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1.
Acta Biomater ; 2023 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-36603734

RESUMO

Reactive oxygen species (ROS) generated during photodynamic therapy (PDT) can induce autophagy to protect tumor cell from PDT-induced apoptosis. In this work, a self-delivery autophagy regulator (designated as CeCe) is developed for autophagy promotion sensitized PDT against tumor. Briefly, CeCe is prepared by the assembly of a photosensitizer of chlorin e6 (Ce6) and autophagy promoter of celastrol. By virtue of intermolecular interactions, Ce6 and celastrol are able to self-assemble into nanomedicine with great photodynamic performance and autophagy regulation capacity. Under light irradiation, CeCe would produce ROS in tumor cells to amplify the oxidative stress and promote cell autophagy. As a result, CeCe exhibits an enhanced photo toxicity by inducing autophagic cell death. In vivo experiments indicate that CeCe can predominantly accumulate in tumor tissue for a robust PDT. Moreover, CeCe has a superior therapeutic efficiency compared to monotherapy and combined treatment of Ce6 and celastrol, suggesting a synergistic antitumor effect of PDT and autophagy promotion. This self-delivery nanomedicine may advance the development of the co-delivery nanoplatform to improve the antitumor efficacy of PDT by promoting autophagy. STATEMENT OF SIGNIFICANCE: Autophagy is a "double-edged sword" in cellular homeostasis and metabolism, which can promote tumor progression but also induce an unknown impact on tumor inhibition. In this work, a self-delivery autophagy regulator (designated as CeCe) was developed for autophagy promotion sensitized photodynamic therapy (PDT). By virtue of intermolecular interactions, Ce6 and celastrol were found to self-assemble into stable CeCe without drug excipients, which exhibited great photodynamic performance and autophagy regulation capacity. In vitro and in vivo findings demonstrated a superior tumor suppression ability of CeCe over the monotherapy as well as the combined treatment of Ce6 and celastrol, suggesting a synergistic antitumor efficacy by PDT and autophagy promotion.

2.
BMC Med Inform Decis Mak ; 23(1): 13, 2023 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-36658545

RESUMO

BACKGROUND: Visual electrophysiology is an objective visual function examination widely used in clinical work and medical identification that can objectively evaluate visual function and locate lesions according to waveform changes. However, in visual electrophysiological examinations, the flash visual evoked potential (FVEP) varies greatly among individuals, resulting in different waveforms in different normal subjects. Moreover, most of the FVEP wave labelling is performed automatically by a machine, and manually corrected by professional clinical technicians. These labels may have biases due to the individual variations in subjects, incomplete clinical examination data, different professional skills, personal habits and other factors. Through the retrospective study of big data, an artificial intelligence algorithm is used to maintain high generalization abilities in complex situations and improve the accuracy of prescreening. METHODS: A novel multi-input neural network based on convolution and confidence branching (MCAC-Net) for retinitis pigmentosa RP recognition and out-of-distribution detection is proposed. The MCAC-Net with global and local feature extraction is designed for the FVEP signal that has different local and global information, and a confidence branch is added for out-of-distribution sample detection. For the proposed manual features,a new input layer is added. RESULTS: The model is verified by a clinically collected FVEP dataset, and an accuracy of 90.7% is achieved in the classification task and 93.3% in the out-of-distribution detection task. CONCLUSION: We built a deep learning-based FVEP classification algorithm that promises to be an excellent tool for screening RP diseases by using FVEP signals.


Assuntos
Aprendizado Profundo , Potenciais Evocados Visuais , Humanos , Estudos Retrospectivos , Inteligência Artificial , Exame Neurológico
3.
Hum Cell ; 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36627545

RESUMO

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy. Uncontrolled angiogenesis plays a critical role in hepatocellular tumor growth and metastasis. In this study, we aimed to investigate the effects of circular RNA hsa_circ_0000519 and the potential involvement of microRNA (miR)-1296 and E2F transcription factor 7 (E2F7) in HCC development. Hsa_circ_0000519 was highly expressed in HCC cells and hepatocellular tumor tissues, and correlated with poor prognosis of HCC patients. Knockdown of hsa_circ_0000519 significantly reduced HCC cell viability, suppressed cell proliferation, and induced cell cycle arrest in G0/G1. Downregulation of hsa_circ_0000519 also inhibited formation of capillary-like endothelial structures in vitro and impeded microvessel formation in mice bearing HCC tumors. The migration and invasive capacities of HCC cells were markedly reduced by hsa_circ_0000519 knockdown. Hsa_circ_0000519 possessed a binding site for microRNA (miR)-1296. Upregulation of hsa_circ_0000519 significantly decreased the miR-1296 expression in both HCC cells and mouse xenografts. Furthermore, E2F7 was a target of miR-1296. Hsa_circ_0000519 positively regulated E2F7 via acting as a miR-1296 sponge. Upregulation of E2F7 abolished the inhibitory effects of hsa_circ_0000519 knockdown on HCC cell proliferation and angiogenesis. In conclusion, hsa_circ_0000519 promoted tumor progression and angiogenesis in HCC through the miR-1296/E2F7 axis. These data suggest the potential clinical application of hsa_circ_0000519 in HCC treatment.

5.
Cell Rep Med ; : 100912, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36669488

RESUMO

Medical artificial intelligence (AI) has been moving from the research phase to clinical implementation. However, most AI-based models are mainly built using high-quality images preprocessed in the laboratory, which is not representative of real-world settings. This dataset bias proves a major driver of AI system dysfunction. Inspired by the design of flow cytometry, DeepFundus, a deep-learning-based fundus image classifier, is developed to provide automated and multidimensional image sorting to address this data quality gap. DeepFundus achieves areas under the receiver operating characteristic curves (AUCs) over 0.9 in image classification concerning overall quality, clinical quality factors, and structural quality analysis on both the internal test and national validation datasets. Additionally, DeepFundus can be integrated into both model development and clinical application of AI diagnostics to significantly enhance model performance for detecting multiple retinopathies. DeepFundus can be used to construct a data-driven paradigm for improving the entire life cycle of medical AI practice.

6.
Biomaterials ; 293: 121952, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36502580

RESUMO

Tumor cells are characterized by unlimited proliferation and escape of immune clearance, which are closely associated with the down regulation of surface antigens. In this work, a carrier free photodynamic modulator (CeTaz) is developed to improve immunosuppressive tumor microenvironment and promote the recognition of tumors by T cells by epigenetic reprogramming. Specifically, CeTaz is assembled by chlorine e6 (Ce6) and tazemetostat (Taz) through intermolecular interactions. Upon light irradiation, CeTaz is able to promote the generation of reactive oxygen species (ROS) for a robust photodynamic therapy (PDT) to inhibit localized tumor growth. Meanwhile, the PDT also induces immunogenic cell death (ICD) to initiate immune response, leading to the activation of effector T cells. More importantly, CeTaz could inhibit the epigenetic regulator of EZH2 to suppress the methylation of H3K27, which would promote tumor cells to express MHC-I and release CXCL10. Consequently, the epigenetically reprogrammed tumor cells are readily recognized by effector T cells to enhance the antitumor immunity. Results indicate that the PDT activated immunotherapy of CeTaz could simultaneously inhibit the growth of primary and distant tumors with a low system toxicity. This study would advance the development of carrier free nanomedicine for precise treatment of metastatic tumor.


Assuntos
Nanopartículas , Fotoquimioterapia , Fármacos Fotossensibilizantes/uso terapêutico , Fotoquimioterapia/métodos , Linhagem Celular Tumoral , Imunoterapia/métodos , Epigênese Genética , Microambiente Tumoral
7.
Neural Regen Res ; 18(7): 1584-1590, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36571366

RESUMO

Neurotrophic factors, particularly nerve growth factor, enhance neuronal regeneration. However, the in vivo applications of nerve growth factor are largely limited by its intrinsic disadvantages, such as its short biological half-life, its contribution to pain response, and its inability to cross the blood-brain barrier. Considering that let-7 (human miRNA) targets and regulates nerve growth factor, and that let-7 is a core regulator in peripheral nerve regeneration, we evaluated the possibilities of let-7 application in nerve repair. In this study, anti-let-7a was identified as the most suitable let-7 family molecule by analyses of endogenous expression and regulatory relationship, and functional screening. Let-7a antagomir demonstrated biosafety based on the results of in vivo safety assessments and it entered into the main cell types of the sciatic nerve, including Schwann cells, fibroblasts and macrophages. Use of hydrogel effectively achieved controlled, localized, and sustained delivery of let-7a antagomir. Finally, let-7a antagomir was integrated into chitosan conduit to construct a chitosan-hydrogel scaffold tissue-engineered nerve graft, which promoted nerve regeneration and functional recovery in a rat model of sciatic nerve transection. Our study provides an experimental basis for potential in vivo application of let-7a.

8.
Biomater Sci ; 2022 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-36398488

RESUMO

Tumor cells activate DNA repair pathways to combat the oxidative damage induced by reactive oxygen species (ROS), contributing to their resistance to photodynamic therapy (PDT). Herein, a self-delivery photodynamic sensitizer is developed to enhance oxidative damage by blocking the DNA repair pathway through poly(ADP-ribose) polymerase (PARP) inhibition. Specifically, the photodynamic sensitizer (CeOla) is constructed based on the self-assembly of the photosensitizer chlorine e6 (Ce6) and the PARP inhibitor olaparib (Ola). Of note is that carrier free CeOla has a high drug content and favorable water stability, which could be effectively internalized by tumor cells for robust PDT upon light irradiation. Moreover, CeOla could inhibit the activation of PARP, promote the upregulation of γ-H2AX and reduce the expression of Rad51, thereby blocking the DNA repair pathway to sensitize tumor cells for PDT. As a consequence, the self-delivery CeOla greatly promotes the tumor cell apoptosis and shows a high antitumor performance with low side effects. It serves as a novel platform for the development of self-delivery nanomedicine to overcome oxidative resistance in tumor treatment.

9.
Cell Stem Cell ; 29(11): 1594-1610.e8, 2022 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-36332572

RESUMO

The molecular diversity of glia in the human hippocampus and their temporal dynamics over the lifespan remain largely unknown. Here, we performed single-nucleus RNA sequencing to generate a transcriptome atlas of the human hippocampus across the postnatal lifespan. Detailed analyses of astrocytes, oligodendrocyte lineages, and microglia identified subpopulations with distinct molecular signatures and revealed their association with specific physiological functions, age-dependent changes in abundance, and disease relevance. We further characterized spatiotemporal heterogeneity of GFAP-enriched astrocyte subpopulations in the hippocampal formation using immunohistology. Leveraging glial subpopulation classifications as a reference map, we revealed the diversity of glia differentiated from human pluripotent stem cells and identified dysregulated genes and pathological processes in specific glial subpopulations in Alzheimer's disease (AD). Together, our study significantly extends our understanding of human glial diversity, population dynamics across the postnatal lifespan, and dysregulation in AD and provides a reference atlas for stem-cell-based glial differentiation.


Assuntos
Doença de Alzheimer , Transcriptoma , Humanos , Transcriptoma/genética , Longevidade/genética , Neuroglia/patologia , Hipocampo , Astrócitos/patologia , Doença de Alzheimer/patologia
10.
ACS Appl Mater Interfaces ; 14(48): 53501-53510, 2022 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-36399048

RESUMO

Lipid peroxide (LPO) is the hallmark of ferroptosis, which is a promising antitumor modality for its unique advantages. However, a cellular defense system would weaken the antitumor efficacy of ferrotherapy. Herein, a GPX4 inhibitor of ML162 and a photosensitizer of chlorine e6 (Ce6) are used to prepare the self-delivery nanomedicine (C-ML162) through hydrophobic and electrostatic interactions to enhance ferroptosis by photodynamic therapy (PDT). Specifically, carrier-free C-ML162 improves the solubility, stability, and cellular uptake of antitumor agents. Upon light irradiation, the internalized C-ML162 generates large amounts of reactive oxygen species (ROS) to oxidize cellular unsaturated lipid into LPO. More importantly, C-ML162 can directly inactivate GPX4 to enhance the accumulation of toxic LPO, inducing ferroptotic cell death. Additionally, C-ML162 is capable of accumulating at a tumor site for effective treatment. This self-delivery system to amplify lipid peroxidation via GPX4 inactivation for PDT initiated ferrotherapy might provide an appealing strategy against malignancies.

11.
Adv Healthc Mater ; : e2202307, 2022 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-36349844

RESUMO

Safe and effective strategies are urgently needed to fight against the life-threatening diseases of various cancers. However, traditional therapeutic modalities, such as radiotherapy, chemotherapy and surgery, exhibit suboptimal efficacy for malignant tumors owing to the serious side effects, drug resistance and even relapse. Phototherapies, including photodynamic therapy (PDT) and photothermal therapy (PTT), are emerging therapeutic strategies for localized tumor inhibition, which can produce a large amount of reactive oxygen species (ROS) or elevate the temperature to initiate cell death by non-invasive irradiation. In consideration of the poor bioavailability of phototherapy agents (PTAs), lots of drug delivery systems have been developed to enhance the tumor targeted delivery. Nevertheless, the carriers of drug delivery systems inevitably bring biosafety concerns on account of their metabolism, degradation, and accumulation. Of note, carrier-free nanomedicine attracts great attention for clinical translation with synergistic antitumor effect, which is characterized by high drug loading, simplified synthetic method and good biocompatibility. In this review, the latest advances of phototherapy with various carrier-free nanomedicines are summarized, which may provide a new paradigm for the future development of nanomedicine and tumor precision therapy.

12.
Nutrients ; 14(21)2022 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-36364766

RESUMO

LncRNA H19 has been reported to regulate apoptosis and neurological diseases. Hippocampal neuron apoptosis damages cognitive ability. Methionine restriction (MR) can improve cognitive impairment. However, the effect of MR on hippocampal neuronal apoptosis induced by a high-fat diet (HFD) in middle-aged mice remains unclear. For 25 weeks, middle-aged mice (C57BL/6J) were given a control diet (CON, 0.86% methionine + 4.2% fat), a high-fat diet (HFD, 0.86% methionine + 24% fat), or an HFD + MR diet (HFMR, 0.17% methionine + 24% fat). The HT22 cells were used to establish the early apoptosis model induced by high glucose (HG). In vitro, the results showed that MR significantly improved cell viability, suppressed the generation of ROS, and rescued HT22 cell apoptosis in a gradient-dependent manner. In Vivo, MR inhibited the damage and apoptosis of hippocampal neurons caused by a high-fat diet, reduced hippocampal oxidative stress, improved hippocampal glucose metabolism, relieved insulin resistance, and enhanced cognitive ability. Furthermore, MR could inhibit the overexpression of H19 and caspase-3 induced by HFD, HG, or H2O2 in vivo and in vitro, and promoted let-7a, b, e expression. These results indicate that MR can protect neurons from HFD-, HG-, or H2O2-induced injury and apoptosis by inhibiting H19.


Assuntos
Insulina , Metionina , Animais , Camundongos , Apoptose , Cognição , Dieta Hiperlipídica , Hipocampo/metabolismo , Peróxido de Hidrogênio/metabolismo , Insulina/metabolismo , Metionina/metabolismo , Camundongos Endogâmicos C57BL , Obesidade/metabolismo , Racemetionina/metabolismo
13.
Small ; : e2205694, 2022 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-36366925

RESUMO

Photodynamic therapy (PDT) can generate reactive oxygen species (ROS) to cause cell apoptosis and induce immunogenic cell death (ICD) to activate immune response, becoming a promising antitumor modality. However, the overexpressions of indoleamine 2,3-dioxygenase (IDO) and programmed cell death ligand 1 (PD-L1) on tumor cells would reduce cytotoxic T cells infiltration and inhibit the immune activation. In this paper, a simple but effective nanosystem is developed to solve these issues for enhanced photodynamic immunotherapy. Specifically, it has been constructed a self-delivery biomedicine (CeNB) based on photosensitizer chlorine e6 (Ce6), IDO inhibitor (NLG919), and PD1/PDL1 blocker (BMS-1) without the need for extra excipients. Of note, CeNB possesses fairly high drug content (nearly 100%), favorable stability, and uniform morphology. More importantly, CeNB-mediated IDO inhibition and PD1/PDL1 blockade greatly improve the immunosuppressive tumor microenvironments to promote immune activation. The PDT of CeNB not only inhibits tumor proliferation but also induces ICD response to activate immunological cascade. Ultimately, self-delivery CeNB tremendously suppresses the tumor growth and metastasis while leads to a minimized side effect. Such simple and effective antitumor strategy overcomes the therapeutic resistance against PDT-initiated immunotherapy, suggesting a potential for metastatic tumor treatment in clinic.

14.
Front Endocrinol (Lausanne) ; 13: 1034374, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36329888

RESUMO

Objective: Treatment decision-making in Graves' disease (GD) with severe liver dysfunction (LD) is a clinical challenge. This research was carried out to evaluate the effect of radioiodine (131I) with or without an artificial liver support system (ALSS) in GD patients with severe LD. Methods: In total, 45 patients diagnosed with GD and severe LD were enrolled and allocated to two groups: patients treated with 131I alone (n=30) (Group A)and patients by a combination of 131I and ALSS (n=15)(Group B). Liver function, thyroid hormone concentrations, therapeutic efficacy, and the cost of treatment were compared between the two groups. Results: Thyroid hormone concentrations were lower 2 weeks after 131I treatment, but no deterioration in liver function was identified. There was no statistically significant difference in the treatment efficacy between the two groups. The hospital stay, total cost, and daily cost were lower in patients treated with 131I alone than in those treated with 131I and an ALSS (p<0.05). Conclusion: The key point of treating GD patients with severe LD is to control the GD.131I is recommended as an effective and safe and should be applied as soon as possible once the diagnosis is clarified; however, when used in combination with an ALSS, there was no substantial improvement in therapeutic efficacy.


Assuntos
Doença de Graves , Hepatopatias , Fígado Artificial , Humanos , Radioisótopos do Iodo/uso terapêutico , Estudos Retrospectivos , Doença de Graves/complicações , Doença de Graves/radioterapia , Doença de Graves/tratamento farmacológico , Hormônios Tireóideos
15.
Artigo em Inglês | MEDLINE | ID: mdl-36239566

RESUMO

Context: The totally implantable venous access port (TIVAP) is an intravenous-infusion device, with a lower complication rate than other such devices. If patients fail to maintain the catheter, however, complications can still occur. Patients' needs may vary by the period of the port's use. Objective: The study intended to explore the differences in the needs of breast-cancer (BC) patients with TIVAPs for health education and nursing care at different periods of the port's use and to determine the kinds of targeted health education that can improve patients' quality of life. Design: The research team designed a questionnaire that the participants completed. Setting: The study took place at the Breast Center at the Fourth Hospital of Hebei Medical University in Shijiazhuang, China. Participants: Participants were 442 BC patients at the hospital between March and June 2020, who had TIVAPs at different stages. Groups: The study included three groups: (1) the preoperative group-participants in the preoperative period prior to the TIVAP implantation after they had signed a consent; (2) the chemotherapy group-participants in the chemotherapy period during the TIVAP's use for chemotherapy-agent transfusion, and (3) the maintenance group-participants in the maintenance period during which the TIVAD was in place but wasn't being used. Outcome Measures: The research team analyzed the results from the questionnaires, categorizing them as: (1) methods of knowledge acquisition, (2) methods of distribution of knowledge, (3) needs of participants in the different groups, and (4) distribution of symptoms among the groups. Results: Compared to other methods, the nursing staff was the main source that participants used to access the TIVAP-related information at different periods: preoperative group (79.6%), chemotherapy group (90.7%), and maintenance group (90.2%).The differences between the periods were statistically significant (P = .00). A traditional mode of education-the medical staff's explanations-was the most common in all groups: preoperative group (79.6%), chemotherapy group (83.3%), and (3) maintenance group (80.7%). Patients wanted new modes of receiving information: talks, a poster, and a medical system. TIVAP patients paid different amounts of attention to educational contents at the different stages (χ2 = 29.816, P = .00). Conclusions: BC patients' needs for health education and nursing vary at different stages when using TIVAPs. Nurses are the main source of knowledge about TIVAP in different periods for BC patients, and the nurses should obtain multidisciplinary health knowledge to enhance the benefits of the education for patients. The current education for patient is traditional, and hospitals need to implement new modes of education such as medical systems and network platforms, lectures, and posters for health education.

16.
World J Clin Cases ; 10(27): 9961-9963, 2022 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-36186206

RESUMO

To achieve awareness of the initiative practice for health concept in the Chinese population, traditional Chinese medicine (TCM) doctors should popularize TCM culture and knowledge among young people, people with a low level of education, in low-income populations, and in rural populations.

17.
Aging (Albany NY) ; 14(17): 7137-7155, 2022 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-36107005

RESUMO

OBJECTIVE: To investigate the mechanism of alanine aminotransferase 1 (ALT1) in the progression of HCC, the differentially expressed proteins (DEPs) in the ALT1 interaction network were identified by targeted proteomic analysis. METHODS: Wound healing and transwell assays were conducted to assess the effect of ALT1 on cellular migration and invasion. Cell Counting Kit-8 (CCK-8), colony formation, and flow cytometry assays were performed to identify alterations in proliferation and apoptosis. After coimmunoprecipitation processing, mass spectrometry with iso-baric tags for relative and absolute quantitation was utilized to explore the protein interactions in ALT1 knockdown HepG2 cells. RESULTS: The results showed that ALT1 knockdown inhibits the migration, invasion, proliferation of HepG2 cells, and promotes apoptosis. A total of 116 DEPs were identified and the bioinformatics analysis suggested that the ALT1-interacting proteins were primarily associated with cellular and metabolic processes. Knockdown of ALT1 in HepG2 cells reduced the expression of Ki67 and epithelial cell adhesion molecule (EP-CAM), while the expression of apoptosis-stimulating protein 2 of p53 (ASPP2) was increased significantly. Suppression of the ALT1 and EP-CAM expression contributed to alterations in epithelial-mesenchymal transition (EMT) -associated markers and matrix metalloproteinases (MMPs). Additionally, inhibition of ALT1 and Ki67 also decreased the expression of apoptosis and proliferation factors. Furthermore, inhibition of ALT1 and ASPP2 also changed the expression of P53, which may be the signaling pathway by which ALT regulates these biological behaviors. CONCLUSIONS: This study indicated that the ALT1 protein interaction network is associated with the biological behaviors of HepG2 cells via the p53 signaling pathway.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , RNA Longo não Codificante/metabolismo , Alanina Transaminase/metabolismo , Apoptose , Carcinoma Hepatocelular/genética , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Molécula de Adesão da Célula Epitelial/metabolismo , Regulação Neoplásica da Expressão Gênica , Células Hep G2 , Humanos , Antígeno Ki-67/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Metaloproteinases da Matriz/metabolismo , Proteômica , Sincalida/metabolismo , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo
18.
Photodiagnosis Photodyn Ther ; 40: 103122, 2022 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-36115558

RESUMO

BACKGROUND: Cholangiocarcinoma recurs frequently following excision surgery and is usually inoperable, while radiotherapy, chemotherapy, and immunotherapy are of limited benefit. As palliative care, percutaneous transhepatic cholangial drainage (PTCD) can relieve biliary obstruction, prevent jaundice, and maintain quality of life (QOL), but does not improve overall survival. In contrast, photodynamic therapy (PDT) has been demonstrated to prolong the survival of inoperable cancer patients. OBJECTIVE: This study evaluated the clinical efficacy of percutaneous transhepatic cholangioscopy (PTCS)-guided PDT following PTCD versus PTCD alone for recurrent inoperable cholangiocarcinoma. METHODS: The case files of 39 patients with postoperative recurrence were retrospectively analyzed, including 18 receiving PTCS-guided PDT (PTCS-PDT group) and 21 receiving PTCD only as a control (PTCD group). Survival time was compared by Kaplan-Meier analysis and log-rank test, and QOL by the Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-HEP) questionnaire. Clinicodemographic factors, including serum bilirubin and adverse reaction rates, were compared by Student's t-test or Fisher's exact test. The maximum follow-up period was 71 months. RESULTS: Median survival time was significantly longer in the PTCS-PDT group than the PTCD group (23 months vs. 10 months, P = 0.00001). At 6 and 12 months post-treatment, total FACT-HEP score was lower in the PTCS-PDT group (P < 0.05), indicating improved QOL. There was no significant difference in total adverse events incidence between groups (19 [51.4%] vs. 15 [71.4%]; P = 0.131). CONCLUSION: PTCS-guided PDT can prolong survival and improve the QOL of patients with postoperative cholangiocarcinoma recurrence without increasing complications. SIGNIFICANT AND/OR NEW FINDINGS: Compared to PTCD alone, PTCS-guided PDT significantly prolonged the survival time of patients with postoperative recurrent extrahepatic cholangiocarcinoma. Photodynamic therapy also improved patient quality of life by facilitating timely removal of the PTCD drainage tube. PTCS-guided PDT did not increase surgery-related complications except for skin phototoxicity, which can be easy avoided and treated.

19.
NAR Genom Bioinform ; 4(3): lqac069, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36128423

RESUMO

Single-cell RNA sequencing thoroughly quantifies the individual cell transcriptomes but renounces the spatial structure. Conversely, recently emerged spatial transcriptomics technologies capture the cellular spatial structure but skimp cell or gene resolutions. Ligand-receptor interactions reveal the potential of cell proximity since they are spatially constrained. Cell-cell affinity values estimated by ligand-receptor interaction can partially represent the structure of cells but falsely include the pseudo affinities between distant or indirectly interacting cells. Here, we develop a software package, SPROUT, to reconstruct the single-cell resolution spatial structure from the transcriptomics data through diminished pseudo ligand-receptor affinities. For spatial data, SPROUT first curates the representative single-cell profiles for each spatial spot from a candidate library, then reduces the pseudo affinities in the intercellular affinity matrix by partial correlation, spectral graph sparsification, and spatial coordinates refinement. SPROUT embeds the estimated interactions into a low-dimensional space with the cross-entropy objective to restore the intercellular structures, which facilitates the discovery of dominant ligand-receptor pairs between neighboring cells at single-cell resolution. SPROUT reconstructed structures achieved shape Pearson correlations ranging from 0.91 to 0.97 on the mouse hippocampus and human organ tumor microenvironment datasets. Furthermore, SPROUT can solely de novo reconstruct the structures at single-cell resolution, i.e., reaching the cell-type proximity correlations of 0.68 and 0.89 between reconstructed and immunohistochemistry-informed spatial structures on a human developing heart dataset and a tumor microenvironment dataset, respectively.

20.
J Pharm Pharmacol ; 2022 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-36130331

RESUMO

BACKGROUND: Berberine, a non-prescription medicine clinically applied for diarrhoea and gastroenteritis. Recent studies have demonstrated that it possesses anti-tumour properties in colorectal cancer, but the exact molecular mechanism remains obscure. OBJECTIVES: To elucidate the underly molecular mechanisms of berberine in colorectal cancer from a perspective of epigenetics, and tried to explore the role of lincROR-Wnt/ß-catenin molecular axis in the berberine induced the anti-tumour activity in colorectal cancer. METHODS: The effects of berberine on cell growth, cell cycle and apoptosis were examined in CRC cells. The in vivo effect of berberine on tumour growth was investigated using a xenograft mice model. Moreover, lincROR and Wnt/ß-catenin signalling were detected by luciferase activity, qRT-PCR and western blotting assays. KEY FINDINGS: Berberine suppressed cell growth in vitro via inducing cell cycle arrest and apoptosis in CRC cell, and inhibited tumourigenesis in vivo. LincROR was significantly down-regulated by berberine, inducing the inactivation of the canonical Wnt/ß-catenin signalling, meanwhile, the overexpression of lincROR partially reversed the suppressive effects on tumour growth and Wnt/ß-catenin signalling induced by berberine. CONCLUSIONS: Berberine inhibits tumour growth partially via regulating the lincROR-Wnt/ß-catenin regulatory axis, which provides a strategy for the design of anti-tumour drugs for CRC patients after our advanced validation.

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