OBJECTIVES: To explore the relationship between white matter injury (WMI) and cerebral perfusion in preterm infants using arterial spin labeling (ASL). METHODS: A total of 293 preterm infants (gestational age <34 weeks) hospitalized at the Third Affiliated Hospital of Zhengzhou University between June 2022 and June 2024 were included. After achieving clinical stability, the infants underwent brain magnetic resonance imaging (MRI) and ASL. Based on MRI findings, infants were classified into WMI (n=66) and non-WMI (n=227) groups. Cerebral perfusion parameters were compared between groups, and the association between WMI and perfusion alterations was evaluated. RESULTS: The WMI group showed a higher incidence of mild intraventricular hemorrhage (IVH) than the non-WMI group (P<0.05). Significantly lower cerebral perfusion was observed in the WMI group across bilateral frontal, temporal, parietal, and occipital lobes, as well as the basal ganglia and thalamus (P<0.05). After adjusting for gestational age, corrected gestational age at ASL scan, and mild IVH, WMI remained significantly associated with reduced regional perfusion (P<0.05). CONCLUSIONS WMI in preterm infants correlates with localized cerebral hypoperfusion. ASL-detected perfusion abnormalities may provide novel insights into WMI pathogenesis.
Humans ; White Matter/blood supply* ; Infant, Newborn ; Spin Labels ; Infant, Premature ; Female ; Male ; Cerebrovascular Circulation ; Magnetic Resonance Imaging

BACKGROUND: Hyperthermia (HT), while a cancer treatment approach, isn't always effective alone. Therefore, identifying hyperthermia enhancers is crucial. We demonstrated that Mito-TEMPO ([2-[(1-Hydroxy-2,2,6,6-tetramethylpiperidin-4-yl) amino]-2-oxoethyl]-triphenylphosphanium, MT) acts as a potent thermosensitizer, promoting cell death in human cervical cancer (HeLa) cells. METHODS: Cells were pretreated with 0.4 mM MT for 5 minutes, followed by exposure to hyperthermia (42 °C for 60 minutes). The impacts of MT/HT on cell viability, proliferation, apoptosis, endoplasmic reticulum (ER) stress, apoptosis-related proteins and autophagy, autophagy-related proteins expression were measured. The relationships between autophagy and apoptosis were further investigated using the specific autophagy inhibitor chloroquine (CQ) and the autophagy inducer rapamycin (Rapa). RESULTS: The combined treatment reduced the mitochondrial membrane potential (MMP) and increased ROS production. It also upregulated the pro-apoptotic protein Bax and downregulated anti-apoptotic proteins such as Bcl-2 and MCL-1. As a result, Caspase-3 was activated. Additionally, the combined treatment upregulated the expression of p-PERK/PERK, ATF-4, CHOP proteins. Moreover, the combined treatment also increased the expression of LC3 II and p62, decreased expression of LAMP 1 and Cathepsin D and increased lysosomal pH, indicating coordinated changes in autophagy regulation. Notably, intensification of apoptosis induced by the combined treatment was observed with CQ, whereas attenuation was seen with Rapa. CONCLUSIONS MT effectively enhanced HT-induced apoptosis in HeLa cells. Elevated ER stress and interruption of autophagy flux are the possible underlying molecular mechanisms for this phenomenon. These findings suggested MT can act as a potential thermosensitizer, highlighting its versatility in cancer treatment strategies.
Humans ; Apoptosis/drug effects* ; Autophagy/drug effects* ; HeLa Cells ; Uterine Cervical Neoplasms/therapy* ; Female ; Hyperthermia, Induced ; Spin Labels ; Endoplasmic Reticulum Stress/drug effects* ; Cyclic N-Oxides/pharmacology* ; Cell Survival/drug effects*

OBJECTIVES: The patients with mild traumatic brain injury (mTBI) accounts for more than 80% of the patients with brain injury. Most patients with mTBI have no abnormalities in CT examination. Therefore, most patients choose to self-care and recover rather than seeking medical treatment. In fact, mTBI may result in persistent cognitive decline and neurobehavioral dysfunction. In addition, changes occurred in neurochemistry, metabolism, and cells after injury may cause changes in cerebral blood flow (CBF), which is one of the causes of secondary injury and slow brain repair. This study aims to evaluate the changes of CBF with the progression of the disease in patients with mTBI based on arterial spin labeling (ASL) magnetic resonance imaging technology. METHODS: In the outpatient or emergency department of the Second Affiliated Hospital of Wenzhou Medical University, 43 mTBI patients were collected as an mTBI group, and 43 normal subjects with age, gender, and education level matching served as a control group. They all received clinical neuropsychology and cognitive function evaluation and magnetic resonance imaging. In the mTBI group, 22 subjects were followed up at acute phase, 1 month, 3 months, and 12 months. Based on the control group, the abnormal regions of CBF in the whole brain of mTBI patients were analyzed. The abnormal regions were taken as the regions of interest (ROI). The correlation of the values of the CBF in ROIs with clinical indications, cognitive function, and the changes of CBF in ROI at each time point during the follow-up were analyzed. RESULTS: Compared with the control group, the CBF in the bilateral dorsolateral superior frontal gyrus and auxiliary motor areas in the cortical region, as well as the right putamen, caudate nucleus, globus pallidus, and parahippocampus in the subcutaneous regions in the acute phase of the mTBI group were significantly increased (all P<0.01, TFCE-FWE correction). The analysis results of correlation of CBF with neuropsychology and cognitive domain showed that in the mTBI group, whole brain (r=0.528, P<0.001), right caudate nucleus (r=0.512, P<0.001), putamen (r=0.486, P<0.001), and globus pallidus (r=0.426, P=0.006) values of the were positively correlated with Backward Digit Span Test (BDST) score (reflectting working memory ability), and the right globus pallidus CBF was negatively correlated with the Post-Traumatic Stress Disorder Cheeklist-CivilianVersion (PCL-C) score (r=-0.402, P=0.010). Moreover, the follow-up study showed that abnormal CBF in these areas had not been restored. The correlation of CBF was negatively correlated with PCL-C and BDST at 1 months, 3 months, and 12 months (all P>0.05). CONCLUSIONS The elevated CBF value is one of the stress characteristics of brain injury in the mTBI patients at the acute phase. There is abnormal elevation of CBF values in multiple cortex or subcortical areas. Multi-time point studies show that there is no obvious change of CBF in abnormal areas, suggesting that potential clinical treatment is urgently needed for the mTBI patients.
Brain Concussion/diagnostic imaging* ; Brain Injuries ; Cerebrovascular Circulation/physiology* ; Follow-Up Studies ; Humans ; Magnetic Resonance Imaging/methods* ; Magnetic Resonance Spectroscopy ; Spin Labels

OBJECTIVE: Acute lung injury (ALI) is a serious respiratory dysfunction caused by pathogen or physical invasion. The strong induced inflammation often causes death. Tanshinone IIA (Tan-IIA) is the major constituent of Salvia miltiorrhiza Bunge and has been shown to display anti-inflammatory effects. The aim of the current study was to investigate the effects of Tan-IIA on ALI. METHODS: A murine model of lipopolysaccharide (LPS)-induced ALI was used. The lungs and serum samples of mice were extracted at 3 days after treatment. ALI-induced inflammatory damages were confirmed from cytokine detections and histomorphology observations. Effects of Tan-IIA were investigated using in vivo and in vitro ALI models. Tan-IIA mechanisms were investigated by performing Western blot and flow cytometry experiments. A wound-healing assay was performed to confirm the Tan-IIA function. RESULTS: The cytokine storm induced by LPS treatment was detected at 3 days after LPS treatment, and alveolar epithelial damage and lymphocyte aggregation were observed. Tan-IIA treatment attenuated the LPS-induced inflammation and reduced the levels of inflammatory cytokines released not only by inhibiting neutrophils, but also by macrophage. Moreover, we found that macrophage activation and polarization after LPS treatment were abrogated after applying the Tan-IIA treatment. An in vitro assay also confirmed that including the Tan-IIA supplement increased the relative amount of the M2 subtype and decreased that of M1. Rebalanced macrophages and Tan-IIA inhibited activations of the nuclear factor-κB and hypoxia-inducible factor pathways. Including Tan-IIA and macrophages also improved alveolar epithelial repair by regulating macrophage polarization. CONCLUSION This study found that while an LPS-induced cytokine storm exacerbated ALI, including Tan-IIA could prevent ALI-induced inflammation and improve the alveolar epithelial repair, and do so by regulating macrophage polarization.
Abietanes ; Acute Lung Injury/drug therapy* ; Animals ; Cytokine Release Syndrome ; Cytokines ; Inflammation/drug therapy* ; Lipopolysaccharides/toxicity* ; Macrophage Activation ; Macrophages ; Mice ; Triacetoneamine-N-Oxyl/pharmacology*

Arterial spin labeling is a noninvasive,quantitative method for perfusion imaging,which does not need any contrast media.This technique has been used in the renal perfusion analysis.In this article,we briefly introduced this technique and summarized its application in healthy volunteers,acute kidney injury,chronic kidney diseases,renovascular diseases,renal tumors,and renal transplantation.
Humans ; Kidney/diagnostic imaging* ; Magnetic Resonance Imaging ; Perfusion ; Perfusion Imaging ; Renal Insufficiency, Chronic ; Spin Labels

OBJECTIVE: To investigate the effect of the chemoprotectant tempol on the anti-tumor activity of cisplatin (DDP). METHODS: The cellular toxicity of tempol in human colon cancer SW480 cells and mouse colon cancer CT26 cells were evaluated using MTT and cell counting kit-8 assays. CalcuSyn software analysis was used to determine the interaction between tempol and DDP in inhibition of the cell viability. A subcutaneous homograft mouse model of colon cancer was established. The mice were randomly divided into control group, tempol group, cisplatin group and tempol + DDP treatment group with intraperitoneal injections of the indicated agents. The tumor size, body weight and lifespan of the mice were measured, and HE staining was used to analyze the cytotoxic effect of the agents on the kidney and liver. Immunohistochemistry and Western blotting were performed to detect the expression of Bax and Bcl2 in the tumor tissue, and TUNEL staining was used to analyze the tumor cell apoptosis. The level of reactive oxygen species (ROS) in the tumor tissue was determined using flow cytometry. RESULTS: Tempol showed inhibitory effects on the viability of SW480 and CT26 cells. CalcuSyn software analysis showed that tempol had a synergistic anti-tumor effect with DDP (CI < 1). In the homograft mouse model, tempol treatment alone did not produce obvious anti-tumor effect. HE staining showed that the combined use of tempol and DDP alleviated DDP-induced fibrogenesis in the kidneys, but tempol also reduced the anti-tumor activity of DDP. Compared with the mice treated with DDP alone, the mice treated with both tempol and DDP had a significantly larger tumor size ( < 0.01) and a shorter lifespan ( < 0.05). Tempol significantly reversed DDP-induced expression of Bax and Bcl2 in the tumor tissue and tumor cell apoptosis ( < 0.001), and obviously reduced the elevation of ROS level in the tumor tissue induced by DDP treatment ( < 0.05). CONCLUSIONS Tempol can attenuate the anti-tumor effect of DDP while reducing the side effects of DDP. Caution must be taken and the risks and benefits should be carefully weighed when considering the use of tempol as an anti-oxidant to reduce the toxicities of DDP.
Animals ; Antineoplastic Agents ; Antioxidants ; Apoptosis ; Cell Line, Tumor ; Cell Proliferation ; Cisplatin ; Cyclic N-Oxides ; pharmacology ; Drug Resistance, Neoplasm ; Humans ; Mice ; Spin Labels

Progressive cribriform and zosteriform hyperpigmentation (PCZH) is a distinctive pigmentary disorder observed along the lines of Blaschko. Clinically, the lesions appear as uniformly tan, cribriform macular hyperpigmentation with a zosteriform distribution, without a history of rash, injury, inflammation, or other associated cutaneous or internal abnormalities. Histopathological specimens show increased melanin pigmentation in the basal cell layer with a complete absence of nevus cells. We report 8 cases of PCZH and review the literature on this peculiar disorder.
Exanthema ; Hyperpigmentation* ; Inflammation ; Melanins ; Nevus ; Pigmentation ; Triacetoneamine-N-Oxyl

Two Whooper swan (Cygnus cygnus) died after suffering from pododermatitis, lethargy, and ataxia; necropsy was performed. Grossly, the liver was swollen and firm. The kidney and spleen were also enlarged and a pale tan color. On histopathologic examination with Congo red staining, amyloidosis was noted in liver, spleen, and kidney. In addition, marked osseous metaplasia was present in the liver. Based on these results, systemic amyloidosis involving liver, spleen, and kidney with osseous metaplasia in the liver was diagnosed. Study results indicate that an inflammatory reaction associated with pododermatitis had a role in the amyloidosis in this particular case.
Amyloidosis* ; Ataxia ; Congo Red ; Kidney ; Lethargy ; Liver ; Metaplasia ; Spleen ; Triacetoneamine-N-Oxyl

Tanshinone IIA (Tan IIA) is a pharmacologically active substance extracted from the rhizome of Salvia miltiorrhiza Bunge (also known as the Chinese herb Danshen), and is widely used to treat atherosclerosis. The pregnane X receptor (PXR) is a nuclear receptor that is a key regulator of xenobiotic and endobiotic detoxification. Tan IIA is an efficacious PXR agonist that has a potential protective effect on endothelial injuries induced by xenobiotics and endobiotics via PXR activation. Previously numerous studies have demonstrated the possible effects of Tan IIA on human umbilical vein endothelial cells, but the further mechanism for its exerts the protective effect is not well established. To study the protective effects of Tan IIA against hydrogen peroxide (H₂O₂) in human umbilical vein endothelial cells (HUVECs), we pretreated cells with or without different concentrations of Tan IIA for 24 h, then exposed the cells to 400 μM H₂O₂ for another 3 h. Therefore, our data strongly suggests that Tan IIA may lead to increased regeneration of glutathione (GSH) from the glutathione disulfide (GSSG) produced during the GSH peroxidase-catalyzed decomposition of H₂O₂ in HUVECs, and the PXR plays a significant role in this process. Tan IIA may also exert protective effects against H₂O₂-induced apoptosis through the mitochondrial apoptosis pathway associated with the participation of PXR. Tan IIA protected HUVECs from inflammatory mediators triggered by H₂O₂ via PXR activation. In conclusion, Tan IIA protected HUVECs against H₂O₂-induced cell injury through PXR-dependent mechanisms.
Apoptosis ; Asian Continental Ancestry Group ; Atherosclerosis ; Endothelial Cells* ; Glutathione ; Glutathione Disulfide ; Human Umbilical Vein Endothelial Cells ; Humans ; Hydrogen Peroxide ; Inflammation ; Oxidative Stress ; Regeneration ; Rhizome ; Salvia miltiorrhiza ; Triacetoneamine-N-Oxyl ; Xenobiotics

OBJECTIVETo evaluate the clinical value of three-dimensional pseudo-continuous arterial spin labeling (3D pCASL) perfusion magnetic resonance imaging (MRI) and dynamic susceptibility contrast (DSC) enhanced perfusion MRI in the diagnosis of transient ischemic attack (TIA).

METHODSThirty-nine consecutive patients with suspected TIA underwent multi-modal MRI scans including DSC, magnetic resonance angiography (MRA), diffusion-weighted imaging (DWI) and 3D pCASL (post-labeling delay, PLD=1.5 s and 2.5 s) within 24 h of symptom onset. Cerebral blood flow (CBF) from ASL and the time to the maximum of tissue residual function (Tmax) map from DSC were calculated using AW workstation. DWI and MRA were applied to detect acute cerebral infarction and intracranial artery stenosis. Two neuroradilogists who were blinded to the patients' clinical data assessed the presence of perfusion deficit, ischemic lesion and the lesion sites both from 1.5 s, 2.5 s PLD ASL-CBF and DSC-Tmax independently, and then graded them. The differences in the ranking grades between 1.5 s, 2.5 s PLD ASL and DSC were analyzed, and the frequency of lesion detection was compared between ASL-CBF, Tmax and MRA combining DWI method.

RESULTSNo significant differences was found in hypoperfusion grades detected by 3D pCASL (including PLD1.5 s and 2.5 s) CBF and Tmax maps, while significant differences were detected between 1.5 s PLD ASL-CBF and MRA combining DWI method; ASL with PLD 1.5 s CBF detected ischemic lesions and lesion site significantly more frequently than MRA combining DWI method.

CONCLUSIONs Three dimensional pCASL is a non-invasive perfusion method free of radiation exposure, and short PLD ASL is more sensitive than long PLD ASL for detecting ischemic lesions and lesion sites.

Arteries ; physiopathology ; Brain ; physiopathology ; Brain Infarction ; diagnosis ; Brain Ischemia ; diagnosis ; Cerebrovascular Circulation ; Diffusion Magnetic Resonance Imaging ; Humans ; Magnetic Resonance Angiography ; Perfusion ; Perfusion Imaging ; Spin Labels