores de Puntos de Control Inmunológico , Inmunoconjugados , Neoplasias Urogenitales , Humanos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/farmacología , Neoplasias Urogenitales/tratamiento farmacológico , Neoplasias Urogenitales/inmunología , Neoplasias Urogenitales/patología , Inmunoconjugados/uso terapéutico , Inmunoconjugados/farmacología , Ensayos Clínicos Fase III como AsuntoRESUMEN
Manganese(II)-based contrast agents (MBCAs) are potential candidates for gadolinium-free enhanced magnetic resonance imaging (MRI). In this work, a rigid binuclear MBCA (Mn2-PhDTA2) with a zero-length linker was developed via facile synthetic routes, while the other dimer (Mn2-TPA-PhDTA2) with a longer rigid linker was also synthesized via more complex steps. Although the molecular weight of Mn2-PhDTA2 is lower than that of Mn2-TPA-PhDTA2, their T1 relaxivities are similar, being increased by over 71% compared to the mononuclear Mn-PhDTA. In the presence of serum albumin, the relaxivity of Mn2-PhDTA2 was slightly lower than that of Mn2-TPA-PhDTA2, possibly due to the lower affinity constant. The transmetalation reaction with copper(II) ions confirmed that Mn2-PhDTA2 has an ideal kinetic inertness with a dissociation half-life of approximately 10.4 h under physiological conditions. In the variable-temperature 17O NMR study, both Mn-PhDTA and Mn2-PhDTA2 demonstrated a similar estimated q close to 1, indicating the formation of monohydrated complexes with each manganese(II) ion. In addition, Mn2-PhDTA2 demonstrated a superior contrast enhancement to Mn-PhDTA in in vivo vascular and hepatic MRI and can be rapidly cleared through a dual hepatic and renal excretion pattern. The hepatic uptake mechanism of Mn2-PhDTA2 mediated by SLC39A14 was validated in cellular uptake studies.
Asunto(s)
Medios de Contraste , Hígado , Imagen por Resonancia Magnética , Manganeso , Manganeso/química , Hígado/diagnóstico por imagen , Hígado/metabolismo , Imagen por Resonancia Magnética/métodos , Animales , Medios de Contraste/química , Medios de Contraste/síntesis química , Humanos , Proteínas de Transporte de Catión/metabolismo , Proteínas de Transporte de Catión/química , Ratones , Complejos de Coordinación/química , Complejos de Coordinación/síntesis químicaRESUMEN
Chimeric antigen receptor engineered T (CAR T) cell therapy has developed rapidly in recent years, leading to profound developments in oncology, especially for hematologic malignancies. However, given the pressure of immunosuppressive tumor microenvironments, antigen escape, and diverse other factors, its application in solid tumors is less developed. Urinary system tumors are relatively common, accounting for approximately 24% of all new cancers in the United States. CAR T cells have great potential for urinary system tumors. This review summarizes the latest developments of CAR T cell therapy in urinary system tumors, including kidney cancer, bladder cancer, and prostate cancer, and also outlines the various CAR T cell generations and their pathways and targets that have been developed thus far. Finally, the current advantages, problems, and side effects of CAR T cell therapy are discussed in depth, and potential future developments are proposed in view of current shortcomings.
Asunto(s)
Inmunoterapia Adoptiva , Receptores Quiméricos de Antígenos , Neoplasias Urológicas , Humanos , Inmunoterapia Adoptiva/métodos , Neoplasias Urológicas/terapia , Neoplasias Urológicas/inmunología , Receptores Quiméricos de Antígenos/inmunología , Linfocitos T/inmunología , Animales , Resultado del Tratamiento , Microambiente Tumoral/inmunología , Receptores de Antígenos de Linfocitos T/inmunología , Receptores de Antígenos de Linfocitos T/metabolismoRESUMEN
N6-methyladenosine (m6A) methylation, a prevalent eukaryotic post-transcriptional modification, is involved in multiple biological functions, including mediating variable splicing, RNA maturation, transcription, and nuclear export, and also is vital for regulating RNA translation, stability, and cytoplasmic degradation. For example, m6A methylation can regulate pre-miRNA expression by affecting both splicing and maturation. Non-coding RNA (ncRNA), which includes microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), does not encode proteins but has powerful impacts on transcription and translation. Conversely, ncRNAs may impact m6A methylation by affecting the expression of m6A regulators, including miRNAs targeting mRNA of m6A regulators, or lncRNAs, and circRNAs, acting as scaffolds to regulate transcription of m6A regulatory factors. Dysregulation of m6A methylation is common in urinary tumors, and the regulatory role of ncRNAs is also important for these malignancies. This article provides a systematic review of the role and mechanisms of action of m6A methylation and ncRNAs in urinary tumors.
Asunto(s)
Adenosina , ARN no Traducido , Humanos , Adenosina/análogos & derivados , Adenosina/metabolismo , ARN no Traducido/genética , ARN no Traducido/metabolismo , Metilación , Regulación Neoplásica de la Expresión Génica , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , ARN Circular/genética , ARN Circular/metabolismo , MicroARNs/metabolismo , MicroARNs/genéticaRESUMEN
In a solid, the electronic subsystem can exhibit incipient order with lower point group symmetry than the crystal lattice. Ultrafast external fields that couple exclusively to electronic order parameters have rarely been investigated, however, despite their potential importance in inducing exotic effects. Here we show that when inversion symmetry is broken by the antiferromagnetic order in Cr2O3, transmitting a linearly polarized light pulse through the crystal gives rise to an in-plane rotational symmetry-breaking (from C3 to C1) via optical rectification. Using interferometric time-resolved second harmonic generation, we show that the ultrafast timescale of the symmetry reduction is indicative of a purely electronic response; the underlying spin and crystal structures remain unaffected. The symmetry-broken state exhibits a dipole moment, and its polar axis can be controlled with the incident light. Our results establish a coherent nonlinear optical protocol by which to break electronic symmetries and produce unconventional electronic effects in solids.
RESUMEN
Electric currents have the intriguing ability to induce magnetization in nonmagnetic crystals with sufficiently low crystallographic symmetry. Some associated phenomena include the non-linear anomalous Hall effect in polar crystals and the nonreciprocal directional dichroism in chiral crystals when magnetic fields are applied. In this work, we demonstrate that the same underlying physics is also manifested in the electronic tunneling process between the surface of a nonmagnetic chiral material and a magnetized scanning probe. In the paramagnetic but chiral metallic compound Co1/3NbS2, the magnetization induced by the tunneling current is shown to become detectable by its coupling to the magnetization of the tip itself. This results in a contrast across different chiral domains, achieving atomic-scale spatial resolution of structural chirality. To support the proposed mechanism, we used first-principles theory to compute the chirality-dependent current-induced magnetization and Berry curvature in the bulk of the material. Our demonstration of this magnetochiral tunneling effect opens up an avenue for investigating atomic-scale variations in the local crystallographic symmetry and electronic structure across the structural domain boundaries of low-symmetry nonmagnetic crystals.
RESUMEN
Urothelial carcinoma (UC) is a prevalent malignant tumor involving the urinary system. Although there are various treatment modalities, including surgery, chemotherapy, and immune checkpoint inhibitor (ICI) therapy, some patients experience disease recurrence and metastasis with poor prognosis and dismal long-term survival. Antibody-drug conjugates (ADCs), which combine the targeting ability of antibody drugs with the cytotoxicity of chemotherapeutic drugs, have recently emerged as a prominent research focus in the development of individualized precision cancer therapy. Although ADCs have improved the overall response rate in patients with UC, their effectiveness remains limited. Currently, ADC-based combination therapies, particularly ADC combined with ICIs, have demonstrated promising efficacy. This combination approach has advanced the treatment of UC, exhibiting the potential to become the standard first-line therapy for advanced UC in the future. This article reviewed clinical trials involving ADC-based combination therapy for UC and discussed the possible challenges and future perspectives to provide guidance for the clinical treatment of UC.
Asunto(s)
Carcinoma de Células Transicionales , Inmunoconjugados , Neoplasias de la Vejiga Urinaria , Humanos , Neoplasias de la Vejiga Urinaria/patología , Carcinoma de Células Transicionales/tratamiento farmacológico , Recurrencia Local de Neoplasia , InmunoterapiaRESUMEN
Soil carbon (C) cycling processes in terrestrial ecosystems are significantly influenced by global changes, and soil microorganisms play a crucial role in soil organic carbon (SOC) and its feedbacks to climate change. To investigate the potential future changes in soil C dynamics under different scenarios in the Ziwuling Forest region, China, we conducted a soil observation and sampling experiment from April 2021 to July 2022. By utilizing a microbial ecological model (MEND), we aimed to predict the future dynamics of soil C under different scenarios in the area. Our results demonstrate that under the RCP2.6 (Representative Concentration Pathway) scenario, SOC showed a rapid increase, SOC under the RCP2.6 scenario will be significantly higher than those under the RCP4.5 scenario and RCP8.5 scenario in the topsoil and whole soil. Furthermore, the positive correlation between total litter carbon (LC) and SOC under the RCP2.6 scenario highlights the potential role of total litter carbon in driving SOC dynamics. Our study also revealed that the low greenhouse gas (GHG) emission scenario favors the accumulation of SOC in the study area, while the high GHG emission scenario leads to greater soil carbon loss. Overall, these results underscore the importance of considering the impact of climate change, especially global warming, on soil ecosystems in the future. Protecting the soil ecosystem of the Loess Plateau is critical for maintaining soil carbon sinks, preventing soil erosion, and improving and regulating the surrounding environmental climate.
RESUMEN
In the phase 3 QUAZAR AML-001 trial (NCT01757535) of patients with acute myeloid leukaemia (AML) in remission following intensive chemotherapy (IC) and ineligible for haematopoietic stem cell transplant (HSCT), oral azacitidine (Oral-AZA) maintenance significantly prolonged overall survival (OS) versus placebo. The impact of subsequent treatment following maintenance has not been evaluated. In this post hoc analysis, OS was estimated for patients who received subsequent AML therapy, and by regimen received (IC or lower-intensity therapy). First subsequent therapy (FST) was administered after treatment discontinuation in 134/238 Oral-AZA and 173/234 placebo patients. OS from randomization in patients who received FST after Oral-AZA versus placebo was 17.8 versus 12.9 months (HR: 0.82 [95% CI: 0.64-1.04], median follow-up: 56.7 months); OS from FST was similar between arms. Among patients who received injectable hypomethylating agents as FST, median OS was 8.2 versus 4.9 months in the Oral-AZA versus placebo groups (HR: 0.66 [95% CI: 0.41-1.06]). Forty-eight patients (16/238 Oral-AZA, 32/234 placebo) received HSCT following treatment discontinuation, including six Oral-AZA patients still in first remission; Oral-AZA OS benefit persisted when censoring these patients. Oral-AZA maintenance can prolong AML remission duration without negatively impacting survival outcomes after salvage therapies.
Asunto(s)
Azacitidina , Leucemia Mieloide Aguda , Humanos , Azacitidina/uso terapéutico , Antimetabolitos Antineoplásicos/uso terapéutico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Leucemia Mieloide Aguda/tratamiento farmacológico , Inducción de Remisión , Enfermedad Crónica , Antimetabolitos/uso terapéuticoRESUMEN
It has been known for decades that the incidence of chronic lymphocytic leukemia (CLL) is significantly lower in Asia than in Western countries, but the reason responsible for this difference still remains a major knowledge gap. Using GeneChip® miRNA array to analyze the global microRNA expression in B lymphocytes from Asian and Western CLL patients and healthy individuals, we have identified microRNA with CLL-promoting or suppressive functions that are differentially expressed in Asian and Western individuals. In particular, miR-4485 is upregulated in CLL patients of both ethnic groups, and its expression is significantly lower in Asian healthy individuals. Genetic silencing of miR-4485 in CLL cells suppresses leukemia cell growth, whereas ectopic expression of miR-4485 promotes cell proliferation. Mechanistically, miR-4485 exerts its CLL-promoting activity by inhibiting the expression of TGR5 and activating the ERK1/2 pathway. In contrast, miR-138, miR-181a, miR- 181c, miR-181d, and miR-363 with tumor-suppressive function are highly expressed in Asian healthy individuals. Our study suggests that differential expression of several important microRNA with pro- or anti-CLL functions in Asian and Western B lymphocytes likely contributes to the difference in CLL incidence between the two ethnic groups, and that miR-4485 and its downstream molecule TGR5 could be potential therapeutic targets.
Asunto(s)
Leucemia Linfocítica Crónica de Células B , MicroARNs , Humanos , Leucemia Linfocítica Crónica de Células B/epidemiología , Leucemia Linfocítica Crónica de Células B/genética , Incidencia , MicroARNs/genética , MicroARNs/metabolismo , Linfocitos B/metabolismo , Silenciador del GenRESUMEN
Biomolecules play a vital role in the regulation of biomineralization. However, the characteristics of practical nucleation domains are still sketchy. Herein, the effects of the representative biomolecular sequence and conformations on calcium phosphate (Ca-P) nucleation and mineralization are investigated. The results of computer simulations and experiments prove that the line in the arrangement of dual acidic/essential amino acids with a single interval (Bc (Basic) -N (Neutral) -Bc-N-Ac (Acidic)- NN-Ac-N) is most conducive to the nucleation. 2α-helix conformation can best induce Ca-P ion cluster formation and nucleation. "Ac- × × × -Bc" sequences with α-helix are found to be the features of efficient nucleation domains, in which process, molecular recognition plays a non-negligible role. It further indicates that the sequence determines the potential of nucleation/mineralization of biomolecules, and conformation determines the ability of that during functional execution. The findings will guide the synthesis of biomimetic mineralized materials with improved performance for bone repair.
Asunto(s)
Biomineralización , Fosfatos de Calcio , Fosfatos de Calcio/química , Conformación MolecularRESUMEN
Unlike what happens in conventional ferroics, the ferrorotational (FR) domain manipulation and visualization in FR materials are nontrivial as they are invariant under both space-inversion and time-reversal operations. FR domains have recently been observed by using the linear electrogyration (EG) effect and X-ray diffraction (XRD) diffraction mapping. However, ferrorotational selectivity, such as the selective processing of the FR domains and direct visualization of the FR domains, e.g., under an optical microscope, would be the next step to study the FR domains and their possible applications in technology. Unexpectedly, we discovered that the microscopic FR structural distortions in ilmenite crystals can be directly coupled with macroscopic mechanical rotations in such a way that FR domains can be visualized under an optical microscope after innovative rotational polishing, a combined ion milling with a specific rotational polishing, or a twisting-induced fracturing process. Thus, the FR domains could be a unique medium to register the memory of a rotational mechanical process due to a novel selective coupling between its microscopic structural rotations and an external macroscopic rotation. Analogous to the important enantioselectivity in modern chemistry and the pharmaceutical industry, this newly discovered ferrorotational selectivity opens up opportunities for FR manipulation and new FR functionality-based applications.
RESUMEN
Background: Since abnormal aerobic glycolysis was first identified in cancer cells, many studies have focused on its mechanisms. The purpose of this study was to analyze the global research status of the Warburg effect in cancer using bibliometrics. Methods: Articles published from 01 January 2013 to 31 December 2022 (n=2,067) were retrieved from the Web of Science core collection database and analyzed using VOSviewer and CiteSpace software. Results: Over the past decade, there was an overall increase in the number of annual publications. China was the most productive country with 790 articles, while the United States received the most citations, with 25,657 citations in total. Oncotarget was the most productive and most cited journal, with 99 articles and 4,191 citations, respectively. International cooperation was common, with the USA cooperating most with other countries. Lactate metabolism, citrate production, and non-coding RNAs related to the Warburg effect have received increasing attention in cancer research. These areas may become future research trends. Conclusion: The study findings help summarize the research status and hotspots of the Warburg effect cancer, and will inform subsequent research.
RESUMEN
This study aimed to conduct a bibliometric analysis in the field of bladder cancer (BC) immunotherapy, and explore the research trends, hotspots and frontiers from 2000 to 2022. VOSviewer software was used to analyze the collaborative relationships between authors, institutions, countries/regions, and journals through citation, co-authorship, and co-citation analysis, to identify research hotspots and frontiers in this field. Researchers based in the United States of America have published a total of 627 papers with 27,308 citations. Indeed, the USA ranked first among the top 10 most active countries and showed the most extensive collaboration with other countries. The University of Texas MD Anderson CANC CTR has published 58 articles, making it the top most institution in terms of published articles and active collaborative research. Kamat AM and Lamm DL were the most active and co-cited authors with 28 papers and 980 co-citations, respectively. Chang Yuan and Xu le were the most active collaborative authors with a total link strength of 195. The J UROLOGY was the most active and frequently co-cited journal, with 100 papers and 6,668 co-citations. Studies of BC immunotherapy can be broadly classified into three categories: "basic research", "clinical trial", and "prognosis". Our findings provide an overview of the research priorities and future directions of BC immunotherapy. Tumor microenvironment and immune checkpoint inhibitors (ICIs) of BC, as well as the combination of ICIs with other drugs, may become the main direction of future research.
Asunto(s)
Neoplasias de la Vejiga Urinaria , Humanos , Bibliometría , Instituciones de Salud , Inhibidores de Puntos de Control Inmunológico , Inmunoterapia , Microambiente Tumoral , Neoplasias de la Vejiga Urinaria/terapiaRESUMEN
Cancer is a major health hazard for humans. Recent studies have indicated the involvement of small nucleolar RNAs (snoRNAs) in the occurrence and development of cancer and indicated its potential role as a diagnostic/prognostic marker and therapeutic target. The purpose of this study was to use the bibliometrics method to analyze the published literature on this subject. We collected articles pertaining to the field of snoRNA and cancer from the Web of Science Core Collection database. The data were analyzed to identify the research hotspots and frontiers. The number of articles in this field was low in the early period. Chu Liang and Montanaro Lorenzo were the most prolific authors on this subject, while Jiang and Feng were the most frequently cited authors. In China, three institutions published the most articles, namely Wuhan Univ, China Med Univ, and Guangxi Med Univ. The journal with the highest number of articles on this subject was Oncotarget. The country with the most published articles was China. Analysis of keywords and burst words indicated that early studies mainly focused on molecular mechanisms. Available evidence suggests the involvement of snoRNAs in the molecular mechanism of cancer development and their potential role as a diagnostic and prognostic biomarker.