Inflammation has a dual nature; excessive or uncontrolled inflammation can trigger metabolic inflammatory diseases, in which immune cells, especially macrophages, play a crucial role. Mitochondria, as the core of cellular energy metabolism, are closely related to macrophage polarization and inflammation regulation. Mitochondrial dysfunction can trigger inflammatory responses through the activation of multiple signaling pathways, involving multiple signaling pathways, including Cyclic GMP-AMP Synthase – Stimulator of Interferon Genes 1, inflammasomes, and Retinoic acid-Inducible Gene I (RIG-I). Currently, the role of mitochondria in regulating inflammatory responses is increasingly prominent; however, current research still faces many challenges, such as a lack of mechanistic connections, unclear details of key molecules, insufficiently refined experimental strategies, and difficulties in clinical translation. Future research needs to leverage advanced technologies to delve deeper into the mechanisms, improve the bioavailability and tissue-specific delivery of mitochondrial-targeted drugs, establish personalized evaluation criteria, and promote interdisciplinary innovation to facilitate the transition of mitochondrial-targeted therapy from basic research to clinical application.

Lead (Pb) facilitates neurological deficits. Silybin is a flavonoid with neuroprotective properties. Heterogeneous nuclear ribonucleoprotein U (hnRNP U) has been implicated in neurodevelopmental disorders and predicted to regulate Repressor Element-1 Silencing Transcription (REST) expression. STAT3 can form a complex with hnRNP U and is inhibited by Silybin. We aim to elucidate the role of hnRNP U/STAT3 in Pb neurotoxicity and the neuroprotective effects of Silybin in Pb-exposed rats. We found that Pb increased the nuclear protein levels of hnRNP U and STAT3 and REST expression, which Silybin can partially reverse. Silencing hnRNP U reduced REST expression. Inhibiting STAT3 blocked hnRNP U nuclear transport. Silybin improves Pb-induced learning and memory impairment. Silybin reduced the expression of hnRNP U and NFκB. Inhibiting NFκB reduced hnRNP U expression. These suggest that Silybin improves Pb-induced learning and memory impairment by antagonizing STAT3/hnRNP U/REST and hnRNP U/NFκB.

Chronic lead (Pb) exposure is known to cause neuronal inflammation and autophagy dysfunction. However, the precise mechanism by which Pb exposure triggers neuronal autophagy remains elusive. This study aimed to elucidate the molecular mechanisms underlying Pb-induced neuronal autophagy. Inflammation and autophagy are closely interconnected cellular processes, with Toll-like receptor 4 (TLR4) playing a significant role in the inflammatory response to Pb. We observed that inhibiting TLR4 resulted in increased expression of Eukaryotic elongation factor 2 (EEF2), which regulated cellular autophagy. The rats and HT22 cells were utilized to establish chronic Pb exposure models. Our data reveals that Pb exposure promotes neuronal autophagy, activates TLR4, and increases EEF2 expression in rat hippocampus and HT22 cells. Additionally, inhibiting TLR4 partially reverses the Pb-induced increase in autophagy and the enhanced expression of EEF2. Overexpression of EEF2 partially counteracted the autophagy induced by Pb exposure. These findings suggest that Pb-induced activation of TLR4 may upregulate EEF2 expression, thereby leading to augmented neuronal autophagy and potential neuronal dysfunction.

Chronic lead (Pb) exposure is known to cause neuronal inflammation and autophagy dysfunction. However, the precise mechanism by which Pb exposure triggers neuronal autophagy remains elusive. This study aimed to elucidate the molecular mechanisms underlying Pb-induced neuronal autophagy. Inflammation and autophagy are closely interconnected cellular processes, with Toll-like receptor 4 (TLR4) playing a significant role in the inflammatory response to Pb. We observed that inhibiting TLR4 resulted in increased expression of Eukaryotic elongation factor 2 (EEF2), which regulated cellular autophagy. The rats and HT22 cells were utilized to establish chronic Pb exposure models. Our data reveals that Pb exposure promotes neuronal autophagy, activates TLR4, and increases EEF2 expression in rat hippocampus and HT22 cells. Additionally, inhibiting TLR4 partially reverses the Pb-induced increase in autophagy and the enhanced expression of EEF2. Overexpression of EEF2 partially counteracted the autophagy induced by Pb exposure. These findings suggest that Pb-induced activation of TLR4 may upregulate EEF2 expression, thereby leading to augmented neuronal autophagy and potential neuronal dysfunction.

Hepatic ischemia-reperfusion injury (HIRI) is a major clinical cause of morbidity and mortality in liver surgery and transplantation. Many studies have found that nitric oxide (NO) plays an important role in the HIRI and its increase or decrease can affect the progression and outcome of HIRI. However, the role of NO in HIRI is controversial and complicated. NO derived by endothelial NO synthase (eNOS) shows a protective role in HIRI, while excessive NO derived by inducible NO synthase (iNOS) accelerates inflammation and increases oxidative stress, further aggravating HIRI. Nevertheless, the overexpression of eNOS may exacerbate HIRI and iNOS-derived NO in some cases reduces HIRI. Here we review the new progress in the understanding of the roles of NO during HIRI: (1) NO possesses different roles in HIRI by increasing NO bioavailability, down-regulating leukotriene C4 synthase, inhibiting the activation of the nuclear factorκB (NFκB) pathway, enhancing cell autophagy, and reducing inflammatory cytokines and reactive oxygen species (ROS). And NO has both protective and deleterious effects by regulating apoptotic factors; (2) eNOS promotes NO production and suppresses its own overexpression, exerting a hepatoprotective effect reversely. Its activation is regulated by the PI3K/Akt and KLF2/AMPK pathways; and (3) iNOS derived NO mainly has deteriorating effects on HIRI, while it may have a protective function under some conditions. Their expression should reach a balance to reduce the adverse side and make NO protective in the treatment of HIRI. Thus, it can be inferred that NO modulating drugs may be a new direction in the treatment of HIRI or may be used as an adjunct to mitigate HIRI for the purpose of protecting the liver.

Objective: The purpose of this study is to evaluate the association between left iliac vein (LIV) compression and inferior vena cava thrombosis (IVCT) in patients with LIV involvement of deep vein thrombosis (DVT). Methods: A total of 263 consecutive patients with DVT were reviewed retrospectively and divided into a group with IVCT and a group without IVCT. The influences of LIV smallest diameter and percentage compression on the risk of IVCT were investigated using logistic regression analysis. Results: The mean age of patients with IVCT was significantly younger than that of patients without IVCT (55.5 +/- 1.8 vs 62.7 +/- 1.1; P= .001). The percentage of provoked DVT in patients with IVCT was higher than that in patients without IVCT (67.1% vs 48.2%; P = .01). The smallest diameter of the LIV in patients with ICVT was larger than that in patients without IVCT (4.1 +/- 0.3 vs 2.5 +/- 0.2; P < .001). The mean percentage compression of LIV in patients with IVCT was significantly lower than that in patients without IVCT (63.5 +/- 2.2 vs 74.3 +/- 1.3; P < .001). Age was associated with a decreased odds of ICVT (odds ratio [OR], 0.965; 95% confidence interval [CI], 0.965-0.985; P = .001). Provoked DVT was associated with an increased odds of ICVT (OR, 2.011; 95% CI,1.070-3.782; P= .03). LIV compression was associated with a decreased odds of ICVT for each 1-mm decrease in smallest diameter of the LIV (OR, 0.717; 95% CI, 0.627-0.820; P < .001), and for each 10% increase in percentage compression of the LIV (OR, 0.715; 95% CI, 0.612-0.835; P < .001). Conclusions: For LIV involvement in patients with DVT, patients without IVCT had more severe LIV compression than patients with IVCT. Severe LIV compression may be a protective factor for the risk of IVCT.

Cardiovascular disease (CVD) is a significant public health issue due to its high prevalence and considerable contribution to the global disease burden. Recent studies suggest that genetic factors, including noncoding RNAs, have an important role in the progression of CVD. Noncoding RNA plays a critical role in genetic programming and gene regulation during development. Ferroptosis is a form of iron-dependent regulated cell death (RCD), which is mainly caused by increased lipid hydroperoxide and redox imbalance. Ferroptosis is essentially different from other forms of RCD in morphology and mechanism, such as apoptosis, autophagic cell death, pyroptosis, and necroptosis. Much evidence suggested ferroptosis is involved in the development of various CVDs, especially in cardiac ischemia/reperfusion injury, heart failure, and aortic dissection. Here, we review the latest findings based on noncoding RNA regulation of ferroptosis and its involvement in the pathogenesis of CVD and related treatments, aimed at providing insights into the impact of noncoding RNA regulation of ferroptosis for CVD.

Nitric oxide (NO), a free radical, plays a critical role in a wide range of physiological and pathological processes. Due to its pleiotropic function, it has been widely investigated in various types of cancers and is strongly associated with cancer development. Mounting pieces of evidence show that NO regulates various cancer-related events, which mainly depends on phosphorylating the key proteins in several signaling pathways. However, phosphorylation of proteins modulated by NO signaling pathway may lead to different effects in different types of cancer, which is complex and remains unclear. Therefore, in this review, we focus on the effect of protein phosphorylation modulated by NO signaling pathway in different types of cancers including breast cancer, lung cancer, prostate cancer, colon cancer, gastric cancer, pancreatic cancer, ovarian cancer, and neuroblastoma. Phosphorylation of key proteins, including p38 MAPK, ERK, PI3K, STAT3, and p53, modified by NO in various signaling pathways affects different cancer-related processes including cell apoptosis, proliferation, angiogenesis, metastasis, and several cancer therapies. Our review links the NO signaling pathway to protein phosphorylation in cancer development and provides new insight into potential targets and cancer therapy.

抑郁症是以显著而持久性的心境低落为主要临床特征的一种心理障碍性疾病.抑郁症发病率较高,预计2020年将成为第二大疾病,但抑郁症受多方面因素的影响,迄今病因仍不明了.脑源性神经生长因子(brain-derived neurotrophic factor,BDNF)与阿尔茨海默病[1]、精神分裂症[2]、帕金森病[3]等多种精神性疾病有关.近年来,抑郁症中 BDNF 的相关研究已成为热门话题,本文对抑郁症中 BDNF的相关研究综述如下.