Neural Stem Cell-Derived Small Extracellular Vesicles: key Players in Ischemic Stroke Therapy - A Comprehensive Literature Review.

Ischemic stroke, being a prominent contributor to global disability and mortality, lacks an efficacious therapeutic approach in current clinical settings. Neural stem cells (NSCs) are a type of stem cell that are only found inside the nervous system. These cells can differentiate into various kinds of cells, potentially regenerating or restoring neural networks within areas of the brain that have been destroyed. This review begins by providing an introduction to the existing therapeutic approaches for ischemic stroke, followed by an examination of the promise and limits associated with the utilization of NSCs for the treatment of ischemic stroke. Subsequently, a comprehensive overview was conducted to synthesize the existing literature on the underlying processes of neural stem cell-derived small extracellular vesicles (NSC-sEVs) transplantation therapy in the context of ischemic stroke. These mechanisms encompass neuroprotection, inflammatory response suppression, and endogenous nerve and vascular regeneration facilitation. Nevertheless, the clinical translation of NSC-sEVs is hindered by challenges such as inadequate targeting efficacy and insufficient content loading. In light of these limitations, we have compiled an overview of the advancements in utilizing modified NSC-sEVs for treating ischemic stroke based on current methods of extracellular vesicle modification. In conclusion, examining NSC-sEVs-based therapeutic approaches is anticipated to be prominent in both fundamental and applied investigations about ischemic stroke.

CHES1 modulated tumorigenesis and senescence of pancreas cancer cells through repressing AKR1B10.

Pancreatic ductal adenocarcinoma (PDAC), is characteristic by a heterogeneous tumor microenvironment and gene mutations, conveys a dismal prognosis and low response to chemotherapy and immunotherapy. Here, we found that checkpoint suppressor 1 (CHES1) served as a tumor repressor in PDAC and was associated with patient prognosis. Functional experiments indicated that CHES1 suppressed the proliferation and invasion of PDAC by modulating cellular senescence. To further identify the downstream factor of CHES1 in PDAC, label-free quantitative proteomics analysis was conducted, which showed that the oncogenic Aldo-keto reductase 1B10 (AKR1B10) was transcriptionally repressed by CHES1 in PDAC. And AKR1B10 facilitated the malignant activity and repressed senescent phenotype of PDAC cells. Moreover, pharmaceutical inhibition of AKR1B10 with Oleanolic acid (OA) significantly induced tumor regression and sensitized PDAC cells to gemcitabine, and this combined therapy did not cause obvious side effects. Rescued experiments revealed that CHES1 regulated the tumorigenesis and gemcitabine sensitivity through AKR1B10-mediated senescence in PDAC. In summary, this study revealed that the CHES1/AKR1B10 axis modulated the progression and cellular senescence in PDAC, which might provide revenues for drug-targeting and senescence-inducing therapies for PDAC.

A homologous-targeting cGAS-STING agonist multimodally activates dendritic cells for enhanced cancer immunotherapy.

Herein, we developed a doxorubicin (Dox)-loaded and 4T1 cancer cell membrane-modified hydrogenated manganese oxide nanoparticles (mHMnO-Dox) to elicit systemic antitumor immune responses. The results revealed that mHMnO-Dox actively recognized tumor cells and then effectively delivered Dox into the cells. Upon entering tumor cells, the mHMnO-Dox underwent rapid degradation and abundant release of Mn2+ and chemotherapeutic drugs. The released Mn2+ not only catalysed a Fenton-type reaction to produce excessive reactive oxygen species (ROS) but also activated the cGAS-STING pathway to boost dendritic cell (DC) maturation. This process increased cytotoxic T lymphocyte infiltration as well as natural killer cell recruitment into the tumor site. In addition, the released Dox could contribute to a chemotherapeutic effect, while activating DC cells and subsequently intensifying immune responses through immunogenic cell death (ICD) of tumor cells. Consequently, the mHMnO-Dox suppressed the primary and distal tumor growth and inhibited tumor relapse and metastasis, as well as prolonged the lifespan of tumor-bearing mice. Thus, the mHMnO-Dox multimodally activated DC cells to demonstrate synergistic antitumor activity, which was mediated via the activation of the cGAS-STING signalling pathway to regulate tumor microenvironment, ICD-mediated immunotherapy and ROS-mediated CDT. These findings suggest the therapeutic potential of mHMnO-Dox in cancer immunotherapy. STATEMENT OF SIGNIFICANCE: A cancer cell membrane-camouflaged hydrogenated mesoporous manganese oxide (mHMnO) has been developed as a cGAS-STING agonist and ICD inducer. The mHMnO effectively induced abundance of ROS production in cancer cells, which caused cancer cell death and then promoted DC maturation via tumour-associated antigen presentation. Meanwhile, the mHMnO significantly activated cGAS-STING pathway to facilitate DC maturation and cytotoxic T lymphocyte infiltration as well as natural killer cell recruitment, which further enhanced tumour immune response. In addition, the combination of the mHMnO and Dox could synergistically promote tumour ICD and then multimodally induce DC maturation, achieving an enhanced CIT. Overall, this study provides a potential strategy to design novel immunologic adjuvant for enhanced CIT.

NIR-IIb fluorescence antiangiogenesis copper nano-reaper for enhanced synergistic cancer therapy.

The formation of blood vessel system under a relatively higher Cu2+ ion level is an indispensable precondition for tumor proliferation and migration, which was assisted in forming the tumor immune microenvironment. Herein, a copper ions nano-reaper (LMDFP) is rationally designed not only for chelating copper ions in tumors, but also for combination with photothermal therapy (PTT) to improve antitumor efficiency. Under 808 nm laser irradiation, the fabricated nano-reaper converts light energy into thermal energy to kill tumor cells and promotes the release of D-penicillamine (DPA) in LMDFP. Photothermal properties of LMDFP can cause tumor ablation in situ, which further induces immunogenic cell death (ICD) to promote systematic antitumor immunity. The released DPA exerts an anti-angiogenesis effect on the tumor through chelating copper ions, and inhibits the expression of programmed death ligand 1 (PD-L1), which synergizes with PTT to enhance antitumor immunity and inhibit tumor metastasis. Meanwhile, the nanoplatform can emit near-infrared-IIb (NIR-IIb) fluorescence under 980 nm excitation, which can be used to track the nano-reaper and determine the optimal time point for PTT. Thus, the fabricated nano-reaper shows powerful potential in inhibiting tumor growth and metastasis, and holds great promise for the application of copper nanochelator in precise tumor treatment.

Cancer cell membrane-camouflaged CuPt nanoalloy boosts chemotherapy of cisplatin prodrug to enhance anticancer effect and reverse cisplatin resistance of tumor.

The biotoxicity and chemotherapeutic resistance of cisplatin (CDDP) pose a challenge for tumor therapy. Practically, the change in the therapeutic response of tumor from resistance to sensitivity are impressive but challenging. To this end, we propose a strategy of "one stone, three birds" by designing a CuPt nanoalloy to simultaneously eliminate GSH, relieve hypoxia, and promote ROS production for effectively reversing the platinum (IV) (Pt(IV), (c,c,t-[Pt(NH3)2Cl2(OOCCH2CH2COOH)2)) resistance. Notably, the CuPt nanoalloy exhibits ternary catalytic capabilities including mimicking GSH oxidase, catalase and peroxidase. With the subsequent disguise of tumor cell membrane, the CuPt nanoalloy is conferred with homologous targeting ability, making it actively recognize tumor cells and then effectively internalized by tumor cells. Upon entering tumor cell, it gives rise to GSH depletion, hypoxia relief, and oxidative stress enhancement by catalyzing the reaction of GSH and H2O2, which mitigates the vicious milieu and ultimately reinforces the tumor response to Pt(IV) treatment. In vivo results prove that combination therapy of mCuPt and Pt(IV) realizes the most significant suppression on A549 cisplatin-resistant tumor. This study provides a potential strategy to design novel nanozyme for conquering resistant tumor.

Glucagon Enhances Chemotherapy Efficacy By Inhibition of Tumor Vessels in Colorectal Cancer.

Chemotherapy is widely used to treat colorectal cancer (CRC). Despite its substantial benefits, the development of drug resistance and adverse effects remain challenging. This study aimed to elucidate a novel role of glucagon in anti-cancer therapy. In a series of in vitro experiments, glucagon inhibited cell migration and tube formation in both endothelial and tumor cells. In vivo studies demonstrated decreased tumor blood vessels and fewer pseudo-vessels in mice treated with glucagon. The combination of glucagon and chemotherapy exhibited enhanced tumor inhibition. Mechanistic studies demonstrated that glucagon increased the permeability of blood vessels, leading to a pronounced disruption of vessel morphology. Signaling pathway analysis identified a VEGF/VEGFR-dependent mechanism whereby glucagon attenuated angiogenesis through its receptor. Clinical data analysis revealed a positive correlation between elevated glucagon expression and chemotherapy response. This is the first study to reveal a role for glucagon in inhibiting angiogenesis and vascular mimicry. Additionally, the delivery of glucagon-encapsulated PEGylated liposomes to tumor-bearing mice amplified the inhibition of angiogenesis and vascular mimicry, consequently reinforcing chemotherapy efficacy. Collectively, the findings demonstrate the role of glucagon in inhibiting tumor vessel network and suggest the potential utility of glucagon as a promising predictive marker for patients with CRC receiving chemotherapy.

Tumor Microenvironment-Activated Nanostructure to Enhance MRI Capability and Nanozyme Activity for Highly Tumor-Specific Multimodal Theranostics.

Copper-based nanozymes exhibit excellent antitumor activity but are easily inactivated due to the disturbance of proteins or other macromolecules with sulfhydryl. A tumor microenvironment-responsive CuMnO@Fe3O4 (CMF) core-shell nanozyme for highly efficient tumor theranostics is developed. A platelet-derived growth factor receptor-ß-recognizing cyclic peptide (PDGFB) target is conjugated to the surface of CMF to fabricate a tumor-specific nanozyme (PCMF). The core-shell nanostructure significantly avoids the oxidation and inactivation of copper-based nanozyme, promoting the antitumor activity of PCMF. The weak acid- and GSH-activated T1 and T2 relaxation rate of PCMF contributes to T1 and T2 dual contrast imaging at the tumor site. In addition, the PCMF disintegrates and produces some metal ions that possess Fenton catalytic activity (i.e., Cu+, Mn2+, and Fe2+) under TME. This process significantly depletes GSH, accelerates Fenton and Fenton-like reactions, enhances cellular reactive oxygen species (ROS) levels, and induces cancer cell apoptosis and ferroptosis. PCMF also exhibits photothermal functions, so it can be used in combined photothermal therapy, ferroptosis therapy, and chemodynamic therapy, improving anticancer activity. This work provides insights into the design of an exquisite nanostructure for high-sensitive and tumor-specific theranostics.

PDK4-dependent hypercatabolism and lactate production of senescent cells promotes cancer malignancy.

Senescent cells remain metabolically active, but their metabolic landscape and resulting implications remain underexplored. Here, we report upregulation of pyruvate dehydrogenase kinase 4 (PDK4) upon senescence, particularly in some stromal cell lines. Senescent cells display a PDK4-dependent increase in aerobic glycolysis and enhanced lactate production but maintain mitochondrial respiration and redox activity, thus adopting a special form of metabolic reprogramming. Medium from PDK4+ stromal cells promotes the malignancy of recipient cancer cells in vitro, whereas inhibition of PDK4 causes tumor regression in vivo. We find that lactate promotes reactive oxygen species production via NOX1 to drive the senescence-associated secretory phenotype, whereas PDK4 suppression reduces DNA damage severity and restrains the senescence-associated secretory phenotype. In preclinical trials, PDK4 inhibition alleviates physical dysfunction and prevents age-associated frailty. Together, our study confirms the hypercatabolic nature of senescent cells and reveals a metabolic link between cellular senescence, lactate production, and possibly, age-related pathologies, including but not limited to cancer.

Photodynamic Cationic Ultrasmall Copper Oxide Nanoparticles-Loaded Liposomes for Alleviation of MRSA Biofilms.

Introduction: As we enter the post-antibiotic era, the rise of antibiotic-resistant pathogenic bacteria is becoming a serious threat to public health. This problem is further complicated by antibiotic-resistant biofilms, for which current treatment options are limited. Methods: To tackle this challenge, we propose a novel approach that involves the use of photodynamic cationic pH-sensitive liposomes loaded with ultra-small copper oxide (Ce6@Lipo/UCONs) to effectively eliminate drug-resistant bacteria and eradicate biofilms while minimizing safety concerns and the risk of resistance development. Results: Our study demonstrates that Ce6@Lipo/UCONs have minimal toxicity to mammalian cells and can significantly enhance the association affinity with methicillin-resistant Staphylococcus aureus (MRSA) as confirmed by fluorescent microscope and flow cytometry, thereby greatly improving the bactericidal effect against planktonic MRSA. The cationic nature of Ce6@Lipo/UCONs also enables them to penetrate MRSA biofilms and respond to the acidic microenvironment within the biofilm, effectively releasing the loaded UCONs. Our results indicate that Ce6@Lipo/UCONs could effectively eliminate biofilms under light irradiation conditions, as evidenced by both biomass analysis and scanning electron microscopy observations. In addition, significant antibacterial effects and abscess healing were observed in MRSA-infected mice treated with Ce6@Lipo/UCONs upon light irradiation, while good biocompatibility was achieved in vivo. Conclusion: Taken together, our findings suggest that photodynamic cationic ultrasmall copper oxide nanoparticles-loaded liposomes are a highly promising nano platform for combating antibiotic-resistant microbial pathogens and biofilms. The effective biofilm penetration and synergistic effect between photodynamic inactivation and metal sterilization make them a valuable tool for overcoming the challenges posed by antibiotic resistance.

The effects of different biochars on Caenorhabditis elegans and the underlying transcriptomic mechanisms.

Different biochars have diverse properties, with ambiguous effects on soil nematodes. This study investigated how aspen sawdust (ABC), bamboo powder (BBC), maize straw (MBC) and peanut-shell biochars (PBC) affected Caenorhabditis elegans via culture assays and RNA-seq analysis. The results showed that biochars derived from different agricultural materials varied significantly in physicochemical properties, and PBC produced more volatile organic compounds (VOCs) to attract C. elegans than ABC, BBC and MBC. Moreover, worms in ABC experienced the worst outcomes, while worms in PBC experienced milder impacts. Nematode body length decreased to 724.6 µm, 784.0 µm and 799.7 µm on average in ABC, BBC and MBC, respectively, compared to the control (1052 µm) and PBC treatments (960 µm). The brood size in ABC, MBC, BBC and PBC decreased 41.1%, 39.4%, 39.2% and 19.1% compared to the control, respectively. Furthermore, the molecular mechanisms of biochar-induced developmental effects on C. elegans were explored. Although several differentially expressed genes (DEGs) were different among the four biochars, worm phenotypic changes were mainly related to col genes (col-129; col-140; col-40; col-184), bli-6, sqt-3, perm-2/4, cdk-8, daf-16 and sod-1/2/5, which are associated with cuticle collagen synthesis, eggshell formation in postembryonic growth and rhythmic processes. Our study suggests that different properties of biochars could be crucial to soil nematodes, as well as the worms' biochemical changes are important for the health in agriculture soil.

[Impacts of Land Use Intensification Level on Fluvo-aquic Cropland Soil Microbial Community Abundance and Necromass Accumulation in North China].

Despite the essential role of soil microorganisms in nutrient turnover in soil ecological systems and the recognized paramount significance of microbial necromass to soil organic carbon accumulation, how microbial community abundance and necromass respond to land use intensification level regulation remains poorly understood. To address this knowledge gap, based on the land use intensification level, three treatments were set up[annual wheat-maize rotation (CC), alternating temporary grassland with wheat planting (TG), and perennial grassland (PG)], and a long-term fixed filed experiment was established to investigate the influences of the regulation of land use intensification level on bacterial and fungal community abundances; the accumulation of bacterial, fungal, and total microbial necromass; and their contributions to SOC sequestration using droplet digital PCR and amino sugar detection technologies. We further sought to determine the key factors driving the bacterial, fungal, and total microbial necromass C accumulation. Our results demonstrated that fungal community abundance was strongly affected by land use intensification level regulation compared to that of the bacterial community, which increased with decreasing land use intensification level. The total microbial necromass C predominated the SOC accumulation across all three land use intensification levels, which contributed 52.78%, 58.36%, and 68.87% to SOC, respectively, exhibiting an increasing trend with the decline in land use intensification level. Fungal necromass C accounted for more than 80% of the total microbial necromass C, indicating its predominance in the accumulation of the total microbial necromass C and active variation via the reduction in land use intensification level. There was no significant difference in bacterial necromass C (MurA) content, with the trend of CC

Soil organic carbon changes in China's croplands: A newly estimation based on DNDC model.

Soil Organic Carbon (SOC) in cropland represents a significant facet of the terrestrial ecosystem's carbon reservoirs, playing a pivotal role in global climate change mitigation efforts. Within the specific context of China, cropland SOC not only extends its implications beyond environmental impact but also serves as a critical factor in ensuring the stability and security of the nation's food supply. However, there is an ongoing argument about the changes in SOC and their spatial and temporal distribution patterns within China's croplands. In this study, we constructed a new county-level DNDC database for 2020, building upon 2003 research that quantified SOC stock in China's cropland using the DNDC model. Our aim was to assess the SOC storage and temporal changes of China's cropland in 2020 using same methodology to enhance estimation accuracy. The simulation results of the validated DNDC model revealed that the average SOC storage of China's croplands (0-30 cm) in 2020 was 6.02 Pg C, with the Northeast region contributing 23 % (1.37 Pg C). The SOC density in China varied from 18.55 to 152.57 t C ha-1, averaging at 49.65 t C ha-1. In 2020, China's cropland transitioned from a net loss of SOC in 2003 to a carbon sink, with cropland SOC density and SOC storage increased by 18.2 % and 21.6 % respectively. Notably, despite experiencing a loss of SOC compared to 2003, the Northeast region had the highest average SOC density in China. This study highlights that despite the increase in SOC density and storage in China's croplands over the last 17 years, there remains substantial potential for carbon sequestration given the current spatial distribution of SOC density's significant heterogeneity within China. The findings of this study offer data support for China's strategy to achieve food security and carbon neutrality.

The coupling effects of carbon fractions, bacteria, and protists on carbon emissions among various ditch levels in the Lower Yellow River.

Inland waters are receiving increasing attention due to their importance in the global carbon cycle. However, the dynamics of CO2 emissions and the related mechanisms from ditches remain unclear. In this study, field sampling and an incubation experiment were conducted to explore the effects and mechanisms, especially the coupling effects between carbon fractions, bacteria, and protists on carbon dynamics of different ditch levels (sublateral ditch, farm ditch, and lateral ditch) and sediment depths (0-20cm, 20-40cm) in the Lower Yellow River. Results indicated that sublateral ditches nearest to farmland had the highest accumulative carbon mineralization (0-20 cm 1.38 g C kg-1; 20-40 cm 0.89 g C kg-1), equivalent to that of farmland, followed by the lateral ditch (0-20 cm 0.84 g C kg-1; 20-40 cm 0.50 g C kg-1) and the farm ditch (0-20 cm 0.67 g C kg-1; 20-40 cm 0.26 g C kg-1). Carbon emissions from ditches are mainly regulated by SOC (36.97 %), bacteria (29.2 %), and protists (18.95 %). Specifically, the mineralization of flooded lateral ditches is attributed to protist diversity. SOC, bacterial and protistan diversity in the farm ditch significantly impacted carbon emissions, with SOC as the dominant factor, while the bacterial composition and SOC contributed more to CO2 emissions in the sublateral ditch. Our results highlight the importance of carbon emissions from ditches, especially those closest to farmland. This study provides new insights into the construction and management of farmland irrigation and drainage in the aspects of carbon sequestration.

Mawangdui-Guidance Qigong Exercise for patients with chronic non-specific low back pain: Study protocol of a randomized controlled trial.

Introduction: Worldwide, there is a high frequency of chronic non-specific low back pain (CNLBP), which is a significant public health concern. The etiology is complicated and diverse, and it includes a number of risk factors such as diminished stability and weak core muscles. Mawangdui-Guidance Qigong has been employed extensively to bolster the body in China for countless years. However, the effectiveness of treating CNLBP has not been assessed by a randomized controlled trial (RCT). In order to verify the results of the Mawangdui-Guidance Qigong Exercise and examine its biomechanical mechanism, we intend to perform a randomized controlled trial. Methods and analysis: Over the course of 4 weeks, 84 individuals with CNLBP will be randomly assigned to receive either Mawangdui-Guidance Qigong Exercise, motor control exercise, or medication (celecoxib). Electromyographic data, including muscle activation time, iEMGs, root mean square value (RMS) and median frequency (MF), will be the main outcomes. The Japanese Orthopedic Association (JOA) Score, the Mcgill Pain Questionnaire (MPQ), beta-endorphin, and substance P are examples of secondary outcomes. At the start of treatment and 4 weeks later, all outcomes will be evaluated. SPSS version 20.0 (SPSS Inc., Chicago, IL, USA) will be used for all of the analysis. Discussion: The prospective findings are anticipated to offer an alternative treatment for CNLBP and provide a possible explanation of the mechanism of Mawangdui-Guidance Qigong Exercise on CNLBP. Ethics and dissemination: The Sichuan Regional Ethics Review Committee on Traditional Chinese Medicine has given the study approval (Approval No. 2020KL-067). It has also registered at the website of China Clinical Trial Center Registration. The application adheres to the Declaration of Helsinki's tenets (Version Edinburgh 2000). Peer-reviewed papers will be used to publicize the trial's findings. Trial registration number: ClinicalTrials.gov, identifier ChiCTR2000041080.

Increased level of exosomal miR-20b-5p derived from hypothermia-treated microglia promotes neurite outgrowth and synapse recovery after traumatic brain injury.

Mild hypothermia has been proven to inhibit microglia activation after TBI. Exosomal microRNA derived from microglia played a critical role in promoting neurite outgrowth and synapse recovery. Here, we aimed to investigate the role of microRNAs in microglial exosomes after hypothermia treatment on neuronal regeneration after TBI. For in vitro study, stretch-injured neurons were co-cultured with microglial exosomes. For in vivo study, C57BL/6 mice were under controlled cortical impact and injected with microglial exosomes. The results showed that MG-LPS-EXOHT increased the number of dendrite branches and total length of dendrites both in vitro and in vivo, elevated the expression levels of PSD-95 and GluR1 in stretch-injured neurons, and increased spine density in the pericontusion region. Moreover, MG-LPS-EXOHT improved motor function and motor coordination. A high-throughput sequencing showed that miR-20b-5p was upregulated in MG-LPS-EXOHT. Elevating miR-20b-5p promoted neurite outgrowth and synapse recovery of injured neurons both in vitro and in vivo. Following mechanistic study demonstrated that miR-20b-5p might promote neurite outgrowth and synapse recovery by directly targeting PTEN and activating PI3K-AKT pathway. In conclusion, mild hypothermia could modify the microRNA prolife of exosomes derived from LPS activated BV2 cells. Furthermore, high level of microglial exosomal miR-20b-5p induced by mild hypothermia could transfer into injured neurons and promote neurite outgrowth and synapse recovery after TBI via activating the PI3K-AKT pathway by suppressing PTEN expression.

Biodegradable nanoplatform upregulates tumor microenvironment acidity for enhanced cancer therapy via synergistic induction of apoptosis, ferroptosis, and anti-angiogenesis.

Chemodynamic therapy of cancer is limited by insufficient endogenous H2O2 generation and acidity in the tumor microenvironment (TME). Herein, we developed a biodegradable theranostic platform (pLMOFePt-TGO) involving composite of dendritic organosilica and FePt alloy, loaded with tamoxifen (TAM) and glucose oxidase (GOx), and encapsulated by platelet-derived growth factor-B (PDGFB)-labeled liposomes, that effectively uses the synergy among chemotherapy, enhanced chemodynamic therapy (CDT), and anti-angiogenesis. The increased concentration of glutathione (GSH) present in the cancer cells induces the disintegration of pLMOFePt-TGO, releasing FePt, GOx, and TAM. The synergistic action of GOx and TAM significantly enhanced the acidity and H2O2 level in the TME by aerobiotic glucose consumption and hypoxic glycolysis pathways, respectively. The combined effect of GSH depletion, acidity enhancement, and H2O2 supplementation dramatically promotes the Fenton-catalytic behavior of FePt alloys, which, in combination with tumor starvation caused by GOx and TAM-mediated chemotherapy, significantly increases the anticancer efficacy of this treatment. In addition, T2-shortening caused by FePt alloys released in TME significantly enhances contrast in the MRI signal of tumor, enabling a more accurate diagnosis. Results of in vitro and in vivo experiments suggest that pLMOFePt-TGO can effectively suppress tumor growth and angiogenesis, thus providing an exciting potential strategy for developing satisfactory tumor theranostics.

PDGFB-targeted functional MRI nanoswitch for activatable T1-T2 dual-modal ultra-sensitive diagnosis of cancer.

As one of the most significant imaging modalities currently available, magnetic resonance imaging (MRI) has been extensively utilized for clinically accurate cancer diagnosis. However, low signal-to-noise ratio (SNR) and low specificity for tumors continue to pose significant challenges. Inspired by the distance-dependent magnetic resonance tuning (MRET) phenomenon, the tumor microenvironment (TME)-activated off-on T1-T2 dual-mode MRI nanoswitch is presented in the current study to realize the sensitive early diagnosis of tumors. The tumor-specific nanoswitch is designed and manufactured on the basis of PDGFB-conjugating ferroferric oxide coated by Mn-doped silica (PDGFB-FMS), which can be degraded under the high-concentration GSH and low pH in TME to activate the T1-T2 dual-mode MRI signals. The tumor-specific off-on dual-mode MRI nanoswitch can significantly improve the SNR and is used successfully for the accurate diagnosis of early-stage tumors, particularly for orthotopic prostate cancer. In addition, the systemic delivery of the nanoswitch did not cause blood or tissue damage, and it can be excreted out of the body in a timely manner, demonstrating excellent biosafety. Overall, the strategy is a significant step in the direction of designing off-on dual-mode MRI nanoprobes to improve imaging accuracy, which opens up new avenues for the development of new MRI probes.

pH-Responsive Selenium Nanoplatform for Highly Efficient Cancer Starvation Therapy by Atorvastatin Delivery.

Recently, starvation-inducing nutrient deprivation has been regarded as a promising strategy for tumor suppression. As a first-line lipid-lowering drug, atorvastatin (ATV) significantly reduces caloric intake, suggesting its potential in starvation therapy for suppressing tumors. Accordingly, we developed a novel starvation therapy agent (HA-Se-ATV) in this study to suppress tumor growth by using hyaluronic acid (HA)-conjugated chitosan polymer-coated nano-selenium (Se) for loading ATV. HA-Se-ATV targets cancer cells, following which it effectively accumulates in the tumor tissue. The HA-Se-ATV nanoplatform was then activated by inducing a weakly acidic tumor microenvironment and subsequently releasing ATV. ATV and Se synergistically downregulate the levels of cellular adenosine triphosphate while inhibiting the expression of thioredoxin reductase 1. Consequently, the starvation-stress reaction of cancer cells is significantly elevated, leading to cancer cell death. Furthermore, the in vivo results indicate that HA-Se-ATV effectively suppresses tumor growth with a low level of toxicity, demonstrating its great potential for clinical translation.

Primary angioleiomyoma of right frontal cranial base with intracranial and extracranial communication.

INTRODUCTION: Primary intracranial angioleiomyoma (ALM) is quite rare and ALM of the adolescent is even rarer. To date, only three cases of adolescents have been reported. MATERIAL AND METHODS: We carefully introduced a new location of intracranial ALM in an adolescent. The clinical, pathological and imaging features of intracranial ALM were described in detail and published literature was reviewed. RESULTS: To our best knowledge, we presented the fourth primary intracranial ALM of adolescent and the first ALM of the right frontal cranial base with intracranial and extracranial communication. We not only summarize the generalities of ALM but also illustrate the difference between adult and adolescent ALM in the aspects of gender and age predominance, etiology, common location and pathologic subtype. CONCLUSIONS: We reported the first ALM of the right frontal cranial base with intracranial and extracranial communication of an adolescent with a good prognosis. We also summarize the generalities of ALM and illustrate the difference between adult and adolescent ALM. Future investigation of control study with large patient cohorts is needed for both adult and adolescent ALM to compare the difference between them.