[Retracted] MicroRNA­744 inhibits tumor cell proliferation and invasion of gastric cancer via targeting brain­derived neurotrophic factor.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that certain of the cell migration assay data shown in Fig. 2D were strikingly similar to data that had appeared in different form in other articles by different authors. Owing to the fact that the contentious data in the above article had already been published elsewhere, or were already under consideration for publication, prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [the original article was published in Molecular Medicine Reports 16: 5055­5061, 2017; DOI: 10.3892/mmr.2017.7167].

Immune Checkpoint Inhibitors-Related Thyroid Dysfunction: Epidemiology, Clinical Presentation, Possible Pathogenesis, and Management.

Immune checkpoint inhibitors (ICIs) are a group of drugs employed in the treatment of various types of malignant tumors and improve the therapeutic effect. ICIs blocks negative co-stimulatory molecules, such as programmed cell death gene-1 (PD-1) and its ligand (PD-L1) and cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), reactivating the recognition and killing effect of the immune system on tumors. However, the reactivation of the immune system can also lead to the death of normal organs, tissues, and cells, eventually leading to immune-related adverse events (IRAEs). IRAEs involve various organs and tissues and also cause thyroid dysfunction. This article reviews the epidemiology, clinical manifestations, possible pathogenesis, and management of ICIs-related thyroid dysfunction.

The distinct manifestation of young-onset amyotrophic lateral sclerosis in China.

OBJECTIVE: Young-onset amyotrophic lateral sclerosis (ALS) refers to ALS patients with initial symptoms earlier than 45 years, representing a novel disease pattern. We aim to summarize the clinical and genetic features of 102 young-onset ALS patients in China. Methods: Clinical information and blood samples were collected from all registered patients, and we performed next generation sequencing techniques in an ALS customized panel to detect ALS-related genes. Results: A total of 95 sporadic ALS and seven familial ALS were involved in this study. Young-onset ALS showed male prevalence and had more spinal onset. With 44 patients carrying one or more variants, mutations in SPG11, ALS2, and SETX were the most frequent, followed by FUS variants. Other prevalent genes like SOD1, TARDBP, and C9ORF72 were relatively rare in young-onset patients. Conclusions: Our study highlighted distinct clinical manifestation and genetic background in young-onset ALS patients in China. These features should be verified in further investigations in other populations.

The impacts of ubiquilin 1 (UBQLN1) knockdown on cells viability, proliferation, and apoptosis are mediated by p53 in A549 lung cancer cells.

BACKGROUND: Little is known about the relationship between ubiquilin 1 (UBQLN1) and p53, both of them have been implicated in the development and progression of non-small cell lung cancer (NSCLC). In this study, we aimed to explore the role of loss of UBQLN1 in cell viability and proliferation, and cell apoptosis in human lung adenocarcinoma A549 cells. METHODS: Cell viability, proliferation, and apoptosis were determined by MTT, BrdU, and TUNEL assays, respectively. Adenoviruses carrying cDNA or siRNA were used to overexpress or silence target protein. Dihydroethidium (DHE) staining was performed to measure the real-time formation of intracellular reactive oxygen species (ROS). The chymotrypsin-like activity of 20S proteasome core was determined by using synthetic fluorogenic peptide substrate. RESULTS: UBQLN1 silencing led to a reduction of p53 protein levels and overexpression of p53 reversed the effects of UBQLN1 knockdown (KD) on cell viability, proliferation, and apoptosis. Furthermore, deficiency of UBQLN1 activated autophagy activity but did not affect proteasome activity. Inhibition of autophagy restored p53 protein levels in UBQLN1-KD A549 cells. In addition, UBQLN1 KD markedly inhibited phosphorylation of mammalian target of rapamycin (mTOR) and its downstream ribosomal S6 kinase (S6K). CONCLUSIONS: Our experiments suggested that the regulation of UBQLN1 on cell viability, proliferation, and apoptosis was mediated by mTOR/autophagy/p53 signaling pathway.

Muscular involvement and tendon contracture in limb-girdle muscular dystrophy 2Y: a mild adult phenotype and literature review.

BACKGROUND: Limb girdle muscular dystrophy type 2Y (LGMD2Y) is a rare subgroup of limb girdle muscular dystrophy featuring limb-girdle weakness, tendon contracture and cardiac involvement. It is caused by the mutation of TOR1AIP1, which encodes nuclear membrane protein LAP1 (lamina-associated polypeptide 1) and comprises heterogeneous phenotypes. The present study reported a patient with a novel homozygous TOR1AIP1 mutation that presented with selective muscle weakness, which further expanded the phenotype of LGMD2Y- and TOR1AIP1-associated nuclear envelopathies. CASE PRESENTATION: A 40-year-old male presented with Achilles tendon contracture and muscle weakness that bothered him from 8 years old. While the strength of his distal and proximal upper limbs was severely impaired, the function of his lower limbs was relatively spared. Muscle pathology showed dystrophic features, and electron microscopy showed ultrastructural abnormalities of disrupted muscle nuclei envelopes. Whole-exome sequencing showed a frameshift mutation in TOR1AIP1 (c.98dupC). CONCLUSION: We reported a novel mild phenotype of LGMD2Y with relatively selective distal upper limb weakness and joint contracture and revealed the heterogeneity of LGDM2Y and the role of the LAP1 isoform by literature review.

The role of carbon nanoparticles in guiding central neck dissection and protecting the parathyroid in transoral vestibular endoscopic thyroidectomy for thyroid cancer.

INTRODUCTION: Transoral vestibular endoscopic thyroidectomy (TOET) is sometimes used in young and middle-aged patients with papillary thyroid microcarcinoma (PTMC), but it is still difficult to identify lymph nodes (LNs) and parathyroid glands (PGs). Carbon nanoparticle (CN) is a novel lymph node tracer and has been widely used in open thyroid surgery. AIM: To evaluate the efficacy of CN in identifying LNs and preserving PGs in TOET with central neck dissection (CND). MATERIAL AND METHODS: A total of 72 PTMC patients undergoing TOET with CND were retrospectively enrolled from January 2017 to January 2019. Patients were divided into a CN group (n = 38) and a control group (n = 34). The parameters including pathological characteristics, surgery related indicators, serum Ca2+ and parathyroid hormone (PTH) levels were compared. RESULTS: No significant differences were found in patient characteristics, operative complications and superior PGs preserved in situ (all p > 0.05). Total LNs and number of LNs less than 5 mm were significantly higher in the CN group than in the control group (p = 0.021, p < 0.01). The number of superior PGs preserved in situ discovered in the CN group was greater than the control group (p = 0.038). Serum PTH and Ca2+ levels dropped markedly in each group after surgery and gradually recovered in time. The CN group recovered faster than the control group. CONCLUSIONS: CN may be a good choice for TOET for PTMC because of better protection and faster recovery of parathyroid function, and more LNs removed.

CircC3P1 attenuated pro-inflammatory cytokine production and cell apoptosis in acute lung injury induced by sepsis through modulating miR-21.

Acute lung injury (ALI) induced by sepsis is characterized by an inflammatory process related to the up-regulation of inflammatory cytokines and chemokines. In the present study, we explored the role of circC3P1 in sepsis-induced ALI in vitro and in vivo. The caecal ligation and puncture (CLP)-induced sepsis model was established through CLP surgery. Forty adult male C57BL/6 mice were randomly assigned into sham, CLP, CLP + vector and CLP + circC3P1 (each n = 10). Primary murine pulmonary microvascular endothelial cells (MPVECs) were transfected with circC3P1 or empty vector 24 hours prior to LPS treatment via Lipofectamine 2000. The expressions of circC3P1, tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6) and IL-1ß were evaluated after 6-h LPS treatment. Cell apoptosis was evaluated via flow cytometry. The CLP group demonstrated pulmonary morphological abnormalities, increased concentrations of TNF-α, IL-6 and IL-1ß in the lung tissue, compared with the sham group. MPVECs treated with LPS significantly elevated TNF-α, IL-6 and IL-1ß levels and increased cell apoptosis than that in the control group. The circC3P1 overexpression in sepsis-induced ALI mice attenuated pulmonary injury, inflammation and apoptosis. Besides, circC3P1 revealed anti-inflammatory and anti-apoptotic effect in MPVEC-treated LPS. CircC3P1 overexpression reduced cell apoptosis and pro-inflammatory cytokines levels via down-regulating miR-21. CircC3P1 attenuated pro-inflammatory cytokine production and cell apoptosis in ALI induced by sepsis through modulating miR-21, indicating that circC3P1 is a promising therapeutic biomarker for sepsis-induced ALI.

Endoplasmic reticulum stress-induced exosomal miR-27a-3p promotes immune escape in breast cancer via regulating PD-L1 expression in macrophages.

Immune escape of breast cancer cells contributes to breast cancer pathogenesis. Tumour microenvironment stresses that disrupt protein homeostasis can produce endoplasmic reticulum (ER) stress. The miRNA-mediated translational repression of mRNAs has been extensively studied in regulating immune escape and ER stress in human cancers. In this study, we identified a novel microRNA (miR)-27a-3p and investigated its mechanistic role in promoting immune evasion. The binding affinity between miR-27a-3p and MAGI2 was predicted using bioinformatic analysis and verified by dual-luciferase reporter assay. Ectopic expression and inhibition of miR-27a-3p in breast cancer cells were achieved by transduction with mimics and inhibitors. Besides, artificial modulation of MAGI2 and PTEN was done to explore their function in ER stress and immune escape of cancer cells. Of note, exosomes were derived from cancer cells and co-cultured with macrophages for mechanistic studies. The experimental data suggested that ER stress biomarkers including GRP78, PERK, ATF6, IRE1α and PD-L1 were overexpressed in breast cancer tissues relative to paracancerous tissues. Endoplasmic reticulum stress promoted exosome secretion and elevated exosomal miR-27a-3p expression. Elevation of miR-27a-3p and PD-L1 levels in macrophages was observed in response to exosomes-overexpressing miR-27a-3p in vivo and in vitro. miR-27a-3p could target and negatively regulate MAGI2, while MAGI2 down-regulated PD-L1 by up-regulating PTEN to inactivate PI3K/AKT signalling pathway. Less CD4+ , CD8+ T cells and IL-2, and T cells apoptosis were observed in response to co-culture of macrophages and CD3+ T cells. Conjointly, exosomal miR-27a-3p promotes immune evasion by up-regulating PD-L1 via MAGI2/PTEN/PI3K axis in breast cancer.

Klippel-Trenaunay and Sturge-Weber Overlap Syndrome with KRAS and GNAQ mutations.

Patients with combined phenotypes of Sturge-Weber syndrome and Klippel-Trenaunay syndrome have been reported, though the underlying genetic spectrum in these individuals remains to be elucidated. We reported the patient presenting with Klippel-Trenaunay and Sturge-Weber overlap syndrome in mainland China. Histopathologic study confirmed the hemangioma of vein and capillary. Co-existence of a novel somatic KRAS c.182_183 delins TC mutation and GNAQ c.548G>A mutation was identified in the affected skin tissue rather than paired peripheral blood. The somatic mutations of GNAQ and KRAS may affect MAPK-ERK signaling pathway, resulting in endothelial anomaly and blood vessel malformation.

Endoplasmic reticulum stress confers 5-fluorouracil resistance in breast cancer cell via the GRP78/OCT4/lncRNA MIAT/AKT pathway.

5-Fluorouracil (5-FU) is an effective anticancer drug. However, high drug resistance limits its chemotherapeutic efficacy. Cancer cell resistance in colon cancer to 5-FU has been attributed to endoplasmic reticulum (ER) stress. But little is known about any similar role in resistance of breast cancer (BC). Here, we aim to investigate the role of ER stress played in BC cell resistance to 5-FU and to describe relevant molecular mechanisms. The expression patterns of 78-kDa glucose-regulated protein (GRP78), octamer 4 (OCT4), long non-coding RNA (lncRNA) myocardial infarction associated transcript (MIAT), and Protein kinase B (AKT) in BC MCF-7 cells resistant to 5-FU were determined by Western blot assay. Next, gain- and loss of-function experiments were conducted to verify effects of GRP78, OCT4, MIAT, and AKT on the to 5-FU sensitivity of MCF-7 cells and 5-FU resistant MCF cells (MCF-7/5-FU). Besides, the in vivo roles of the GRP78/OCT4/lncRNA MIAT/AKT pathway were assessed in tumor-bearing nude mice. 5-FU induced ER stress increased the expression of GRP78 in MCF-7 cells. GRP78 could positively regulate the expression of MIAT and AKT through upregulating OCT4, thereby contributing to 5-FU resistance in BC cells. Additionally, the function of GRP78 silencing in promoting tumor cell sensitivity was confirmed in vivo. These data supported an important role of the ER stress-mediated GRP78/OCT4/lncRNA MIAT/AKT pathway in BC cell resistance to 5-FU, highlighting potential molecular targets for combating 5-FU resistance in BC.

USF1-mediated upregulation of lncRNA GAS6-AS2 facilitates osteosarcoma progression through miR-934/BCAT1 axis.

Long noncoding RNAs (lncRNAs) have been certified as important regulators in tumorigenesis. LncRNA GAS6-AS2 (GAS6-AS2) was a newly identified tumor-related lncRNA, and its dysregulation and oncogenic effects in melanoma and bladder cancer had been reported in previous studies. However, the expression pattern and potential function of GAS6-AS2 in osteosarcoma (OS) have not been investigated. In this study, we identified a novel OS-related lncRNA GAS6-AS2. We found that GAS6-AS2 was distinctly upregulated in both OS specimens and cell lines. Distinct up-regulation of GAS6-AS2 in OS was correlated with advanced clinical stages and shorter survivals. In addition, USF1 could directly bind to the GAS6-AS2 promoter and contribute to its overexpression. Furthermore, GAS6-AS2 knockdown caused tumor suppressive effects via reducing cellular proliferation, migration and invasion, and promoting OS cell apoptosis. Besides, GAS6-AS2 directly bound to miR-934 and downregulated its expression. Mechanistically, GAS6-AS2 positively regulated the expression of BCAT1 through sponging miR-934. Taken together, our data illustrated how GAS6-AS2 played an oncogenic role in OS and might offer a potential therapeutic target for treating OS.

Fish oil protects the blood-brain barrier integrity in a mouse model of Alzheimer's disease.

BACKGROUND: Alzheimer's disease (AD) is ranked as the most prevalent neurodegenerative disease. However, the exact molecular mechanisms underlying pathophysiological alterations in AD remain unclear, especially at the prodromal stage. The decreased proteolytic degradation of Aß, blood-brain barrier (BBB) disruption, and neuroinflammation are considered to play key roles in the course of AD. METHODS: Male APPswe/PS1dE9 C57BL/6 J double-transgenic (APP/PS1) mice in the age range from 1 month to 6 months and age-matched wild type mice were used in this study, intending to investigate the expression profiles of Aß-degrading enzymes for Aß degradation activities and zonula occludens-1 (zo-1) for BBB integrity at the prodromal stage. RESULTS: Our results showed that there were no significant genotype-related alterations in mRNA expression levels of 4 well-characterized Aß-degrading enzymes in APP/PS1 mice within the ages of 6 months. Interestingly, a significant decrease in zo-1 expression was observed in APP/PS1 mice starting from the age of 5 months, suggesting that BBB disrupt occurs at an early stage. Moreover, treatment of fish oil (FO) for 4 weeks remarkably increased zo-1 expression and significantly inhibited the glial activation and NF-κB activation in APP/PS1 mice. CONCLUSION: The results of our study suggest that FO supplement could be a potential therapeutic early intervention for AD through protecting the BBB integrity and suppressing glial and NF-κB activation.

Omega-3 polyunsaturated fatty acids promote brain-to-blood clearance of ß-Amyloid in a mouse model with Alzheimer's disease.

Amyloid-ß (Aß) plaques is one of the typical pathological hallmark of Alzheimer disease (AD). Accumulating evidence suggests that the imbalance between Aß production and clearance leads to extracellular Aß accumulation in the brain. It is reported that the blood-brain barrier (BBB) transport plays a predominant role in Aß clearance from brain to blood. In the present study, we investigated dynamic alterations of BBB transport function in the early disease stage of AD using APPswe/PS1dE9 C57BL/6J (APP/PS1) transgenic mice. Our results showed that the expression of lipoprotein receptor-related protein 1 (LRP-1), a main efflux transporter of BBB, started to decrease at the age of 4 months old. Interestingly, supplementing with fish oil which is rich in omega-3 polyunsaturated fatty acids (PUFAs) significantly enhanced the expression level of LRP-1 and promoted Aß clearance from the bran to circulation, as revealed by reduced soluble/insoluble Aß levels and senile plaques in the brain parenchyma and a corresponding increase of Aß levels in plasma. Besides, fish oil supplement significantly inhibited the NF-κB activation, reduced the expression of interleukin-1ß and tumor necrosis factor-α, and suppressed the glial activation in APP/PS1 mice. The results of the study provide evidence that BBB transport function could be impaired at a very early disease stage, which might contribute to Aß pathological accumulation in AD, and omega-3 PUFAs intervention could be an effective strategy for the prevention of the progression of AD through promoting Aß clearance from brain-to-blood.

Fish oil treatment reduces chronic alcohol exposure induced synaptic changes.

Alcohol addiction is a chronic neuropsychiatric disorder that represents one of the most serious global public health problems. Yet, currently there still lacks an effective pharmacotherapy. Omega-3 polyunsaturated fatty acids (N-3 PUFAs) have exhibited beneficial effects in a variety of neurological disorders, particularly in reversing behavioral deficits and neurotoxicity induced by prenatal alcohol exposure and binge drinking. In the present study, we investigated if fish oil, which is rich in N-3 PUFAs, had beneficial effects on preventing relapse and alleviating withdrawal symptoms after chronic alcohol exposure. Our results demonstrated that fish oil significantly reduced the chronic alcohol exposure-induced aberrant dendritic morphologic changes of the medium-sized spiny neurons in the core and the shell of nucleus accumbens. This inhibited the expression of AMPAR2-lacking AMPARs and their accumulation on the post synaptic membranes of medium-sized spiny neurons and eventually alleviated withdrawal symptoms and alcohol dependence. Our study therefore suggests that N-3 PUFAs are promising for treating withdrawal symptoms and alcohol dependence.

Simple prosthesis versus prosthesis plus titanium-coated polypropylene mesh for implant-based immediate breast reconstruction after total mastectomy for breast cancer.

BACKGROUND: Our study compares the cosmetic effects, postoperative complications, and quality of life of immediate breast reconstruction with simple prosthesis or prosthesis plus titanium-coated polypropylene mesh (TCPM) after total mastectomy for breast cancer. METHODS: In total, 69 patients who underwent total mastectomy, sentinel lymph node biopsy, and immediate prosthetic breast reconstruction from January 2015 to December 2018 in our hospital were selected, and their cosmetic effects, complications, and quality of life after reconstruction were recorded immediately after surgery and 6 months after surgery. RESULTS: Of these 69 patients, 29 were in the simple prosthesis group and 40 in the prosthesis + TCPM group. The incidence of surgical complications was 17.2% in the simple prosthesis group (5/29; including 4 cases of capsular contracture and 1 case of infection) 15.0% in the prosthesis + TCPM group (6/40; 1 case of flap necrosis, 2 cases of poor wound healing, 2 cases of hematomas, and 1 case of inadequate blood supply to nipple). The complications were successfully managed after symptomatic treatment in both groups. No prosthesis loss was noted. The incidence of postoperative complications showed there to be no significant differences between these two groups (P=0.06, χ2=0.80). The satisfaction rate of patients on cosmetic effects was 95.0% (38/40) in the prosthesis + TCPM group, significantly higher than that in the simple prosthesis group (75.90%, 22/29) (P=0.05, χ2=3.87). The quality of life in the simple prosthesis group at 2 weeks and six months after the operation was significantly lower than that in the prosthesis + TCPM group. The incidence rate of arm pain and fatigue at 2 weeks after operation was significantly higher than that in the prosthesis + TCPM group (P=0.04, χ2=4.42). The satisfaction of family life and sexual interest 6 months after the operation was also significantly lower in the simple prosthesis group than in the prosthesis + TCPM group (P=0.03, χ2=4.95). CONCLUSIONS: Breast reconstruction with prosthesis combined with TCPM does not increase surgical complications and has a good cosmetic effect and high patient satisfaction. Thus, it is a safe and reconstruction method.

Glucagon-Like Peptide-2 Receptor is Involved in Spatial Cognitive Dysfunction in Rats After Chronic Cerebral Hypoperfusion.

Chronic cerebral hypoperfusion (CCH) affects the aging population and especially patients with neurodegenerative diseases, such as Alzheimer's disease or Parkinson's disease. CCH is closely related to the cognitive dysfunction in these diseases. Glucagon-like peptide-2 receptor (GLP2R) mRNA and protein are highly expressed in the gut and in hippocampal neurons. This receptor is involved in the regulation of food intake and the control of energy balance and glucose homeostasis. The present study employed behavioral techniques, electrophysiology, western blotting, immunohistochemistry, quantitative real time polymerase chain reaction (qRT-PCR), and Golgi staining to investigate whether the expression of GLP2R changes after CCH and whether GLP2R is involved in cognitive impairment caused by CCH. Our findings show that CCH significantly decreased hippocampal GLP2R mRNA and protein levels. GLP2R upregulation could prevent CCH-induced cognitive impairment. It also improved the CCH-induced impairment of long-term potentiation and long-term depression. Additionally, GLP2R modulated after CCH the AKT-mTOR-p70S6K pathway in the hippocampus. Moreover, an upregulation of the GLP2R increased the neurogenesis in the dentate gyrus, neuronal activity, and density of dendritic spines and mushroom spines in hippocampal neurons. Our findings reveal the involvement of GLP2R via a modulation of the AKT-mTOR-p70S6K pathway in the mechanisms underlying CCH-induced impairments of spatial learning and memory. We suggest that the GLP2R and the AKT-mTOR-p70S6K pathway in the hippocampus are promising targets to treat cognition deficits in CCH.

Knockdown of B7H6 inhibits tumor progression in triple-negative breast cancer.

The B7 family, the most common family of secondary signaling molecules, consists of eight cell-surface proteins, which regulate the T-cell mediated immune response by delivering co-inhibitory or co-stimulatory signals through their corresponding ligands. Among them, natural killer cell cytotoxicity receptor 3 ligand 1 (NCR3LG1, also known as B7H6) has been reported as a new member, and is involved in tumor progression of various types of human cancer. However, the role of B7H6 in triple-negative breast cancer (TNBC) remains unknown. In the present study, western blotting was performed to determine the protein expression levels of B7H6 in a normal mammary epithelial cell line (MCF-10A), non-TNBC breast cancer cell lines (MCF-7 and AU565) and TNBC cell lines (MDA-MB-231 and MDA-MB-468). B7H6 was knocked down using small interfering RNA, and an MTT assay was performed to determine proliferation ability, flow cytometry was used to analyze apoptosis, and Transwell and wound-healing assays were performed to measure migration ability. Expression of proliferation-associated proteins (SMAD family member 4 and ß-catenin) and apoptosis-associated proteins (BCL2 associated X, BCL2 apoptosis regulator and caspase-3) were analyzed by western blotting. The results demonstrated that B7H6 was highly expressed in TNBC cells, and that knockdown of B7H6 inhibited cell proliferation and migration, and promoted apoptosis. Furthermore, the results revealed that proliferation and apoptosis-associated proteins were altered in the B7H6-knockdown MDA-MB-231 cells. In conclusion, the present study demonstrated that B7H6 may have significant roles in the regulation of cell proliferation, apoptosis and migration of TNBC cells.

Luteolin Could Improve Cognitive Dysfunction by Inhibiting Neuroinflammation.

Neuroinflammation and oxidative stress play an important role in cognition deficit following chronic cerebral hypoperfusion (CCH). Luteolin, a natural flavonoid found in many plants, is known for a variety of pharmacological activities, such as its anti-inflammatory, anti-allergy, urate, anti-tumor, antibacterial, and antiviral effects. To assess whether luteolin could prevent CCH-induced cognitive dysfunction, through its anti-inflammatory and anti-oxidative-stress effects, we used enzyme-linked immunosorbent assays, enzyme activity assays, behavioral methods, immunohistochemistry, and electrophysiology to detect neuroinflammation and oxidative stress, cognition alterations, and long-term potential (LTP), in a bilateral common carotid arteries ligation (2VO) rat model. We demonstrated that CCH increased tumor necrosis factor α (TNF-α), interleukin 1ß (IL-1ß), interleukin 6 (IL-6), and malondialdehyde (MDA), and decreased superoxide dismutase (SOD) and glutathione peroxidase (GPx) levels. Further, it caused microglia over-activation and astrogliosis, learning and short-term memory dysfunction, and an LTP deficit. Luteolin treatment reversed CCH-induced changes. Specifically, luteolin prevented the increase of TNF-α and IL-1ß, IL-6, and MDA, improved the activity of SOD and GPx, inhibited microglia over-activation and astrogliosis (particularly in the hippocampus and cortex), and ameliorated learning and short-term memory dysfunction, and LTP deficit. Thus, our study suggested that luteolin could be a preferable anti-inflammatory agent to protect cognitive function and synaptic plasticity following CCH. Luteolin could also be putative therapeutic candidate for other inflammation-related brain diseases.

Thermal tomography for monitoring tumor response to neoadjuvant chemotherapy in women with locally advanced breast cancer.

BACKGROUND & AIMS: This study aims to analyze the feasibility and predictive value of thermal tomography (TT) for monitoring early treatment response in patients with locally advanced breast cancer (LABC) receiving neoadjuvant chemotherapy (NAC). METHODS: Patients with LABC who were due to receive six cycles of NAC were examined by TT prior to NAC, the second cycle of NAC, the fourth cycle of NAC and surgery. Changes in TT parameters and ultrasonography were correlated with pathologic response to NAC, and the predictive value was assessed. RESULTS: Forty-four patients were evaluable for response (25 pathologic responders and 19 nonresponders). As early as after the first cycle of NAC, changes in the TT parameters ΔTs, ΔTn, and ΔTa correlated significantly with pathologic response (P < 0.05). The best predictor of pathologic response after the 6th cycle of NAC was TT (area under the receiver operating characteristic curve, 0.794), as opposed to cross-sectional areas and the longest diameter by ultrasonography. CONCLUSIONS: TT allows for monitoring early tumor response to NAC and can predict pathologic response in the early stages of therapy. Therefore, TT could be used as a novel imaging modality to monitor NAC treatment.

MicroRNA­744 inhibits tumor cell proliferation and invasion of gastric cancer via targeting brain­derived neurotrophic factor.

Gastric cancer is the fourth most common malignancy and the third leading cause of cancer­associated deaths worldwide. It has previously been demonstrated that microRNAs (miRNAs) are actively involved in the pathogenesis of gastric cancer. Therefore, miRNAs have been proposed as promising therapeutic targets in gastric cancer patients. MiR­744 is aberrantly expressed in different types of human cancer. However, the expression pattern and biological roles of miR­744 in gastric cancer remain unknown. The present study demonstrated that miR­744 expression was low in gastric cancer tissues and cell lines. Low expression levels of miR­744 was significantly correlated with lymph node metastasis, invasive depth and TNM staging in gastric cancer patients. The restoration of miR­744 expression inhibited cell proliferation and invasion in vitro. Bioinformatic prediction, luciferase reporter assay, reverse transcription­quantitative polymerase chain reaction and western blot analysis verified that brain­derived neurotrophic factor (BDNF) is a direct target of miR­744 in gastric cancer cells. Furthermore, BDNF was upregulated in gastric cancer tissues and inversely correlated with miR­744 expression. Furthermore, enforced BDNF expression reversed the tumor­suppressing effects of miR­744 on the proliferation and invasion of gastric cancer cells, indicating that BDNF is a functional mediator of miR­744 in gastric cancer. The present study suggests that miR­744 is a potential prognostic biomarker and treatment target in gastric cancer patients.