LINC00115 regulates lung adenocarcinoma progression via sponging miR-154-3p to modulate Sp3 expression.

The most commonly diagnosed and most lethal subtype of lung cancer is lung adenocarcinoma (LUAD). Therefore, more detailed understanding of the potential mechanism and identification of potential targets of lung adenocarcinoma is needed. A growing number of reports reveals that long non-coding RNAs (lncRNAs) play crucial roles in cancer progression. In present study, we found that lncRNA LINC00115 was upregulated in LUAD tissues and cells. Functional studies revealed that LINC00115 knockdown inhibits the proliferation, growth, invasion, and migration of LUAD cells. Mechanically, we indicated that miR-154-3p is target microRNA of LINC00115, and the effect of downregulated LINC00115 on LUAD cells was partially reversed by the miR-154-3p antisense oligonucleotide (ASO-miR-154-3p). Further investigation revealed that Specificity protein 3 (Sp3) directly interacted with miR-154-3p, and the Sp3 level was positively correlated with the LINC00115 expression. Rescue experiments further showed that Sp3 overexpression partially restored the effect of downregulated LINC00115 on LUAD cells. Similarly, in vivo experiments confirmed that downregulated LINC00115 inhibited xenograft growth and Sp3 expression. Our results demonstrated that LINC00115 knockdown inhibited LUAD progression via sponging miR-154-3p to modulate Sp3 expression. These data indicate that the LINC00115/miR-154-3p/Sp3 axis can be a potential therapeutic target of LUAD.

Antiangiogenic effect of arsenic trioxide in HUVECs by FoxO3a-regulated autophagy.

Arsenic trioxide (ATO) has been shown to have antitumor effect in different tumors, although the underlying mechanisms are not fully understood. Autophagy plays a critical role in tumorigenesis and cancer therapy and has been found to be activated by ATO in different cells. However, the role of autophagy in the antitumor effect of ATO has not yet been elucidated. In this study, we investigated the role of autophagy in the antiangiogenic effect of ATO in human umbilical vein endothelial cells (HUVECs) in vitro and its underlying mechanism. Our data showed that ATO suppresses angiogenesis and induces autophagy in HUVECs through upregulation of forkhead box protein O3 (FoxO3a). Co-incubated with autophagy inhibitor or knockdown of FoxO3a effectively inhibited ATO-induced autophagy and reversed the antiangiogenic effect of ATO, indicating that ATO-induced autophagy plays an antiangiogenic role in HUVECs. Our results highlight the importance of autophagy in the antiangiogenic effect of ATO and provide an improved understanding of the function of ATO.

Towards a biomimetic cellular structure and physical morphology with liposome-encapsulated agarose sol systems.

The cytoplasm, serving as the primary hub of cellular metabolism, stands as a pivotal cornerstone for the harmonious progression of life. The ideal artificial cell should not only have a biomembrane structure system similar to that of a cell and the function of carrying genetic information, but also should have an intracellular environment. In this pursuit, we employed a method involving the incorporation of glycerol into agarose, resulting in the formation of agarose-glycerol mixed sol (AGs). This dynamic sol exhibited fluidic properties at ambient temperature, closely mimicking the viscosity of authentic cytoplasm. Harnessing the electroformation technique, AGs was encapsulated within liposomes, enabling the efficient creation of artificial cells that closely resembled native cellular dimensions through meticulous parameter adjustments of the alternating current (AC) field. Subsequently, artificial cells harboring AGs were subjected to diverse electrolyte and non-electrolyte solutions, enabling a comprehensive exploration of their deformation phenomena, encompassing both inward and outward budding. This study represents a significant stride forward in addressing one of the most fundamental challenges in the construction of artificial cytoplasm. It is our fervent aspiration that this work shall offer invaluable insights and guidance for future endeavors in the realm of artificial cell construction.

Ketogenic diet therapy leads to antiseizure medication reduction in children and adults with drug-resistant epilepsy.

AIMS: This study aimed to evaluate the safety of reducing or withdrawing anti-seizure medications (ASMs) in a cohort comprising both adults and children with drug-resistant epilepsy (DRE) undergoing ketogenic diet therapy (KDT). METHODS: We conducted a comprehensive analysis of clinical profiles in adults and children with DRE who had adhered to KDT for at least 6 months. Successful withdrawal or reduction of an ASM was defined as discontinuation or dose reduction without subsequent resumption or increase and without initiation of any new ASM throughout the entire follow-up period. Changes in the ASM load were calculated specifically for adult patients. RESULTS: The study enrolled 56 participants (34 children and 22 adults) with DRE, with 64.3% achieving successful withdrawal of at least one ASM. The probability of ASM withdrawal remained consistent for children (64.7%) versus adults (63.6%), as well as for responders (62.5%) versus non-responders (68.8%), and it was not associated with other clinical factors. Early ASM reduction (including withdrawal) after diet initiation occurred in 15 patients (26.8%), with treatment outcomes comparable to those of the remaining participants. Among the 22 adults, the mean values of ASM load reduced by 24.5%, with a similar magnitude observed for responders (24.2%) versus non-responders (25.1%). In addition, adults tend to have a slower elevation in serum ketone levels compared to children. CONCLUSION: This study demonstrates the safe achievability of ASM withdrawal through KDT in most patients with DRE, irrespective of age or seizure frequency reduction.

Altered structural network in temporal lobe epilepsy with focal to bilateral tonic-clonic seizures.

OBJECTIVES: This study aims to investigate whether alterations in white matter topological networks are associated with focal to bilateral tonic-clonic seizures (FBTCS) in temporal lobe epilepsy (TLE). Additionally, we investigated the variables contributing to memory impairment in TLE. METHODS: This cross-sectional study included 88 unilateral people with TLE (45 left/43 right), and 42 healthy controls. Graph theory analysis was employed to compare the FBTCS (+) group (n = 51) with the FBTCS (-) group (n = 37). The FBTCS (+) group was subcategorized into current-FBTCS (n = 31) and remote-FBTCS (n = 20), based on the history of FBTCS within 1 year or longer than 1 year before scanning, respectively. We evaluated the discriminatory power of topological network properties by receiver operating characteristic (ROC) analysis. Generalized linear models (GLMs) were employed to investigate variables associated with memory impairment in TLE. RESULTS: Global efficiency (Eg) was significantly reduced in the FBTCS (+) group, especially in the current-FBTCS subgroup. Greater disruption of regional properties in the ipsilateral occipital and temporal association cortices was observed in the FBTCS (+) group. ROC analysis revealed that Eg, normalized characteristic shortest path length, and nodal efficiency of the ipsilateral middle temporal gyrus could distinguish between FBTCS (+) and FBTCS (-) groups. Additionally, GLMs linked the occurrence of current FBTCS with poorer verbal memory outcomes in TLE. INTERPRETATION: Our study suggests that abnormal networks could be the structural basis of seizure propagation in FBTCS. Strategies aimed at reducing the occurrence of FBTCS could potentially improve the memory outcomes in people with TLE.

Loss of Pten in Renal Tubular Cells Leads to Water Retention by Upregulating AQP2.

Introduction: Phosphatase and tensin (PTEN) is a multifunctional gene associated with the normal development and physiological function of various tissues including the kidney. However, its role in renal tubular reabsorption function has not been well elucidated. Methods: We generated a renal tubule-specific Pten knockout mouse model by crossing Ptenfl/fl mice with Ksp-Cre transgenic mice, evaluated the effect of Pten loss on renal tubular function, and investigated the underlying mechanisms. Results: Pten loss resulted in abnormal renal structure and function and water retention in multiple organs. Our results also demonstrated that aquaporin-2 (AQP2), an important water channel protein, was upregulated and concentrated on the apical plasma membrane of collecting duct cells, which could be responsible for the impaired water balance in Pten loss mice. The regulation of Pten loss on AQP2 was mediated by protein kinase B (AKT) activation. Conclusions: Our results reveal a connection between PTEN gene inactivation and water retention, suggesting the importance of PTEN in normal kidney development and function.

Primary intramedullary melanocytoma in the thoracic cord: a case report and literature review.

Background: Primary intramedullary melanocytoma (PIM) is extremely rare, only 25 cases of PIM have been reported previously. Herein we report a case of PIM in the thoracic cord and reviewed its clinicopathological features, imaging features, therapeutic strategies and prognosis to provide helpful information in the diagnosis and treatment of PIM. Case Description: A 56-year-old man presented with weakness and numbness in both legs for several years. Contrast-enhanced magnetic resonance imaging (MRI) of the spinal cord was performed. Based on the imaging examination, cavernous malformation with subacute hematoma was considered as the initial diagnosis. However, histopathological and immunohistochemical analyses confirmed the final diagnosis of PIM in the thoracic cord after surgical resection. The patient had no signs of recurrence or metastasis during a 17-month follow-up. Conclusions: MRI is the preferred method for the evaluation of PIM. PIM is characterized by a high signal on T1WI and a low signal on T2WI. It is difficult to make the differential diagnosis from cavernous malformation with hematoma before surgery due to its rarity. However, the symptom is not sudden but gradually worsened over a relatively long period in the PIM patients, which is an important difference from the cavernous malformation with hematoma. Therefore, PIM should receive diagnostic con¬sideration for an intramedullary lesion that is high signal on T1WI and low signal on T2WI in a patient with gradually worsened symptoms rather than sudden onset. It is of great importance for neurosurgeons and radiologists to recognize the characteristics of this disease, make the correct diagnosis in time and avoid delayed treatment.

ORP5 promotes tumor metastasis via stabilizing c-Met in renal cell carcinoma.

ORP5, a lipid transporter, has been reported to increase the metastasis of several cancers. However, the potential mechanisms of ORP5 in renal cell carcinoma (RCC) remain unclear. In this study, we demonstrated that ORP5 was commonly overexpressed in tumor cells and tissues of RCC, and associated with tumor progression. Overexpression of ORP5 could promote RCC cells migration and invasion. In addition, the results suggested that the expression of ORP5 was favorably associated with c-Met expression, and ORP5 promoted RCC cells metastasis by upregulating c-Met in vitro and in vivo. Mechanistically, ORP5 facilitated the ubiquitination and degradation of c-Cbl (the E3 ligase of c-Met), and thus inhibited c-Met lysosomal degradation, which resulted in the stabilization of c-Met. In general, these findings revealed the role of ORP5 in contributing to tumorigenesis via upregulating c-Met in RCC.

Liposomes encapsulating artificial cytosol as drug delivery system.

The fabrication of cell models containing artificial cytosol is challenging. Herein we constructed an artificial cytosol contained cell model by electroformation method. Agarose was selected as the main component of the artificial cytosol, and sucrose was added into the agarose to regulate the sol viscosity and the phase transition temperature. The viscosity of the sol with the mass ratio (agarose-sucrose) 1:9 was closest to the natural cytosol. DSPC/20 mol% cholesterol was used to form large unilamellar vesicles (LUVs) as cell model compartment. The rhodamine release experiment confirmed that the unique release profile of agarose-sucrose@LUVs is suitable as a drug carrier. Doxorubicin is loaded in the agarose-sucrose@LUVs, and their half maximum inhibition concentration on HeLa cells is 0.016 µmol L-1, which means 28.7 times increase in inhibition efficiency over free doxorubicin.

Xanthogranuloma of the sellar region: A case report.

RATIONALE: Xanthogranuloma of the sellar region is exceedingly rare, and described in only a handful of case reports. Herein, we present a case of xanthogranuloma of the sellar region to improve our knowledge for the diagnosis and management of this unusual disease. PATIENT CONCERNS: A 50-year-old female presented with the symptoms of intermittent vomiting, occasional head discomfort, and diabetes insipidus of 1 month duration. DIAGNOSES: Magnetic resonance imaging showed a large well-defined, vase-like, heterogeneous mass in the sellar region. The lesion showed mixed signal with hierarchical signal presentation. Fluid-fluid level sign can be found within the lesion. The upper part of the lesion was hyperintense, and the lower part was hypointense on both T1-weighted images and T2-weighted images. The lesion showed no enhancement following the intravenous administration of gadolinium. The normal pituitary tissue was not clearly visible. Optic chiasm was compressed and displaced by the lesion. Initial diagnosis of pituitary macroadenoma with hemorrhage in the sellar region was made before surgery. Final diagnosis of sellar xanthogranuloma was confirmed by histopathological examination after surgical resection. INTERVENTIONS: Gross total resection of the lesion was achieved using the microscope through endonasal transsphenoidal approach. OUTCOMES: The patient recovered well with improved binocular vision and no symptom of diabetes insipidus, and was discharged 5 days after operation. LESSONS: Sellar xanthogranuloma should receive diagnostic consideration for the lesion that is a heterogeneously mixed mass with a degree of T1-weighted images hyperintense in the sellar region.

Case Report: Radiological Features of Sclerosing Epithelioid Fibrosarcoma in the Right Fibula.

BACKGROUND: Sclerosing epithelioid fibrosarcoma (SEF) is an extremely rare, aggressive malignant subtype of fibrosarcoma. Only dozens of cases of primary SEF in the bone have been reported so far, without case involving fibula reported in literature to date. Herein we report the first case of primary SEF in the right fibula in a 19-year-old man. In this case report, we firstly give a comprehensive description of fibula SEF, including its complete clinical course and radiological findings. CASE PRESENTATION: A 19-year-old man presented with a half-year history of soreness in the right lower leg. Contrast-enhanced computed tomography (CE-CT) and magnetic resonance imaging (MRI) of the right lower leg were performed. Based on the radiological examinations, a diagnosis of malignant tumor arising in the fibular diaphysis was made. Final diagnosis of primary SEF in the right fibula was confirmed by histopathological and immunohistochemical examinations after surgical resection. The patient had no signs of recurrence or metastasis during a 24-month follow-up. CONCLUSION: We report an exceedingly rare case of primary SEF in the right fibula and its radiological features with CE-CT and MRI.

Fas and GIT1 signalling in the prefrontal cortex mediate behavioural sensitization to methamphetamine in mice.

PURPOSE: Repeated methamphetamine (METH) administration in mice readily produces behavioural sensitization, but the underlying mechanisms remain elusive. The present research aimed to identify new targets affecting METH-induced behavioural sensitization. METHODS: We first established a mouse model of METH-induced behavioural sensitization. To characterize the animal model, we performed behavioural tests at different stages of behavioural sensitization and simultaneously detected changes in several neurotransmitters in the prefrontal cortex (PFC). Next, we perfromed RNA sequencing (RNA-seq) to screen new targets, which were subsequently and verified by RT-PCR and western blot. Finally, we confirmed the roles of the new targets in METH-induced behavioural sensitization by injection of overexpressed lentiviruses and further detected related protein levels by western blot and histological changes by haematoxylin and eosin (HE) staining. RESULTS: We successfully established a mouse model of METH-induced behavioural sensitization. The locomotor activities of the mice changed at different stages of sensitization, accompanied by changes in the levels of DA, 5-HT, GABA and glutamate. For RNA-seq analysis, we chose Fas as target, meanwhile, we chose GIT1 as target through literature. The detection of gene expression by RT-PCR indicated that METH-sensitized mice exhibited decreased levels of Fas, MEK1 and CREB and increased levels of Erk1/2 in the PFC. Western blot analysis revealed decreased Fas, GIT1, MEK1 and phosphorylated CREB levels and increased phosphorylated Erk1/2 levels in METH-sensitized mice. Injection of Fas and GIT1 injection showed that overexpression of Fas and GIT1 inhibited the induction of METH sensitization and reversed the changes in neurotransmitter levels and related protein levels, including MEK1, phosphorylated CREB and phosphorylated Erk1/2, in METH-sensitized mice. Overexpression of Fas and GIT1 also reduced histological lesions induced by METH. CONCLUSION: The findings indicated that the development of behavioural sensitization to METH may be mediated by Fas and GIT1 through the MEK1-Erk1/2-CREB pathway.

Predicting intraprocedural rupture and thrombus formation during coiling of ruptured anterior communicating artery aneurysms.

BACKGROUND: Intraprocedural rupture and thrombus formation are serious complications during coiling of ruptured intracranial aneurysms, and they more often occur in patients with anterior communicating artery (ACoA) aneurysms. OBJECTIVE: To identify independent predictors of intraprocedural rupture and thrombus formation during coiling of ruptured ACoA aneurysms. METHODS: Between January 2008 and February 2015, 254 consecutive patients with 255 ACoA aneurysms were treated with coiling. We retrospectively reviewed intraoperative angiograms and medical records to identify intraprocedural rupture and thrombus formation, and re-measured aneurysm morphologies using CT angiography images. Multivariate logistic regression models were used to determine independent predictors of intraprocedural rupture and thrombus formation. RESULTS: Of the 231 patients included, intraprocedural rupture occurred in 10 (4.3%) patients, and thrombus formation occurred in 15 (6.5%) patients. Patients with smaller aneurysms more often experienced intraprocedural rupture than those with larger aneurysms (3.5±1.3 mm vs 5.7±2.3 mm). Multivariate analysis showed that smaller ruptured aneurysms (p=0.003) were independently associated with intraprocedural rupture. The threshold of aneurysm size separating rupture and non-rupture groups was 3.5 mm. Multivariate analysis showed that a history of hypertension (p=0.033), aneurysm neck size (p=0.004), and parent vessel angle (p=0.023) were independent predictors of thrombus formation. The threshold of parent vessel angle separating thrombus and non-thrombus groups was 60.0°. CONCLUSIONS: Ruptured aneurysms <3.5 mm were associated with an increased risk of intraprocedural rupture, and parent vessel angle <60.0°, wider-neck aneurysms, and a history of hypertension were associated with increased risk of thrombus formation during coiling of ruptured ACoA aneurysms.

Larger size ratio associated with the rupture of very small (≤3†mm) anterior communicating artery aneurysms.

BACKGROUND: Anterior communicating artery (AcoA) aneurysms have a high rupture risk, and ruptured AcoA aneurysms tend to be smaller than other intracranial aneurysms. We aimed to determine the incidence and morphologic predictors of aneurysm rupture of very small AcoA aneurysms. METHODS: We conducted a retrospective analysis of 519 consecutive patients with single AcoA aneurysms between December 2007 and February 2015 in our hospital. Aneurysm morphologies were re-measured using CT angiography images. Very small aneurysms were defined as those with a maximum size ≤3 mm, and small aneurysms were defined as those with a maximum size ≤5 mm. Multivariate regression analyses were used to determine the association between aneurysm morphology and aneurysm rupture status. RESULTS: Of the 474 ruptured AcoA aneurysms, 134 (28.3%) aneurysms were very small and 278 (58.6%) aneurysms were small. In the univariate analysis for very small aneurysms, larger aneurysm size (p=0.037), larger size ratio (p=0.002), higher aneurysm height (p=0.038), smaller vessel size (p=0.012), and dominant A1 segment configuration (p=0.011) were associated with aneurysm rupture. Multivariate analysis revealed that a larger size ratio was independently associated with the rupture status of the very small aneurysms (OR 3.69, 95% CI 1.5 to 9.0; p=0.004), and larger aneurysm size, larger size ratio, and dominant A1 segment configuration were associated with the rupture of small aneurysms. CONCLUSIONS: About one-third of ruptured AcoA aneurysms were very small. A larger size ratio, rather than other aneurysm morphologies, was independently associated with the rupture of very small AcoA aneurysms.

The effect of anterior projection of aneurysm dome on the rupture of anterior communicating artery aneurysms compared with posterior projection.

OBJECTIVE: Recent studies have shown that anterior projection aneurysms are associated with increased risk of rupture of anterior communicating artery (ACoA) aneurysms. We aimed to determine differences in patient characteristics and aneurysm morphologies between the anterior projection and posterior projection aneurysm groups and to determine morphological predictors of rupture of the anterior projection aneurysms. MATERIALS AND METHODS: December 2007 to February 2015, 503 consecutive patients with single ACoA aneurysms were included in this report. The ACoA aneurysms were dichotomized as the anterior and posterior projection groups. Multivariate regression models were used to determine differences in patient and aneurysm characteristics between the 2 groups and to determine predictors of rupture in the anterior projection aneurysms. RESULTS: 363 (72.2%) patients had anterior projection aneurysms and 140 (27.8%) had posterior projection aneurysms. In univariate analysis, the anterior projection aneurysms were associated with a larger aneurysm size, a higher aneurysm height, a higher perpendicular height, a larger aspect ratio, and a larger size ratio. The multivariate analysis showed that the anterior projection aneurysms were independently associated with a larger size ratio compared with the posterior projection aneurysms. A larger size ratio and a smaller vessel size were independently associated with rupture status in the anterior projection aneurysms. CONCLUSIONS: Compared with posterior projection aneurysms, the anterior projection aneurysms have a higher risk of rupture probably because of significant differences in aneurysm morphologies. A larger size ratio and a smaller vessel size may be helpful to predict the risk of rupture in the anterior projection aneurysms.

Protective effect of compound K on diabetic rats.

Purpose: Compound K (CK), the metabolic product of protopanaxadiol saponin in vivo, has many pharmacological activities. In this study, we discuss the preparation of CK, and its protective effect on kidneys of diabetic rats. CK was prepared from ginsenoside Rbt after transformation by 3-glucosidase, separation and purification by silica gel column chromatography. In the present study, we established a rat model of diabetes mellitus using high-fat diet and streptozotocin (STZ). After seven weeks of treatment, the levels of fasting blood glucose (FBG), total cholesterol (TC), total glycerin (TG), high-density lipoprotein (HDL-C), low-density lipoprotein (LDL-C), blood urea nitrogen (BUN), uric acid (UA), serum creatinine (Scr), malondialdehyde (MDA), glutathione (GSH), and superoxide dismutase (SOD) activity and glutathione peroxidase (GSH-PX) were evaluated in normal and diabetic rats. Also, renal pathomorphism changes were observed by HE stain, and TGF-ß1 protein expression in the renal tissue was measured by Western blot. The yield of CK was 14.55 mg/mL, which was higher than that of other methods. After seven weeks, CK could decrease FBG, TC, TG, LDL-C, BUN, UA, Scr and MDA of diabetic rats, while CK also enhanced HDL-C and GSH, SOD and GSH-PX. Additionally, CK improved the pathological changes and decreased TGF-ß1 protein expression in the renal tissue. CK improved the pathological changes in the renal tissue, enhanced the antioxidant capacity, reduced the damage of TGF-ß1 to renal tissue, and protected the diabetic rats.