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The insufficient antioxidant reserves in tumor cells play a critical role in reactive oxygen species (ROS)-mediated therapeutics. Metallothionein-2 (MT-2), an intracellular cysteine-rich protein renowned for its potent antioxidant properties, is intricately involved in tumor development and correlates with a poor prognosis. Consequently, MT-2 emerges as a promising target for tumor therapy. Herein, we present the development of copper-doped carbon dots (Cu-CDs) to target MT-2 to compromise the delicate antioxidant reserves in tumor cells. These Cu-CDs with high tumor accumulation and prolonged body retention can effectively suppress tumor growth by inducing oxidative stress. Transcriptome sequencing unveils a significant decrease in MT-2 expression within the in vivo tumor samples. Further mechanical investigations demonstrate that the antitumor effect of Cu-CDs is intricately linked to apolipoprotein E (ApoE)-mediated downregulation of MT-2 expression and the collapse of the antioxidant system. The robust antitumor efficacy of Cu-CDs provides invaluable insights into developing MT-2-targeted nanomedicine for cancer therapies.
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Antioxidantes , Carbono , Cobre , Metalotioneína , Puntos Cuánticos , Metalotioneína/genética , Metalotioneína/metabolismo , Cobre/química , Cobre/farmacología , Carbono/química , Carbono/farmacología , Humanos , Animales , Ratones , Antioxidantes/farmacología , Antioxidantes/química , Puntos Cuánticos/química , Puntos Cuánticos/uso terapéutico , Línea Celular Tumoral , Estrés Oxidativo/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Antineoplásicos/farmacología , Antineoplásicos/química , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismoRESUMEN
BACKGROUND: Tumor treatment still remains a clinical challenge, requiring the development of biocompatible and efficient anti-tumor nanodrugs. Carbon dots (CDs) has become promising nanomedicines for cancer therapy due to its low cytotoxicity and easy customization. RESULTS: Herein, we introduced a novel type of "green" nanodrug for multi-level cancer therapy utilizing Fe-doped carbon dots (Fe-CDs) derived from iron nutrient supplement. With no requirement for target moieties or external stimuli, the sole intravenous administration of Fe-CDs demonstrated unexpected anti-tumor activity, completely suppressing tumor growth in mice. Continuous administration of Fe-CDs for several weeks showed no toxic effects in vivo, highlighting its exceptional biocompatibility. The as-synthesized Fe-CDs could selectively induce tumor cells apoptosis by BAX/Caspase 9/Caspase 3/PARP signal pathways and activate antitumoral macrophages by inhibiting the IL-10/Arg-1 axis, contributing to its significant tumor immunotherapy effect. Additionally, the epithelial-mesenchymal transition (EMT) process was inhibited under the treatment of Fe-CDs by MAPK/Snail pathways, indicating the capacity of Fe-CDs to inhibit tumor recurrence and metastasis. CONCLUSIONS: A three-level tumor treatment strategy from direct killing to activating immunity to inhibiting metastasis was achieved based on "green" Fe-CDs. Our findings reveal the broad clinical potential of Fe-CDs as a novel candidate for anti-tumor nanodrugs and nanoplatform.
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Neoplasias , Puntos Cuánticos , Animales , Ratones , Carbono/farmacología , Neoplasias/tratamiento farmacológicoRESUMEN
Physiological microenvironment engineering has shown great promise in combating a variety of diseases. Herein, we present the rational design of reinforced and injectable blood-derived protein hydrogels (PDA@SiO2-PRF) composed of platelet-rich fibrin (PRF), polydopamine (PDA), and SiO2 nanofibers that can act as dual-level regulators to engineer the microenvironment for personalized bone regeneration with high efficacy. From the biophysical level, PDA@SiO2-PRF with high stiffness can withstand the external loading and maintaining the space for bone regeneration in bone defects. Particularly, the reinforced structure of PDA@SiO2-PRF provides bone extracellular matrix (ECM)-like functions to stimulate osteoblast differentiation via Yes-associated protein (YAP) signaling pathway. From the biochemical level, the PDA component in PDA@SiO2-PRF hinders the fast degradation of PRF to release autologous growth factors in a sustained manner, providing sustained osteogenesis capacity. Overall, the present study offers a dual-level strategy for personalized bone regeneration by engineering the biophysiochemical microenvironment to realize enhanced osteogenesis efficacy.
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Hidrogeles , Fibrina Rica en Plaquetas , Regeneración Ósea , Osteogénesis , Fibrina Rica en Plaquetas/metabolismo , Dióxido de Silicio/metabolismoRESUMEN
Atherosclerosis is a risk factor for various cardiovascular diseases, and is linked to high rates of morbidity and mortality across the globe. Although numerous complex processes are involved in the development and progression of atherosclerosis, the exact mechanisms behind its pathogenesis remain unclear. Inflammation and endothelial cell damage exert a lasting effect on atherosclerosis, causing lipid and fibrous tissue accumulation in the intima of the artery to form plaques, and subsequently promoting atherosclerosis. Nod-like receptor protein 3 (NLRP3) inflammatory corpuscle is thought to be the link between lipid metabolism and inflammation. Long Potassium outflow is a vital activator of NLRP3, with a simultaneous effect as a start-up and adjustment. The majority of existing drugs for atherosclerosis targeting the NLRP3 signaling pathway target IL-1, whereas drugs targeting the critical link of potassium efflux are relatively new. This review discusses the NLRP3 inflammatory corpuscle as a critical regulator of the immunological inflammatory pathway in atherosclerosis. Moreover, current knowledge on NLRP3 inflammatory corpuscle start and activation pathways were integrated, emphasizing potassium-involved outflow-related proteins. We highlight potential treatment approaches for NLRP3 inflammatory corpuscle pathways, specifically targeting potassium outflow channels of targeted drugs. Collectively, these insights indicate that targeting the NLRP3 inflammatory corpuscle is a vital anti-inflammatory therapy for treating atherosclerosis.
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Although environmental tobacco smoke (ETS) exposure is considered to be a severe public health problem and a modifiable risk factor for preterm birth (PTB), we still lack a comprehensive understanding of the PTB risk associated with trimester-specific prenatal ETS exposure. This study aimed to examine the accumulation of risk across trimester ETS exposure and the critical window of the association between maternal ETS exposure during pregnancy and PTB. A total of 63,038 mother-child pairs were involved in the analysis of the 2017 survey of Longhua Child Cohort Study. Information about socio-demographic characteristics, prenatal ETS exposure, and birth outcomes were collected using a self-report questionnaire. A series of logistic regression models were employed to assess the associations between prenatal ETS exposure and PTB. We found that maternal ETS exposure during pregnancy significantly increased the risk of PTB and this association increased with both the average level of daily ETS exposure and the number of trimesters of ETS exposure. Moreover, mothers who were initially exposed to ETS in the 1st trimester of pregnancy had significant higher risk of PTB (OR = 1.34, 95% CI: 1.25-1.44). Furthermore, mothers exposed to ETS in the 1st trimester only (OR = 1.26, 95%CI: 1.04-1.50), in both 1st and 2nd trimester (OR = 1.35, 95%CI: 1.08-1.67) and throughout pregnancy (OR = 1.35, 95%CI: 1.24-1.46) experienced a significantly high risk of PTB. Prenatal maternal ETS exposure during only the 2nd trimester also resulted in a high risk of PTB with marginal significance (OR = 1.33, 95% CI:0.78-2.13). To conclude, the 1st and early 2nd trimester might be the critical window for prenatal ETS exposure causing PTB.
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Nacimiento Prematuro , Efectos Tardíos de la Exposición Prenatal , Contaminación por Humo de Tabaco , Estudios de Cohortes , Exposición a Riesgos Ambientales , Femenino , Humanos , Recién Nacido , Exposición Materna/efectos adversos , Embarazo , Trimestres del Embarazo , Nacimiento Prematuro/epidemiología , Nacimiento Prematuro/etiología , Efectos Tardíos de la Exposición Prenatal/epidemiología , Contaminación por Humo de Tabaco/efectos adversosRESUMEN
People are sometimes tempted to lie for their own benefit if it would not harm others. For adults, dishonesty is the default response in these circumstances. The developmental origins of this phenomenon were investigated between 2019 and 2021 among 6- to 11-year-old Han Chinese children from China (N = 548, 49% female). Children had an opportunity to win prizes in a behavioral economics game (Experiment 1) or a temptation resistance game adapted from developmental psychology (Experiment 2). In each experiment, the youngest children showed a default tendency of honesty and there was an overall age-related shift toward a default tendency of dishonesty. These findings provide direct evidence of developmental change in the automatic and controlled processes that underlie moral behavior.
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Decepción , Principios Morales , Adulto , Niño , China , Femenino , Humanos , Masculino , MotivaciónRESUMEN
Tumor-associated macrophage (TAM), a crucial component of immune cell infiltrated in tumor microenvironment, is associated with progression of oral squamous cell carcinoma (OSCC). However, it is still unclear how TAM is induced/accumulated and activated around/in OSCC. In the study herein, we tried to understand how TAM accumulates and activates in the OSCC and how TAM promotes OSCC to convert cancer stem cell (CSC). In this study, first important finding was that the M2 macrophages significantly increased in all twenty human OSCC samples in vivo. Cancer-associated fibroblast (CAF)-derived CXCL12 effectively attracted monocytes, which displayed M2 macrophage phenotype. Blocking CXCL12 receptor (CXCR4) significantly reduced chemotaxis of M2 macrophage. Polarized M2 macrophage promoted CSC-like transition in OSCC cell line, Cal27 cells. These CSC-like cells significantly expressed higher Sox2, Oct4, and Nanog genes, were stronger positive for CD44 and CD105, increased cell proliferation with less apoptosis, enhanced cell migration, and were resistant to chemotherapy drug, vineristine. These results indicate that CAF effectively attracts monocytes via the CXCL12/CXCR4 pathway and induces their differentiation to M2 macrophages. Interestingly, these polarized M2 macrophages promote formation of CSC-like cells from the OSCC lead to enhance OSCC proliferation with less apoptosis. Therefore, our findings have potential to lead to novel therapy for the OSCC to target CXCL12-mediated TAM recruitment.
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Fibroblastos Asociados al Cáncer/inmunología , Carcinoma de Células Escamosas/inmunología , Quimiocina CXCL12/metabolismo , Macrófagos/inmunología , Neoplasias de la Boca/inmunología , Receptores CXCR4/metabolismo , Apoptosis , Carcinoma de Células Escamosas/patología , Diferenciación Celular , Línea Celular , Línea Celular Tumoral , Polaridad Celular , Proliferación Celular , Quimiotaxis , Epitelio/patología , Humanos , Monocitos/inmunología , Mucosa Bucal/inmunología , Mucosa Bucal/patología , Neoplasias de la Boca/patología , Células Madre Neoplásicas/patología , Transducción de SeñalRESUMEN
Twenty-eight captive Sichuan snub-nosed monkeys (Rhinopithecus roxellana) were involved in the current study. Many individuals showed handedness, with a modest tendency toward left-hand use especially for animate targets, although no group-level handedness was found. There was no significant gender difference in the direction and strength of hand preference for both targets. Females showed a significantly higher overall rate of actions toward animate targets than inanimate targets for both hands, whereas males displayed almost the reversed pattern. There were no significant interactions between lateral hand use and target animacy for either males or females. Most individuals showed rightward or leftward laterality shift trends between inanimate and animate targets. These findings to some extent support the existence of a potential trend concerning a categorical neural distinction between targets demanding functional manipulation (inanimate objects) and those demanding social manipulation (animate objects), even though specialized hand preference based on target animacy has not been fully established in this arboreal Old World monkey species.
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Colobinae , Lateralidad Funcional , Animales , Femenino , Mano , MasculinoRESUMEN
The gut microbiota of wild animals can regulate host physical health to adapt to the environment. High-throughput sequencing from fecal samples was used to analyze the gut microbiota communities in common cranes (Grus grus) without harming them. Herein, we compared the fecal microbiome of fifteen G. grus in Tianjin Tuanbo Bird Natural Reserve (wild group) and six G. grus sampled from Beijing Wildlife Park (semi-captive group) in China, using 16S amplicon sequencing and bioinformatic analysis. The results showed that microbiota diversity and composition varied in different groups, suggesting that the gut microbiota was interactively influenced by diet and the environment. A total of 38 phyla and 776 genera were analyzed in this study. The dominant phyla of the G. grus were Firmicutes and Proteobacteria. Meanwhile, the microbiota richness of the semi-captive group was higher than the wild group. Data on beta diversity highlighted significant differences based on different dietary compositions. Zea mays, Glycine max, and Phragmites australia showed a significant correlation with intestinal bacteria of G. grus. This study provides a comprehensive analysis of diet and microbiomes in semi-captive and wild G. grus living in different environments, thus helping us to evaluate the influence on animal microbiomes and improve conservation efforts for this species.
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BACKGROUND: To evaluate the economic loss of hospital-acquired infections (HAIs) among tumor patients so as to help policymakers to allocate health care resources and address the issue. METHODS: We conducted a retrospective, 1:1 matched case-control study in a large region cancer hospital between January 1 and December 31, 2022. The economic burden was estimated as the median of the 1:1 pair differences of various hospitalization fees and hospital length of stay (LOS). RESULTS: In this study of 329 matched pairs, the patients with HAIs incurred higher hospitalization cost (ie, $16,927) and experienced longer hospital LOS (ie, 22 days), compared to the non-HAI groups. The extra hospitalization cost and the prolonged hospital LOS caused by HAIs were $4,919 and 9 days, respectively. Accordingly, the direct nonmedical economic loss attributable to HAI was approximately $478 to 835 per case. Furthermore, the increment of hospitalization costs varied by sites of infection, types of tumors, and stratum of age. CONCLUSIONS: HAIs lead to the increment of direct economic burden and hospital LOS in tumor patients. Our findings highlight the importance of implementing effective infection control measures in hospitals to reduce the financial burden on tumor patients.
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Infección Hospitalaria , Neoplasias , Humanos , Infección Hospitalaria/economía , Infección Hospitalaria/epidemiología , China/epidemiología , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Neoplasias/economía , Neoplasias/epidemiología , Estudios de Casos y Controles , Anciano , Adulto , Costo de Enfermedad , Tiempo de Internación/economía , Tiempo de Internación/estadística & datos numéricos , Hospitalización/economía , Hospitalización/estadística & datos numéricos , Instituciones Oncológicas/economía , Anciano de 80 o más Años , Costos de la Atención en Salud/estadística & datos numéricosRESUMEN
Pyroptosis is a form of pro-inflammatory programmed cell death and it represents a potential therapeutic target for alleviating drug-induced acute kidney injury (AKI). However, there is a lack of effective and kidney-targeted pyroptosis inhibitors for AKI treatment so far. Herein, we report a pharmacologically active carbonized nanoinhibitor (P-RCDs) derived from 3,4',5-trihydroxystilbene that can preferentially accumulate in the kidneys and ameliorate chemotherapeutic drug-induced AKI by inhibiting pyroptosis. In particular, such a carbonized nanoformulation enables the transfer of desired pyroptosis inhibitory activity as well as the radical eliminating activity to the nanoscale, endowing P-RCDs with a favorable kidney-targeting ability. In cisplatin-induced AKI mice, P-RCDs can not only pharmacologically inhibit GSDME-mediated pyroptosis in renal cells with high efficacy, but also exhibit high antioxidative activity that protects the kidneys from oxidative injury. The present study proposes a feasible but efficacious strategy to construct versatile carbonized nanomedicine for targeted delivery of the desired pharmacological activities.
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Lesión Renal Aguda , Piroptosis , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/tratamiento farmacológico , Piroptosis/efectos de los fármacos , Animales , Ratones , Cisplatino/farmacología , Humanos , Ratones Endogámicos C57BL , Carbono/química , Masculino , Nanopartículas/química , Tamaño de la PartículaRESUMEN
Anticancer nanomedicines used for ferroptosis therapy generally rely on the direct delivery of Fenton catalysts to drive lipid peroxidation in cancer cells. However, the therapeutic efficacy is limited by the ferroptosis resistance caused by the intracellular anti-ferroptotic signals. Herein, we report the intrinsic ATPase-mimicking activity of a vanadium carbide MXene nanozyme (PVCMs) to pharmacologically modulate the nuclear factor erythroid 2-related factor 2 (Nrf2) program, which is the master anti-ferroptotic mediator in the ironclad defense system in triple-negative breast cancer (TNBC) cells. The PVCMs perform high ATPase-like activity that can effectively and selectively catalyze the dephosphorylation of ATP to generate ADP. Through a cascade mechanism initiated by falling energy status, PVCMs can powerfully hinder the Nrf2 program to selectively drive ferroptosis in TNBC cells in response to PVCMs-induced glutathione depletion. This study provides a paradigm for the use of pharmacologically active nanozymes to moderate specific cellular signals and elicit desirable pharmacological activities for therapeutic applications.
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Ferroptosis , Nitritos , Elementos de Transición , Neoplasias de la Mama Triple Negativas , Humanos , Adenosina Trifosfatasas , Factor 2 Relacionado con NF-E2 , Neoplasias de la Mama Triple Negativas/tratamiento farmacológicoRESUMEN
Chemotherapeutic drug-induced acute kidney injury (AKI) involves pathologically increased labile iron species in the kidneys that mediate the excessive generation of reactive oxygen species (ROS) to induce ferroptosis and apoptosis, subsequently driving renal dysfunction. Herein, we report renal clearable quantum dot-drug conjugates (QDCs) composed of carbon quantum dot (CDs), deferoxamine (DFO), and poly(ethylene glycol) (PEG) for attenuating chemotherapeutic drug-induced AKI. The CDs component in QDCs can not only provide DFO with high renal specificity to effectively remove the pathological labile iron species in the kidneys to block the source of ROS generation but also exert high antioxidative effects to avoid renal oxidative damage caused by the ROS that have been overproduced. In cisplatin-induced AKI mice, QDCs can inhibit ferroptosis and apoptosis with high efficacy for AKI treatment. This study will provide a new paradigm to realize enhanced therapeutic efficacy for AKI by simultaneously removing the pathological labile iron species and eliminating overproduced ROS in the kidneys to achieve the goal of addressing both symptoms and root causes.
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Lesión Renal Aguda , Puntos Cuánticos , Ratones , Animales , Especies Reactivas de Oxígeno/farmacología , Hierro/farmacología , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/tratamiento farmacológico , Radicales Libres , RiñónRESUMEN
Purpose: To explore the safety and effectiveness of the Pure Retroperitoneal Laparoscopic Peritoneum Incision Technique (PREP-IT) in laparoscopic radical nephrectomy (LRN) and inferior vena cave (IVC) tumor thrombectomy for right renal-cell carcinoma (RCC) with level Mayo I to III venous tumor thrombus (VTT). Patients and Methods: From May 2015 to September 2020, 92 patients with right RCC and Mayo I to III VTT were retrospectively reviewed, including 57 patients who underwent retroperitoneal LRN and IVC thrombectomy using PREP-IT, and 35 patients who underwent open surgery. PREP-IT refers to dissecting the retroperitoneum and temporarily placing the right kidney into the abdominal cavity to enlarge the retroperitoneal workspace for a safer and faster IVC operation. Results: Compared with the open surgery group, the PREP-IT group had a larger tumor diameter, while a larger proportion of Mayo I tumor thrombus and smaller maximum tumor thrombus width. Two patients (3.5%) in the PREP-IT group had a history of abdominal surgery. No conversion to open surgery or standard laparoscopic surgery occurred in PREP-IT group. Laparoscopic surgery with PREP-IT was characterized by shorter operative time, less surgical blood loss, shorter postoperative hospital stay, and lower postoperative complication rate. With a 33-month (ranges: 2-86) follow-up time period, the estimated mean overall survival time was 57.2 ± 5.3 and 58.1 ± 71.5 months in the PREP-IT group and open surgery group, respectively. Log-rank test indicated no significant difference between the two groups in terms of overall survival and cancer-specific survival. Conclusions: The PREP-IT is relatively safe and feasible for retroperitoneal LRN with right renal tumor and IVC tumor thrombus, allowing for a large workspace and wide exposure for IVC operations.
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Carcinoma de Células Renales , Neoplasias Renales , Laparoscopía , Trombosis , Trombosis de la Vena , Humanos , Carcinoma de Células Renales/cirugía , Neoplasias Renales/cirugía , Laparoscopía/métodos , Nefrectomía/métodos , Peritoneo , Estudios Retrospectivos , Trombectomía/métodos , Trombosis/patología , Vena Cava Inferior/patología , Trombosis de la Vena/cirugíaRESUMEN
Oocyte maturation is vital to attain full competence required for fertilization and embryogenesis. NLRP14 is preferentially expressed in mammalian oocytes and early embryos. Yet, the role and molecular mechanism of NLRP14 in oocyte maturation and early embryogenesis are poorly understood, and whether NLRP14 deficiency accounts for human infertility is unknown. Here, we found that maternal loss of Nlrp14 resulted in sterility with oocyte maturation defects and early embryonic arrest (EEA). Nlrp14 ablation compromised oocyte competence due to impaired cytoplasmic and nuclear maturation. Importantly, we revealed that NLRP14 maintained cytoplasmic UHRF1 abundance by protecting it from proteasome-dependent degradation and anchoring it from nuclear translocation in the oocyte. Furthermore, we identified compound heterozygous NLRP14 variants in women affected by infertility with EEA, which interrupted the NLRP14-UHRF1 interaction and decreased UHRF1 levels. Our data demonstrate NLRP14 as a cytoplasm-specific regulator of UHRF1 during oocyte maturation, providing insights into genetic diagnosis for female infertility.
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Infertilidad Femenina , Animales , Femenino , Humanos , Infertilidad Femenina/genética , Infertilidad Femenina/metabolismo , Oocitos/metabolismo , Oogénesis , Citoplasma , Desarrollo Embrionario/genética , Mamíferos , Proteínas Potenciadoras de Unión a CCAAT/genética , Proteínas Potenciadoras de Unión a CCAAT/metabolismo , Ubiquitina-Proteína Ligasas/genética , Ubiquitina-Proteína Ligasas/metabolismo , Nucleósido-Trifosfatasa/metabolismoRESUMEN
The task of point cloud upsampling aims to acquire dense and uniform point sets from sparse and irregular point sets. Although significant progress has been made with deep learning models, state-of-the-art methods require ground-truth dense point sets as the supervision, which makes them limited to be trained under synthetic paired training data and not suitable to be under real-scanned sparse data. However, it is expensive and tedious to obtain large numbers of paired sparse-dense point sets as supervision from real-scanned sparse data. To address this problem, we propose a self-supervised point cloud upsampling network, named SPU-Net, to capture the inherent upsampling patterns of points lying on the underlying object surface. Specifically, we propose a coarse-to-fine reconstruction framework, which contains two main components: point feature extraction and point feature expansion, respectively. In the point feature extraction, we integrate the self-attention module with the graph convolution network (GCN) to capture context information inside and among local regions simultaneously. In the point feature expansion, we introduce a hierarchically learnable folding strategy to generate upsampled point sets with learnable 2D grids. Moreover, to further optimize the noisy points in the generated point sets, we propose a novel self-projection optimization associated with uniform and reconstruction terms as a joint loss to facilitate the self-supervised point cloud upsampling. We conduct various experiments on both synthetic and real-scanned datasets, and the results demonstrate that we achieve comparable performances to state-of-the-art supervised methods.
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Ultrasound (US)-mediated sonodynamic therapy (SDT) has emerged as a spatiotemporally controllable therapeutic modality in combating cancer because of its high tissue-penetration depth and minimal invasiveness. However, the elevated nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidant program in cancer cells can serve as a chief reactive oxygen species (ROS) detoxification system to alleviate oxidative injury and promote tumorigenesis, and thus greatly antagonize the therapeutic efficacy of ROS-mediated anticancer therapies. Herein, we report that vanadium carbide MXene-derived carbon dots (PMQDs) can act as high-efficacy sonosensitizers to efficiently generate ROS upon US irradiation and simultaneously hinder the Nrf2 antioxidant program for enhanced sonodynamic therapy of cancer. These PMQDs show superior US-triggered ROS generating ability because of their efficient migration/separation of electron-hole pairs and narrow bandgap. Importantly, these PMQDs can serve as efficient redox homeostasis regulators to perturb the Nrf2 antioxidant mechanism and thus reduce its effects on ROS neutralization for enhanced SDT efficacy. Overall, the present study will not only provide a new paradigm to augment SDT by perturbing the Nrf2 antioxidant program, but also give valuable insights into developing high-efficacy MXene-derived nanoagents for cancer therapy.
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Human dental pulp stem cells (hDPSCs) have been a focus of pulp regeneration research because of their excellent odontogenic potential and availability. Applying the odontoblastic differentiation of hDPSCs to tooth regeneration has been challenging. Metformin-based carbon nanodots (MCDs) were synthesized and characterized to investigate their effects in vitro on odontoblastic hDPSC differentiation and the underlying mechanism. MCDs were synthesized by a hydrothermal treatment method and characterized using transmission electron microscopy (TEM), Fourier transform infrared spectroscopy, and X-ray photoelectron spectroscopy. The biocompatibility and fluorescence properties of the MCDs in Dulbecco's modified Eagle's medium high-glucose culture medium and the in vitro odontogenic potential and related mechanism of the bioactive nanomaterial was explored. TEM images showed that MCDs were spherical in shape with a size of approximately 5.9 nm. MCDs showed biological safety in cell viability, apoptosis, and fluorescence labelling ability at a concentration up to 200 µg/ml in vitro. The presence of MCDs facilitated high-efficiency odontogenic differentiation of hDPSCs by promoting odontogenic gene and protein expression. Moreover, MCDs promoted odontoblastic hDPSC differentiation via autophagy. MCDs are capable of activating autophagy and enhancing the odontogenic differentiation of hDPSCs by upregulating odontoblast gene marker (DMP1, DSPP, RUNX2, and SP7) and protein (DSPP and DMP1) expression.
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Mosquito coils are efficient mosquito repellents and mosquito coil smoke (MCS) contributes to indoor air pollution. However, no prior population-based study has investigated whether prenatal MCS exposure is a risk factor for preterm birth (PTB) and whether exposure to MCS in different trimesters of pregnancy is associated with different levels of risk. The sample involved 66,503 mother-child dyads. Logistic regression models were used to examine the relationships between prenatal MCS exposure during different trimesters of pregnancy and PTB. We found that prenatal MCS exposure was associated with a greater likelihood of PTB (OR = 1.12, 95%CI: 1.05-1.20). The prenatal MCS exposure during the first trimester was associated with 1.17 (95%CI: 1.09-1.25) times the odds of being PTB, which was higher than exposure during the second trimester (OR = 1.11, 95%CI: 1.03-1.19) and during the third trimester (OR = 1.08, 95%CI: 1.01-1.16). In the stratified analysis, prenatal MCS exposure significantly increased PTB risk among girls but not among boys. Our results indicated that maternal MCS exposure during pregnancy was associated with PTB and that the first trimester might be the sensitive period. In light of these findings, public health interventions are needed to reduce prenatal exposure to MCS, particularly during the first trimester of pregnancy.
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Contaminantes Atmosféricos , Contaminación del Aire , Insecticidas , Nacimiento Prematuro , Contaminantes Atmosféricos/análisis , Contaminación del Aire/análisis , Femenino , Humanos , Recién Nacido , Insecticidas/análisis , Masculino , Exposición Materna/efectos adversos , Material Particulado/análisis , Embarazo , Primer Trimestre del Embarazo , Nacimiento Prematuro/epidemiología , Nacimiento Prematuro/etiología , Humo/análisisRESUMEN
Autologous blood-derived protein hydrogels have shown great promise in the field of personalized regenerative medicine. However, the inhospitable regenerative microenvironments, especially the unfavorable immune microenvironment, are closely associated with their limited tissue-healing outcomes. Herein, novel immunomodulatory blood-derived hybrid hydrogels (PnP-iPRF) are rationally designed and constructed for enhanced bone regeneration via multichannel regulation of the osteogenic microenvironment. Such double-network hybrid hydrogels are composed of clinically approved injectable platelet-rich fibrin (i-PRF) and polycaprolactone/hydroxyapatite composite nanofibers by using enriched polydopamine (PDA) as the anchor. The polycaprolactone component in PnP-iPRF provides a reinforced structure to stimulate osteoblast differentiation in a proper biomechanical microenvironment. Most importantly, the versatile PDA component in PnP-iPRF can not only offer high adhesion capacity to the growth factors of i-PRF and create a suitable biochemical microenvironment for sustained osteogenesis but also reprogram the osteoimmune microenvironment via the induction of M2 macrophage polarization to promote bone healing. The present study will provide a new paradigm to realize enhanced osteogenic efficacy by multichannel microenvironment regulations and give new insights into engineering high-efficacy i-PRF hydrogels for regenerative medicine.