Lemur Tyrosine Kinase-3 Suppresses Growth of Prostate Cancer Via the AKT and MAPK Signaling Pathways.

BACKGROUND/AIMS: Lemur tyrosine kinase (LMTK)-3 is a member of the receptor tyrosine kinase (RTK) family. Abnormal expression of LMTK-3 exists in various types of cancers, especially in endocrine-resistant breast cancers; however, the precise level of expression and the biological function in prostate cancer are poorly understood. METHODS: In the present study, we determined the expression of LMTK-3 in prostate cancer using immunohistochemistry and Western blotting. We infected PC3 and LNCaP cells with lentivirus-LMTK-3 and observed the biologic characteristics of the PC3 and LNCaP cells in vitro with TUNEL, and migration and invasion assays, respectively. We also established a transplant tumor model of human prostate cancer with infected cells in 15 BALB/c-nu/nu nude mice. RESULTS: LMTK-3 was expressed in prostate epithelial cells. There was a significant decline in the level of LMTK-3 expression in prostate cancers compared to normal tissues. LMTK-3 inhibited PC3 and LNCaP cell growth, migration, and invasion, and induced cell apoptosis in vitro. We also observed that LMTK-3 induced PC3 cell apoptosis in vivo. Further study showed that LMTK-3 inhibited phosphorylation of AKT and ERK, and promoted phosphorylation and activation of p38 kinase and Jun kinase (JNK). CONCLUSION: Recombinant lentivirus with enhanced expression of LMTK-3 inhibited prostate cancer cell growth and induced apoptosis in vitro and in vivo. AKT and MAPK signaling pathways may contribute to the process.

The clinical value of dynamic contrast-enhanced MRI in differential diagnosis of malignant and benign ovarian lesions.

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is widely used in preoperative diagnosis of various tumors. We investigated the clinical value of DCE-MRI in differential diagnosis of malignant and benign ovarian lesions. The study involved 48 subjects with surgical pathology-confirmed ovarian tumors with solid components. Early dynamic phase enhancement performances of the ovarian lesions in patients were assessed, including the enhancement pattern, time-signal intensity curve (TIC), signal intensity rate at the initial 60 s (SI60), time to peak within 200 s (TTP200), and slope ratio. There were significant differences in enhancement patterns between benign and malignant ovarian tumors (P < .05). A total of 30 malignant tumors (30/31) displayed type I TIC, 8 benign tumors (8/13) showed type III TIC, and significant differences were found in TIC type between malignant and benign ovarian lesions (P < 0.01). Benign ovarian tumors showed lower SI60 (%) and slope ratio, as well as significantly prolonged TTP20, compared to malignant ovarian tumors (all P < 0.01). The microvessel count (MVC) of malignant tumors was significantly higher than that of benign tumors (P < 0.05). Receiver operating characteristic (ROC) curve analyses revealed that DCE-MRI provided an optimal diagnostic performance with threshold values of SI60 at 83.40 %, TTP200 at 77.65 s, and slope ratio at 4.12. These findings revealed that DCE-MRI provides critical information required for differential diagnosis of malignant and benign ovarian lesions.

Sensitivity and Specificity of Diffusion-Weighted Magnetic Resonance Imaging in Diagnosis of Bladder Cancers.

PURPOSE: Our study is designed to examine the diagnostic performance of diffusion-weighted magnetic resonance imaging (DW-MRI) for bladder cancers (BC), and to determine whether DW-MRI can differentiate muscle invasive bladder cancer (MIBC) from non-MIBC (NMIBC). METHODS: A meta-analysis was performed of published studies that investigated the performance of DW-MRI for BC. These studies were retrieved from scientific literature databases using sensitive electronic search strategies. The STATA 12.0 and Meta-disc software were employed for statistical analyses of data extracted from selected studies. RESULTS: Our search initially returned 230 articles, of which 11 met the inclusion criteria and were enrolled into the final meta-analysis. Five of the included studies reported the diagnostic performance of DW-MRI for BC with a cumulative total of 243 BC patients and 82 healthy subjects. Eight studies investigated the diagnostic performance of DW-MRI for differentiating MIBC from NMIBC, involving 259 MIBC lesions and 515 NMIBC lesions. Meta-analysis results were as follows: the diagnostic performance of DW-MRI for BC (sensitivity: 0.95 [0.75-0.99]; specificity: 0.85 [0.74-0.92]; positive likelihood ratio: 6.45 [3.64-11.42]; negative likelihood ratio: 0.055 [0.009-0.333]; diagnostic odds ratio: 117.11 [19.37-708.05]; area under the curve (AUC): 0.91); the diagnostic performance of DW-MRI to differentiate MIBC from NMIBC (sensitivity: 0.85 [0.76 - 0.91]; specificity: 0.90 [0.87 - 0.93]; positive likelihood ratio:8.81[6.43 - 12.07]; negative likelihood ratio: 0.16 [0.10 - 0.28]; diagnostic odds ratio: 53.95 [25.68 - 113.33]; AUC: 0.92). CONCLUSION: DW-MRI has an outstanding diagnostic performance, with advanced sensitivity and specificity, for imaging of bladder cancers and for differentiating MIBC from NMIBC.

Brain metabolite changes in patients with type 2 diabetes and cerebral infarction using proton magnetic resonance spectroscopy.

The aim of this study was to investigate the possible brain metabolic alterations in patients with type 2 diabetes mellitus (T2DM) and cerebral infarction (DMCI) using proton magnetic resonance spectroscopy (MRS). Thirty-four patients with T2DM and DMCI were scanned together with 33 patients with nondiabetic cerebral infarction (NDCI) on a 1.5-T MRI/MRS imager. Voxels were placed in the infarcted area and the contralateral normal area in the basal ganglia. N-acetylaspartate (NAA)/creatine (Cr), choline (Cho)/Cr, and lactate (Lac)/Cr ratios were calculated. Cerebral NAA/Cr ratios in the infarcted area were lower than those in the contralateral normal area of the NDCI group. There was a significant decrease in NAA/Cr in the infarcted area of the DMCI group as compared with the infarcted area of the NDCI group. NAA/Cr ratios in the contralateral normal area of DMCI group were lower than those of the NDCI group. Lac/Cr ratios were increased in the infarcted area of both the DMCI group and NDCI group, and Lac/Cr ratios tended to be higher in the infarcted area of the DMCI group than those of the NDCI group. Glycosylated hemoglobin (HbA1c) levels were negatively correlated with NAA/Cr ratios. The study suggested that the metabolite changes were different between DMCI patients and NDCI patients, which may provide important information in the treatment of DMCI.

Identification of a novel prognostic cuproptosis-associated LncRNA signature for predicting prognosis and immunotherapy response in patients with esophageal cancer.

Nowadays, effective prognostic models for esophageal cancer (ESCA) are still lacking. Long noncoding RNAs (lncRNAs) are commonly utilized as indicators for diagnosing cancer and forecasting patient outcomes. Cuproptosis is regulated by multiple genes and is crucial to the progression of ESCA. However, it is not yet clear what role the cuproptosis-associated lncRNAs (CuALs) play in ESCA. To tackle this problem, a prognostic signature incorporating three CuALs was created. This signature was constructed by the use of the least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression. Subsequently, the signature effectively stratified ESCA samples into a high-risk group and a low-risk group. Those in the low-risk group demonstrated extended overall survival (OS), as well as increased infiltration of T cells, macrophages, and NK cells, suggesting a potentially enhanced response to immunotherapy. The ROC curve analysis demonstrated that this prognostic signature outperformed conventional clinical factors in predicting patient prognosis (AUC = 0.708). K-M survival analysis and correlation analysis identified UGDH-AS1 (a CuAL) as a protective factor positively associated with patient prognosis. The results of RT-qPCR and wound healing assays indicated that UGDH-AS1 is overexpressed in ESCA and could inhibit cancer cell migration. In general, the prognostic signature of CuALs demonstrated a robust capability in forecasting the immune environment and patient prognosis, highlighting its potential as a tool for enhancing personalized treatment strategies in ESCA.

Boosting photothermal-assisted photocatalytic H2 production over black g-C3N4 nanosheet photocatalyst via incorporation with carbon dots.

Although photocatalytic H2 production based on semiconductor materials has a wide potential application, it still facing challenges such as slow reaction kinetics or complex synthesis processes. To meet these challenges, the carbon dots loaded black g-C3N4 (CN-B-CDs) was synthesized by simple calcination method to achieve efficient photothermal-assisted photocatalytic H2 production. Photothermal imaging experiments confirmed the photothermal effect of CN-B and CDs as dual heat sources to increase the temperature of the composite system, thus improving the effective separation of photo-generated charges. In addition, multiple photocatalytic H2 production tests exhibited that CN-B-CDs photocatalysts not only have strong stability but also can accommodate a variety of complex water bodies, which displayed the potential for industrial application. This study combined the photothermal effect and the mechanism by which the CDs promote the charge transfer to design a new photocatalytic H2 production system and provided a new scheme for achieving efficient photothermal-assisted photocatalytic H2 production using carbon-based materials.

Plasmonic coupling-boosted photothermal nanoreactor for efficient solar light-driven photocatalytic water splitting.

Photothermal nanoreactor with rapid charge transfer and improved spectral utilization is a key point in photocatalysis research. Herein, silver sulfide quantum dots (Ag2S QDs) were coating on the surface of porous graphitic carbon nitride nano vesicles (PCNNVs) to form Ag2S/PCNNVs nanoreactors by a simple calcination method for obtaining efficient photothermal-assisted photocatalytic hydrogen (H2) evolution under simulated/real sunlight irradiation. In particularly, the as-prepared optimal 3% Ag2S/PCNNVs sample exhibited the H2 production rate of 34.8 mmol h-1 g-1, which was 3.5 times higher than that of bare PCNNVs. The enhancement of photothermal-assisted activity over the Ag2S/PCNNVs composite system is mainly attributed to the coupling of the photothermal conversion performance of Ag2S QDs and the thermal insulation performance of PCNNVs based on the plasmonic coupling-boosted photothermal nanoreactor. This study presents a promising strategy for the development of high-efficient photothermal-assisted photocatalysts.

RIPK1 and RIPK3 inhibitors: potential weapons against inflammation to treat diabetic complications.

Diabetes mellitus is a metabolic disease that is characterized by chronic hyperglycemia due to a variety of etiological factors. Long-term metabolic stress induces harmful inflammation leading to chronic complications, mainly diabetic ophthalmopathy, diabetic cardiovascular complications and diabetic nephropathy. With diabetes complications being one of the leading causes of disability and death, the use of anti-inflammatories in combination therapy for diabetes is increasing. There has been increasing interest in targeting significant regulators of the inflammatory pathway, notably receptor-interacting serine/threonine-kinase-1 (RIPK1) and receptor-interacting serine/threonine-kinase-3 (RIPK3), as drug targets for managing inflammation in treating diabetes complications. In this review, we aim to provide an up-to-date summary of current research on the mechanism of action and drug development of RIPK1 and RIPK3, which are pivotal in chronic inflammation and immunity, in relation to diabetic complications which may be benefit for explicating the potential of selective RIPK1 and RIPK3 inhibitors as anti-inflammatory therapeutic agents for diabetic complications.

Ferroptosis, necroptosis and cuproptosis: Novel forms of regulated cell death in diabetic cardiomyopathy.

Diabetes is a common chronic metabolic disease, and its incidence continues to increase year after year. Diabetic patients mainly die from various complications, with the most common being diabetic cardiomyopathy. However, the detection rate of diabetic cardiomyopathy is low in clinical practice, and targeted treatment is lacking. Recently, a large number of studies have confirmed that myocardial cell death in diabetic cardiomyopathy involves pyroptosis, apoptosis, necrosis, ferroptosis, necroptosis, cuproptosis, cellular burial, and other processes. Most importantly, numerous animal studies have shown that the onset and progression of diabetic cardiomyopathy can be mitigated by inhibiting these regulatory cell death processes, such as by utilizing inhibitors, chelators, or genetic manipulation. Therefore, we review the role of ferroptosis, necroptosis, and cuproptosis, three novel forms of cell death in diabetic cardiomyopathy, searching for possible targets, and analyzing the corresponding therapeutic approaches to these targets.

Characterization of the Roles of Suppressor of Cytokine Signaling-3 in Esophageal Carcinoma.

This study was aimed to analyze the diagnostic, therapeutic, and prognostic value of the suppressor of cytokine signaling 3 (SOCS3) in pancancer, especially in esophageal carcinoma (ESCA), and investigate the role of SOCS3 in the tumorigenesis and progression of ESCA. We used a variety of bioinformatics methods to explore the expression of SOCS3 in 33 kinds of cancers and evaluate its potential role in the pathogenesis, prognosis, immune microenvironment, immune evasion, and therapeutic response of cancers. The results indicated that SOCS3 was upregulated in 10 cancers, downregulated in 12 cancers, and upregulated in ESCA. Mutation and amplification were the main causes of abnormal expression of SOCS3 in pancancer. In ESCA, expression of SOCS3 was negatively correlated with methylation. The analysis showed that ESCA patients with low SOCS3 levels had better overall survival. Furthermore, the SOCS3 level was positively related to the ESTIMATE score, immune score, stromal score, and negatively related to tumor purity. In ESCA, a significant association was found between SOCS3 and several immune checkpoint genes. In addition, SOCS3 was associated with sensitivity to 59 drugs. Next, the role of SOCS3 in ESCA was investigated in ECA109, EC9706 cells, and in xenografted mouse model. SOCS3 was confirmed to be upregulated in ESCA cells. Knockdown of SOCS3 decreased the proliferation, migration, and invasion of ESCA cells while increasing apoptosis. Meanwhile, downregulation of SOCS3 activated the nuclear factor kappa-B signaling pathway and inhibited ESCA tumorigenesis in vivo. In conclusion, high SOCS3 expression is closely related to the occurrence and progression of ESCA and can be used as a therapeutic target and prognostic biomarker for ESCA.

Prognostic value of perfusion-weighted magnetic resonance imaging in acute intracerebral hemorrhage.

OBJECTIVE: This study intends to investigate the prognostic value of perfusion-weighted magnetic resonance imaging in acute intracerebral hemorrhage. METHODS: Demographic, clinical and biochemical data between acute intracerebral hemorrhage (AICH) and healthy volunteer groups were assessed in this study, such as rCBV and MTT values. The optimal cutoff values of rCBV and MTT for diagnosing AICH were determined by the ROC curves. Apart from that, we also investigated the association between rCBV/MTT values and cerebral hematoma volumes of AICH patients. The unconditional logistic regression was conducted to determine significant risk factors for AICH. RESULT: AICH patients have significantly lower rCBV and higher MTT compared to the control group (all P < 0.05). As suggested by the relatively high sensitivity and specificity, both rCBV and MTT values could be utilized for AICH diagnosis. Moreover, rCBV and MTT were significantly associated with the cerebral hematoma volumes of AICH patients (all P < 0.05). Results from unconditional logistic regression analysis revealed that MTT was a significant risk factor for AICH (P < 0.05 and OR > 1), while rCBV is considered as a protective factor (P < 0.05 and OR < 1). CONCLUSION: Perfusion-weighted magnetic resonance imaging produces a high prognostic value for diagnosing AICH.

A pilot fMRI study of the effect of stressful factors on the onset of depression in female patients.

The goal of this study was to observe the differences in brain activation under negative emotional picture stimuli in drug-naïve female patients with a first major depressive episode, comparing patients with and without stressful life experiences prior to the onset of depression. Using a 3.0 T magnetic resonance imaging (MRI) system, 18 patients who experienced stressful life events (SLEs) and 15 patients who did not experience SLEs were scanned under a task-fMRI paradigm designed to distinguish between negative and neutral neural responses to visual stimuli. SPM 8.0 software was used to process the fMRI data; the significantly activated brain regions were recorded and organized in the Montreal Neurological Institute (MNI) standard space. Upon stimulation with negative emotional pictures, depressed patients who had experienced SLEs showed significantly increased activation of the bilateral superior temporal gyrus, left middle temporal gyrus, left middle occipital gyrus, left medial frontal gyrus, right inferior frontal gyrus, bilateral precentral gyrus, bilateral postcentral gyrus, bilateral middle frontal gyrus, right precuneus, left paracentral lobule, bilateral thalamus, bilateral hippocampus, and left cerebellum when compared with depressed patients who did not experience SLEs.The brain regions that showed increased activation in depressed patients who experienced SLEs were primarily located in the neural circuits of the emotion processing system; this result likely indicates that these patients may have an increased negative cognitive bias in the perception, experience, and memory of negative emotional events, as well as their response to those events.

Nonspecific Effect of Stress on Brain Gray Matter Volume in Drug-naive Female Patients with First Depressive Episode.

BACKGROUND: This study aimed to observe the differences in brain gray matter volume in drug-naive female patients after the first episode of major depression with and without stressful life events (SLEs) before the onset of depression. METHODS: Forty-three drug-naive female patients voluntarily participated in the present study after the first major depressive episode. The life event scale was used to evaluate the severity of the impact of SLEs during 6 months before the onset of the major depressive episode. High-field magnetic resonance imaging (MRI) scans were obtained, and the VBM and SPM8 software process were used to process and analyze the MRI. RESULTS: Compared to that in patients without SLEs, the volume of brain gray matter was lower in the bilateral temporal lobe, right occipital lobe, and right limbic lobe in the SLE group. However, the gray matter volume did not differ significantly between the two groups after the application of false discovery rate (FDR) correction. CONCLUSIONS: Although the results of the present study suggest the absence of significant differences in brain gray matter volume between female drug-naive patients after the first episode of major depression with and without SLEs after FDR correction, the study provides useful information for exploring the definitive role of stress in the onset of depression.

Brain metabolite alterations demonstrated by proton magnetic resonance spectroscopy in diabetic patients with retinopathy.

Due to the homology between retinal and cerebral microvasculatures, retinopathy is a putative indicator of cerebrovascular dysfunction. This study aimed to detect metabolite changes of brain tissue in type 2 diabetes mellitus (T2DM) patients with diabetic retinopathy (DR) using proton magnetic resonance spectroscopy ((1)H-MRS). Twenty-nine T2DM patients with DR (DR group), thirty T2DM patients without DR (DM group) and thirty normal controls (NC group) were involved in this study. Single-voxel (1)H-MRS (TR: 2000ms, TE: 30ms) was performed at 3.0T MRI/MRS imager in cerebral left frontal white matter, left lenticular nucleus, and left optic radiation. Our data showed that NAA/Cr ratios of the DR group were significantly lower than those of the DM group in the frontal white matter and optic radiation. In the lenticular nucleus, MI/Cr ratios were significantly higher in the DM group than those in the NC group, while MI/Cr ratios were significantly lower in the DR group than those in the DM group. In the frontal white matter, NAA/Cho ratios were found to be decreased in the DR group as compared to the NC group. Additionally, our finding indicated that NAA/Cr ratios were negatively associated with DR severity in both the frontal white matter and optic radiation. A decrease in NAA indicated neuronal loss and the likely explanation for a decrease in MI was glial loss. In conclusion, we inferred that cerebral neurons and glia cells were damaged in patients with DR. Our data support that DR is associated with brain tissue damage.

MRI diagnosis of perivascular epithelioid cell tumor (PEComa) of the liver.

INTRODUCTION: Perivascular epithelioid cell tumor (PEComa) has been rarely reported in the liver. PATIENT, METHODS AND RESULTS: We present a liver PEComa case diagnosed by magnetic resonance imaging (MRI) findings. The patient was incidentally found to have an abnormal mass in the liver. MRI revealed early and strikingly homogeneous enhancement of the lesion. Partial hepatectomy was performed, and a pathological examination revealed signs of typical of PEComa. The patient was closely monitored for 12 months after the surgery, with no clinical or radiographic evidence of recurrence or metastatic disease. CONCLUSION: MRI diagnosis is applicable for PEComa.

[Imaging features of duplication of the internal auditory canal].

OBJECTIVE: To explore multiple slices computed tomography (MSCT) and magnetic resonance imaging (MRI) features of duplication of the internal auditory canal (DIAC) in order to improve the accuracy of diagnosis. METHODS: Four cases (5 ears) were analyzed and the related documents were reviewed retrospectively. MSCT was performed on all cases, and two cases had MRI scanning at the same time. RESULTS: MSCT has shown that the internal auditory canal were divided into two canals by a bony septum in 5 ears. The superior canal ended in a very narrow connection to the facial canal, the inferior portion ended in connection to the cochlea and vestibule. The bony septums from the 2 ears were found no longer intact. The sum of diameter of the two canals was greater than 2 mm. In addition, 5 ears were found to have an enlarged vestibules and the hypoplasia lateral semicircular canals, and meanwhile, 2 ears of them were combined with ipsilateral microtia. Also 1 case of them was combined with microtia, outer acoustic atresia as well as abnormal middle ear. Multiplanar reconstruction and volume rendering images can entirely show the bony septum and two canals. In this study, the vestibular nerve, cochlear nerve and facial nerve were total hypoplastic in one ear, in the other ear, the vestibular and cochlear nerve were hypoplastic, and however, the facial nerve was intact. CONCLUSIONS: MSCT can clearly depict duplication of the internal auditory canals and concomitant anomalies. MRI can clearly show the neural components and their associated malformation.