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1.
Pharmacol Res ; : 107313, 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-39025169

RESUMEN

Acute ischemic stroke (AIS) is the most prevalent type of stroke, and due to its high incidence, disability rate, and mortality rate, it imposes a significant burden on the health care system. Amino acids constitute one of the most crucial metabolic products within the human body, and alterations in their metabolic pathways have been identified in the microenvironment of AIS, thereby influencing the pathogenesis, severity, and prognosis of AIS. The amino acid metabolism characteristics in AIS are complex. On one hand, the dynamic progression of AIS continuously reshapes the amino acid metabolism pattern. Conversely, changes in the amino acid metabolism pattern also exert a double-edged effect on AIS. This interaction is bidirectional, dynamic, heterogeneous, and dose-specific. Therefore, the distinctive metabolic reprogramming features surrounding amino acids during the AIS process are systematically summarized in this paper, aiming to provide potential investigative strategies for the early diagnosis, treatment approaches, and prognostic enhancement of AIS.

2.
Br J Dermatol ; 2024 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-39026424

RESUMEN

BACKGROUND: Monilethrix is a rare hereditary hair disorder that is characterised by a beaded hair shaft structure and increased hair fragility. Patients may also present with keratosis pilaris and nail changes. Research has identified three genes for autosomal-dominant monilethrix (KRT81, KRT83, and KRT86), and one gene for the autosomal-recessive form (DSG4). OBJECTIVES: To investigate the genetic basis of autosomal-dominant monilethrix in families with no pathogenic variants in any of the known monilethrix genes, and to understand the mechanistic basis of variant pathogenicity using a cellular model. METHODS: Nine affected individuals from four unrelated families were included in this study. A clinical diagnosis of monilethrix was assigned based on clinical examination and/or trichoscopy. Exome sequencing (ES) was performed in six individuals to identify pathogenic variants, and Sanger sequencing was used for co-segregation and haplotype analyses. Cell culture experiments (immunoblotting, immunofluorescence, and reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) analyses) were used to confirm variant pathogenicity, to determine expression and subcellular localisation of proteins, and to identify a possible nonsense-mediated mRNA decay. RESULTS: In six affected individuals with clinically suggested monilethrix, ES led to the identification of the nonsense variant c.1081G>T; p.(Glu361*) in KRT31, which was subsequently identified in other affected members of these families by Sanger sequencing. This variant led to the abolition of both the last three amino acids of the 2B subdomain and the complete C-terminal tail domain of keratin 31. Immunoblotting demonstrated that when co-expressed with its binding partner keratin 85, the truncated keratin 31 was still expressed, albeit less abundantly than the wild type protein. Immunofluorescence revealed that p.(Glu361*) keratin 31 had an altered cytoskeletal localisation and formed vesicular-like structures in the cell cytoplasm near the cell membrane. RT-qPCR analysis did not generate evidence for a nonsense mediated decay of the mutant transcript. CONCLUSIONS: This study is the first to identify pathogenic variants in KRT31 as a cause of autosomal-dominant monilethrix. This highlights the importance of hair keratin proteins in hair biology, and will increase the molecular diagnostic yield for rare ectodermal phenotypes of hair and nail tissues.

3.
Zhongguo Zhong Yao Za Zhi ; 49(13): 3684-3692, 2024 Jul.
Artículo en Chino | MEDLINE | ID: mdl-39041141

RESUMEN

Coronary heart disease is a common cardiovascular disease, attacking about 11.4 million patients in China. With increasing prevalence and mortality year by year, coronary heart disease has become a major factor threatening human health and public health. Although primary and secondary prevention, intervention, coronary artery bypass grafting and other interventions have reduced the death rate, there are drug(aspirin) resistance, secondary nitroglycerin failure, post-intervention fatigue, chest tightness, and an-xiety, and complication with a high risk of bleeding, which have become the key clinical and scientific issues needed to be resolved. Coronary heart disease belongs to the category of chest impediment and heart pain in traditional Chinese medicine(TCM). The TCM etiology of this disease includes external contraction of cold, emotional disorders, constitutional insufficiency, physical weakness, and labor injury, which are closely related to sympathetic nerve activity, state of cardiac and psychological diseases, family history, and cardiovascular metabolic disorders in modern medicine. The TCM causes of coronary heart disease include Qi depression, phlegm turbidity, blood stasis, fire-heat, cold congealing, and healthy Qi deficiency, which are associated with emotional factors such as anxiety and depression, abnormal lipid metabolism, abnormalities in blood circulation and coagulation, inflammatory responses, hyperactive immune responses, and heart failure, chronic wasting disease, or aging, respectively. Accordingly, the patients with Qi depression should be treated with Chaihu Longgu Muli Decoction, and those with phlegm turbidity should be treated with Wendan Decoction and Gualou Xiebai Banxia Decoction. Xuefu Zhuyu Decoction and Guizhi Fuling Pills are recommended for blood stasis, Xiaoxianxiong Decoction and Sanhuang Xiexin Decoction for fire-heat, Zhishi Xiebai Guizhi Decoction for cold congealing, and Renshen Decoction for healthy Qi deficiency. Due to the changes in the spectrum of diseases from ancient to modern times as well as the differences in physical constitution, the key cause of coronary heart disease has evolved from the chest Yang deficiency and cold congealing to Qi depression, phlegm turbidity, phlegm combined with stasis, and fire-heat, showing a shift from cold to heat and from deficiency to excess. The combination of classic formulas presents a pattern. That is, the core formula-syndrome correspondence of a disease often fixedly appears with other formula-syndrome correspondence, which may be related to the development of the pathophysiological mechanism of the disease. In the clinical application of modern pharmacological results, the research team has formulated the clinical principle of pathogenesis corresponding to pathological changes and medicinal nature corresponding pharmacological effects. The modern pharmacological research on classic formulas is conducive to targeted treatment. Moreover, classic formulas help to ameliorate aspirin resistance, clopidogrel resistance, post-intervention anxiety, and high risk of bleeding and address the lack of effective blockade of critical lesions in the coronary artery and the progression of post-infarction heart failure. The innovative understanding of the etiology and pathogenesis of co-ronary heart disease helps to improve the clinical efficacy of TCM and the clinical system for treating coronary heart disease with classic formulas.


Asunto(s)
Enfermedad Coronaria , Medicamentos Herbarios Chinos , Medicina Tradicional China , Humanos , Medicamentos Herbarios Chinos/uso terapéutico , Enfermedad Coronaria/tratamiento farmacológico
4.
J Dermatol ; 2024 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-38923025

RESUMEN

Atrichia with papular lesions (APL) is a hair abnormality characterized by loss of hair on the scalp and rest of the body. In a few cases, hair loss is accompanied by the appearance of keratotic papules on the body. It is inherited in an autosomal recessive manner. Sequence variants in the HR (hairless) gene are responsible for this hair abnormality. Here, we present nine consanguineous families and one nonconsanguineous family with clinical manifestations of APL. Whole exome followed by Sanger sequencing and/or direct Sanger sequencing was performed to identify pathogenic variants. The study revealed seven novel pathogenic variants c.794del;p.(Pro265Argfs*98), c.2921-2936del;p.(Tyr974Leufs*16), c.2889C>A;p.(Cys963*), c.2689C>T;p.(Gln897*), c.3186_3187dup;p.(Gln1063Profs*43), c.560dup;p.(Tyr188Ilefs*131), c.2203+5G>C, c.2776+5G>A, and the previously reported variant c.1837C>T;p.(Arg613*) in HR in these families. The study not only expands the mutational spectrum in the HR gene but also highlights the unusual phenotypic findings and will facilitate genetic counseling of families with members showing various types of hair loss disorders in the local population.

5.
Ibrain ; 10(2): 197-216, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38915944

RESUMEN

This review comprehensively assesses the epidemiology, interaction, and impact on patient outcomes of perioperative sleep disorders (SD) and perioperative neurocognitive disorders (PND) in the elderly. The incidence of SD and PND during the perioperative period in older adults is alarmingly high, with SD significantly contributing to the occurrence of postoperative delirium. However, the clinical evidence linking SD to PND remains insufficient, despite substantial preclinical data. Therefore, this study focuses on the underlying mechanisms between SD and PND, underscoring that potential mechanisms driving SD-induced PND include uncontrolled central nervous inflammation, blood-brain barrier disruption, circadian rhythm disturbances, glial cell dysfunction, neuronal and synaptic abnormalities, impaired central metabolic waste clearance, gut microbiome dysbiosis, hippocampal oxidative stress, and altered brain network connectivity. Additionally, the review also evaluates the effectiveness of various sleep interventions, both pharmacological and nonpharmacological, in mitigating PND. Strategies such as earplugs, eye masks, restoring circadian rhythms, physical exercise, noninvasive brain stimulation, dexmedetomidine, and melatonin receptor agonists have shown efficacy in reducing PND incidence. The impact of other sleep-improvement drugs (e.g., orexin receptor antagonists) and methods (e.g., cognitive-behavioral therapy for insomnia) on PND is still unclear. However, certain drugs used for treating SD (e.g., antidepressants and first-generation antihistamines) may potentially aggravate PND. By providing valuable insights and references, this review aimed to enhance the understanding and management of PND in older adults based on SD.

6.
Zhongguo Zhong Yao Za Zhi ; 49(7): 1974-1980, 2024 Apr.
Artículo en Chino | MEDLINE | ID: mdl-38812210

RESUMEN

Hypertension is the most common chronic disease in clinics and has become the most common risk factor for cardiovascular diseases. Because of its high incidence rate, disability rate, and mortality, it has attracted worldwide attention. Despite continuous progress in modern medicine in the treatment of hypertension with new antihypertensive drugs such as Zilebesiran, a nucleic acid drug that acts on microRNA, direct renin inhibitors, and renal sympathetic blockade, the control rate is still not ideal. How to effectively prevent and control hypertension has become one of the urgent clinical challenges to be solved. Traditional Chinese medicine(TCM) has a long record of treating hypertension and has accumulated rich experience, including theoretical understanding, effective single medicine, compound medicine, traditional Chinese patent medicines, and classic famous prescriptions. In TCM, hypertension belongs to the categories of diseases such as dizziness and headache. Previous literature and clinical studies have found that hypertension has key pathogenesis such as fire syndrome, fluid syndrome, deficiency syndrome, and blood stasis syndrome. Among them, the hyperactivity of liver Yang is closely related to blood pressure fluctuations, blood pressure variability, inflammation, and sympathetic activity stimulation. Internal obstruction by blood stasis is closely related to the damage of target organs such as the heart, brain, and kidneys in hypertension. Therefore, the two key pathogenesis of liver yang hyperactivity and internal obstruction by blood stasis run through the entire process of hypertension. Previous studies have found that the effective empirical formula Tianxiong Granules, based on the principles of suppressing Yang and promoting blood circulation, originated from the classic formula Xiongqiong Tianma Pills in Yu Yao Yuan Fang. It is composed of Gastrodiae Rhizoma, Chuanxiong Rhizoma, Puerariae Lobatae Radix, Achyranthis Bidentatae Radix, and Cyathulae Radix and has significant therapeutic effects in the treatment of hypertension. The clinical indications include headache, dizziness, bloating, strong neck, and weak waist and legs. At the same time, it may be accompanied by poor speech, thirst, normal or loose stools, soreness in the waist and legs, lower limb pain, muscle and pulse spasm, menstrual and abdominal pain, dark red tongue, strong pulse strings, or straight and long pulse strings that pass through the mouth of an inch. In the combination rule, it can be used according to the different pathogenesis stages of hypertension patients. In the fire syndrome stage, it is often combined with Tianma Gouteng Decoction and Chaihu Jia Longgu Muli Decoction. In the fluid syndrome stage, it is often combined with Banxia Baizhu Tianma Decoction. In the deficiency syndrome stage, it is often combined with Liuwei Dihuang Pills and Shenqi Pills. In terms of dosage, it is important to focus on the main symptoms and adjust the dosage of key drugs based on blood pressure values. Some drugs can be used in sufficient quantities. By analyzing the compatibility of Tianxiong Granules, clinical application indications, combined formula experience, and dosage application experience, we provide effective treatment methods and more options for TCM to treat hypertension with Yang hyperactivity and blood stasis syndrome.


Asunto(s)
Medicamentos Herbarios Chinos , Hipertensión , Humanos , Hipertensión/tratamiento farmacológico , Hipertensión/fisiopatología , Medicamentos Herbarios Chinos/administración & dosificación , Medicamentos Herbarios Chinos/uso terapéutico , Circulación Sanguínea/efectos de los fármacos , Presión Sanguínea/efectos de los fármacos , Medicina Tradicional China , Antihipertensivos/farmacología
8.
Genome Biol ; 25(1): 51, 2024 02 20.
Artículo en Inglés | MEDLINE | ID: mdl-38378658

RESUMEN

The FokI catalytic domain can be fused to various DNA binding architectures to improve the precision of genome editing tools. However, evaluation of off-target effects is essential for developing these tools. We use Genome-wide Off-target analysis by Two-cell embryo Injection (GOTI) to detect low-frequency off-target editing events in mouse embryos injected with FokI-based architectures. Specifically, we test FokI-heterodimers fused with TALENs, FokI homodimers fused with RYdCas9, or FokI catalytic domains alone resulting in no significant off-target effects. These FokI genome editing systems exhibit undetectable off-target effects in mouse embryos, supporting the further development of these systems for clinical applications.


Asunto(s)
Edición Génica , Genoma , Animales , Ratones , Dominio Catalítico , Edición Génica/métodos , Sistemas CRISPR-Cas
9.
J Headache Pain ; 25(1): 1, 2024 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-38178029

RESUMEN

BACKGROUND: Prior MRI studies on vestibular migraine (VM) have revealed abnormalities in static regional intrinsic brain activity (iBA) and dynamic functional connectivity between brain regions or networks. However, the temporal variation and concordance of regional iBA measures remain to be explored. METHODS: 57 VM patients during the interictal period were compared to 88 healthy controls (HC) in this resting-state functional magnetic resonance imaging (fMRI) study. The dynamics and concordance of regional iBA indices, including amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo), were examined by utilizing sliding time-window analysis. Partial correlation analyses were performed between clinical parameters and resting-state fMRI indices in brain areas showing significant group differences. RESULTS: The VM group showed increased ALFF and ReHo dynamics, as well as increased temporal concordance between ALFF and ReHo in the bilateral paracentral lobule and supplementary motor area relative to the HC group. We also found decreased ReHo dynamics in the right temporal pole, and decreased ALFF dynamics in the right cerebellum posterior lobe, bilateral angular gyrus and middle occipital gyrus (MOG) in the VM group compared with the HC group. Moreover, a positive correlation was observed between ALFF dynamics in the left MOG and vertigo disease duration across all VM patients. CONCLUSION: Temporal dynamics and concordance of regional iBA indices were altered in the motor cortex, cerebellum, occipital and temporoparietal cortex, which may contribute to disrupted multisensory processing and vestibular control in patients with VM. ALFF dynamics in the left MOG may be useful biomarker for evaluating vertigo burden in this disorder.


Asunto(s)
Trastornos Migrañosos , Corteza Motora , Humanos , Mapeo Encefálico/métodos , Imagen por Resonancia Magnética/métodos , Encéfalo/diagnóstico por imagen , Trastornos Migrañosos/diagnóstico por imagen , Vértigo
10.
Biomed Eng Online ; 23(1): 8, 2024 Jan 19.
Artículo en Inglés | MEDLINE | ID: mdl-38243275

RESUMEN

PURPOSE: Recent technological advancements in data acquisition tools allowed neuroscientists to acquire different modality data to diagnosis Alzheimer's disease (AD). However, how to fuse these enormous amount different modality data to improve recognizing rate and find significance brain regions is still challenging. METHODS: The algorithm used multimodal medical images [structural magnetic resonance imaging (sMRI) and positron emission tomography (PET)] as experimental data. Deep feature representations of sMRI and PET images are extracted by 3D convolution neural network (3DCNN). An improved Transformer is then used to progressively learn global correlation information among features. Finally, the information from different modalities is fused for identification. A model-based visualization method is used to explain the decisions of the model and identify brain regions related to AD. RESULTS: The model attained a noteworthy classification accuracy of 98.1% for Alzheimer's disease (AD) using the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset. Upon examining the visualization results, distinct brain regions associated with AD diagnosis were observed across different image modalities. Notably, the left parahippocampal region emerged consistently as a prominent and significant brain area. CONCLUSIONS: A large number of comparative experiments have been carried out for the model, and the experimental results verify the reliability of the model. In addition, the model adopts a visualization analysis method based on the characteristics of the model, which improves the interpretability of the model. Some disease-related brain regions were found in the visualization results, which provides reliable information for AD clinical research.


Asunto(s)
Enfermedad de Alzheimer , Humanos , Enfermedad de Alzheimer/diagnóstico por imagen , Reproducibilidad de los Resultados , Neuroimagen/métodos , Imagen por Resonancia Magnética/métodos , Tomografía de Emisión de Positrones/métodos
11.
Radiol Oncol ; 58(1): 43-50, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38183278

RESUMEN

BACKGROUND: The aim of the study was to evaluate whether virtual calcium subtraction (VNCa) image extracted from dual-layer spectral CT could estimate bone marrow (BM) infiltration with MRI as the reference standard and characterize tumor burden in patients with multiple myeloma (MM). PATIENTS AND METHODS: Forty-seven patients with newly diagnosed MM were retrospectively enrolled. They had undergone whole-body low-dose dual-layer spectral CT (DLCT) and whole-body MRI within one week. VNCa images with calcium-suppressed (CaSupp) indices ranging from 25 to 95 at an interval of 10 and apparent diffusion coefficient (ADC) maps were quantitatively analyzed on vertebral bodies L1-L5 at the central slice of images. The optimal combination was selected by correlation analysis between CT numbers and ADC values. Then, it was used to characterize tumor burden by correlation analysis and receiver operating characteristic (ROC) curves analysis, including plasma cell infiltration rate (PCIR), high serum-free light chains (SFLC) ratio and the high-risk cytogenetic (HRC) status. RESULTS: The most significant quantitative correlation between CT numbers of VNCa images and ADC values could be found at CaSupp index 85 for averaged L1-L5 (r = 0.612, p < 0.001). It allowed quantitative evaluation of PCIR (r = 0.835, p < 0.001). It could also anticipate high SFLC ratio and the HRC status with area under the curve (AUC) of 0.876 and 0.760, respectively. CONCLUSIONS: The VNCa measurements of averaged L1-L5 showed the highest correlation with ADC at CaSupp index 85. It could therefore be used as additional imaging biomarker for non-invasive assessment of tumor burden if ADC is not feasible.


Asunto(s)
Médula Ósea , Mieloma Múltiple , Humanos , Médula Ósea/diagnóstico por imagen , Médula Ósea/patología , Mieloma Múltiple/diagnóstico por imagen , Calcio , Estudios Retrospectivos , Carga Tumoral , Tomografía Computarizada por Rayos X/métodos
13.
Adv Healthc Mater ; 13(3): e2302128, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37922434

RESUMEN

Peripheral nerve injuries (PNI) can lead to mitochondrial dysfunction and energy depletion within the affected microenvironment. The objective is to investigate the potential of transplanting mitochondria to reshape the neural regeneration microenvironment. High-purity functional mitochondria with an intact structure are extracted from human umbilical cord-derived mesenchymal stem cells (hUCMSCs) using the Dounce homogenization combined with ultracentrifugation. Results show that when hUCMSC-derived mitochondria (hUCMSC-Mitos) are cocultured with Schwann cells (SCs), they promote the proliferation, migration, and respiratory capacity of SCs. Acellular nerve allografts (ANAs) have shown promise in nerve regeneration, however, their therapeutic effect is not satisfactory enough. The incorporation of hUCMSC-Mitos within ANAs has the potential to remodel the regenerative microenvironment. This approach demonstrates satisfactory outcomes in terms of tissue regeneration and functional recovery. Particularly, the use of metabolomics and bioenergetic profiling is used for the first time to analyze the energy metabolism microenvironment after PNI. This remodeling occurs through the enhancement of the tricarboxylic acid cycle and the regulation of associated metabolites, resulting in increased energy synthesis. Overall, the hUCMSC-Mito-loaded ANAs exhibit high functionality to promote nerve regeneration, providing a novel regenerative strategy based on improving energy metabolism for neural repair.


Asunto(s)
Células Madre Mesenquimatosas , Tejido Nervioso , Traumatismos de los Nervios Periféricos , Humanos , Nervio Ciático , Células de Schwann , Traumatismos de los Nervios Periféricos/terapia , Matriz Extracelular , Regeneración Nerviosa/fisiología
14.
Oncogene ; 43(1): 35-46, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38007537

RESUMEN

Homologous recombination (HR) is a major DNA double-strand break (DSB) repair pathway of clinical interest because of treatment with poly(ADP-ribose) polymerase inhibitors (PARPi). Cooperation between RAD51 and BRCA2 is pivotal for DNA DSB repair, and its dysfunction induces HR deficiency and sensitizes cancer cells to PARPi. The depletion of the DEAD-box protein DDX11 was found to suppress HR in hepatocellular carcinoma (HCC) cells. The HR ability of HCC cells is not always dependent on the DDX11 level because of natural DDX11 mutations. In Huh7 cells, natural DDX11 mutations were detected, increasing the susceptibility of Huh7 cells to olaparib in vitro and in vivo. The HR deficiency of Huh7 cells was restored when CRISPR/Cas9-mediated knock-in genomic editing was used to revert the DDX11 Q238H mutation to wild type. The DDX11 Q238H mutation impeded the phosphorylation of DDX11 by ATM at serine 237, preventing the recruitment of RAD51 to damaged DNA sites by disrupting the interaction between RAD51 and BRCA2. Clinically, a high level of DDX11 correlated with advanced clinical characteristics and a poor prognosis and served as an independent risk factor for overall and disease-free survival in patients with HCC. We propose that HCC with a high level of wild-type DDX11 tends to be more resistant to PARPi because of enhanced recombination repair, and the key mutation of DDX11 (Q238H) is potentially exploitable.


Asunto(s)
Antineoplásicos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Inhibidores de Poli(ADP-Ribosa) Polimerasas/farmacología , Inhibidores de Poli(ADP-Ribosa) Polimerasas/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/genética , Línea Celular Tumoral , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/genética , Antineoplásicos/farmacología , Recombinación Homóloga/genética , ADN , Recombinasa Rad51/genética , Recombinasa Rad51/metabolismo , ADN Helicasas/genética , ARN Helicasas DEAD-box/genética , Proteína BRCA2/genética
15.
Pharmacol Res ; 199: 107042, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38142878

RESUMEN

Drugs acting on dopamine D2 receptors are widely used for the treatment of several neuropsychiatric disorders, including schizophrenia and depression. Social deficits are a core symptom of these disorders. Pharmacological manipulation of dopamine D2 receptors (Drd2), a Gi-coupled subtype of dopamine receptors, in the medial prefrontal cortex (mPFC) has shown that Drd2 is implicated in social behaviors. However, the type of neurons expressing Drd2 in the mPFC and the underlying circuit mechanism regulating social behaviors remain largely unknown. Here, we show that Drd2 were mainly expressed in pyramidal neurons in the mPFC and that the activation of the Gi-pathway in Drd2+ pyramidal neurons impaired social behavior in male mice. In contrast, the knockdown of D2R in pyramidal neurons in the mPFC enhanced social approach behaviors in male mice and selectively facilitated the activation of mPFC neurons projecting to the nucleus accumbens (NAc) during social interaction. Remarkably, optogenetic activation of mPFC-to-NAc-projecting neurons mimicked the effects of conditional D2R knockdown on social behaviors. Altogether, these results demonstrate a cell type-specific role for Drd2 in the mPFC in regulating social behavior, which may be mediated by the mPFC-to-NAc pathway.


Asunto(s)
Células Piramidales , Receptores de Dopamina D2 , Ratones , Masculino , Animales , Receptores de Dopamina D2/metabolismo , Células Piramidales/fisiología , Neuronas/metabolismo , Corteza Prefrontal/metabolismo , Núcleo Accumbens/fisiología , Conducta Social
16.
Minerva Anestesiol ; 90(3): 144-153, 2024 03.
Artículo en Inglés | MEDLINE | ID: mdl-38127467

RESUMEN

BACKGROUND: Challenging separation from cardiopulmonary bypass (CPB) has been associated with multiple medical adversities, while its incidence, associated factors, and prognosis among cardiac surgery populations are substantially understudied. METHODS: Adult cardiac surgical patients in two medical centers were retrospectively analyzed. Separation from CPB was stratified as easy, difficult, or complex, based on the use of pharmacologic assistance agents and mechanical supports. The various in-hospital adverse outcomes (e.g., mortality, common complications) were assessed. RESULTS: The incidence of difficult and complex separation from CPB was 21.9% (1159 cases, 95% CI 20.8% to 23.1%), and 6.1% (320 cases, 95% CI 5.4% to 6.7%), respectively. High age, the presence of pulmonary hypertension or unstable angina, decreased ejection fraction, and emergency surgery were more frequently associated with challenging separation from CPB. Patients who experienced challenging separation from CPB had an elevated risk of adverse outcomes, including in-hospital mortality (complex: odds ratio [OR] 2.85), composite infection events (difficult: OR=1.82; complex: OR=1.88), major adverse cardiac events (difficult: OR=1.40; complex: OR=1.57), pulmonary complications (difficult: OR=1.31; complex: OR=1.20), acute kidney injury (difficult: OR=1.75; complex: OR=2.64), and prolonged postoperative hospital stays. CONCLUSIONS: We depicted the incidence of challenging separation from CPB among cardiac surgery population. Additionally, results of influential factors and various adverse outcome analyses emphasize the potential of interventions aimed at preventing difficult or complex separation from CPB and reducing associated adverse outcomes.


Asunto(s)
Procedimientos Quirúrgicos Cardíacos , Puente Cardiopulmonar , Adulto , Humanos , Puente Cardiopulmonar/efectos adversos , Estudios Retrospectivos , Pronóstico , Incidencia , Procedimientos Quirúrgicos Cardíacos/efectos adversos , China , Complicaciones Posoperatorias/prevención & control , Factores de Riesgo
17.
Mil Med Res ; 10(1): 64, 2023 Dec 12.
Artículo en Inglés | MEDLINE | ID: mdl-38082365

RESUMEN

BACKGROUND: Cell metabolism plays a pivotal role in tumor progression, and targeting cancer metabolism might effectively kill cancer cells. We aimed to investigate the role of hexokinases in prostate cancer (PCa) and identify a crucial target for PCa treatment. METHODS: The Cancer Genome Atlas (TCGA) database, online tools and clinical samples were used to assess the expression and prognostic role of ADP-dependent glucokinase (ADPGK) in PCa. The effect of ADPGK expression on PCa cell malignant phenotypes was validated in vitro and in vivo. Quantitative proteomics, metabolomics, and extracellular acidification rate (ECAR) and oxygen consumption rate (OCR) tests were performed to evaluate the impact of ADPGK on PCa metabolism. The underlying mechanisms were explored through ADPGK overexpression and knockdown, co-immunoprecipitation (Co-IP), ECAR analysis and cell counting kit-8 (CCK-8) assays. RESULTS: ADPGK was the only glucokinase that was both upregulated and predicted worse overall survival (OS) in prostate adenocarcinoma (PRAD). Clinical sample analysis demonstrated that ADPGK was markedly upregulated in PCa tissues vs. non-PCa tissues. High ADPGK expression indicates worse survival outcomes, and ADPGK serves as an independent factor of biochemical recurrence. In vitro and in vivo experiments showed that ADPGK overexpression promoted PCa cell proliferation and migration, and ADPGK inhibition suppressed malignant phenotypes. Metabolomics, proteomics, and ECAR and OCR tests revealed that ADPGK significantly accelerated glycolysis in PCa. Mechanistically, ADPGK binds aldolase C (ALDOC) to promote glycolysis via AMP-activated protein kinase (AMPK) phosphorylation. ALDOC was positively correlated with ADPGK, and high ALDOC expression was associated with worse survival outcomes in PCa. CONCLUSIONS: In summary, ADPGK is a driving factor in PCa progression, and its high expression contributes to a poor prognosis in PCa patients. ADPGK accelerates PCa glycolysis and progression by activating ALDOC-AMPK signaling, suggesting that ADPGK might be an effective target and marker for PCa treatment and prognosis evaluation.


Asunto(s)
Glucoquinasa , Neoplasias de la Próstata , Humanos , Masculino , Glucoquinasa/genética , Glucoquinasa/metabolismo , Próstata , Proteínas Quinasas Activadas por AMP
18.
Radiol Oncol ; 57(4): 455-464, 2023 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-38038425

RESUMEN

BACKGROUND: The purpose of our study was to explore and compare the tumor burden of different bone marrow infiltration patterns and evaluate the feasibility of apparent diffusion coefficient (ADC) value to identify patterns in multiple myeloma (MM). PATIENTS AND METHODS: Ninety-three patients with newly diagnosed multiple myeloma and 23 controls had undergone routine magnetic resonance imaging (MRI) and diffusion-weighted MRI (DWI) from January 2019 to November 2020. Five bone marrow (BM) infiltration patterns were allocated according to routine MRI. The laboratory data and ADC values of patterns were analyzed and compared. ROC analysis was used to establish the best diagnostic ADC threshold value for identifying these patterns and distinguishing normal pattern from controls. Besides, the correlation between the ADC values of diffuse pattern and the plasma cells ratio was assessed. RESULTS: The values of hemoglobin, beta-2 microglobulin (ß2-MG), plasma cell, M protein, the percentages of stage, high-risk fluorescence in situ hybridization, and ADC values showed significant difference among patterns. ADCmean at a specific value (368.5×10-6 mm2/s) yielded a maximum specificity (95.5%) and sensitivity (92.0%) in diagnosing MM. A specific value (335.5×10-6mm2/s) yielded a maximum specificity (84.7%) and sensitivity (88.0%) in discriminating visually normal pattern in MM from controls. There was a moderate positive correlation between the plasma cells ratio and ADCs of diffuse infiltration patterns (r = 0.648, P < 0.001). CONCLUSIONS: The bone marrow infiltration patterns in MM patients can indicate the tumor burden and ADC value has the ability to discriminate these patterns objectively.


Asunto(s)
Mieloma Múltiple , Humanos , Mieloma Múltiple/diagnóstico por imagen , Médula Ósea/diagnóstico por imagen , Médula Ósea/patología , Estudios de Factibilidad , Carga Tumoral , Hibridación Fluorescente in Situ
19.
Hortic Res ; 10(4): uhad023, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37786860

RESUMEN

Cold acclimation is a complex biological process leading to the development of freezing tolerance in plants. In this study, we demonstrated that cold-induced expression of protease inhibitor FmASP in a Citrus-relative species kumquat [Fortunella margarita (Lour.) Swingle] contributes to its freezing tolerance by minimizing protein degradation. Firstly, we found that only cold-acclimated kumquat plants, despite extensive leaf cellular damage during freezing, were able to resume their normal growth upon stress relief. To dissect the impact of cold acclimation on this anti-freezing performance, we conducted protein abundance assays and quantitative proteomic analysis of kumquat leaves subjected to cold acclimation (4°C), freezing treatment (-10°C) and post-freezing recovery (25°C). FmASP (Against Serine Protease) and several non-specific proteases were identified as differentially expressed proteins induced by cold acclimation and associated with stable protein abundance throughout the course of low-temperature treatment. FmASP was further characterized as a robust inhibitor of multiple proteases. In addition, heterogeneous expression of FmASP in Arabidopsis confirmed its positive role in freezing tolerance. Finally, we proposed a working model of FmASP and illustrated how this extracellular-localized protease inhibitor protects proteins from degradation, thereby maintaining essential cellular function for post-freezing recovery. These findings revealed the important role of protease inhibition in freezing response and provide insights on how this role may help develop new strategies to enhance plant freezing tolerance.

20.
Exp Ther Med ; 26(5): 518, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37854500

RESUMEN

Esophageal foreign body impaction is a notable clinical emergency. If the high-risk esophageal foreign bodies are not removed in time, life-threatening complications, such as perforation, infection and injury to the vessels, may occur. In the present study, the case of a patient experiencing a foreign body sensation in the throat after ingesting a fish bone by mistake is presented. A high risk of impending arterial puncture was confirmed using thoracic CT and thoracic aorta CT angiography scanning. The ends of the fish bone were first confirmed using a fibro-bronchoscopy light source passing through the bronchial and esophageal walls, before biopsy forceps were used to successively free the thoracic aorta and bronchial ends under gastroscopy. Finally, the fish bone was safely removed using a combination of gastroscopy and the rarely used fibro-bronchoscopy, and the patient recovered well after standard care. In certain cases of foreign bodies, it is necessary to use multiple strategies in a timely manner according to the type and location of the ingested foreign body.

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