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1.
Commun Biol ; 7(1): 935, 2024 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-39095659

RESUMEN

The mislocalization of proteins leads to breast cancer, one of the world's most prevalent cancers, which can be identified from immunohistochemical images. Here, based on the deep learning framework, location prediction models were constructed using the features of breast immunohistochemical images. Ultimately, six differentially localized proteins that with stable differentially predictive localization, maximum localization differences, and whose predicted results are not affected by removing a single image are obtained (CCNT1, NSUN5, PRPF4, RECQL4, UTP6, ZNF500). Further verification reveals that these proteins are not differentially expressed, but are closely associated with breast cancer and have great classification performance. Potential mechanism analysis shows that their co-expressed or co-located proteins and RNAs may affect their localization, leading to changes in interactions and functions that further causes breast cancer. They have the potential to help shed light on the molecular mechanisms of breast cancer and provide assistance for its early diagnosis and treatment.


Asunto(s)
Neoplasias de la Mama , Aprendizaje Profundo , Inmunohistoquímica , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Neoplasias de la Mama/diagnóstico , Humanos , Femenino , Biomarcadores de Tumor/metabolismo , Biomarcadores de Tumor/genética
2.
Artículo en Inglés | MEDLINE | ID: mdl-39103638

RESUMEN

PURPOSE: To investigate the influence of transarterial embolization (TAE) on programmed cell death-ligand 1(PD-L1) expression and CD8+T tumour infiltrative lymphocyte cytotoxicity in the Sprague-Dawley (SD) rat model of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: An orthotopic HCC model was established in twenty SD rats treated with TAE (lipiodol, n = 10) or sham (normal saline, n = 10) using homologous N1S1 hepatoma cells. Rats were euthanized 1 week after embolization. Flow cytometry was used to assess the proportion of CD4+T, CD8+T and programmed cell death-1+(PD-1+) CD8+T lymphocytes in the spleens and tumours. Distribution of CD8+T, granzyme-B+CD8+T lymphocytes and PD-L1+ cells was assessed by immunohistochemistry (IHC) or multiplex IHC. p value < 0.05 was considered statistically significant. RESULTS: The CD4/CD8 ratio and PD-1+CD8+ T lymphocytes exhibited higher values in TAE-treated tumours compared to sham-treated tumours (p = 0.021 and p = 0.071, respectively). Conversely, the number of CD8+T lymphocytes was decreased in TAE-treated tumours (p = 0.043), especially in the central region (p = 0.045). However, more CD8+T lymphocytes were found infiltrating the marginal region than central region in TAE-treated tumours (p = 0.046). The proportion of granzyme-B+CD8+T lymphocytes and the PD-L1 positive areas was elevated in tumours that treated with TAE (p all < 0.05). There was a negative correlation between PD-L1 expression and the number of infiltration of CD8+ T lymphocytes (p = 0.036). CONCLUSIONS: Immune cells are distributed unevenly in the tumours after TAE. The intrinsic induction state of the tumour after embolization may be insufficient to elicit a maximal response to PD-1/PD-L1 inhibitors.

3.
Cell Oncol (Dordr) ; 2024 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-39141317

RESUMEN

Interferon Gamma Inducible Protein 30 (IFI30), also known as Gamma-Interferon-Inducible Lysosomal Thiol Reductase (GILT), is predominantly found in lysosomes and the cytoplasm. As the sole enzyme identified to catalyze disulfide bond reduction in the endocytic pathway, IFI30 contributes to both major histocompatibility complex (MHC) class I-restricted antigen cross-presentation and MHC class II-restricted antigen processing by decreasing the disulfide bonds of endocytosed proteins. Remarkably, emerging research has revealed that IFI30 is involved in tumorigenesis, tumor development, and the tumor immune response. Targeting IFI30 may provide new strategies for cancer therapy and improve the prognosis of patients. This review provided a comprehensive overview of the research progress on IFI30 in tumor progression, cellular redox status, autophagy, tumor immune response, and drug sensitivity, with a view to providing the theoretical basis for pharmacological intervention of IFI30 in tumor therapy, particularly in immunotherapy.

4.
Skin Res Technol ; 30(8): e13919, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39113612

RESUMEN

BACKGROUND: Diabetes mellitus (DM) presents impediment to wound healing. While ultraviolet B (UVB) exposure showed therapeutic potential in various skin conditions, its capacity to mediate diabetic wound healing remains unclear. To investigate the efficacy of UVB on wound healing and its underlying basis. MATERIALS AND METHODS: Male C57BL/6 mice were subjected to the high-fat diet followed by streptozotocin administration to establish the diabetic model. Upon confirmation of diabetes, full-thickness wounds were inflicted and the treatment group received UVB radiation at 50 mJ/cm2 for 5 min every alternate day for 2 weeks. Wound healing rate was then assessed, accompanied by evaluations of blood glucose, lipid profiles, CD31 expression, and concentrations of ghrelin and leptin. Concurrently, in vitro studies were executed to evaluate the protective role of ghrelin on human umbilical vein endothelial cells (HUVEC) under high glucose (HG) conditions. RESULTS: Post UVB exposure, there was a marked acceleration in wound healing in DM mice without alterations in hyperglycemia and lipid profiles. Compared to non-UVB-exposed mice, the UVB group showed enhanced angiogenesis manifested by a surge in CD31 expression. This trend appeared to be in harmony with the elevated ghrelin levels. In vitro experiments indicated that ghrelin significantly enhanced the migratory pace and angiogenic properties of HUVEC under HG-induced stress, potentially mediated by an upregulation in vascular endothelial growth factor expression. CONCLUSION: UVB exposure bolstered wound healing in diabetic mice, plausibly mediated through augmented angiogenesis induced by ghrelin secretion. Such findings underscore the vast potential of UVB-induced ghrelin in therapeutic strategies targeting diabetic wound healing.


Asunto(s)
Diabetes Mellitus Experimental , Ghrelina , Células Endoteliales de la Vena Umbilical Humana , Ratones Endogámicos C57BL , Cicatrización de Heridas , Animales , Humanos , Masculino , Ratones , Glucemia/metabolismo , Ghrelina/metabolismo , Ghrelina/efectos de la radiación , Leptina/metabolismo , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/metabolismo , Piel/efectos de la radiación , Piel/patología , Piel/metabolismo , Rayos Ultravioleta/efectos adversos , Terapia Ultravioleta/métodos , Cicatrización de Heridas/efectos de la radiación
6.
World J Clin Cases ; 12(20): 4121-4129, 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-39015902

RESUMEN

BACKGROUND: Acute myeloid leukemia (AML) is a disease in which immature hematopoietic cells accumulate in the bone marrow and continuously expand, inhibiting hematopoiesis. The treatment and prognosis of this disease have always been unsatisfactory. AIM: To investigate the correlation between vascular endothelial growth factor (VEGF) and transforming growth factor-ß1 (TGFß1) expression and prognosis in older adults with AML. METHODS: This study enrolled 80 patients with AML (AML group), including 36 with complete response (AML-CR), 23 with partial response (AML-PR), and 21 with no response (AML-NR). The expression levels of VEGF and TGFß1 were detected by reverse transcription polymerase chain reaction in bone marrow mononuclear cells isolated from 56 healthy controls. Kaplan-Meier analysis was performed to assess overall survival (OS) and progression- or disease-free survival (DFS). Prognostic risk factors were analyzed using a Cox proportional hazards model. RESULTS: The AML group showed a VEGF level of 2.68 ± 0.16. VEGF expression was lower in patients with AML-CR than those with AML-PR or AML-NR (P < 0.05). TGFß1 expression in the AML group was 0.33 ± 0.05. Patients with AML-CR showed a higher TGFß1 expression than those with AML-PR or AML-NR (P < 0.05). VEGF and TGFß1 expression in patients with AML was significantly correlated with the counts of leukocytes, platelets, hemoglobin, and peripheral blood immature cells (P < 0.05); Kaplan-Meier survival analysis revealed that patients with high TGFß1 expression had better OS and DFS than those with low TGFß1 expression (P < 0.05), whereas patients with low VEGF levels showed better OS and DFS than those with high VEGF levels (P < 0.05). VEGF, TGFß1, and platelet count were identified by the Cox proportional hazards model as independent risk factors for OS (P < 0.05), while VEGF, TGFß1, and white blood cell count were independent risk factors for DFS (P < 0.05). CONCLUSION: Decreased VEGF expression and increased TGFß1 expression in patients with AML provide valuable references for determining and individualizing clinical treatment strategies.

7.
Nucleic Acids Res ; 2024 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-39021337

RESUMEN

Trichoderma reesei is an economically important enzyme producer with several unique meiotic features. spo11, the initiator of meiotic double-strand breaks (DSBs) in most sexual eukaryotes, is dispensable for T. reesei meiosis. T. reesei lacks the meiosis-specific recombinase Dmc1. Rad51 and Sae2, the activator of the Mre11 endonuclease complex, promote DSB repair and chromosome synapsis in wild-type and spo11Δ meiosis. DNA methyltransferases (DNMTs) perform multiple tasks in meiosis. Three DNMT genes (rid1, dim2 and dimX) differentially regulate genome-wide cytosine methylation and C:G-to-T:A hypermutations in different chromosomal regions. We have identified two types of DSBs: type I DSBs require spo11 or rid1 for initiation, whereas type II DSBs do not rely on spo11 and rid1 for initiation. rid1 (but not dim2) is essential for Rad51-mediated DSB repair and normal meiosis. rid1 and rad51 exhibit a locus heterogeneity (LH) relationship, in which LH-associated proteins often regulate interconnectivity in protein interaction networks. This LH relationship can be suppressed by deleting dim2 in a haploid rid1Δ (but not rad51Δ) parental strain, indicating that dim2 and rid1 share a redundant function that acts earlier than rad51 during early meiosis. In conclusion, our studies provide the first evidence of the involvement of DNMTs during meiotic initiation and recombination.

8.
Open Life Sci ; 19(1): 20220923, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39071492

RESUMEN

The aim of this study is to assess the impact of serum magnesium (Mg) levels on prognostic outcomes in patients with non-small cell lung cancer (NSCLC) undergoing treatment with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI). A cohort comprising 91 patients with NSCLC with epidermal growth factor receptor mutations received EGFR-TKI therapy. Assessments of liver and kidney function and electrolyte levels were conducted before treatment initiation and after completing two cycles of EGFR-TKI therapy. Data on variables such as age, gender, presence of distant metastasis, smoking history, other therapeutic interventions, and the specific TKI used were collected for analysis. Cox regression analysis revealed that patients with higher Mg levels prior to EGFR-TKI therapy had significantly longer progression-free survival (PFS) and overall survival (OS). Elevated Mg levels remained predictive of PFS and OS after two cycles of EGFR-TKI therapy. Multiple regression analysis confirmed these findings. Additionally, it was observed that smokers might represent a unique population, demonstrating a correlation between OS and Mg levels. Our findings indicate that serum Mg level is a prognostic factor in patients with NSCLC undergoing EGFR-TKI therapy. This may provide new insights into the underlying mechanisms of EGFR-TKI therapy related to electrolyte balance.

9.
Pestic Biochem Physiol ; 203: 106009, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39084775

RESUMEN

Fall armyworm, Spodoptera frugiperda (J. E. Smith), is a widely recognized global agricultural pest that has significantly reduced crop yields all over the world. S. frugiperda has developed resistance to various insecticides. Insect cytochrome P450 monooxygenases (CYPs or P450s) play an important role in detoxifying insecticides, leading to increased resistance in insect populations. However, the function of the specific P450 gene for lambda-cyhalothrin resistance in S. frugiperda was unclear. Herein, the expression patterns of 40 P450 genes in the susceptible and lambda-cyhalothrin-resistant populations were analyzed. Among them, CYP321A7 was found to be overexpressed in the resistant population, specifically LRS (resistance ratio = 25.38-fold) derived from a lambda-cyhalothrin-susceptible (SS) population and FLRS (a population caught from a field, resistance ratio = 63.80-fold). Elevated enzyme activity of cytochrome P450 monooxygenases (P450s) was observed for LRS (2.76-fold) and the FLRS (4.88-fold) as compared to SS, while no significant differences were observed in the activities of glutathione S-transferases and esterases. Furthermore, the knockdown of CYP321A7 gene by RNA interference significantly increased the susceptibility to lambda-cyhalothrin. Remarkably, the knockdown of CYP321A7 reduced the enzymatic activity of P450 by 43.7%, 31.9%, and 22.5% in SS, LRS, and FLRS populations, respectively. Interestingly, fourth-instar larvae treated with lambda-cyhalothrin at the LC30 dosage had a greater mortality rate due to RNA interference-induced suppression of CYP321A7 (with increases of 61.1%, 50.0%, and 45.6% for SS, LRS, and FLRS populations, respectively). These findings suggest a link between lambda-cyhalothrin resistance and continual overexpression of CYP321A7 in S. frugiperda larvae, emphasizing the possible importance of CYP321A7 in lambda-cyhalothrin detoxification in S. frugiperda.


Asunto(s)
Sistema Enzimático del Citocromo P-450 , Resistencia a los Insecticidas , Insecticidas , Nitrilos , Piretrinas , Spodoptera , Animales , Piretrinas/farmacología , Piretrinas/toxicidad , Spodoptera/efectos de los fármacos , Spodoptera/genética , Nitrilos/toxicidad , Nitrilos/farmacología , Sistema Enzimático del Citocromo P-450/genética , Sistema Enzimático del Citocromo P-450/metabolismo , Insecticidas/farmacología , Insecticidas/toxicidad , Resistencia a los Insecticidas/genética , Proteínas de Insectos/genética , Proteínas de Insectos/metabolismo , Interferencia de ARN , Inactivación Metabólica , Larva/efectos de los fármacos , Larva/genética
10.
Pestic Biochem Physiol ; 203: 106017, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39084778

RESUMEN

Emamectin benzoate (EMB), commonly used as an insecticide in fishery production, inevitably leaves residual chemicals in aquatic environments. High-level EMB exposure can cause severe damage to multiple systems of marine animals, potentially through mechanisms involving severe mitochondrial damage and oxidative stress. However, it is not clear yet how EMB exposure at a certain level can cause damage to fish kidney tissue. In this study, we exposed carps to an aquatic environment containing 2.4 µg/L of EMB and cultured carp kidney cells in vitro, established a cell model exposed to EMB. Our findings revealed that EMB exposure resulted in severe kidney tissue damage in carp and compromised the viability of grass carp kidney cells (CIK cells). By RNA-seq analysis, EMB exposure led to significant differences in mitochondrial homeostasis, response to ROS, ferroptosis, and autophagy signals in carp kidney tissue. Mechanistically, EMB exposure induced mitochondrial oxidative stress by promoting the generation of mitochondrial superoxide and reducing the activity of antioxidant enzymes. Additionally, EMB exposure triggered loss of mitochondrial membrane potential, an imbalance in mitochondrial fusion/division homeostasis, and dysfunction in oxidative phosphorylation, ultimately impairing ATP synthesis. Notably, EMB exposure also accelerated excessive autophagy and ferroptosis of cells by contributing to the formation of lipid peroxides and autophagosomes, and the deposition of Fe2+. However, N-acetyl-L-cysteine (NAC) treatment alleviated the damage and death of CIK cells by inhibiting oxidative stress. Overall, our study demonstrated that EMB exposure induced mitochondrial oxidative stress, impaired mitochondrial homeostasis, and function, promoted autophagy and ferroptosis of kidney cells, and ultimately led to kidney tissue damage in carp. Our research enhanced the toxicological understanding on EMB exposure and provides a model reference for comparative medicine.


Asunto(s)
Autofagia , Carpas , Ferroptosis , Ivermectina , Riñón , Mitocondrias , Estrés Oxidativo , Animales , Carpas/metabolismo , Estrés Oxidativo/efectos de los fármacos , Ivermectina/análogos & derivados , Ivermectina/toxicidad , Ferroptosis/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Autofagia/efectos de los fármacos , Riñón/efectos de los fármacos , Riñón/patología , Insecticidas/toxicidad , Especies Reactivas de Oxígeno/metabolismo , Potencial de la Membrana Mitocondrial/efectos de los fármacos
11.
Inorg Chem ; 63(31): 14609-14622, 2024 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-39049593

RESUMEN

Metal-organic cages form well-defined microenvironments that can enhance the catalytic proficiency of encapsulated transition metal complexes (TMCs). We introduce a screening protocol to efficiently identify TMCs that are promising candidates for encapsulation in the Ga4L612- nanocage. We obtain TMCs from the Cambridge Structural Database with geometric and electronic characteristics amenable to encapsulation and mine the text of associated manuscripts to curate TMCs with documented catalytic functionality. By docking candidate TMCs inside the nanocage cavity and carrying out electronic structure calculations, we identify a subset of successfully optimized candidates (TMC-34) and observe that encapsulated guests occupy an average of 60% of the cavity volume, in line with previous observations. Notably, some guests occupy as much as 72% of the cavity as a result of linker rotation. Encapsulation has a universal effect on the electrostatic potential (ESP), systematically decreasing the ESP at the metal center of each TMC in the TMC-34 data set, while minimally altering TMC metal partial charges. Collectively these observations support geometry-based screening of potential guests and suggest that encapsulation in Ga4L612- cages could electrostatically stabilize diverse cationic or electropositive intermediates. We highlight candidate guests with associated known reactivity and solubility most amenable for encapsulation in experimental follow-up studies.

13.
Clin Psychol Psychother ; 31(4): e3023, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38978207

RESUMEN

OBJECTIVE: This study aims to assess the clinical effectiveness of combining mindfulness-based stress reduction (MBSR) with exercise intervention in improving anxiety, depression, sleep quality and mood regulation in patients with non-small cell lung cancer (NSCLC). METHODS: A total of 60 patients with NSCLC who had not received surgical treatment were selected using convenience sampling and divided into an intervention group and control group, with 30 patients in each group. The control group received conventional psychological nursing care, whereas the intervention group received a combination of MBwSR and exercise therapy. Before the intervention, a questionnaire was completed to collect the basic data of the two groups. Further questionnaires were administered at 6 and 8 weeks after treatment to assess anxiety, depression, sleep quality and other items included in the five-item Brief Symptom Rating Scale (BSRS-5). RESULTS: No significant differences between the intervention and control groups were identified in terms of personal and clinical characteristics (p > 0.05). No significant differences were determined in the BSRS-5, Self-Rating Anxiety Scale (SAS), Self-Rating Depression Scale (SDS) or Pittsburgh Sleep Quality Index (PSQI) scores between the intervention and control groups before the intervention. However, 6 and 8 weeks after the intervention, scores were significantly lower in both groups (p < 0.001). Significant differences in the BSRS-5, SAS, SDS and PSQI scores were identified between the two groups at different time points (p < 0.001). CONCLUSION: The combination of MBSR and exercise intervention demonstrated improvements in anxiety, depression, sleep quality and BSRS-5 scores in patients with NSCLC.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Terapia por Ejercicio , Neoplasias Pulmonares , Atención Plena , Estrés Psicológico , Humanos , Atención Plena/métodos , Femenino , Masculino , Carcinoma de Pulmón de Células no Pequeñas/psicología , Carcinoma de Pulmón de Células no Pequeñas/terapia , Persona de Mediana Edad , Neoplasias Pulmonares/psicología , Neoplasias Pulmonares/terapia , Terapia por Ejercicio/métodos , Terapia por Ejercicio/psicología , Estrés Psicológico/terapia , Estrés Psicológico/psicología , Resultado del Tratamiento , Anciano , Encuestas y Cuestionarios , Adulto , Calidad del Sueño , Terapia Combinada , Bienestar Psicológico
14.
Front Public Health ; 12: 1366327, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38962768

RESUMEN

Introduction: Enhancing the efficiency of primary healthcare services is essential for a populous and developing nation like China. This study offers a systematic analysis of the efficiency and spatial distribution of primary healthcare services in China. It elucidates the fundamental landscape and regional variances in efficiency, thereby furnishing a scientific foundation for enhancing service efficiency and fostering coordinated regional development. Methods: Employs a three-stage DEA-Malmquist model to assess the efficiency of primary healthcare services across 31 provincial units in mainland China from 2012 to 2020. Additionally, it examines the spatial correlation of efficiency distribution using the Moran Index. Results: The efficiency of primary healthcare services in China is generally suboptimal with a noticeable declining trend, highlighting significant potential for improvement in both pure technical efficiency and scale efficiency. There is a pronounced efficiency gap among provinces, yet a positive spatial correlation is evident. Regionally, efficiency ranks in the order of East > Central > West. Factors such as GDP per capita and population density positively influence efficiency enhancements, while urbanization levels and government health expenditures appear to have a detrimental impact. Discussion: The application of the three-stage DEA-Malmquist model and the Moran Index not only expands the methodological framework for researching primary healthcare service efficiency but also provides scientifically valuable insights for enhancing the efficiency of primary healthcare services in China and other developing nations.


Asunto(s)
Eficiencia Organizacional , Atención Primaria de Salud , China , Humanos , Análisis Espacial , Gastos en Salud/estadística & datos numéricos , Modelos Teóricos
15.
Zhongguo Zhong Yao Za Zhi ; 49(12): 3132-3143, 2024 Jun.
Artículo en Chino | MEDLINE | ID: mdl-39041073

RESUMEN

The traditional Chinese medicine(TCM) single preparation refers to the innovative TCM made from the whole or the effective part(including the effective ingredient) extract of a TCM single herb by modern technology. They have a long history of applications, definite effects and few side effects. It is an indispensable part of the research of innovative TCM. In recent years, with the optimization of national policies, the development of TCM single preparation shows a positive trend. However, because of the imbalance in the composition ratio, the need for expansion of indications, the need for further basic research, and the low conversion rate of existing patent achievements in universities and institutes, the TCM single preparation still has significant development space. In this review, we analyze and study the current situation, characteristics and difficulties of TCM single preparation, as well as relevant clinical application, basic research, industrialization and patent application information through statistical analysis of TCM single preparations in the Chinese Pharmacopoeia, which helps to provide direction for the development and research of single preparation of TCM.


Asunto(s)
Medicamentos Herbarios Chinos , Medicina Tradicional China , Medicamentos Herbarios Chinos/química , Humanos
16.
Metabolomics ; 20(4): 74, 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38980520

RESUMEN

BACKGROUND AND AIMS: Biopterins, including tetrahydrobiopterin (BH4), dihydrobiopterin (BH2), and biopterin (B), were crucial enzyme cofactors in vivo. Despite their recognized clinical significance, there remain notable research gaps and controversies surrounding experimental outcomes. This study aims to clarify the biopterins-related issues, including analytical art, physiological intervals, and pathophysiological implications. MATERIALS AND METHODS: A novel LC-MS/MS method was developed to comprehensively profile biopterins in plasma, utilizing chemical derivatization and cold-induced phase separation. Subsequently, apparently healthy individuals were enrolled to investigate the physiological ranges. And the relationships between biopterins and biochemical indicators were analyzed to explore the pathophysiological implications. RESULTS: The developed method was validated as reliable for detecting biopterins across the entire physiological range. Timely anti-oxidation was found to be essential for accurate assessment of biopterins. The observed overall mean ± SDs levels were 3.51 ± 0.94, 1.54 ± 0.48, 2.45 ± 0.84 and 5.05 ± 1.14 ng/mL for BH4, BH2, BH4/BH2 and total biopterins. The status of biopterins showed interesting correlations with age, gender, hyperuricemia and overweight. CONCLUSION: In conjunction with proper anti-oxidation, the newly developed method enables accurate determination of biopterins status in plasma. The observed physiological intervals and pathophysiological implications provide fundamental yet inspiring support for further clinical researches.


Asunto(s)
Biopterinas , Espectrometría de Masas en Tándem , Humanos , Biopterinas/análogos & derivados , Biopterinas/sangre , Biopterinas/metabolismo , Femenino , Masculino , Adulto , Espectrometría de Masas en Tándem/métodos , Persona de Mediana Edad , Cromatografía Liquida/métodos , Adulto Joven , Anciano , Biomarcadores/sangre
17.
Org Lett ; 26(31): 6664-6669, 2024 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-39078505

RESUMEN

A photocatalytic method for the ring-closing 1,7-enyne metathesis using the α-amino radical as an alkene deconstruction auxiliary is present. Preliminary mechanistic studies suggest that intramolecular 1,5-hydrogen atom transfer is the key to the generation and ß-scission of the α-amino radical, while the dearomatization of arenes and ring opening of cyclopropanes are the key to construct spirocyclic quinolin-2-ones. This approach highlights the potential of ring-closing 1,7-enyne metathesis, providing a green, efficient, and step-economical way for the synthesis of spirocyclic quinolin-2-ones.

18.
Ear Nose Throat J ; : 1455613241264482, 2024 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-39049579

RESUMEN

Objective: Intracapsular enucleation (ICE) of cervical sympathetic chain schwannoma (CSCS) is associated with technical difficulties, with diffuse hemorrhage being the main challenge in our previous attempts. This article presents our new strategy for achieving better hemostasis during ICE procedures in CSCS cases. Methods: A retrospective review of CSCS cases treated at our tertiary medical institution was undertaken between April 2018 and February 2024. Only cases with successful ICE were included. Results: A total of 8 cases were included, with 4 male and 4 female patients and an age range of 23 to 77 (average and median ages were 48.5 and 49.5 years, respectively). The presenting symptom was a neck mass for all the patients, with 4 masses on the left and 4 on the right sides. Enucleation was first undertaken for the first 3 cases (before March 2022), followed by hemostasis; this strategy was quite difficult and time-consuming. For the remaining 5 cases, a new strategy was developed to preemptively manage any potential nourishing vessel between the capsule and tumor parenchyma, which significantly decreased operation time (P = .0155) and facilitated hemorrhage control. First bite syndrome (FBS) was avoided in all cases. Postoperative Horner's syndrome (HS) was avoided in 1 patient (Case 6, new strategy) but occurred in 7 patients, taking 8 days to 1 month to recover with the new strategy (4 patients), significantly shorter (P = .0364) than before (3 patients, 1-3 months). The median duration of follow-up was 20 months. No recurrence was documented. Conclusions: ICE was achieved for CSCS cases, especially with our newly developed strategy, by preemptively and securely managing potential nourishing vessels. Operation time and duration of recovery of postoperative HS could both be shortened. Moreover, FBS could be avoided.

19.
Chin J Integr Med ; 2024 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-39073516

RESUMEN

OBJECTIVE: To investigate changes of myeloid differentiation factor 2 (MD2) in inflammation-induced pain and acupuncture-mediated analgesia. METHODS: Mice were randomly divided into three groups by a random number table method: saline group (n=16), complete Freund's adjuvant (CFA) group (n=24) and CFA+electroacupuncture (EA) group (n=26). Inflammation-induced pain was modelled by injecting CFA to the plantar surface of the hind paw of mice and EA was applied to bilateral Zusanli (ST 36) to alleviate pain. Only mice in the CFA+EA group received EA treatment (30 min/d for 2 weeks) 24 h after modelling. Mice in the saline and CFA groups received sham EA. von-Frey test and Hargreaves test were used to assess the pain threshold. Brain and spinal tissues were collected for immunofluorescence staining or Western blotting to quantify changes of MD2 expression. RESULTS: CFA successfully induced plantar pain and EA significantly alleviated pain 3 days after modelling (P<0.01). Compared with the CFA group, the number of MD2+/c-fos+ neurons was significantly increased in the dorsal horn of the spinal cord 7 and 14 days after EA, especially in laminae I - IIo (P<0.01). The proportion of double positive cells to the number of c-fos positive cells and the mean fluorescence intensity of MD2 neurons were also significantly increased in laminae I - IIo (P<0.01). Western blotting showed that the level of MD2 was significantly decreased by EA only in the hippocampus on day 7 and 14 (both P<0.01) and no significant changes were observed in the cortex, thalamus, cerebellum, or the brainstem (P<0.05). Fluorescence staining showed significant decrease in the level of MD2 in periagueductal gray (PAG) and locus coeruleus (LC) after CFA injection on day 7 (P<0.01 for PAG, P<0.05 for LC) and EA significantly reversed this decrease (P<0.01 for PAG, P<0.05 for LC). CONCLUSION: The unique changes of MD2 suggest that EA may exert the analgesic effect through modulating neuronal activities of the superficial laminae of the spinal cord and certain regions of the brain.

20.
Neurosci Lett ; 836: 137884, 2024 Jul 27.
Artículo en Inglés | MEDLINE | ID: mdl-38914277

RESUMEN

The nucleus accumbens (NAc) and the anterior limb of internal capsule (ALIC) are effective targets for treating addiction using deep brain stimulation (DBS). However, there have been no reports on the electrophysiological characteristics of addiction nuclei at the single-cell level in humans. This study aimed to investigate the electrical activity characteristics of neurons in the NAc and ALIC using microelectrode recording (MER) during DBS surgery in patients with addiction, and six patients with addiction were included (five with heroin addiction and one with alcohol addiction). The microelectrode recording trajectories were reconstructed and recording sites at different depths were determined by merging the pre- and post-operative images in the FrameLink system. The results showed that among the 256 neurons, 204 (80 %) were burst neurons. NAc neurons accounted for the majority (57 %), and the mean firing rate (MFR) was the highest (1.94 Hz). ALIC neurons accounted for the least (14 %), and MFR was the lowest (0.44 Hz). MFR increased after entering the NAc and decreased after entering the ALIC. In the patients with addiction treated using DBS, the single-cell level electrophysiological characteristics of the different nuclei were found to be distinct along the surgical trajectory.


Asunto(s)
Estimulación Encefálica Profunda , Cápsula Interna , Microelectrodos , Neuronas , Núcleo Accumbens , Núcleo Accumbens/fisiología , Núcleo Accumbens/fisiopatología , Humanos , Masculino , Estimulación Encefálica Profunda/métodos , Adulto , Cápsula Interna/fisiología , Cápsula Interna/fisiopatología , Neuronas/fisiología , Persona de Mediana Edad , Femenino , Potenciales de Acción/fisiología , Alcoholismo/fisiopatología , Dependencia de Heroína/fisiopatología
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