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1.
World J Clin Cases ; 12(19): 3717-3724, 2024 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-38994302

RESUMO

BACKGROUND: The serratus anterior muscle, located in the lateral aspect of the thorax, plays a crucial role in shoulder movement and stability. Thoracoscopic surgery, while minimally invasive, often results in significant postoperative pain, complicating patient recovery and potentially extending hospital stays. Traditional anesthesia methods may not adequately address this pain, leading to increased complications such as agitation due to inadequate pain management. AIM: To evaluate the application value of ultrasound-guided serratus anterior plane block (SAPB) in patients undergoing thoracoscopic surgery, focusing on its effects on postoperative analgesia and rehabilitation. METHODS: Eighty patients undergoing thoracoscopic surgery between August 2021 and December 2022 were randomly divided into two groups: An observation group receiving ultrasound-guided SAPB and a control group receiving standard care without SAPB. Both groups underwent general anesthesia and were monitored for blood pressure, heart rate (HR), oxygen saturation, and pulse. The primary outcomes measured included mean arterial pressure (MAP), HR, postoperative visual analogue scale (VAS) scores for pain, supplemental analgesic use, and incidence of agitation. RESULTS: The observation group showed significantly lower cortisol and glucose concentrations at various time points post-operation compared to the control group, indicating reduced stress responses. Moreover, MAP and HR levels were lower in the observation group during and after surgery. VAS scores were significantly lower in the observation group at 1 h, 4 h, 6 h, and 12 h post-surgery, and the rates of analgesic supplementation and agitation were significantly reduced compared to the control group. CONCLUSION: Ultrasound-guided SAPB significantly improves postoperative analgesia and reduces agitation in patients undergoing thoracoscopic surgery. This technique stabilizes perioperative vital signs, decreases the need for supplemental analgesics, and minimizes postoperative pain and stress responses, underscoring its high application value in enhancing patient recovery and rehabilitation post-thoracoscopy.

2.
Sci Transl Med ; 16(756): eadn0136, 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39018367

RESUMO

Postacute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC) represent an urgent public health challenge and are estimated to affect more than 60 million individuals globally. Although a growing body of evidence suggests that dysregulated immune reactions may be linked with PASC symptoms, most investigations have primarily centered around blood-based studies, with few focusing on samples derived from affected tissues. Furthermore, clinical studies alone often provide correlative insights rather than causal mechanisms. Thus, it is essential to compare clinical samples with relevant animal models and conduct functional experiments to understand the etiology of PASC. In this study, we comprehensively compared bronchoalveolar lavage fluid single-cell RNA sequencing data derived from clinical PASC samples and a mouse model of PASC. This revealed a pro-fibrotic monocyte-derived macrophage response in respiratory PASC, as well as abnormal interactions between pulmonary macrophages and respiratory resident T cells, in both humans and mice. Interferon-γ (IFN-γ) emerged as a key node mediating the immune anomalies in respiratory PASC. Neutralizing IFN-γ after the resolution of acute SARS-CoV-2 infection reduced lung inflammation and tissue fibrosis in mice. Together, our study underscores the importance of performing comparative analysis to understand the cause of PASC and suggests that the IFN-γ signaling axis might represent a therapeutic target.


Assuntos
Líquido da Lavagem Broncoalveolar , COVID-19 , Interferon gama , SARS-CoV-2 , Análise de Célula Única , COVID-19/imunologia , COVID-19/patologia , COVID-19/virologia , COVID-19/complicações , Animais , Interferon gama/metabolismo , Humanos , Camundongos , Líquido da Lavagem Broncoalveolar/virologia , Modelos Animais de Doenças , Pulmão/patologia , Pulmão/virologia , Camundongos Endogâmicos C57BL , Macrófagos Alveolares/imunologia , Masculino , Feminino , Linfócitos T/imunologia
3.
Case Rep Cardiol ; 2024: 3766536, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39015672

RESUMO

Frank's sign (FS) refers to a diagonal skin fold between the tragus and the outer edge of the earlobe. FS has been identified as an independent variable in coronary artery disease (CAD). Young patients with FS and previous myocardial infarction are still rarely reported in clinical studies. We report the case of a 49-year-old male smoker and diabetic, with a history of myocardial infarction, who presented to the emergency department due to 2 h typical cardiac chest pain. His urgent electrocardiography (ECG) showed ST elevation, and cardiac biomarkers were elevated after admission. A diagonal earlobe crease (DELC) was observed in physical tests. The preliminary diagnosis considered acute coronary syndrome (ACS). Subsequently, acute coronary artery angiography demonstrated a slit-like contrast defect in the proximal right coronary artery (RCA), with stenosis and occlusion in the distal segment. The percutaneous coronary intervention (PCI) was performed immediately. The patient's chest pain symptoms were relieved significantly after intervention. Our case indicates that FS should be highly regarded as a routine cardiovascular clinical examination, which can be effortlessly applied and be easily interpreted for screening to suspect the presence of ischemic heart disease. This may set strategies for primary screening in a younger population and prompt early diagnosis and treatment.

4.
Front Microbiol ; 15: 1412991, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38974029

RESUMO

Age and gender have been recognized as two pivotal covariates affecting the composition of the gut microbiota. However, their mediated variations in microbiota seem to be inconsistent across different countries and races. In this study, 613 individuals, whom we referred to as the "healthy" population, were selected from 1,018 volunteers through rigorous selection using 16S rRNA sequencing. Three enterotypes were identified, namely, Escherichia-Shigella, mixture (Bacteroides and Faecalibacterium), and Prevotella. Moreover, 11 covariates that explain the differences in microbiota were determined, with age being the predominant factor. Furthermore, age-related differences in alpha diversity, beta diversity, and core genera were observed in our cohort. Remarkably, after adjusting for 10 covariates other than age, abundant genera that differed between age groups were demonstrated. In contrast, minimal differences in alpha diversity, beta diversity, and differentially abundant genera were observed between male and female individuals. Furthermore, we also demonstrated the age trajectories of several well-known beneficial genera, lipopolysaccharide (LPS)-producing genera, and short-chain fatty acids (SCFAs)-producing genera. Overall, our study further elucidated the effects mediated by age and gender on microbiota differences, which are of significant importance for a comprehensive understanding of the gut microbiome spectrum in healthy individuals.

5.
J Genet Genomics ; 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-39002897

RESUMO

Facial morphology, a complex trait influenced by genetics, holds great significance in evolutionary research. However, due to limited fossil evidence, the facial characteristics of Neanderthals and Denisovans have remained largely unknown. In this study, we conducted a large-scale multi-ethnic meta-analysis of Genome-Wide Association Study (GWAS), including 9674 East Asians and 10,115 Europeans, quantitatively assessing 78 facial traits using 3D facial images. We identified 71 genomic loci associated with facial features, including 21 novel loci. We developed a facial polygenic score (FPS) that enables the prediction of facial features based on genetic information. Interestingly, the distribution of FPSs among populations from diverse continental groups exhibited significant correlations with observed facial features. Furthermore, we applied the FPS to predict the facial traits of seven Neanderthals and one Denisovan using ancient DNA, and aligned predictions with the fossil records. Our results suggested that Neanderthals and Denisovans likely shared similar facial features, such as a wider but shorter nose and a wider endocanthion distance. The decreased mouth width was characterized specifically in Denisovan. The integration of genomic data and facial trait analysis provides valuable insights into the evolutionary history and adaptive changes in human facial morphology.

6.
J Anim Sci ; 1022024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38908013

RESUMO

Mulberry leaves (MLs) are an unconventional feed with fiber and various active ingredients, and are acknowledged as likely to regulate lipid metabolism, while the molecular mechanism remains undefined. Therefore, our objective was to define the role of MLs on the overall lipid metabolism. We conducted a feeding experiment of three groups on growing mutton sheep fed with dried mulberry leaves (DMLs), with fermented mulberry leaves (FMLs), or without MLs (as control). Analyses of transcriptome and widely target lipids demonstrated the addition of MLs triggered big perturbations in genes and metabolites related to glycerolipid, phospholipid, ether lipid, and sphingolipid metabolism. Additionally, the variations of the above lipids in the treatment of MLs possibly facilitate immunity enhancement of growing mutton sheep via the activation of complement and coagulation cascades. Furthermore, treatments with MLs could expedite proceedings of lipid degradation and fatty acid ß oxidation in mitochondria, thereby to achieve the effect of lipid reduction. Besides, added DMLs also fuel fatty acid ß-oxidation in peroxisomes and own much stronger lipolysis than added FMLs, possibly attributed to high fiber content in DMLs. These findings establish the novel lipid-lowering role and immune protection of MLs, which lays the foundation for the medicinal application of MLs.


Mulberry leaves (MLs) are rich in a wide variety of active ingredients and are also a kind of traditional Chinese medicine with the same origin as medicine and food. Previous studies have found that MLs may regulate lipid metabolism. But the exact mechanism remains unclear. Our study reveals that ML supplement not only alters lipid metabolism including glycerol phospholipid, ether lipid as well as sphingolipid metabolism, which may help to improve immunity but also promote fatty acid degradation as well as ß oxidation to achieve the effect of fat reduction.


Assuntos
Ração Animal , Dieta , Suplementos Nutricionais , Ácidos Graxos , Metabolismo dos Lipídeos , Morus , Folhas de Planta , Animais , Metabolismo dos Lipídeos/efeitos dos fármacos , Ovinos , Ácidos Graxos/metabolismo , Ração Animal/análise , Dieta/veterinária , Oxirredução
7.
Front Mol Biosci ; 11: 1391046, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38841190

RESUMO

Dendritic cells (DCs) are involved in the initiation and maintenance of immune responses against malignant cells by recognizing conserved pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) through pattern recognition receptors (PRRs). According to recent studies, tumor cell-derived DNA molecules act as DAMPs and are recognized by DNA sensors in DCs. Once identified by sensors in DCs, these DNA molecules trigger multiple signaling cascades to promote various cytokines secretion, including type I IFN, and then to induce DCs mediated antitumor immunity. As one of the potential attractive strategies for cancer therapy, various agonists targeting DNA sensors are extensively explored including the combination with other cancer immunotherapies or the direct usage as major components of cancer vaccines. Moreover, this review highlights different mechanisms through which tumor-derived DNA initiates DCs activation and the mechanisms through which the tumor microenvironment regulates DNA sensing of DCs to promote tumor immune escape. The contributions of chemotherapy, radiotherapy, and checkpoint inhibitors in tumor therapy to the DNA sensing of DCs are also discussed. Finally, recent clinical progress in tumor therapy utilizing agonist-targeted DNA sensors is summarized. Indeed, understanding more about DNA sensing in DCs will help to understand more about tumor immunotherapy and improve the efficacy of DC-targeted treatment in cancer.

8.
Nat Commun ; 15(1): 4696, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38824133

RESUMO

Age-related microangiopathy, also known as small vessel disease (SVD), causes damage to the brain, retina, liver, and kidney. Based on the DNA damage theory of aging, we reasoned that genomic instability may underlie an SVD caused by dominant C-terminal variants in TREX1, the most abundant 3'-5' DNA exonuclease in mammals. C-terminal TREX1 variants cause an adult-onset SVD known as retinal vasculopathy with cerebral leukoencephalopathy (RVCL or RVCL-S). In RVCL, an aberrant, C-terminally truncated TREX1 mislocalizes to the nucleus due to deletion of its ER-anchoring domain. Since RVCL pathology mimics that of radiation injury, we reasoned that nuclear TREX1 would cause DNA damage. Here, we show that RVCL-associated TREX1 variants trigger DNA damage in humans, mice, and Drosophila, and that cells expressing RVCL mutant TREX1 are more vulnerable to DNA damage induced by chemotherapy and cytokines that up-regulate TREX1, leading to depletion of TREX1-high cells in RVCL mice. RVCL-associated TREX1 mutants inhibit homology-directed repair (HDR), causing DNA deletions and vulnerablility to PARP inhibitors. In women with RVCL, we observe early-onset breast cancer, similar to patients with BRCA1/2 variants. Our results provide a mechanistic basis linking aberrant TREX1 activity to the DNA damage theory of aging, premature senescence, and microvascular disease.


Assuntos
Dano ao DNA , Exodesoxirribonucleases , Fosfoproteínas , Animais , Exodesoxirribonucleases/genética , Exodesoxirribonucleases/metabolismo , Humanos , Fosfoproteínas/genética , Fosfoproteínas/metabolismo , Camundongos , Reparo de DNA por Recombinação , Fenótipo , Mutação , Drosophila/genética , Envelhecimento/genética , Envelhecimento/metabolismo , Feminino , Drosophila melanogaster/genética , Masculino , Doenças Retinianas , Doenças Vasculares , Doenças Desmielinizantes Hereditárias do Sistema Nervoso Central
9.
Proteomics ; : e2400025, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38895962

RESUMO

Extracellular vesicles (EVs) carry diverse biomolecules derived from their parental cells, making their components excellent biomarker candidates. However, purifying EVs is a major hurdle in biomarker discovery since current methods require large amounts of samples, are time-consuming and typically have poor reproducibility. Here we describe a simple, fast, and sensitive EV fractionation method using size exclusion chromatography (SEC) on a fast protein liquid chromatography (FPLC) system. Our method uses a Superose 6 Increase 5/150, which has a bed volume of 2.9 mL. The FPLC system and small column size enable reproducible separation of only 50 µL of human plasma in 15 min. To demonstrate the utility of our method, we used longitudinal samples from a group of individuals who underwent intense exercise. A total of 838 proteins were identified, of which, 261 were previously characterized as EV proteins, including classical markers, such as cluster of differentiation (CD)9 and CD81. Quantitative analysis showed low technical variability with correlation coefficients greater than 0.9 between replicates. The analysis captured differences in relevant EV proteins involved in response to physical activity. Our method enables fast and sensitive fractionation of plasma EVs with low variability, which will facilitate biomarker studies in large clinical cohorts.

10.
Biomed Opt Express ; 15(6): 3523-3540, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38867772

RESUMO

Surface-enhanced Raman spectroscopy (SERS), a rapid, low-cost, non-invasive, ultrasensitive, and label-free technique, has been widely used in-situ and ex-situ biomedical diagnostics questions. However, analyzing and interpreting the untargeted spectral data remains challenging due to the difficulty of designing an optimal data pre-processing and modelling procedure. In this paper, we propose a Multi-branch Attention Raman Network (MBA-RamanNet) with a multi-branch attention module, including the convolutional block attention module (CBAM) branch, deep convolution module (DCM) branch, and branch weights, to extract more global and local information of characteristic Raman peaks which are more distinctive for classification tasks. CBAM, including channel and spatial aspects, is adopted to enhance the distinctive global information on Raman peaks. DCM is used to supplement local information of Raman peaks. Autonomously trained branch weights are applied to fuse the features of each branch, thereby optimizing the global and local information of the characteristic Raman peaks for identifying diseases. Extensive experiments are performed for two different neurological disorders classification tasks via untargeted serum SERS data. The results demonstrate that MBA-RamanNet outperforms commonly used CNN methods with an accuracy of 88.24% for the classification of healthy controls, mild cognitive impairment, Alzheimer's disease, and Non-Alzheimer's dementia; an accuracy of 90% for the classification of healthy controls, elderly depression, and elderly anxiety.

11.
Reprod Toxicol ; 128: 108634, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38851359

RESUMO

Vinorelbine is a commonly used drug to treat various malignancies, such as breast cancer, non-small cell lung cancer, and metastatic pleural mesothelioma. Its side effects include severe neutropenia, local phlebitis, gastrointestinal reactions, and neurotoxicity. In view of the scarcity of research on vinorelbine's reproductive toxicity, this study evaluated the impact of vinorelbine ditartrate, a commonly used form of vinorelbine, on oocyte maturation in vitro. Our investigation revealed that vinorelbine ditartrate had no effect on oocyte meiotic resumption. However, it did reduce the rate of first polar body extrusion, suggesting that it could significantly impede the meiotic maturation of oocytes. Vinorelbine ditartrate exposure was found to disturb the regular spindle assembly and chromosome alignment, leading to the continuous activation of the spindle assembly checkpoint (SAC) and a delayed activation of the anaphase-promoting complex/cyclosome (APC/C), ultimately causing aneuploidy in oocytes. Consequently, the administration of vinorelbine is likely to result in oocyte aneuploidy, which can be helpful in providing a drug reference and fertility guidance in a clinical context.

12.
ACS Nano ; 18(23): 14893-14906, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38801653

RESUMO

Stem cell therapies are gaining traction as promising treatments for a variety of degenerative conditions. Both clinical and preclinical studies of regenerative medicine are hampered by the lack of technologies that can evaluate the migration and behavior of stem cells post-transplantation. This study proposes an innovative method to longitudinally image in vivo human-induced pluripotent stem cells differentiated to retinal pigment epithelium (hiPSC-RPE) cells by multimodal photoacoustic microscopy, optical coherence tomography, and fluorescence imaging powered by ultraminiature chain-like gold nanoparticle cluster (GNC) nanosensors. The GNC exhibits an optical absorption peak in the near-infrared regime, and the 7-8 nm size in diameter after disassembly enables renal excretion and improved safety as well as biocompatibility. In a clinically relevant rabbit model, GNC-labeled hiPSC-RPE cells migrated to RPE degeneration areas and regenerated damaged tissues. The hiPSC-RPE cells' distribution and migration were noninvasively, longitudinally monitored for 6 months with exceptional sensitivity and spatial resolution. This advanced platform for cellular imaging has the potential to enhance regenerative cell-based therapies.


Assuntos
Ouro , Imagem Multimodal , Epitélio Pigmentado da Retina , Coelhos , Animais , Humanos , Ouro/química , Epitélio Pigmentado da Retina/citologia , Transplante de Células-Tronco , Tomografia de Coerência Óptica , Nanopartículas Metálicas/química , Células-Tronco Pluripotentes Induzidas/citologia , Movimento Celular , Diferenciação Celular , Imagem Óptica , Técnicas Fotoacústicas
13.
Cell Rep ; 43(5): 114223, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38748879

RESUMO

Quorum sensing (QS) is a cell-to-cell communication mechanism mediated by small diffusible signaling molecules. Previous studies showed that RpfR controls Burkholderia cenocepacia virulence as a cis-2-dodecenoic acid (BDSF) QS signal receptor. Here, we report that the fatty acyl-CoA ligase DsfR (BCAM2136), which efficiently catalyzes in vitro synthesis of lauryl-CoA and oleoyl-CoA from lauric acid and oleic acid, respectively, acts as a global transcriptional regulator to control B. cenocepacia virulence by sensing BDSF. We show that BDSF binds to DsfR with high affinity and enhances the binding of DsfR to the promoter DNA regions of target genes. Furthermore, we demonstrate that the homolog of DsfR in B. lata, RS02960, binds to the target gene promoter, and perception of BDSF enhances the binding activity of RS02960. Together, these results provide insights into the evolved unusual functions of DsfR that control bacterial virulence as a response regulator of QS signal.


Assuntos
Proteínas de Bactérias , Burkholderia cenocepacia , Coenzima A Ligases , Regulação Bacteriana da Expressão Gênica , Regiões Promotoras Genéticas , Percepção de Quorum , Percepção de Quorum/genética , Burkholderia cenocepacia/patogenicidade , Burkholderia cenocepacia/genética , Burkholderia cenocepacia/metabolismo , Virulência , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Coenzima A Ligases/metabolismo , Coenzima A Ligases/genética , Animais , Transdução de Sinais , Ácidos Graxos Monoinsaturados/metabolismo , Camundongos , Ligação Proteica , Ácidos Láuricos/metabolismo
14.
Infect Dis Ther ; 13(6): 1291-1313, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38720132

RESUMO

INTRODUCTION: Over the past decade, numerous studies have described the types of pathogens and their antibiotic resistance patterns in patients with burn injuries in China; however, the findings have generally been inconsistent. We conducted a literature search and meta-analysis to summarize the infection spectra and antimicrobial resistance patterns in patients with burn injuries. METHODS: We searched the PubMed, Embase, Web of Science, China National Knowledge Infrastructure, China Biomedical Literature, Wanfang, and Weipu databases for relevant articles published between January 2010 and December 2023. The DerSimonian-Laird random-effects model was used to estimate the proportions and 95% confidence intervals (CIs) of pathogens among Chinese patients with burn injuries. Meta-regression analyses were performed to explore differences in the proportions of pathogens among different subgroups and their resistance patterns. This study was registered with PROSPERO (CRD42024514386). RESULTS: The database searches yielded 2017 records; after removing duplicates and conducting initial screening, 219 articles underwent full-text screening. Ultimately, 60 studies comprising a total of 62,819 isolated strains reported the proportions of pathogens in patients with burn injuries and were included in this meta-analysis. Meta-analyses were conducted on 18 types of pathogens. The most common pathogens causing infections in Chinese patients with burn injuries were Staphylococcus aureus, Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae, and Staphylococcus epidermidis. Similar results were observed in the subgroup analysis focusing on wound infections. Since 2015, there has been a significant decrease in the proportion of Pseudomonas aeruginosa (R2 = 4.89%) and a significant increase in the proportion of Klebsiella pneumoniae (R2 = 9.60%). In terms of antibiotic resistance, there has been a significant decrease in the resistance of Staphylococcus aureus to multiple antibiotics and an increasing trend in the resistance of Klebsiella pneumoniae. CONCLUSIONS: We systematically summarized the epidemiological characteristics and antibiotic resistance patterns of pathogens among individuals suffering from burns in China, thus providing guidance for controlling wound infections and promoting optimal empirical antimicrobial therapy. The observed high levels of antibiotic resistance underscore the need for ongoing monitoring of antibiotic usage trends.

15.
Environ Sci Pollut Res Int ; 31(24): 35161-35172, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38724846

RESUMO

Modern life is filled with radiofrequency electromagnetic radiation (RF-EMR) in various frequency bands, while the health risks are not clear. In this study, mice were whole-body exposed to 0.9/1.5/2.65 GHz radiofrequency radiation at 4 W/kg for 2 h per day for 4 weeks to investigate the emotional effects. It was found that the mice showed anxiety but no severe depression. The ELISA results showed a significant decrease in amino acid neurotransmitters (GABA, DA, 5-HT), although acetylcholine (ACH) levels were not significantly altered. Furthermore, Western blot results showed that BDNF, TrkB, and CREB levels were increased in the cerebral cortex, while NF-κB levels were decreased. In addition, pro-inflammatory factors (IL-6, IL-1ß, TNF-α) were significantly elevated, and anti-inflammatory factors (IL-4, IL-10) tended to decrease. In conclusion, multi-frequency electromagnetic radiation induces an inflammatory response through the CREB-BDNF-TrkB and NF-κB pathways in the cerebral cortex and causes a decrease in excitatory neurotransmitters, which ultimately causes anxiety in mice.


Assuntos
Ansiedade , Córtex Cerebral , Radiação Eletromagnética , Inflamação , Animais , Camundongos , Córtex Cerebral/efeitos da radiação , Masculino , Fator Neurotrófico Derivado do Encéfalo/metabolismo , NF-kappa B/metabolismo
16.
Sci Adv ; 10(20): eado1463, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38758782

RESUMO

A ketogenic diet (KD) is a high-fat, low-carbohydrate diet that leads to the generation of ketones. While KDs improve certain health conditions and are popular for weight loss, detrimental effects have also been reported. Here, we show mice on two different KDs and, at different ages, induce cellular senescence in multiple organs, including the heart and kidney. This effect is mediated through adenosine monophosphate-activated protein kinase (AMPK) and inactivation of mouse double minute 2 (MDM2) by caspase-2, leading to p53 accumulation and p21 induction. This was established using p53 and caspase-2 knockout mice and inhibitors to AMPK, p21, and caspase-2. In addition, senescence-associated secretory phenotype biomarkers were elevated in serum from mice on a KD and in plasma samples from patients on a KD clinical trial. Cellular senescence was eliminated by a senolytic and prevented by an intermittent KD. These results have important clinical implications, suggesting that the effects of a KD are contextual and likely require individual optimization.


Assuntos
Senescência Celular , Dieta Cetogênica , Camundongos Knockout , Proteína Supressora de Tumor p53 , Animais , Proteína Supressora de Tumor p53/metabolismo , Proteína Supressora de Tumor p53/genética , Camundongos , Humanos , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Inibidor de Quinase Dependente de Ciclina p21/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Masculino , Especificidade de Órgãos
17.
Zool Res ; 45(3): 633-647, 2024 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-38766746

RESUMO

Painful stimuli elicit first-line reflexive defensive reactions and, in many cases, also evoke second-line recuperative behaviors, the latter of which reflects the sensing of tissue damage and the alleviation of suffering. The lateral parabrachial nucleus (lPBN), composed of external- (elPBN), dorsal- (dlPBN), and central/superior-subnuclei (jointly referred to as slPBN), receives sensory inputs from spinal projection neurons and plays important roles in processing affective information from external threats and body integrity disruption. However, the organizational rules of lPBN neurons that provoke diverse behaviors in response to different painful stimuli from cutaneous and deep tissues remain unclear. In this study, we used region-specific neuronal depletion or silencing approaches combined with a battery of behavioral assays to show that slPBN neurons expressing substance P receptor ( NK1R) (lPBN NK1R) are crucial for driving pain-associated self-care behaviors evoked by sustained noxious thermal and mechanical stimuli applied to skin or bone/muscle, while elPBN neurons are dispensable for driving such reactions. Notably, lPBN NK1R neurons are specifically required for forming sustained somatic pain-induced negative teaching signals and aversive memory but are not necessary for fear-learning or escape behaviors elicited by external threats. Lastly, both lPBN NK1R and elPBN neurons contribute to chemical irritant-induced nocifensive reactions. Our results reveal the functional organization of parabrachial substrates that drive distinct behavioral outcomes in response to sustained pain versus external danger under physiological conditions.


Assuntos
Nociceptividade , Núcleos Parabraquiais , Animais , Núcleos Parabraquiais/fisiologia , Camundongos , Nociceptividade/fisiologia , Neurônios/fisiologia , Dor/fisiopatologia , Masculino , Comportamento Animal/fisiologia
18.
New Phytol ; 243(1): 477-494, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38715078

RESUMO

Cultivated spinach (Spinacia oleracea) is a dioecious species. We report high-quality genome sequences for its two closest wild relatives, Spinacia turkestanica and Spinacia tetrandra, which are also dioecious, and are used to study the genetics of spinach domestication. Using a combination of genomic approaches, we assembled genomes of both these species and analyzed them in comparison with the previously assembled S. oleracea genome. These species diverged c. 6.3 million years ago (Ma), while cultivated spinach split from S. turkestanica 0.8 Ma. In all three species, all six chromosomes include very large gene-poor, repeat-rich regions, which, in S. oleracea, are pericentromeric regions with very low recombination rates in both male and female genetic maps. We describe population genomic evidence that the similar regions in the wild species also recombine rarely. We characterized 282 structural variants (SVs) that have been selected during domestication. These regions include genes associated with leaf margin type and flowering time. We also describe evidence that the downy mildew resistance loci of cultivated spinach are derived from introgression from both wild spinach species. Collectively, this study reveals the genome architecture of spinach assemblies and highlights the importance of SVs during the domestication of cultivated spinach.


Assuntos
Domesticação , Genoma de Planta , Spinacia oleracea , Spinacia oleracea/genética , Cromossomos de Plantas/genética , Filogenia , Recombinação Genética/genética
19.
World Neurosurg ; 187: e282-e288, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38642836

RESUMO

BACKGROUND: Keyhole surgery has been widely used to clip various intracranial aneurysms. Here, the feasibility of microsurgical clipping of multiple intracranial aneurysms via the keyhole approach was further investigated. METHODS: The clinical data of 80 patients with multiple intracranial aneurysms treated with keyhole surgery were retrospectively analyzed. The patients included 25 males and 55 females, with an average age of 57.5 years. There were 13 patients with unruptured aneurysms, 67 patients with ruptured aneurysms (small aneurysms accounted for 52.2% of ruptured aneurysms), and a total of 198 aneurysms. A 4 cm incision and a bone hole of approximately 2.5 cm were used per craniotomy standards. Forty-eight cases were treated via the supraorbital keyhole approach, 45 cases via the pterional keyhole approach, and 3 cases via the interhemispheric keyhole approach. RESULTS: A bilateral and unilateral keyhole approach was applied in 18 and 62 cases, respectively. A total of 170 ipsilateral and 7 contralateral aneurysms were clipped. The complete clipping rate was 98.9%. During the follow-up period of 6-12 months after surgery, the Glasgow outcome scale score was 5 points in 74 cases, 4 points in 5 cases, and 3 points in 1 case. The prognosis was associated with the preoperative Hunt-Hess classification but not with the number of operative sides, the operation opportunity, or the number of clipped aneurysms. CONCLUSION: Early keyhole surgical clipping of multiple intracranial aneurysms is an effective treatment. Among ruptured aneurysms, small aneurysms are common and need attention and timely treatment.


Assuntos
Aneurisma Roto , Craniotomia , Aneurisma Intracraniano , Microcirurgia , Procedimentos Neurocirúrgicos , Humanos , Aneurisma Intracraniano/cirurgia , Masculino , Feminino , Pessoa de Meia-Idade , Microcirurgia/métodos , Adulto , Estudos Retrospectivos , Idoso , Craniotomia/métodos , Procedimentos Neurocirúrgicos/métodos , Aneurisma Roto/cirurgia , Instrumentos Cirúrgicos , Resultado do Tratamento
20.
Diagnostics (Basel) ; 14(7)2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38611678

RESUMO

Bone metastasis has been reported in up to 70% of patients with advanced breast cancer. A total of 55.76% of skeletal metastases in women were derived from breast cancer. However, patients with bone metastasis from an occult primary breast cancer are a rare subset of patients. Here, we present the case of a 38-year-old woman who had sternum pain for 4 months. A whole-body PET-CT scan revealed that the FDG uptake of both the sternum and internal mammary node was significantly increased. The final diagnosis of occult breast cancer was established by immunohistochemical (IHC) staining, which is of great significance for identifying the origin of a metastatic tumor despite no visualized lesions of mammary glands.

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