Livin expression promotes keratinocyte release of inflammatory mediators in psoriasis.

BACKGROUND: Psoriasis is a prevalent, long-term skin condition characterized by inflammation. Keratinocytes (KCs) are important effector cells that release inflammatory factors and chemokines to promote the inflammatory cascade in psoriasis. However, the mechanisms underlying the activation of KCs in psoriasis remain unclear. Livin suppresses apoptotic proteins and directly affects the growth and spread of cancer cells. Livin expression reportedly increases significantly in lesions of patients with psoriasis; however, its specific role in KC activation remains unknown. This study aimed to examine the impact of Livin on KC activation and the subsequent release of inflammatory mediators. METHODS: Immunofluorescence staining, reverse transcription-quantitative polymerase chain reaction, enzyme-linked immunosorbent assay (ELISA), and western blotting were used to assess Livin expression in patients with psoriasis, an imiquimod (IMQ)-induced psoriasis-like mouse model, and M5-treated HaCaT cells. To investigate the role of Livin in KCs, we performed RNA sequencing and proteomic analysis of Livin-knockdown (knockdown-HaCaT) and negative control (NC-HaCaT) cells. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes were used for enrichment analyses. Moreover, the effect of Livin expression on the release of inflammatory mediators in KCs was verified using ELISA. RESULTS: Livin expression was higher in KCs of patients with psoriasis than in those healthy controls. Livin expression in HaCaT cells treated with M5 increased significantly over time. Livin expression was higher in the skin lesions of the IMQ mouse model than in the control group. Proteomic analysis and RNA sequencing used to investigate the function of Livin in HaCaT cells revealed its potential role in mediating KC activation and inflammatory mediator release, which affected the pathology of psoriasis. CONCLUSIONS: Livin expression played an effect on KCs activation, which induced release of inflammatory mediators and up-regulation of keratin. This study provides a new effector molecule for the mechanism of inflammatory response in psoriasis.

Knockdown of long non-coding RNA LINC00941 suppressed cell proliferation, colony-formation, and migration of human glioblastoma cell lines.

INTRODUCTION: Glioblastoma (GBM) represents the most common and lethal type of primary brain tumour in adults, and due to its high invasiveness, treatment of GBM remains challenging. This work is aimed to elucidate the role of LINC00941 in GBM. MATERIAL AND METHODS: Expression of LINC00941 in two GBM cell lines U251 and U87-MG was knocked down using siRNA. Cell proliferation and colony-formation ability of LINC00941 knockdown were examined. Apoptosis of the knockdown was evaluated using flow cytometry, with the levels of Bax, Bcl-2, cleaved caspase-3, and phosphorylation of ERK and Akt to be examined using western blotting. Migration and invasion of the knockdown was studied using transwell assays. RESULTS: Expression of LINC00941 was significantly elevated in GBM compared to non-tumour tissues ( p < 0.01). Statistical analysis on the expression data further revealed the negative correlation between LINC00941 and miR-526b-5p ( r = 0.7494, p < 0.001). LINC00941 was successfully knocked down with RNA interference in U251 and U87-MG. The knockdown significantly suppressed cell proliferation and the ability to form colonies. Percentage of apoptotic cells was elevated by the knockdown in both cell lines as evidenced by flow cytometric analysis, which was accompanied by a significant decrease in Bcl-2 and substantial increases in Bax and cleaved caspase-3. Phosphorylation of ERK and Akt was also enhanced in both cell lines by the knockdown. In addition, knockdown of LINC00941 suppressed migration of both cell lines across transwell membrane and matrigel. CONCLUSIONS: LINC00941 is overexpressed in GBM, exhibiting important roles in cell proliferation and survival, migration and invasion.

Plumbagin induces apoptosis, cell cycle arrest, and inhibits protein synthesis in LoVo colon cancer cells: A proteomic analysis.

Extracted from the roots of Plumbago zeylanica L., plumbagin is a natural naphthoquinone with potential as an anticancer compound. However, no studies have investigated its impact on LoVo (colon cancer) cells, and the specific mechanisms by which plumbagin exerts its anticancer effects remain to be established. The anticancer potential of plumbagin against LoVo cells was evaluated using a battery of assays, including MTT assay, clone formation assay, transwell chamber invasion assay, and wound-curing assay. Cell cycle analysis and cell apoptosis analysis were conducted to break down the anticancer impact of plumbagin on LoVo cells. A label-free proteomics technology was employed to investigate alterations in protein expression in LoVo cells treated with plumbagin. Our investigation indicated that plumbagin markedly inhibited the LoVo cells proliferation, and induced the apoptosis in LoVo cells, simultaneously induced G0/G1 phase cell cycle arrest. The LC-MS/MS proteomics assay revealed 78 proteins that were differentially expressed upon treatment with plumbagin. Bioinformatics and functional analyses indicated that these proteins were predominantly involved in protein synthesis and translation. Our findings revealed that multiple mechanisms are involved in the anticancer activity of plumbagin against LoVo cells, resulting in decreased cell viability. Proteomic analysis suggests that plumbagin may impede protein synthesis by reducing the expression of eukaryotic initiation factors. Our findings demonstrate that plumbagin exerts its anticancer activity against LoVo cells through multiple mechanisms, including inhibition of cell proliferation, induction of apoptosis, cell cycle arrest, and disruption of protein synthesis. These results provide new insights into the therapeutic potential of plumbagin for colon cancer treatment.

Livin upregulation in keratinocytes of psoriasis patients to promote adhesion molecule expression.

BACKGROUND: Activation of keratinocytes (KCs) is the main pathological feature of psoriasis. KCs recruit neutrophils by releasing various antimicrobial peptides and chemokines, which is also related to the expression of KC adhesion molecules. However, the regulatory mechanism governing their expression is still unclear. Livin, an inhibitor of the apoptosis protein family member involved in proliferation and metastasis of tumor cells, is significantly increased in psoriatic lesions. OBJECTIVES: The aim of this study was to investigate the role of Livin in regulating adhesion molecule expression in KCs and release of chemokines that promote the activation and adhesion of neutrophils. METHODS: The expression of Livin in psoriasis patients, imiquimod mouse model, and the combination of IL-17 alpha, IL-22, IL-1 alpha, OSM, and TNF-α (Mix M5)-treated HaCaT cells were detected by immunofluorescence staining, RT-qPCR, and ELISA. Livin-overexpression and knockdown in HaCaT cells transfected with HIV-1-based lentiviral vectors were used to study the function of Livin using RNA-seq. Moreover, differences in the expression of HaCaT cell adhesion molecules after regulation of Livin expression and activation of neutrophils in the co-culture model were verified. RESULTS: Livin was upregulated in the KCs of psoriasis patients, imiquimod mouse model and Mix M5-treated HaCaT cells compared with the control groups. Livin in HaCaT cells might regulate the expression of adhesion molecules in KCs. CONCLUSION: Thus, Livin may be a key effector molecule that regulates the expression of adhesion molecules in KCs and promotes the activation and adhesion of neutrophils.

Honokiol attenuates mitochondrial fission and cell apoptosis by activating Sirt3 in intracerebral hemorrhage.

BACKGROUND: Sirtuin-3 (Sirt3) has been documented to protect against mitochondrial dysfunction and apoptosis. Honokiol (HKL) is a Sirt3 pharmacological activator with reported neuroprotective effects in multiple neurological disorders. The present study aimed to explore the neuroprotective effects of HKL and the role of Sirt3 following intracerebral hemorrhage (ICH). METHODS: An in vivo ICH model in rats was established by injecting autologous blood into the right basal ganglia. PC12 cells were stimulated with hemin. For the in vivo investigation, the modified Neurological Severity Scores and the Morris water maze test were performed to assess neurological deficits. Hematoxylin-Eosin and Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining were employed to evaluate the histopathology and apoptosis. Immunohistochemical staining was used to investigate the expression of Sirt3. Adenosine triphosphate (ATP) levels were quantified to assess mitochondrial dysfunction. Cell counting kit-8, lactate dehydrogenase assay, and flow cytometry were used to analyze cell vitality and apoptosis in vitro. Immunofluorescence staining was performed to observe mitochondrial morphology and dynamin-related protein 1 (Drp1) localization to mitochondria. Western blot was applied to quantify the expression of Sirt3, Bax, Bcl-2, cleaved-caspase-3, Drp1, phosphorylation of Drp1 at serine-616, and phosphorylation of Drp1 at serine-637 in vivo and in vitro. RESULTS: HKL treatment alleviated neurological deficits, attenuated the histopathological damage and cell apoptosis, and restored the decreased ATP levels in ICH rats. HKL improved cell survival rate, reduced cell apoptosis, and inhibited mitochondrial fission in PC12 cells. Moreover, both in vivo and in vitro models showed increased phosphorylation of Drp1 at Ser616, and reduced phosphorylation of Drp1 at Ser637. Meanwhile, immunofluorescence co-localization analysis revealed that hemin increased the overlap of Drp1 and mitochondria in PC12 cells. The phosphorylation and mitochondrial translocation of Drp1 were effectively reversed by HKL treatment. Importantly, the selective Sirt3 inhibitor 3-(1H-1,2,3-triazol-4-yl) pyridine suppressed these effects. CONCLUSION: Our findings demonstrated that HKL ameliorated ICH-induced apoptosis and mitochondrial fission by Sirt3, suggesting that HKL has immense prospects for the treatment of ICH.

Establishment of a modified Kyoto classification scoring model and its significance in the diagnosis of Helicobacter pylori current infection.

BACKGROUND AND AIMS: We aimed to establish a modified model of the Kyoto classification score and verify its accuracy for predicting Helicobacter pylori (HP) infection during endoscopy. METHODS: Patients who underwent gastroscopy from June 2020 to March 2021 were included in this study. Atrophy, intestinal metaplasia, hypertrophy of the gastric fold, nodularity, diffuse redness, sticky mucus, spotty redness, xanthoma, map-like redness, fundic gland polyp, and regular arrangement of collecting venules (RAC) were recorded according to the Kyoto classification of gastritis. The HP infection status of participants was determined by a 13C breath test, anti-HP antibody, and histopathologic hematoxylin and eosin staining. The modified Kyoto classification scoring model was established based on univariate analysis and logistic regression analysis. The modified scoring model was used to judge the status of HP infection in patients undergoing gastroscopy from July to September 2021 and to evaluate the accuracy of the prediction. RESULTS: Of 667 participants in the derivation dataset, 326 cases had HP infection and 341 cases did not. Atrophy, hypertrophy of the gastric fold, nodularity, diffuse redness, sticky mucus, and spotty redness were associated with HP current infection. Thus, a new scoring model, termed the modified Kyoto classification scoring model, was constructed that included atrophy, hypertrophy of the gastric fold, nodularity, diffuse redness, sticky mucus, spotty redness, fundic gland polyp, and RAC as indicators. To test the model, 808 subjects, including 251 HP-positive patients, comprised the validation dataset. CONCLUSIONS: The modified Kyoto classification scoring model improved the accuracy of endoscopic determination of HP current infection and has clinical application potential in the Chinese population.

Long non-coding RNA-LINC00941 promotes the proliferation and invasiveness of glioma cells.

Glioma is one of the most common intracranial malignant tumors worldwide, accounting for 30%-40% of primary brain tumors. Long non-coding RNAs (lncRNAs) have been implicated in cancer malignant progression. Glioma is classified into multiple subtypes, but lncRNA expression pattern in different subtypes are not fully described. Here, we reported that lncRNA-LINC00941 was highly expressed in all glioma subtypes. Overexpression of lncRNA-LINC00941 in U87 cells promoted cellular proliferation and invasiveness, and suppressed apoptosis. Our findings suggest that lncRNA-LINC00941 may function as an oncogenic factor in glioma, and targeting lncRNA-LINC00941 could be developed into a strategy for glioma management.

Bifico relieves irritable bowel syndrome by regulating gut microbiota dysbiosis and inflammatory cytokines.

PURPOSE: Gut microbiota dysbiosis, a core pathophysiology of irritable bowel syndrome (IBS), is closely related to immunological and metabolic functions. Gut microbiota-based therapeutics have been recently explored in several studies. Bifico is a probiotic cocktail widely used in gastrointestinal disorders which relate to the imbalance of gut microbiota. However, the efficacy and potential mechanisms of Bifico treatment in IBS remains incompletely understood. METHODS: Adopting a wrap restraint stress (WRS) -induced IBS mice model. Protective effect of Bifico in IBS mice was examined through abdominal withdrawal reflex (AWR) scores. 16S rDNA, 1H nuclear magnetic resonance (1H-NMR) and western blot assays were performed to analyze alterations of gut microbiota, microbiome metabolites and inflammatory cytokines, respectively. RESULTS: Bifico could decrease intestinal visceral hypersensitivity. Although gut microbiota diversity did not increase, composition of gut microbiota was changed after treatment of Bifico, which were characterized by an increase of Proteobacteria phylum and Actinobacteria phylum, Muribaculum genus, Bifidobacterium genus and a decrease of Parabacteroides genus, Sutterella genus and Lactobacillus genus. Moreover, Bifico elevated the concentration of short-chain fatty acids (SCFAs) and reduced protein levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). From further Spearman's correlation analysis, Bifidobacterium genus were positively correlated with SCFAs including propionate, butyrate, valerate and negatively correlated with IL-6 and TNF-α. CONCLUSION: Bifico could alleviate symptoms of IBS mice through regulation of the gut microbiota, elevating production of SCFAs and reducing the colonic inflammatory response.

Congenital cataract-causing mutation ßB1-L116P is prone to amyloid fibrils aggregation and protease degradation with low structural stability.

Congenital cataract, a common disease with lens opacification, causes blindness in the newborn worldwide and is mainly caused by abnormal aggregation of crystallin. As the main structural protein in the mammalian lens, ßB1-crystallin has an important role in the maintenance of lens transparency. Recently, the L116P mutation in ßB1-CRY was found in a Chinese family with congenital nuclear cataracts, while its underlying pathogenic mechanism remains unclear. In the current study, the ßB1 wild-type protein was purified, and the mutated form, ßB1-L116P, was examined for examining the effect on structural stability and susceptibility against environmental stresses. Our results reveal low solubility and structural stability of ßB1-L116P at physiological temperature, which markedly impaired the protein structure and the oligomerization of ßB1-crystallin. Under guanidine hydrochloride-induced denaturing conditions, ßB1-L116P mutation perturbed the protein unfolding process, making it prone to amyloid fibrils aggregation. More importantly, the L116P mutation increased susceptibility of ßB1-crystallin against UV radiation. ßB1-L116P overexpression led to the formation of more serious intracellular aggresomes under UV radiation or oxidative stress. Furthermore, the ßB1-L116P mutation increased the sensitivity to the proteolysis process. These results indicate that the low structural stability, susceptibility to amyloid fibrils aggregation, and protease degradation of ßB1-L116P may contribute to cataract development and associated symptoms.

Orexin-A exerts neuroprotective effect in experimental intracerebral hemorrhage by suppressing autophagy via OXR1-mediated ERK/mTOR signaling pathway.

Background: Orexin-A (OXA) is a polypeptide produced in the hypothalamus, which binds to specific receptors and exerts multiple physiological effects. Autophagy plays a vital role in early brain injury (EBI) after intracerebral hemorrhage (ICH). However, the relationship between OXA and autophagy after ICH has not been confirmed. Methods: In this study, the protective role of OXA was investigated in a model of hemin-induced injury in PC12 cells and blood-injection ICH model in rats, and its potential molecular mechanism was clarified. Neurobehavioral tests, brain water content, and pathologic morphology were assessed after ICH. Cell survival rate was determined using Cell Counting Kit-8 (CCK-8), while apoptosis was detected using flow cytometry. The autophagy protein LC3 that was originally identified as microtubule-associated protein 1 light 3 was evaluated by immunohistochemistry. The ultrastructural changes of cells following ICH were observed by transmission electron microscopy. Western blotting was performed to determine the expression levels of LC3, p62/SQSTM1 (p62), phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2), total extracellular signal-regulated kinase 1/2 (t-ERK1/2), mammalian target of rapamycin (mTOR), and phosphorylated mammalian target of rapamycin (p-mTOR). Results: OXA treatment significantly improved neurofunctional outcomes, reduced brain edema, and alleviated neuronal apoptosis. OXA administration upregulated p-mTOR and p62, while it downregulated p-ERK1/2 and LC3; this effect was reversed by the orexin receptor 1 (OXR1) antagonist SB-334867. Conclusions: This study demonstrates that OXA suppresses autophagy via the OXR1-mediated ERK/mTOR signaling pathway to exert neuroprotective effects, and it might provide a novel therapeutic approach in patients suffering from ICH.

Tumor stemness and immune infiltration synergistically predict response of radiotherapy or immunotherapy and relapse in lung adenocarcinoma.

Cancer stem cells (CSCs) have been shown to accelerate tumor recurrence, radiotherapy, and chemotherapy resistance. Immunotherapy is a powerful anticancer treatment that can significantly prolong the overall survival of patients with lung adenocarcinoma (LUAD). However, little is known about the function of genes related to tumor stemness and immune infiltration in LUAD. After integrating the tumor stemness index based on mRNA expression (mRNAsi), immune score, mRNA expression, and clinical information from the TCGA database, we screened 380 tumor stemness and immune (TSI)-related genes and constructed a five TSI-specific-gene (CPS1, CCR2, NT5E, ANLN, and ABCC2) signature (TSISig) using a machine learning method. Survival analysis indicated that TSISig could stably predict the prognosis of patients with LUAD. Comparison of mRNAsi and immune score between high- and low-TSISig groups suggested that TSISig characterized tumor stemness and immune infiltration. In addition, enrichment of immune subpopulations showed that the low-TSISig group held more immune subpopulations. GSEA revealed that TSISig had a strong association with the cell cycle and human immune response. Further analysis revealed that TSISig not only had a good predictive ability for prognosis but could also serve as an excellent predictor of tumor recurrence and response to radiotherapy and immunotherapy in LUAD patients. TSISig might regulate the development of LUAD by coordinating tumor stemness and immune infiltration. Finally, a connectivity map (CMap) analysis demonstrated that the HDAC inhibitor could target TSISig.

Ultrasound-assisted extraction of polysaccharide from spent Lentinus edodes substrate: Process optimization, precipitation, structural characterization and antioxidant activity.

Lentinus edodes is the second-most popular and cultivated mushroom worldwide due to its nutritional and health-promoting benefit. However, the mushroom production generates vast amounts of spent L. edodes substrate (SLS) that is generally discharged into the environment, posing a great challenge within mushroom by-product valorization. In this work, SLS polysaccharide (SP) was ultrasonically extracted by optimizing the process conditions with response surface methodology. Using gradient ethanol precipitation, SP was separated into SP40, SP60 and SP80, and their monosaccharide composition, structural properties, and antioxidant potential were further characterized and compared. The results showed the total polysaccharide content reached up to 37.05 ± 0.31 mg/g under the optimal conditions including an extraction temperature of 50 °C, a liquid-solid ratio of 30 mL/g and an ultrasonic power of 120 W. SP and its fractional precipitations were heteropolysaccharides sharing a similar monosaccharide composition including L-rhamnose, D-glucuronic acid, D-galacturonic acid, d-glucose and D-xylose, and a typical infrared spectrum for polysaccharide. These fractions also varied in the surface morphology, where SP80 was looser and more porous than SP40 and SP60. Furthermore, SP and SP80 displayed the strongest antioxidant activities in vitro. This study identified a novel and practical strategy to valorize SLS for valuable polysaccharide.

Prevalence and Clinical Characteristics of Myelinated Retinal Nerve Fibres in a Chinese Teleophthalmology System.

Purpose: To investigate the prevalence and clinical characteristics of myelinated retinal nerve fibre (MRNF) in a large teleophthalmology system.Methods: All records between January 2015 and December 2015 from Daheng Prust teleophthalmology system were reviewed by 2 ophthalmologists independently. MRNF was classified into continuous group and discontinuous group according to the relationship between MRNF patches and optic disc. The number, total area and location of MRNF patches were analysed. Concomitant ocular diseases were documented.Results: Out of 51469 subjects, MRNF was detected in 304 eyes of 263 subjects with a prevalence rate of 0.51 ± 7.1% per subject and 0.30 ± 5.4% per eye. Among 304 eyes with MRNF, 239 (78.6%) eyes were in continuous group and 65 (21.4%) eyes were in discontinuous group. Single MRNF patch was found in 249 (81.9%) eyes and multiple MRNF patches were found in 55 (18.1%) eyes. MRNF of small size was found in 150 (49.3%) eyes. The ratios of multiple MRNF patches and small-sized MRNF in the continuous group were significantly higher than those in the discontinuous group (P = .014 and P < .001). In continuous group, the MRNF patches were located most frequently in the superior region (68.6%) of the optic disc; In discontinuous group, the MRNF patches were located most frequently in the inferotemporal region (38.5%) of the retina. Epiretinal membrane (12 eyes, 3.9%) was the most common concomitant ocular disease.Conclusion: MRNF is uncommon in China. MRNF usually presents unilaterally and as a single small whitish patch that is connected with optic disc.

CuInS/ZnS quantum dots modified intraocular lens for photothermal therapy of posterior capsule opacification.

Posterior capsule opacification (PCO) after cataract surgery is one of the leading causes of visual impairment and blindness. The cause of PCO is the capsule fibrosis developed on implanted Intraocular Lens (IOLs) by the de-differentiation of Lens Epithelial Cells (LECs) undergoing epithelial mesenchymal transition. How to prevent PCO has been a challenge to scientists and ophthalmologists for decades. Here we demonstrated the use of carboxylated CuInS/ZnS quantum dots (ZCIS QDs), which are free of toxic heavy metals and are more biocompatible, as photothermal nanomedicines. The ZCIS QDs are modified onto the non-optical section of IOLs by a facial activation-immersion method. Under mild NIR laser irradiation, ZCIS QDs modified IOLs (QDs-IOLs) will generate localized heat and prevent the proliferation of LECs onto the surface of QDs-IOLs. Our findings provide experimental evidence for further application of combined nanotechnology and photothermal therapy for the clinical treatment of PCO.

Elevated miR-29a Contributes to Axonal Outgrowth and Neurological Recovery After Intracerebral Hemorrhage via Targeting PTEN/PI3K/Akt Pathway.

Spontaneous intracerebral hemorrhage (ICH) is a clinical challenge with high disability and lacks an effective treatment. miR-29a strongly expressed in the brain has been implicated in various neurological disorders. In this study, we investigated the biological roles of miR-29a in axonal outgrowth and neurological outcomes after ICH and relevant molecular mechanism. The rat model of ICH was established by injection of autologous whole blood into the right basal ganglia. First, a significant decrease in miR-29a level was found in perihematomal brain tissues and cerebrospinal fluid (CSF) after ICH in vivo and hemin-treated neurons in vitro. Further study documented that lentivirus-mediated miR-29a overexpression could remarkably attenuate hemorrhagic brain injury, promoted regenerative outgrowth of injured axons and improved neurobehavioral and cognitive impairments after ICH in rats. In addition, we also identified that overexpression of miR-29a obviously alleviated neuronal damage and mitochondrial dysfunctions, and facilitated neurite outgrowth in cultured neurons exposed to hemin in vitro. Furthermore, luciferase reporter assay showed that miR-29a directly targeted the 3'-UTR region of phosphatase and tensin homolog (PTEN) mRNA and negatively regulated its expression. More importantly, pharmacological inhibition of PTEN has similar neuroprotective effects as miR-29a overexpression involving activation of the PI3K/Akt pathway after hemorrhagic stroke. Collectively, these results suggested that elevated miR-29a could contribute to axonal outgrowth and neurological recovery through targeting PTEN/PI3K/Akt pathway after ICH, thereby providing a potential therapeutic target for patients with ICH.

Piceatannol protects against cerebral ischemia/reperfusion­induced apoptosis and oxidative stress via the Sirt1/FoxO1 signaling pathway.

Reperfusion is a critical therapeutic intervention used following acute ischemic stroke; however, it may cause cerebral ischemia/reperfusion injury (CIRI) and aggravate brain damage. Piceatannol (Pic), a hydroxylated analog of resveratrol, has been reported to exhibit anti­inflammatory effects. However, the detailed molecular mechanisms and its effects on CIRI have not been sufficiently assessed, and, to the best of our knowledge, current methods of prevention of CIRI are limited. The aim of the present study was to investigate the effects of Pic on improving neurological function in a mouse model of CIRI. For the animal experiments, 8­week­old C57BL/6 mice were raised and randomly grouped, and an in vivo model of CIRI was established. Mice were administered a low (10 mg/kg/day) or high­dose (20 mg/kg/d) of Pic 1 h after CIRI orally and once daily for the next 6 days. Neurological dysfunction was assessed using a modified neurological severity score and a rotarod test 1 week after CIRI establishment, and the cognitive status of the mice was assessed using a Morris water maze. Hematoxylin and eosin staining was used to evaluate the histopathological changes. The expression levels of sirtuin 1 (Sirt1), FoxO1, cleaved caspase­3 (CC­3), Bax and Bcl­2 were measured using western blotting. Intracellular reactive oxygen species (ROS) generation, antioxidant enzymes [superoxide dismutase, glutathione (GSH) peroxidase and catalase] and non­enzymatic antioxidants (GSH) were also detected using spectrophotometry. After inhibition of the Sirt1/FoxO1 pathway, a TUNEL assay was used for the detection of apoptotic cells in vitro and in vivo. The co­localization of neuron­specific nuclear protein and CC­3 was assessing using immunofluorescent staining. Pic improved neurological functions and ameliorated hippocampal neuronal pathology following CIRI. In addition, the expression levels of CC­3 and Bax and intracellular ROS levels were increased, while levels of antioxidant and non­enzymatic enzymes were decreased in the mouse model of CIRI. Low and high doses of Pic significantly decreased ROS production and the expression levels of apoptosis­related proteins, but increased antioxidant enzyme levels. However, a high­dose of Pic did not result in increased levels of non­enzymatic enzymes. Furthermore, low and high doses of Pic treatment significantly activated the Sirt1/FoxO1 pathway. Following inhibition of the Sirt1/FoxO1 pathway, the percentage of TUNEL­positive cells and expression of CC­3 were increased, and CC­3 was enriched in neurons. The antioxidant effects of Pic were blocked by inhibition of Sirt1 in vitro and in vivo. In conclusion, these results suggested that Pic may exert a neuroprotective effect against in hippocampal neurons via the Sirt1/FoxO1 pathway.

MicroRNA-623 Inhibits Epithelial-Mesenchymal Transition to Attenuate Glioma Proliferation by Targeting TRIM44.

OBJECTIVE: Glioma has the highest incidence among the different tumor types within the nervous system, accounting for about 40% of them. Malignant glioma has a high invasion and metastasis rate, which leads to the poor prognosis of patients. By targeting specific genes, microRNAs serve as key regulators in the epithelial-mesenchymal transformation (EMT) process, which could provide new insights into the treatment of glioblastomas (GBM). The detailed molecular role that miR-623 plays in GBM still remains unclear. MATERIALS AND METHODS: The level of miR-623 in GBM cells was evaluated by RT-PCR. The function of miR-623 overexpression on GBM cell proliferation, migration, and invasion was assessed by MTS, Transwell analysis, and colony formation assay. In addition, a mouse subcutaneous xenograft model was used to study in vivo effects. The binding between miR-623 and TRIM44 was verified by a dual-luciferase reporter assay and the regulatory function of miR-623 on EMT markers was evaluated using Western blot. RESULTS: The expression of miR-623 was repressed in the GBM cancer cell lines. MiR-623 overexpression or TRIM44 knockdown attenuated the proliferation, migration, and invasion of GBM cell lines. TRIM44 could facilitate the reverse suppression of EMT and miR-623 in GBM progression. MiR-623 was found to inhibit TRIM44 expression by directly binding to its 3'UTR. In addition, systemic delivery of miR-623 mimic reduced tumor growth and inhibited TRIM44 protein expression in tumor-bearing nude mice. Furthermore, our findings indicated that miR-623 overexpression or TRIM44 down-regulation impeded the proliferation and migratory ability of LN229 and U251MG glioma cells, and miR-623 attenuates TRIM44-induced EMT by directly targeting the 3'UTR of TRIM44, which could serve as preliminary research to identify potential therapeutic targets for future treatment of GBM. CONCLUSION: Overall, microRNA-623 inhibits epithelial-mesenchymal transition to attenuate glioma proliferation by targeting TRIM44.

Retrospective study of gene signatures and prognostic value of m6A regulatory factor in non-small cell lung cancer using TCGA database and the verification of FTO.

N6-methyladenosine (m6A) is the most common internal modification in eukaryotic mRNA. However, little is known about its role in non-small cell lung cancer (NSCLC). In this study, a total of 1017 NSCLC patients from the cancer genome atlas (TCGA) database with copy number variation (CNV) data were included. Log-rank tests and Cox regression model were used for survival analysis. The relationship between m6A regulators and clinicopathological features was evaluated using the chi-square test. The alteration of m6A regulators were related to T stage. Patients with any CNVs of regulators genes had worse overall survival (OS) than those with diploid genes. The deletion of m6A writer genes was an independent risk factor for poor OS, and the effect synergized with that of copy number gain of eraser genes. High expression of Fat mass-and obesity-associated gene (FTO) was associated with KRAS signaling up. Knockdown of FTO increased m6A content and inhibit proliferation of A549 lung cancer cell. Thus, we identified the genetic changes of m6A regulatory factors in NSCLC for the first time and found a significant relationship between these changes and poor clinical characteristics. FTO might play an important role in promoting NSCLC by decreasing m6A level and activating KRAS signaling.

Resveratrol Attenuates Aortic Dissection by Increasing Endothelial Barrier Function Through the SIRT1 Pathway.

Aortic dissection (AD) is a serious condition and a health issue on a global scale. ß-Aminopropionitrile-induced AD in mice is similar to the pathogenesis of AD in humans. Resveratrol (RSV) is a natural polyphenolic substance that provides anti-inflammatory and cardiovascular effects, but the role of RSV in AD is unclear. In this study, we investigated the effects and mechanisms of RSV on ß-aminopropionitrile-induced AD in mice. Our results indicate that RSV can prevent the occurrence of AD. More meaningfully, we found that the protective effect comprises an increase in sirtuin 1 (SIRT1) expression in endothelial cells for the reconstruction of their structure, reducing the recruitment of inflammatory cells by endothelial cells and inhibiting the inflammation response, thereby suppressing the occurrence of AD.

Polydatin ameliorates chemotherapy-induced cognitive impairment (chemobrain) by inhibiting oxidative stress, inflammatory response, and apoptosis in rats.

Most breast cancer survivors receiving chemotherapy have severe cognitive impairment, often referred to as "chemobrain." Polydatin (PLD) is known to have many biological activities. Thus, this study aimed to determine whether symptoms of chemobrain can be prevented or relieved by PLD. The chemobrain models were established by intraperitoneal injection of doxorubicin (DOX, 2 mg/kg) in rats once a week for 4 weeks (DOX group and DOX+PLD group). In the PLD group and DOX+PLD group, PLD (50 mg/kg) was administered orally to rats every day. We found that PLD treatment significantly protected against DOX-induced learning and memory impairment, restored hippocampal histopathological architecture. Furthermore, PLD suppressed DOX-induced oxidative stress through up-regulating Nrf2, inhibited inflammatory response by activating the NF-κB pathway, and reduced hippocampal apoptosis. Therefore, the present study indicated that PLD offered neuroprotection against DOX-induced chemobrain. PLD may assist in preventing chemobrain after chemotherapy in patients with cancers.