RESUMEN

INTRODUCTION: Brain organoids are believed to be able to regenerate impaired neural circuits and reinstate brain functionality. The neuronal activity of organoids is considered a crucial factor for restoring host function after implantation. However, the optimal stage of brain organoid post-transplantation has not yet been established. External electrical signal plays a crucial role in the physiology and development of a majority of human tissues. However, whether electrical input modulates the development of brain organoids, making them ideal transplant donors, is elusive. METHODS: Bioelectricity was input into cortical organoids by electrical stimulation (ES) with a multi-electrode array (MEA) to obtain a better-transplanted candidate with better viability and maturity, realizing structural-functional integration with the host brain. RESULTS: We found that electrical stimulation facilitated the differentiation and maturation of organoids, displaying well-defined cortical plates and robust functional electrophysiology, which was probably mediated via the pathway of calcium-calmodulin (CaM) dependent protein kinase II (CAMK II)-protein kinase A (PKA)-cyclic-AMP response binding protein (pCREB). The ES-pretreated D40 organoids displayed superior cell viability and higher cell maturity, and were selected to transplant into the damaged primary sensory cortex (S1) of host. The enhanced maturation was exhibited within grafts after transplantation, including synapses and complex functional activities. Moreover, structural-functional integration between grafts and host was observed, conducive to strengthening functional connectivity and restoring the function of the host injury. CONCLUSION: Our findings supported that electrical stimulation could promote the development of cortical organoids. ES-pretreated organoids were better transplanted donors for strengthening connectivity between grafts and host. Our work presented a new physical approach to regulating organoids, potentially providing a novel translational strategy for functional recovery after brain injury. In the future, the development of 3D flexible electrodes is anticipated to overcome the drawbacks of 2D planar MEA, promisingly achieving multimodal stimulation and long-term recordings of brain organoids.

RESUMEN

Polyoxometalates (POMs) are a class of anionic metal-oxygen clusters with versatile biological activities. Over the past decade, an increasing number of POMs, especially Sb-rich POMs, have been proven to exert antitumor activity. However, the antitumor effects and mechanisms of POMs in the treatment of non-small cell lung cancer (NSCLC) remain largely unexplored. This study employed a Sb-rich {Sb21Tb7W56} POM (POM-1) for NSCLC therapy and investigated its mechanism of action. Our results demonstrated that POM-1 exhibited cytotoxicity against H1299 and A549 cells with IC50 values of 3.245 µM and 3.591 µM, respectively. The migration and invasion were also inhibited by 28.05% and 76.18% in H1299 cells, as well as 36.88% and 36.98% in A549 cells at a concentration of 5 µM. In a tumor xenograft mouse model, POM-1 suppressed tumor growth by 76.92% and 84.62% at doses of 25 and 50 mg kg-1, respectively. Transcriptomic analysis indicated the alteration of ferroptosis and apoptosis signaling pathways in POM-treated NSCLC cells. Subsequent experimentation confirmed the induction of ferroptosis, evidenced by 5.6-fold elevated lipid peroxide levels with treatment of 5 µM POM-1, alongside increased expression of ferroptosis-associated proteins. Additionally, the apoptosis induced by POM-1 was also validated by the 19.67% and 30.1% increase in apoptotic cells in H1299 and A549 cells treated with 5 µM POM-1, respectively, as well as the upregulated activation of caspase-3. In summary, this study reveals, for the first time, ferroptosis as the antitumor mechanism of Sb-rich POM, and that synergism with ferroptosis and apoptosis is a highly potent antitumor strategy for POM-based antitumor therapy.

RESUMEN

Prolonged disorders of consciousness (pDOC) are pathological conditions of alterations in consciousness caused by various severe brain injuries, profoundly affecting patients' life ability and leading to a huge burden for both the family and society. Exploring the mechanisms underlying pDOC and accurately assessing the level of consciousness in the patients with pDOC provide the basis of developing therapeutic strategies. Research of non-invasive functional neuroimaging technologies, such as functional magnetic resonance (fMRI) and scalp electroencephalography (EEG), have demonstrated that the generation, maintenance and disorders of consciousness involve functions of multiple cortical and subcortical brain regions, and their networks. Invasive intracranial neuroelectrophysiological technique can directly record the electrical activity of subcortical or cortical neurons with high signal-to-noise ratio and spatial resolution, which has unique advantages and important significance for further revealing the brain function and disease mechanism of pDOC. Here we reviewed the current progress of pDOC research based on two intracranial electrophysiological signals, spikes reflecting single-unit activity and field potential reflecting multi-unit activities, and then discussed the current challenges and gave an outlook on future development, hoping to promote the study of pathophysiological mechanisms related to pDOC and provide guides for the future clinical diagnosis and therapy of pDOC.

Asunto(s)

RESUMEN

Adding supernumerary robotic limbs (SRLs) to humans and controlling them directly through the brain are main goals for movement augmentation. However, it remains uncertain whether neural patterns different from the traditional inherent limbs motor imagery (MI) can be extracted, which is essential for high-dimensional control of external devices. In this work, we established a MI neo-framework consisting of novel supernumerary robotic sixth-finger MI (SRF-MI) and traditional right-hand MI (RH-MI) paradigms and validated the distinctness of EEG response patterns between two MI tasks for the first time. Twenty-four subjects were recruited for this experiment involving three mental tasks. Event-related spectral perturbation was adopted to supply details about event-related desynchronization (ERD). Activation region, intensity and response time (RT) of ERD were compared between SRF-MI and RH-MI tasks. Three classical classification algorithms were utilized to verify the separability between different mental tasks. And genetic algorithm aims to select optimal combination of channels for neo-framework. A bilateral sensorimotor and prefrontal modulation was found during the SRF-MI task, whereas in RH-MI only contralateral sensorimotor modulation was exhibited. The novel SRF-MI paradigm enhanced ERD intensity by a maximum of 117% in prefrontal area and 188% in the ipsilateral somatosensory-association cortex. And, a global decrease of RT was exhibited during SRF-MI tasks compared to RH-MI. Classification results indicate well separable performance among different mental tasks (88.1% maximum for 2-class and 88.2% maximum for 3-class). This work demonstrated the difference between the SRF-MI and RH-MI paradigms, widening the control bandwidth of the BCI system.

RESUMEN

PURPOSE: Knee adduction, flexion moment, and adduction angle are often used as surrogate parameters of knee medial force. To verify whether these parameters are suitable as surrogates under different walking states, we investigated the correlation between knee medial loading with the surrogates during walking and turning. METHODS: Sixteen healthy subjects were recruited to complete straight walk (SW), step turn (ST), and crossover turn (CT). Knee joint moments were obtained using inverse dynamics, and knee medial force was computed using a previously validated musculoskeletal model, Freebody. Linear regression was used to predict the peak of knee medial force with the peaks of the surrogate parameters and walking speed. RESULTS: There was no significant difference in walking speed among these three tasks. The peak knee adduction moment (pKAM) was a significant predictor of the peak knee medial force (pKMF) for SW, ST, and CT (p < 0.001), while the peak knee flexion moment (pKFM) was only a significant predictor of the pKMF for SW (p = 0.034). The statistical analysis showed that the pKMF increased, while the pKFM and the peak knee adduction angle (pKAA) decreased significantly during CT compared to those of SW and ST (p < 0.001). The correlation analysis indicated that the knee parameters during SW and ST were quite similar. CONCLUSIONS: This study investigated the relationship between knee medial force and some surrogate parameters during walking and turning. KAM was still the best surrogate parameter for SW, ST, and CT. It is necessary to consider the type of movement when comparing the surrogate predictors of knee medial force, as the prediction equations differ significantly among movement types.

Asunto(s)

RESUMEN

BACKGROUND: Abnormalities in structural-functional connectivity (SC-FC) coupling have been identified globally in patients with major depressive disorder (MDD). However, investigations have neglected the variability and hierarchical distribution of these abnormalities across different brain regions. Furthermore, the biological mechanisms underlying regional SC-FC coupling patterns are not well understood. METHODS: We enrolled 182 patients with MDD and 157 healthy control (HC) subjects, quantifying the intergroup differences in regional SC-FC coupling. The extreme gradient boosting (XGBoost), support vector machines (SVM) and random forest (RF) models were constructed to assess the potential of SC-FC coupling as biomarkers for MDD diagnosis and symptom prediction. Then, we examined the link between changes in regional SC-FC coupling in patients with MDD, neurotransmitter distributions, and gene expression. RESULTS: We observed increased regional SC-FC coupling in default mode network (T = 3.233) and decreased coupling in frontoparietal network (T = -3.471) in MDD relative to HC. XGBoost (AUC = 0.853), SVM (AUC = 0.832) and RF (p < 0.05) models exhibited good prediction performance. The alterations in regional SC-FC coupling in patients with MDD were correlated with the distributions of four neurotransmitters (p < 0.05) and expression maps of specific genes. These genes were strongly enriched in genes implicated in excitatory neurons, inhibitory neurons, cellular metabolism, synapse function, and immune signaling. These findings were replicated on two brain atlases. CONCLUSIONS: This work enhances our understanding of MDD and pave the way for the development of additional targeted therapeutic interventions.

RESUMEN

Macroautophagy/autophagy activation in renal tubular epithelial cells protects against acute kidney injury (AKI). However, the role of immune cell autophagy, such as that involving macrophages, in AKI remains unclear. In this study, we discovered that macrophage autophagy was an adaptive response during AKI as mice with macrophage-specific autophagy deficiency (atg5-/-) exhibited higher serum creatinine, more severe renal tubule injury, increased infiltration of ADGRE1/F4/80+ macrophages, and elevated expression of inflammatory factors compared to WT mice during AKI induced by either LPS or unilateral ischemia-reperfusion. This was further supported by adoptive transfer of atg5-/- macrophages, but not WT macrophages, to cause more severe AKI in clodronate liposomes-induced macrophage depletion mice. Similar results were also obtained in vitro that bone marrow-derived macrophages (BMDMs) lacking Atg5 largely increased pro-inflammatory cytokine expression in response to LPS and IFNG. Mechanistically, we uncovered that atg5 deletion significantly upregulated the protein expression of TARM1 (T cell-interacting, activating receptor on myeloid cells 1), whereas inhibition of TARM1 suppressed LPS- and IFNG-induced inflammatory responses in atg5-/- RAW 264.7 macrophages. The E3 ubiquitin ligases MARCHF1 and MARCHF8 ubiquitinated TARM1 and promoted its degradation in an autophagy-dependent manner, whereas silencing or mutation of the functional domains of MARCHF1 and MARCHF8 abolished TARM1 degradation. Furthermore, we found that ubiquitinated TARM1 was internalized from plasma membrane into endosomes, and then recruited by the ubiquitin-binding autophagy receptors TAX1BP1 and SQSTM1 into the autophagy-lysosome pathway for degradation. In conclusion, macrophage autophagy protects against AKI by inhibiting renal inflammation through the MARCHF1- and MARCHF8-mediated degradation of TARM1.Abbreviations: AKI, acute kidney injury; ATG, autophagy related; Baf, bafilomycin A1; BMDMs, bone marrow-derived macrophages; CCL2/MCP-1, C-C motif chemokine ligand 2; CHX, cycloheximide; CQ, chloroquine; IFNG, interferon gamma; IL, interleukin; IR, ischemia-reperfusion; MAP1LC3/LC3, microtubule-associated protein 1 light chain 3; LPS, lipopolysaccharide; MARCHF, membrane associated ring-CH-type finger; NC, negative control; NFKB, nuclear factor of kappa light polypeptide gene enhancer in B cells; NLRP3, NLR family, pyrin domain containing 3; NOS2, nitric oxide synthase 2, inducible; Rap, rapamycin; Wort, wortmannin; RT-qPCR, real-time quantitative polymerase chain reaction; Scr, serum creatinine; SEM, standard error of mean; siRNA, small interfering RNA; SYK, spleen tyrosine kinase; TARM1, T cell-interacting, activating receptor on myeloid cells 1; TAX1BP1, Tax1 (human T cell leukemia virus type I) binding protein 1; TECs, tubule epithelial cells; TNF, tumor necrosis factor; WT, wild type.

RESUMEN

Emotion recognition is crucial for human-computer interaction, and electroencephalography (EEG) stands out as a valuable tool for capturing and reflecting human emotions. In this study, we propose a hierarchical hybrid model called Mixed Attention-based Convolution and Transformer Network (MACTN). This model is designed to collectively capture both local and global temporal information and is inspired by insights from neuroscientific research on the temporal dynamics of emotions. First, we introduce depth-wise temporal convolution and separable convolution to extract local temporal features. Then, a self-attention-based transformer is used to integrate the sparse global emotional features. Besides, channel attention mechanism is designed to identify the most task-relevant channels, facilitating the capture of relationships between different channels and emotional states. Extensive experiments are conducted on three public datasets under both offline and online evaluation modes. In the multi-class cross-subject online evaluation using the THU-EP dataset, MACTN demonstrates an approximate 8% enhancement in 9-class emotion recognition accuracy in comparison to state-of-the-art methods. In the multi-class cross-subject offline evaluation using the DEAP and SEED datasets, a comparable performance is achieved solely based on the raw EEG signals, without the need for prior knowledge or transfer learning during the feature extraction and learning process. Furthermore, ablation studies have shown that integrating self-attention and channel-attention mechanisms improves classification performance. This method won the Emotional BCI Competition's final championship in the World Robot Contest. The source code is available at https://github.com/ThreePoundUniverse/MACTN.

Asunto(s)

RESUMEN

Depression, a multifactorial mental disorder, characterized by cognitive slowing, anxiety, and impaired cognitive function, imposes a significant burden on public health. Photobiomodulation (PBM), involving exposure to sunlight or artificial light at a specific intensity and wavelength for a determined duration, influences brain activity, functional connectivity, and plasticity. It is recognized for its therapeutic efficacy in treating depression, yet its molecular and cellular underpinnings remain obscure. Here, we investigated the impact of PBM with 468 nm light on depression-like behavior and neuronal damage in the chronic unpredictable mild stress (CUMS) murine model, a commonly employed animal model for studying depression. Our results demonstrate that PBM treatment ameliorated behavioral deficits, inhibited neuroinflammation and apoptosis, and notably rejuvenates the hippocampal synaptic function in depressed mice, which may be mainly attributed to the up-regulation of brain-derived neurotrophic factor signaling pathways. In addition, in vitro experiments with a corticosterone-induced hippocampal neuron injury model demonstrate reduced oxidative stress and improved mitochondrial function, further validating the therapeutic potential of PBM. In summary, these findings suggest PBM as a promising, non-invasive treatment for depression, offering insights into its biological mechanisms and potential for clinical application.

Asunto(s)

RESUMEN

Resting-state functional magnetic resonance imaging (rs-fMRI) has been widely used in the identification of mild cognitive impairment (MCI) research, MCI patients are relatively at a higher risk of progression to Alzheimer's disease (AD). However, almost machine learning and deep learning methods are rarely analyzed from the perspective of spatial structure and temporal dimension. In order to make full use of rs-fMRI data, this study constructed a dynamic spatiotemporal graph neural network model, which mainly includes three modules: temporal block, spatial block, and graph pooling block. Our proposed model can extract the BOLD signal of the subject's fMRI data and the spatial structure of functional connections between different brain regions, and improve the decision-making results of the model. In the study of AD, MCI and NC, the classification accuracy reached 83.78% outperforming previously reported, which manifested that our model could effectively learn spatiotemporal, and dynamic spatio-temporal method plays an important role in identifying different groups of subjects. In summary, this paper proposed an end-to-end dynamic spatio-temporal graph neural network model, which uses the information of the temporal dimension and spatial structure in rs-fMRI data, and achieves the improvement of the three classification performance among AD, MCI and NC.

Asunto(s)

RESUMEN

Opioids are widely used, effective analgesics to manage severe acute and chronic pain, although they have recently come under scrutiny because of epidemic levels of abuse. While these compounds act on numerous central and peripheral pain pathways, the neuroanatomical substrate for opioid analgesia is not fully understood. By means of single-cell transcriptomics and manipulation of morphine-responsive neurons, we have identified an ensemble of neurons in the rostral ventromedial medulla (RVM) that regulates mechanical nociception in mice. Among these, forced activation or silencing of excitatory RVMBDNF projection neurons mimicked or completely reversed morphine-induced mechanical antinociception, respectively, via a brain-derived neurotrophic factor (BDNF)/tropomyosin receptor kinase B (TrkB)-dependent mechanism and activation of inhibitory spinal galanin-positive neurons. Our results reveal a specific RVM-spinal circuit that scales mechanical nociception whose function confers the antinociceptive properties of morphine.

Asunto(s)

RESUMEN

Vigilance state is crucial for the effective performance of users in brain-computer interface (BCI) systems. Most vigilance estimation methods rely on a large amount of labeled data to train a satisfactory model for the specific subject, which limits the practical application of the methods. This study aimed to build a reliable vigilance estimation method using a small amount of unlabeled calibration data. We conducted a vigilance experiment in the designed BCI-based cursor-control task. Electroencephalogram (EEG) signals of eighteen participants were recorded in two sessions on two different days. And, we proposed a contrastive fine-grained domain adaptation network (CFGDAN) for vigilance estimation. Here, an adaptive graph convolution network (GCN) was built to project the EEG data of different domains into a common space. The fine-grained feature alignment mechanism was designed to weight and align the feature distributions across domains at the EEG channel level, and the contrastive information preservation module was developed to preserve the useful target-specific information during the feature alignment. The experimental results show that the proposed CFGDAN outperforms the compared methods in our BCI vigilance dataset and SEED-VIG dataset. Moreover, the visualization results demonstrate the efficacy of the designed feature alignment mechanisms. These results indicate the effectiveness of our method for vigilance estimation. Our study is helpful for reducing calibration efforts and promoting the practical application potential of vigilance estimation methods.

Asunto(s)

RESUMEN

Mental workload (MWL) assessment is critical for accident prevention and operator safety. However, achieving cross-task generalization of MWL classification models is a significant challenge for real-world applications. Classifiers trained on labeled samples from one task often experience a notable performance drop when directly applied to samples from other tasks, limiting its use cases. To address this issue, we propose a semi-supervised cross-task domain adaptation (SCDA) method using power spectral density (PSD) features for MWL recognition across tasks (MATB-II and n-back). Our results demonstrated that the SCDA method achieved the best cross-task classification performance on our data and COG-BCI public dataset, with accuracies of 90.98% ± 9.36% and 96.61% ± 4.35%, respectively. Furthermore, in the cross-task classification of cross-subject scenarios, SCDA showed the highest average accuracy (75.39% ± 9.56% on our data, 90.98% ± 9.36% on the COG-BCI public dataset). The findings indicate that the semi-supervised transfer learning approach using PSD features is feasible and effective for cross-task MWL assessment.

RESUMEN

Introduction: Idiopathic normal pressure hydrocephalus (iNPH) is a kind of hydrocephalus that is easily to be misdiagnosed with brain atrophy due to the similarity of ventricular dilation and cognitive impairment. In this case, we present an old male patient who was diagnosed with iNPH by multimodality approaches. Outcomes: A 68-year-old male patient, with deteriorated gait, declined cognitive function for at least 3 years and urinary incontinence for 3 months. The doctors suspected him a patient with hydrocephalus or Alzheimer's disease based on his symptoms. We used multimodality diagnostic approaches including brain imaging, cerebrospinal fluid tap test, continuous intracranial pressure monitoring, and infusion study to make the final diagnosis of iNPH. He underwent ventriculoperitoneal shunt surgery and was well recovered. Conclusion: This case demonstrates the efficacy of using multimodality approaches for iNPH diagnosis, which saves patient time and clinical cost, worthy of further promotion.

RESUMEN

The global prevalence rate for congenital hydrocephalus (CH) is approximately one out of every five hundred births with multifaceted predisposing factors at play. Genetic influences stand as a major contributor to CH pathogenesis, and epidemiological evidence suggests their involvement in up to 40% of all cases observed globally. Knowledge about an individual's genetic susceptibility can significantly improve prognostic precision while aiding clinical decision-making processes. However, the precise genetic etiology has only been pinpointed in fewer than 5% of human instances. More occurrences of CH cases are required for comprehensive gene sequencing aimed at uncovering additional potential genetic loci. A deeper comprehension of its underlying genetics may offer invaluable insights into the molecular and cellular basis of this brain disorder. This review provides a summary of pertinent genes identified through gene sequencing technologies in humans, in addition to the 4 genes currently associated with CH (two X-linked genes L1CAM and AP1S2, two autosomal recessive MPDZ and CCDC88C). Others predominantly participate in aqueduct abnormalities, ciliary movement, and nervous system development. The prospective CH-related genes revealed through animal model gene-editing techniques are further outlined, focusing mainly on 4 pathways, namely cilia synthesis and movement, ion channels and transportation, Reissner's fiber (RF) synthesis, cell apoptosis, and neurogenesis. Notably, the proper functioning of motile cilia provides significant impulsion for cerebrospinal fluid (CSF) circulation within the brain ventricles while mutations in cilia-related genes constitute a primary cause underlying this condition. So far, only a limited number of CH-associated genes have been identified in humans. The integration of genotype and phenotype for disease diagnosis represents a new trend in the medical field. Animal models provide insights into the pathogenesis of CH and contribute to our understanding of its association with related complications, such as renal cysts, scoliosis, and cardiomyopathy, as these genes may also play a role in the development of these diseases. Genes discovered in animals present potential targets for new treatments but require further validation through future human studies.

Asunto(s)

RESUMEN

Introduction: We previously reported that ATP1A3 c.823G>C (p.Ala275Pro) mutant causes varying phenotypes of alternative hemiplegia of childhood and rapid-onset dystonia-parkinsonism in the same family. This study aims to investigate the function of ATP1A3 c.823G>C (p.Ala275Pro) mutant at the cellular and zebrafish models. Methods: ATP1A3 wild-type and mutant Hela cell lines were constructed, and ATP1A3 mRNA expression, ATP1A3 protein expression and localization, and Na+-K+-ATPase activity in each group of cells were detected. Additionally, we also constructed zebrafish models with ATP1A3 wild-type overexpression (WT) and p.Ala275Pro mutant overexpression (MUT). Subsequently, we detected the mRNA expression of dopamine signaling pathway-associated genes, Parkinson's disease-associated genes, and apoptosisassociated genes in each group of zebrafish, and observed the growth, development, and movement behavior of zebrafish. Results: Cells carrying the p.Ala275Pro mutation exhibited lower levels of ATP1A3 mRNA, reduced ATP1A3 protein expression, and decreased Na+-K+-ATPase activity compared to wild-type cells. Immunofluorescence analysis revealed that ATP1A3 was primarily localized in the cytoplasm, but there was no significant difference in ATP1A3 protein localization before and after the mutation. In the zebrafish model, both WT and MUT groups showed lower brain and body length, dopamine neuron fluorescence intensity, escape ability, swimming distance, and average swimming speed compared to the control group. Moreover, overexpression of both wild-type and mutant ATP1A3 led to abnormal mRNA expression of genes associated with the dopamine signaling pathway and Parkinson's disease in zebrafish, and significantly upregulated transcription levels of bad and caspase-3 in the apoptosis signaling pathway, while reducing the transcriptional level of bcl-2 and the bcl-2/bax ratio. Conclusion: This study reveals that the p.Ala275Pro mutant decreases ATP1A3 protein expression and Na+/K+-ATPase activity. Abnormal expression of either wild-type or mutant ATP1A3 genes impairs growth, development, and movement behavior in zebrafish.

RESUMEN

Studies have indicated that medium- to long-duration spaceflight may adversely affect astronauts' emotional and social functioning. Emotion modulation can significantly impact astronauts' well-being, performance, mission safety and success. However, with the increase in flight time, the potential alterations in emotional and social performance during spaceflight and their underlying mechanisms remain to be investigated, and targeted therapeutic and preventive interventions have yet to be identified. We evaluated the changes of emotional and social functions in mice with the extension of the time in simulated space complex environment (SSCE), and simultaneously monitored changes in brain tissue of vascular endothelial growth factor (VEGF), matrix metalloproteinase-9 (MMP-9), and inflammation-related factors. Furthermore, we assessed the regulatory role of repetitive transcranial magnetic stimulation (rTMS) in mood and socialization with the extension of the time in SSCE, as well as examining alterations of VEGF signaling in the medial prefrontal cortex (mPFC). Our findings revealed that mice exposed to SSCE for 7 days exhibited depressive-like behaviors, with these changes persisting throughout SSCE period. In addition, 14 days of rTMS treatment significantly ameliorated SSCE-induced emotional and social dysfunction, potentially through modulation of the level of VEGF signaling in mPFC. These results indicates that emotional and social disorders increase with the extension of SSCE time, and rTMS can improve the performance, which may be related to VEGF signaling. This study offers insights into potential pattern of change over time for mental health issues in astronauts. Further analysis revealed that rTMS modulates emotional and social dysfunction during SSCE exposure, with its mechanism potentially being associated with VEGF signaling.

Asunto(s)

RESUMEN

BACKGROUND: Portal vein injury is an uncommon complication of endoscopic retrograde cholangiopancreatography (ERCP), for which stent malpositioning in the portal vein is very rare and can lead to fatal events. We report a case of biliary stent migration to the portal vein and a novel method for its safe removal under the guidance of portal angiography. Moreover, we reviewed the literature and summarized reports on the identification and management of this condition. CASE SUMMARY: A 59-year-old woman with pancreatic cancer presented with abdominal pain and a high fever 20 days after the placement of two plastic biliary stents under the guidance of ERCP. Blood cultures and laboratory tests revealed sepsis, which was treated with antibiotics. A contrast-enhanced computed tomography scan revealed that one of the biliary stents in the main portal vein was malpositioned. To safely remove the stent, portal angiography was performed to visualize the portal vein and to allow the management of any bleeding. The two stents were removed without obvious bleeding, and an uncovered self-expanding metal stent was placed in the common bile duct for drainage. The patient had an uneventful 6-month follow-up period, except for self-resolving portal vein thrombosis. CONCLUSION: The combination of endoscopic and angiographic techniques allowed uneventful management of stent malposition in the portal vein.

RESUMEN

With the development of society and the improvement of people's living standards, there is an increasing demand for melanin-inhibiting products that prioritize health, safety, and efficacy. Therefore, the development of natural products that can safely and efficiently inhibit melanin synthesis is of great social significance and has significant market potential. In this paper, by reviewing the literature reported in recent years, we summarized the natural products with inhibition of melanin synthesis effects that have been put into or not yet put into the market, and classified them according to the chemical groups of their compounds or the extraction methods of the natural products. Through the summary analysis, we found that these compounds mainly include terpenoids, phenylpropanoids, flavonoids and so on, while the natural product extracts mainly include methanol extracts, ethanol extracts, and aqueous extracts. Their main inhibition of melanin synthesis mechanisms include: (1) direct inhibition of tyrosinase activity; (2) down-regulation of the α-MSH-MC1R, Wnt, NO, PI3K/Akt and MAPK pathways through the expression of MITF and its downstream genes TYR, TRP-1, and TRP-2; (3) antioxidant; (4) inhibition of melanocyte growth through cytotoxicity; (5) inhibition of melanosome production and transport. This paper provides an in-depth discussion on the research progress of whitening natural products and their market value. The aim is to offer guidance for future research and development of natural skin whitening products.