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Science Advances Jun 2024The blood-brain barrier (BBB) acts as the crucial physical filtration structure in the central nervous system. Here, we investigate the role of a specific subset of...
The blood-brain barrier (BBB) acts as the crucial physical filtration structure in the central nervous system. Here, we investigate the role of a specific subset of astrocytes in the regulation of BBB integrity. We showed that expressing astrocytes transfer mitochondria to endothelial cells via their endfeet for maintaining BBB integrity. Deletion of the Mitofusin 2 () gene in -expressing astrocytes inhibited the mitochondrial transfer and caused BBB leakage. In addition, the decrease of MFN2 in astrocytes contributes to the age-associated reduction of mitochondrial transfer efficiency and thus compromises the integrity of BBB. Together, we describe a mechanism in which astrocytes regulate BBB integrity through mitochondrial transfer. Our findings provide innnovative insights into the cellular framework that underpins the progressive breakdown of BBB associated with aging and disease.
Topics: Astrocytes; Blood-Brain Barrier; Animals; Mitochondria; Mice; Endothelial Cells; GTP Phosphohydrolases
PubMed: 38941455
DOI: 10.1126/sciadv.adk2913 -
Science Advances Jun 2024Decades of research have uncovered how plants respond to two environmental variables that change across latitudes and over seasons: photoperiod and temperature. However,...
Decades of research have uncovered how plants respond to two environmental variables that change across latitudes and over seasons: photoperiod and temperature. However, a third such variable, twilight length, has so far gone unstudied. Here, using controlled growth setups, we show that the duration of twilight affects growth and flowering time via the clock genes in the model plant Arabidopsis. Using a series of progressively truncated no-twilight photoperiods, we also found that plants are more sensitive to twilight length compared to equivalent changes in solely photoperiods. Transcriptome and proteome analyses showed that twilight length affects reactive oxygen species metabolism, photosynthesis, and carbon metabolism. Genetic analyses suggested a twilight sensing pathway from the photoreceptors , , , and through to flowering modulation through the pathway. Overall, our findings call for more nuanced models of day-length perception in plants and posit that twilight is an important determinant of plant growth and development.
Topics: Arabidopsis; Flowers; Arabidopsis Proteins; Photoperiod; Gene Expression Regulation, Plant; Transcription Factors; Reactive Oxygen Species; Photosynthesis; Cryptochromes
PubMed: 38941453
DOI: 10.1126/sciadv.adl3199 -
Medicine Jun 2024Idiopathic inflammatory myopathies, especially antisynthetase syndrome, often appear outside of the muscles as interstitial lung disease (ILD). Another typical finding... (Observational Study)
Observational Study
Idiopathic inflammatory myopathies, especially antisynthetase syndrome, often appear outside of the muscles as interstitial lung disease (ILD). Another typical finding is the presence of mechanic's hands. The aim of the present study was to describe the clinical, functional, tomographic, and serological data of patients with ILD and mechanic's hands and their response to treatment and survival rates. This is a retrospective study of ILD with concurrent myopathy. Among the 119 patients initially selected, 51 had mechanic's hands. All the patients were screened for anti-Jo-1 antibodies. An expanded panel of myopathy autoantibodies was also performed in 27 individuals. Of the 51 patients, 35 had 1 or more antibodies. The most common were anti-Jo-1, anti-PL-7, and anti-PL-12, while of the associated antibodies, anti-Ro52 was present in 70% of the 27 tested individuals. A significant response to treatment was characterized by an increase in predicted forced vital capacity (FVC) of at least 5% in the last evaluation done after 6 to 24 months of treatment. A decrease in predicted FVC of at least 5%, the need for oxygen therapy, or death were all considered treatment failures. All patients were treated with corticosteroids, and 71% with mycophenolate. After 24 months, 18 patients had an increase in FVC, 11 had a decrease, and 22 remained stable. After a median follow-up of 58 months, 48 patients remained alive and three died. Patients with honeycombing on high-resolution chest tomography (log-rank = 34.65; P < .001) and a decrease in FVC ≥5% (log-rank = 18.28, P < .001) had a poorer survival rate. Patients with ILD and mechanic's hands respond well to immunosuppressive treatment.
Topics: Humans; Lung Diseases, Interstitial; Retrospective Studies; Male; Female; Middle Aged; Myositis; Aged; Treatment Outcome; Adult; Autoantibodies; Outpatients; Adrenal Cortex Hormones; Vital Capacity
PubMed: 38941439
DOI: 10.1097/MD.0000000000038642 -
Medicine Jun 2024Acute pancreatitis (AP) is a common emergency condition with high morbidity, mortality, and socio-economic impact. Soluble urokinase plasminogen activator receptor...
BACKGROUND
Acute pancreatitis (AP) is a common emergency condition with high morbidity, mortality, and socio-economic impact. Soluble urokinase plasminogen activator receptor (suPAR) is a potential biomarker for AP prognosis. This study systematically reviews the literature on suPAR's prognostic roles in assessing AP severity, organ failure, mortality, and other pathological markers.
METHODS
A comprehensive search of 5 databases up to March 19, 2023, was conducted, selecting cohort studies that examined suPAR's relationship with AP outcomes. Outcome variables included AP severity, organ failure, mortality, hospital stay length, and suPAR's association with other inflammatory markers. Our paper has been registered on Prospero (ID: CRD42023410628).
RESULTS
Nine prospective observational studies with 1033 AP patients were included. Seven of eight studies found suPAR significantly elevated in severe acute pancreatitis (P < .05). Four studies showed suPAR effectively predicted organ failure risk, and 4 studies concluded suPAR significantly predicted mortality (P < .05). The review had no high-risk studies, enhancing credibility.
CONCLUSION
suPAR is a valuable prognostic marker in AP, significantly predicting severity, organ failure, hospital stay length, and mortality. Further large-scale studies are needed to explore suPAR's role in other clinical outcomes related to AP disease course, to establish it as a mainstay of AP prognosis.
Topics: Humans; Pancreatitis; Receptors, Urokinase Plasminogen Activator; Prognosis; Biomarkers; Systematic Reviews as Topic; Severity of Illness Index; Length of Stay; Acute Disease
PubMed: 38941433
DOI: 10.1097/MD.0000000000037064 -
Medicine Jun 2024Rosacea is a chronic and recurrent inflammatory skin disease affecting the center of the face that causes burning and itching sensations and changes in aesthetics. Liang...
Rosacea is a chronic and recurrent inflammatory skin disease affecting the center of the face that causes burning and itching sensations and changes in aesthetics. Liang Xue Wu Hua Tang (LXWHT) is a classic herbal formulation that is efficacious and has been widely used in the clinical treatment of rosacea; however, the pharmacological mechanisms remain unclear. The aim of the present study was to investigate the mechanism of action of LXWHT using network pharmacology and molecular docking. The Traditional Chinese Medicine System Pharmacology database was searched to identify the active ingredients and pharmacological targets of LXWHT, and the GeneCard, Disgenet, and Gene Expression Omnibus databases were applied to screen rosacea-related targets. Cytoscape software was used to visualize the protein-protein interaction network, and network topology analysis was used to identify core targets. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed for the core targets. Molecular docking simulations and visualization were performed using Maestro and PyMOL, respectively. A total of 43 active compounds and 28 potential targets for LXWHT treatment of rosacea were selected for analysis. The Gene Ontology/Kyoto Encyclopedia of Genes and Genomes results indicated that LXWHT may exert therapeutic effects on rosacea by intervening in immune pathways including tumor necrosis factor pathway, interleukin-17 pathways, and Toll-like receptor signaling pathways. Chemokine ligand 2, interferon-γ, interleukin-1ß, peroxisome proliferator-activated receptor-γ, and matrix metallopeptidase 9 may be the core therapeutic target. Quercetin, stigmasterol, kaempferol, beta-sitosterol, luteolin, beta-carotene, baicalein, acetin, and isorhamnetin were predicted to be the key active ingredients. LXWHT may exert therapeutic effects in the treatment of rosacea by modulating immunity and angiogenesis, laying the foundation for further research.
Topics: Rosacea; Molecular Docking Simulation; Humans; Drugs, Chinese Herbal; Network Pharmacology; Protein Interaction Maps; Medicine, Chinese Traditional
PubMed: 38941423
DOI: 10.1097/MD.0000000000038705 -
Medicine Jun 2024Multiple myeloma (MM) with extramedullary disease (EMD) is rare in clinical practice, and B cell maturation antigen (BCMA) CAR-T cell therapy is a novel therapy for... (Review)
Review
INTRODUCTION
Multiple myeloma (MM) with extramedullary disease (EMD) is rare in clinical practice, and B cell maturation antigen (BCMA) CAR-T cell therapy is a novel therapy for hematologic malignancies. Very few reports have been published on the effect of CAR-T-cell therapy in MM with EMD. Here, we report a case of MM with extramedullary lesions treated with BCMA CAR-T therapy.
CASE PRESENTATION
A 66-year-old female patient presented to our hospital with an enlarged left maxillary gingiva.
DIAGNOSIS
Diagnosis of indolent MM stage III (DS staging) and stage III (ISS and R ISS) with extramedullary lesions.
INTERVENTION
The patient underwent a clinical trial of humanized anti-BCMA CAR T cell therapy.
RESULTS
Symptoms improved; left gingival hyperplasia and swelling resolved; left buccal mass resolved; and neck and submandibular masses resolved. Pathological examination of the exfoliated masses showed necrotic tissue.
CONCLUSION
MM with extramedullary lesions often has limited treatment options, and traditional chemotherapy methods are ineffective; however, BCMA CAR-T cell therapy can significantly improve the symptoms of extramedullary lesions in MM.
Topics: Humans; Multiple Myeloma; Female; Aged; B-Cell Maturation Antigen; Immunotherapy, Adoptive
PubMed: 38941416
DOI: 10.1097/MD.0000000000038541 -
Medicine Jun 2024Thyroglossal duct carcinoma, a rare clinical condition characterized by ectopic thyroid adenocarcinoma within thyroglossal duct cysts (TGDCs), typically confirmed... (Review)
Review
RATIONALE
Thyroglossal duct carcinoma, a rare clinical condition characterized by ectopic thyroid adenocarcinoma within thyroglossal duct cysts (TGDCs), typically confirmed through intraoperative rapid pathology, this condition generally has a favorable prognosis. Nevertheless, comprehensive treatment guidelines across all disease stages are lacking, the purpose of this study is to report 1 case of the disease and propose the treatment plan for each stage of the disease.
PATIENT CONCERNS
A patient presented with thyroid swelling, classified as C-TIRADS 4A following a physical examination. Preoperative thyroid puncture identified papillary thyroid carcinoma, and genetic testing revealed a BRAF gene exon 15-point mutation. Ancillary tests showed a slightly decreased thyroid stimulating hormone (TSH) level (0.172) with no other significant abnormalities.
DIAGNOSES
Preoperative fine-needle aspiration cytology (FNAC) confirmed right-side thyroid cancer. Intraoperative exploration uncovered a TGDC and intraoperative rapid pathology confirmed thyroglossal duct carcinoma.
INTERVENTIONS
A Sistrunk operation and ipsilateral thyroidectomy were performed.
OUTCOMES
Postoperative recovery was satisfactory.
LESSONS
Thyroglossal duct carcinoma is a rare disease affecting the neck. Due to limited clinical cases and the favorable prognosis associated with this condition, there is currently no established set of diagnostic and treatment guidelines. According to tumor size, lymph node metastasis, thyroid status and other factors, the corresponding treatment methods were established for each stage of thyroglossal duct cancer, which laid the foundation for the subsequent treatment development of this disease.
Topics: Humans; Thyroglossal Cyst; Thyroid Neoplasms; Thyroid Cancer, Papillary; Female; Thyroidectomy; Male; Proto-Oncogene Proteins B-raf; Adult; Biopsy, Fine-Needle
PubMed: 38941410
DOI: 10.1097/MD.0000000000038540 -
Medicine Jun 2024Appendicitis is an inflammation caused by obstruction of the appendiceal lumen or termination of blood supply leading to appendiceal necrosis followed by secondary... (Observational Study)
Observational Study
Appendicitis is an inflammation caused by obstruction of the appendiceal lumen or termination of blood supply leading to appendiceal necrosis followed by secondary bacterial infection. The relationship between TYROBP gene and the nursing of appendicitis remains unclear. The appendicitis dataset GSE9579 profile was downloaded from the gene expression omnibus database generated from GPL571. Differentially expressed genes were screened, followed by weighted gene co-expression network analysis, functional enrichment analysis, gene set enrichment analysis, construction and analysis of protein-protein interaction network, Comparative Toxicogenomics Database analysis, and immune infiltration analysis. Heatmaps of gene expression levels were plotted. A total of 1570 differentially expressed genes were identified. According to gene ontology analysis, they were mainly enriched in organic acid metabolic process, condensed chromosome kinetochore, oxidoreductase activity. In Kyoto Encyclopedia of Gene and Genome analysis, they mainly concentrated in metabolic pathways, P53 signaling pathway, PPAR signaling pathway. The soft threshold power in weighted gene co-expression network analysis was set to 12. Through the construction and analysis of protein-protein interaction network, 5 core genes (FCGR2A, IL1B, ITGAM, TLR2, TYROBP) were obtained. Heatmap of core gene expression levels revealed high expression of TYROBP in appendicitis samples. Comparative Toxicogenomics Database analysis found that core genes (FCGR2A, IL1B, ITGAM, TLR2, TYROBP) were closely related to abdominal pain, gastrointestinal dysfunction, fever, and inflammation occurrence. TYROBP gene is highly expressed in appendicitis, and higher expression of TYROBP gene indicates worse prognosis. TYROBP may serve as a molecular target for appendicitis and its nursing.
Topics: Appendicitis; Humans; Protein Interaction Maps; Data Mining; Toxicogenetics; Gene Regulatory Networks
PubMed: 38941398
DOI: 10.1097/MD.0000000000038667 -
Medicine Jun 2024Ferroptosis was reported to possess the therapeutic potentials in various human cancers. In the present study, we explored the expression, clinical significance and the...
BACKGROUND
Ferroptosis was reported to possess the therapeutic potentials in various human cancers. In the present study, we explored the expression, clinical significance and the molecular mechanism of FK506 binding protein 3 (FKBP3) in the progression of lung adenocarcinoma (LUAD).
MATERIAL AND METHOD
Cox regression was performed to obtain the prognosis related to differentially expressed genes (DEGs) in LUAD datasets from TCGA. We also downloaded the ferroptosis-related gene datasets from GeneCards. Venn diagram was performed to find the intersecting genes and FKBP3 was selected as the targeted gene by analyzing the diagnostic and prognostic values of Top10 intersecting genes. Moreover, univariate and multivariate analyses were performed to evaluate the association between clinicopathological factors and survival rates. GO/KEGG and GSEA analysis was performed to explore the function of FKBP3 in LUAD progression. Protein-protein interaction (PPI) network was performed via STRING database and the top10 hub genes were selected. Finally, the relationship between FKBP3 and immune infiltration was explored by ssGSEA analysis.
RESULTS
Firstly, 184 genes associated with the prognosis of LUAD and ferroptosis were obtained. FKBP3 was found to be significantly associated with a poor overall survival rate of LUAD patients. Immunohistochemical staining results showed that FKBP3 was highly located in cytoplasm and membrane of cells in LUAD tissues. PPI network analysis results showed that HDAC1, YY1, HDAC2, MTOR, PSMA3, PIN1, NCL, C14orf166, PIN4, and LARP6 were the top10 hub genes. Furthermore, spearman analysis results showed that the expression of FKBP3 was positively correlated with the abundance of Th2 cells and T helper cells.
CONCLUSION
High level of FKBP3 was associated with poor prognostic outcomes of LUAD patients, which also inhibited immune infiltration in LUAD tissues. Additionally, FKBP3 was involved in regulating the ferroptosis process in LUAD patients. Thus, FKBP3 possessed the tumor promotion role might be involving in regulating ferroptosis and immune infiltration in LUAD progression.
Topics: Humans; Ferroptosis; Prognosis; Female; Disease Progression; Male; Adenocarcinoma of Lung; Lung Neoplasms; Middle Aged; Tacrolimus Binding Proteins; Biomarkers, Tumor; Aged; Gene Expression Regulation, Neoplastic; Protein Interaction Maps
PubMed: 38941396
DOI: 10.1097/MD.0000000000038606 -
Medicine Jun 2024Hereditary transthyretin-mediated amyloidosis (ATTRv amyloidosis), known as Corino de Andrade disease, is a rare neurodegenerative disorder with a significant global... (Review)
Review
Hereditary transthyretin-mediated amyloidosis (ATTRv amyloidosis), known as Corino de Andrade disease, is a rare neurodegenerative disorder with a significant global impact characterized by the misfolding of transthyretin (TTR) protein leading to amyloid aggregation, ATTRv amyloidosis, especially with polyneuropathy, poses a considerable challenge in managing its rapid progression and debilitating effects. This mini-review focuses on the recent advancements in the treatment landscape for ATTRv amyloidosis with polyneuropathy, specifically the RNA interference therapeutic Vutrisiran and the ligand-conjugated antisense oligonucleotide Eplontersen. We aim to provide a comprehensive overview of the mechanisms, current evidence from clinical trials, and future directions for these novel therapeutic agents. Vutrisiran and Eplontersen have demonstrated significant clinical efficacy in improving neuropathic impairment, quality of life, and serum TTR levels in various trials. The distinct mechanistic approaches of these therapies, coupled with their acceptable safety profiles, offer promising avenues for addressing the complexities of ATTRv amyloidosis with polyneuropathy. The introduction of Vutrisiran and Eplontersen marks a pivotal moment in the quest for effective therapies against ATTRv amyloidosis with polyneuropathy. While clinical evidence is promising, ongoing research is crucial to deepen mechanistic understanding and address research gaps. Future perspectives include the potential expansion of therapeutic options and a more inclusive approach to cater to the diverse needs of individuals globally. This mini-review provides valuable insights into the evolving landscape of ATTRv amyloidosis management and sets the stage for further exploration in this challenging domain.
Topics: Humans; Amyloid Neuropathies, Familial; Polyneuropathies; Oligonucleotides; Oligonucleotides, Antisense; Prealbumin; Quality of Life
PubMed: 38941378
DOI: 10.1097/MD.0000000000038767