• Book : 260()
• Pub. Date : 2025
• Page : pp.125341
• Keyword :

• Book : 1053()
• Pub. Date : 2025
• Page : pp.122962
• Keyword :

• Book : 603()
• Pub. Date : 2025
• Page : pp.155481
• Keyword :

• Book : 558()
• Pub. Date : 2025
• Page : pp.165565
• Keyword :

• Book : 1053()
• Pub. Date : 2025
• Page : pp.122973
• Keyword :

Sirtuin 2 is a member of the sirtuin family nicotinamide adenine dinucleotide (NAD⁺)-dependent deacetylases, known for its regulatory role in different processes, including inflammation. In this context, sirtuin 2 has been involved in the modulation of key inflammatory signaling pathways and transcription factors by deacetylating specific targets, such as nuclear factor κB and nucleotide-binding oligomerization domain-leucine-rich-repeat and pyrin domain-containing protein 3 (NLRP3). However, whether sirtuin 2-mediated pathways induce a pro- or an anti-inflammatory response remains controversial. Sirtuin 2 has been implicated in promoting inflammation in conditions such as asthma and neurodegenerative diseases, suggesting that its inhibition in these conditions could be a potential therapeutic strategy. Conversely, arthritis and type 2 diabetes mellitus studies suggest that sirtuin 2 is essential at the peripheral level and, thus, its inhibition in these pathologies would not be recommended. Overall, the precise role of sirtuin 2 in inflammation appears to be context-dependent, and further investigation is needed to determine the specific molecular mechanisms and downstream targets through which sirtuin 2 influences inflammatory processes in various tissues and pathological conditions. The present review explores the involvement of sirtuin 2 in the inflammation associated with different pathologies to elucidate whether its pharmacological modulation could serve as an effective strategy for treating this prevalent symptom across various diseases.

• Book : 20(3)
• Pub. Date : 2025
• Page : pp.682-694
• Keyword :

JOURNAL/nrgr/04.03/01300535-202502000-00032/figure1/v/2024-06-06T062529Z/r/image-tiff

Invasive inflammation and excessive scar formation are the main reasons for the difficulty in repairing nervous tissue after spinal cord injury. Microglia and astrocytes play key roles in the spinal cord injury micro-environment and share a close interaction. However, the mechanisms involved remain unclear. In this study, we found that after spinal cord injury, resting microglia (M0) were polarized into pro-inflammatory phenotypes (MG1 and MG3), while resting astrocytes were polarized into reactive and scar-forming phenotypes. The expression of growth arrest-specific 6 (Gas6) and its receptor Axl were significantly down-regulated in microglia and astrocytes after spinal cord injury. In vitro experiments showed that Gas6 had negative effects on the polarization of reactive astrocytes and pro-inflammatory microglia, and even inhibited the cross-regulation between them. We further demonstrated that Gas6 can inhibit the polarization of reactive astrocytes by suppressing the activation of the Yes-associated protein signaling pathway. This, in turn, inhibited the polarization of pro-inflammatory microglia by suppressing the activation of the nuclear factor-κB/p65 and Janus kinase/signal transducer and activator of transcription signaling pathways. In vivo experiments showed that Gas6 inhibited the polarization of pro-inflammatory microglia and reactive astrocytes in the injured spinal cord, thereby promoting tissue repair and motor function recovery. Overall, Gas6 may play a role in the treatment of spinal cord injury. It can inhibit the inflammatory pathway of microglia and polarization of astrocytes, attenuate the interaction between microglia and astrocytes in the inflammatory microenvironment, and thereby alleviate local inflammation and reduce scar formation in the spinal cord.

• Book : 20(2)
• Pub. Date : 2025
• Page : pp.557-573
• Keyword :

Programmed cell death (PCD) can occur at every developmental stage as a plant’s response to various biotic and abiotic environmental factors. Silver nanoparticles (AgNPs) are widely used in consumer products and possess antimicrobial properties, making them important in assessing nanoparticle effects on plants. In the present study, we examined the impact of AgNPs (0, 0.5, 1, 5, 10, and 20 mg L-1) on wheat root PCD by evaluating parameters such as the mitotic index, chromosomal behaviors, nuclear deformation, cytochrome c release, caspase-1-like activity, and the expression of cysteine protease genes (TaVPE4, TaMCA1, and TaMCA4). Our findings revealed a dose-dependent decrease in the mitotic index ratio and increased chromosomal abnormalities induced by AgNPs. Additionally, we observed various hallmarks of PCD, including chromatin condensation, slight DNA smear, reduction in mitochondrial inner membrane potential, and cytochrome c release to the cytoplasm as well as increased caspase-1-like activity and TaVPE4 gene expression. Notably, the gene expressions of TaMCA1 and TaMCA4 were found to be antagonistically regulated by AgNPs, further indicating the induction of PCD by AgNP treatment. Overall, our study provides evidence of AgNP-induced PCD in wheat roots, elucidating the involvement of cysteine protease genes in this process.

• Book : 84(1)
• Pub. Date : 2025
• Page :
• Keyword :

Purpose

Among all primary breast tumors, malignant phyllodes tumor of the breast (MPTB) make up less than 1%. In the treatment of phyllode tumors, surgical procedures such as mastectomy and breast-conserving surgery are the mainstay. MPTB has, however, been controversial when it comes to treating it with RT. We aimed to explore the prognostic impact of RT and other clinicopathologic factors on long-term survival for patients with stage T3 or T4 malignant phyllodes tumors.

Methods

We select patients with stage T3 or T4 MPTB who qualified for the criteria between 2000 and 2018 via the Surveillance, Epidemiology, and End Results (SEER) database. We performed 1:1 propensity score matching (PSM) and Kaplan–Meier analysis to explore the role of RT in long-term survival of patients with stage T3 or T4 MPTB. A univariate and multivariate analysis of breast cancer-specific survival (BCSS) and overall survival (OS) risk factors was carried out using a Cox proportional hazards model. In addition, the nomogram graph of OS and BCSS was constructed.

Results

A total of 583 patients with stage T3 or T4 malignant phyllodes tumors were included in this study, of whom 154 (26.4%) received RT, and 429 (73.6%) were treated without RT. Before adjustment, between groups with and without RT, BCSS (p = 0.1) and OS (p = 0.212) indicated no significant difference respectively. Using of PSM, the two groups still did not differ significantly in BCSS (p = 0.552) and OS (p = 0.172). In multivariate analysis, age (p < 0.001), surgery of primary site (p < 0.001) and distant metastatic status (p < 0.001) were related to prognosis, while RT still did not affect BCSS (p = 0.877) and OS (p = 0.554).

Conclusion

Based on the SEER database analysis, the study suggests that the patients with stage T3 or T4 MPTB treated with RT after surgery didn't have significant differences in BCSS or OS compared to those not treated with RT.

• Book : 150(1)
• Pub. Date : 2025
• Page : pp.2
• Keyword :

The globus pallidus plays a pivotal role in the basal ganglia circuit. Parkinson’s disease is characterized by degeneration of dopamine-producing cells in the substantia nigra, which leads to dopamine deficiency in the brain that subsequently manifests as various motor and non-motor symptoms. This review aims to summarize the involvement of the globus pallidus in both motor and non-motor manifestations of Parkinson’s disease. The firing activities of parvalbumin neurons in the medial globus pallidus, including both the firing rate and pattern, exhibit strong correlations with the bradykinesia and rigidity associated with Parkinson’s disease. Increased beta oscillations, which are highly correlated with bradykinesia and rigidity, are regulated by the lateral globus pallidus. Furthermore, bradykinesia and rigidity are strongly linked to the loss of dopaminergic projections within the cortical-basal ganglia-thalamocortical loop. Resting tremors are attributed to the transmission of pathological signals from the basal ganglia through the motor cortex to the cerebellum-ventral intermediate nucleus circuit. The cortico-striato-pallidal loop is responsible for mediating pallidi-associated sleep disorders. Medication and deep brain stimulation are the primary therapeutic strategies addressing the globus pallidus in Parkinson’s disease. Medication is the primary treatment for motor symptoms in the early stages of Parkinson’s disease, while deep brain stimulation has been clinically proven to be effective in alleviating symptoms in patients with advanced Parkinson’s disease, particularly for the movement disorders caused by levodopa. Deep brain stimulation targeting the globus pallidus internus can improve motor function in patients with tremor-dominant and non-tremor-dominant Parkinson’s disease, while deep brain stimulation targeting the globus pallidus externus can alter the temporal pattern of neural activity throughout the basal ganglia-thalamus network. Therefore, the composition of the globus pallidus neurons, the neurotransmitters that act on them, their electrical activity, and the neural circuits they form can guide the search for new multi-target drugs to treat Parkinson’s disease in clinical practice. Examining the potential intra-nuclear and neural circuit mechanisms of deep brain stimulation associated with the globus pallidus can facilitate the management of both motor and non-motor symptoms while minimizing the side effects caused by deep brain stimulation.

• Book : 20(6)
• Pub. Date : 2025
• Page : pp.1628-1643
• Keyword :