Transcriptomics and metabonomics study on the effect of exercise combined with curcumin supplementation on breast cancer in mice.

Curcumin and exercise have been reported to show good anti-tumour effects. However, relevant research on the combined effects of physical exercise and curcumin supplementation on cancer and the underlying mechanisms is still lacking. The current study aimed to construct an anti-breast tumour mouse model using the combined effects of curcumin treatment and swimming exercise. Transcriptomic and metabolomic techniques were used to screen for differentially expressed genes and metabolites, evaluate the anticancer effects, and analyse the molecular regulatory mechanisms related to metabolism. Observation of the mouse phenotypes, including tumour appearance, in-vivo tumour imaging, and HE staining results of pathological sections, suggested a more obvious inhibitory effect of the combination of curcumin administration and exercise intervention on breast cancer than that of a single treatment. The combination treatment group had a total of 445 differentially expressed (154 upregulated and 291 downregulated) genes. Functional enrichment analysis showed the calcium signalling pathway, Wnt signalling pathway, PI3K Akt signalling pathway, and IL-17 signalling pathway to significantly participate in the anti-breast cancer process of curcumin-exercise combination treatment. Results of the intergroup differential metabolite analysis showed that the combined effect of curcumin and exercise involves two unique pathways, namely the amino sugar and nucleotide sugar metabolism, which includes chitosan, d-glucosamine 6-phosphate, l-fucose, and N-acetyl beta-mannosamine, and the amino acid biosynthesis, which includes dl-isoleucine, dl-tyrosine, and homocysteine. Collectively, the top-ranked genes and metabolites with the highest degree of associations were further revealed by O2PLS analysis. Overall, the study helped reveal the mechanism of action of curcumin-exercise combination treatment on breast cancer at multi-omics level.

Effect of pre-treatments and frying conditions on the formation of starch-lipid complex in potato starch chips during deep-frying process.

This study examined the influence of various pretreatment methods, frying durations, and temperatures, as well as the type of frying oil, on the formation and structure of starch-lipid complexes in fried potato chips. Potato starch was processed into dough, sliced, and subjected to deep frying following various pretreatments. Structural analysis showed that steaming as a pretreatment facilitated the generation of V-type starch-lipid complexes, whereas resistant starch type III (RS3) materialized in the desiccated samples instead of the anticipated complexes. The rate of starch-lipid complex formation initially surged but subsequently declined as treatment time increased. A reduction in treatment temperature from 190 °C to 170 °C was conducive to complex formation. Moreover, the maximum relative crystallinity (19.74 %) and ΔH value (7.76 J/g) were recorded for potato starch slices pretreated by steaming and frying in palm oil. Rapeseed oil, which is rich in unsaturated fatty acids (89.98 %), inhibits complex formation. The study concludes that pretreatment methods exert a substantial effect on the formation of starch-lipid complexes and that extended frying duration and elevated temperature may reduce this formation. Oils with longer-chain fatty acids and a lower degree of unsaturation were favorable for complex formation.

Room Temperature Hydroxyl Group-Assisted Preparation of Hydrophobicity-Adjustable Metal-Organic Framework UiO-66 Composites: Towards Continuous Oil Collection and Emulsion Separation.

Developing a straightforward and effective hydrophobic modification for metal-organic frameworks (MOFs) under mild conditions is meaningful for MOF applications. Here, a post-synthetic modification approach assisted with metal hydroxyl groups at room temperature is reported to induce hydrophobicity in the hydrophilic UiO-66. The bonding between Zr-OH in UiO-66 and n-tetradecylphosphonic acid (TDPA) is the vital force for the modifier TDPA. Superhydrophobic and superoleophilic composites were constructed for efficient oil-water separation by coating TDPA-modified UiO-66 (P-UiO-66) on commercial melamine sponges (MS) and filter papers (FP) with water contact angles of 153.2° and 155.6°, respectively. The P-UiO-66/MS composite could quickly and selectively absorb oily liquids up to 43 times its weight from water. The P-UiO-66/MS achieved continuous oil collection with high separation efficiencies (≥99.4 %). In addition, P-UiO-66/FP and P-UiO-66/MS showed high separation efficiencies for water-in-oil emulsions (≥98.5 %) and oil-in-water emulsions, respectively, with high resistance to low/high temperatures and acid/base conditions. The metal hydroxyl group-assisted post-synthetic modification strategy offers a facile and broad way to prepare hydrophobic MOFs for promising applications in environmental fields.

Oral liposomal delivery of an activatable budesonide prodrug reduces colitis in experimental mice.

Inflammatory bowel disease (IBD) is one of the most common intestinal disorders, with increasing global incidence and prevalence. Numerous therapeutic drugs are available but require intravenous administration and are associated with high toxicity and insufficient patient compliance. Here, an oral liposome that entraps the activatable corticosteroid anti-inflammatory budesonide was developed for efficacious and safe IBD therapy. The prodrug was produced via the ligation of budesonide with linoleic acid linked by a hydrolytic ester bond, which was further constrained into lipid constituents to form colloidal stable nanoliposomes (termed budsomes). Chemical modification with linoleic acid augmented the compatibility and miscibility of the resulting prodrug in lipid bilayers to provide protection from the harsh environment of the gastrointestinal tract, while liposomal nanoformulation enables preferential accumulation to inflamed vasculature. Hence, when delivered orally, budsomes exhibited high stability with low drug release in the stomach in the presence of ultra-acidic pH but released active budesonide after accumulation in inflamed intestinal tissues. Notably, oral administration of budsomes demonstrated favorable anti-colitis effect with only ∼7% mouse body weight loss, whereas at least ∼16% weight loss was observed in other treatment groups. Overall, budsomes exhibited higher therapeutic efficiency than free budesonide treatment and potently induced remission of acute colitis without any adverse side effects. These data suggest a new and reliable approach for improving the efficacy of budesonide. Our in vivo preclinical data demonstrate the safety and increased efficacy of the budsome platform for IBD treatment, further supporting clinical evaluation of this orally efficacious budesonide therapeutic.

Eco-Friendly Fluorine Functionalized Superhydrophobic/Superoleophilic Zeolitic Imidazolate Frameworks-Based Composite for Continuous Oil-Water Separation.

Superhydrophobic metal-organic framework (MOF)-based sponges have received increasing attention in terms of treating oil-water mixtures. However, highly fluorinated substances, commonly used as modifiers to improve the hydrophobicity of MOFs, have aroused much environmental concern. Developing a green hydrophobic modification is crucial in order to prepare superhydrophobic MOF-sponge composites. Herein, we report the preparation of a porous composite sponge via a polydopamine (PDA)-assisted growth of zeolitic imidazolate frameworks (ZIF-90) and eco-friendly hydrophobic short-chain fluorinated substances (trifluoroethylamine) on a melamine formaldehyde (MF) sponge. The composite sponge (F-ZIF-90@PDA-MF) exhibited superhydrophobicity (water contact angle, 153°) and superoleophilicity (oil contact angle, 0°), which is likely due to the combination of the low surface energy brought on by the grafted CF3 groups, as well as the rough surface structures that were derived from the in situ growth of ZIF-90 nanoparticles. F-ZIF-90@PDA-MF showed an excellent adsorption capacity of 39.4-130.4 g g-1 for the different organic compounds. The adsorbed organic compounds were easily recovered by physical squeezing. Continuous and selective separation for the different oil-water mixtures was realized by employing the composite sponge as an absorbent or a filter. The separation efficiency and flux reached above 99.5% and went up to 7.1 ×105 L m-2 h-1, respectively. The results illustrate that the superhydrophobic and superoleophilic F-ZIF-90@PDA-MF sponge has potential in the field of water-oil separation, especially for the purposes of large-scale oil recovery in a water environment.

Solitary fibrous tumor of the central nervous system invading and penetrating the skull: A case report.

Solitary fibrous tumor (SFT) of the central nervous system is a rare spindle cell tumor of mesenchymal origin. The present study reports the case of a 44-year-old male patient with SFT. Magnetic resonance imaging demonstrated that the majority of the intracranial tumors exhibited uneven low signals on T1-weighted imaging (T1WI) and low mixed signals on T2WI, and there was an enhancement on enhanced scanning. Furthermore, the distal part of the left occipital lobe exhibited hypersignals on T1WI and T2WI, and this was significantly enhanced following enhanced scanning. The lower part of the scalp exhibited low signals on T1WI and high signals on T2WI, and there was no notable enhancement following enhanced scanning. Magnetic resonance spectroscopy demonstrated an elevated choline/creatine peak in the solid part of the tumor. Under the microscope, the tumor exhibited characteristic 'staghorn-shaped' blood vessels. As SFT is difficult to differentially diagnose via imaging, immunohistochemical analysis of CD34, vimentin and signal transducer and activator of transcription 6 was performed for the definitive diagnosis of SFT. Of note, surgical resection was the preferred treatment for SFT; however, due to the rarity of the tumor, subsequent adjuvant therapy and prognosis require further investigation.

Effect of flaxseed gum on the brittleness of oleogels based on candelilla wax.

The present study aimed to decrease the brittleness of flaxseed oleogels based on candelilla wax (CLW) in combination with flaxseed gum (FG). Effects of flaxseed gum concentrations (0-0.4%) on the characteristics of flaxseed oleogels including oil binding capacity, textural, thermal, and rheological properties, and crystal polymorphisms were investigated. Higher concentrations (≥0.2%) of FG significantly decreased the textural parameters (e.g., hardness, fracturability) of oleogels (p < 0.05), suggesting that FG could decrease brittleness. Rheological results indicated that all flaxseed oleogels exhibited solid-like characteristics because the elastic modulus was larger than the viscous modulus. The elastic modulus of flaxseed oleogels presented a maximum value at 0.1% gum concentration. Any increase in gum concentration beyond this concentration decreased the elastic modulus. Increasing FG concentration up to 0.4% decreased the enthalpy of flaxseed oleogels during the melting process. The ß'-polymorphic form is an orthorhombic perpendicular (O⊥) subcell structure. Similar ß' crystal forms were observed among flaxseed oleogels, indicating that FG did not affect them negatively. The study showed that the physical properties of flaxseed oleogels based on CLW could be significantly changed by FG addition. These results provided a deeper comprehension of the novel system, which should be considered a new way to obtain healthy fats with better plasticity for food applications.

Integrative analysis reveals structural basis for transcription activation of Nurr1 and Nurr1-RXRα heterodimer.

Orphan nuclear receptor Nurr1 plays important roles in the progression of various diseases, including Parkinson's disease, neuroinflammation, Alzheimer's disease, and multiple sclerosis. It can recognize DNA as a monomer or heterodimer with retinoid X receptor α (RXRα). But the molecular mechanism of its transcriptional activity regulation is still largely unknown. Here we obtained a crystal structure of monomer Nurr1 (DNA- and ligand-binding domains, DBD and LBD) bound to NGFI-B response element. The structure exhibited two different forms with distinct DBD orientations, unveiling the conformational flexibility of nuclear receptor monomer. We then generated an integrative model of Nurr1-RXRα heterodimer. In the context of heterodimer, the structural flexibility of Nurr1 would contribute to its transcriptional activity modulation. We demonstrated that the DNA sequence may specifically modulate the transcriptional activity of Nurr1 in the absence of RXRα agonist, but the modulation can be superseded when the agonist binds to RXRα. Together, we propose a set of signaling pathways for the constitutive transcriptional activation of Nurr1 and provide molecular mechanisms for therapeutic discovery targeting Nurr1 and Nurr1-RXRα heterodimer.

Structural Studies Reveal Unique Non-canonical Regulators of G Protein Signaling Homology (RH) Domains in Sorting Nexins.

As a subgroup of sorting nexins (SNXs) that contain regulator of G protein signaling homology (RH) domain, SNX-RH proteins, including SNX13, SNX14 and SNX25, were proposed to play bifunctional roles in protein sorting and GPCR signaling regulation. However, mechanistic details of SNX-RH proteins functioning via RH domain remain to be illustrated. Here, we delineate crystal structures of the RH domains of SNX13 and SNX25, revealing a homodimer of SNX13 RH domain mediated by unique extended α4 and α5 helices, and a thiol modulated homodimer of SNX25-RH triggered by a unique cysteine on α6 helix. Further studies showed that RH domains of SNX-RH do not possess binding capacity toward Gα subunits, owing to the lack of critical residues for interaction. Thus, this study identifies a group of novel non-canonical RH domains that can act as a dimerization module in sorting nexins, which provides structural basis for mechanism studies on SNX-RH protein functions.

Moyamoya syndrome with ruptured aneurysm in α-thalassemia: A case report.

Moyamoya syndrome (MMS) refers to the moyamoya vascular disease associated with various systemic diseases and conditions, including sickle cell anemia, Fanconi anemia and iron deficiency anemia. However, the association between MMS and other hemoglobinopathies is less frequently observed. MMS, like moyamoya disease, is a cerebrovascular condition that is characterized by chronic progressive stenosis or occlusion at the ends of the bilateral internal carotid arteries, anterior cerebral arteries and the beginning of the middle cerebral arteries, and is secondary to the formation of an abnormal vascular network at the base of the skull. Patients with MMS are prone to thrombosis, aneurysm and bleeding. The present study reports the case of a 43-year-old man with α-thalassemia who presented with moyamoya vessels with a ruptured aneurysm bleeding into the ventricle. α-thalassemia is considered as an extremely rare but potential cause of MMS. Since MMS is a progressive disease, early diagnosis and treatment is vital to prevent the disease from worsening.

A Class of Shark-Derived Single-Domain Antibodies can Broadly Neutralize SARS-Related Coronaviruses and the Structural Basis of Neutralization and Omicron Escape.

The identification of a novel class of shark-derived single domain antibodies, named vnarbodies that show picomolar affinities binding to the receptor binding domain (RBD) of Wuhan and Alpha, Beta, Kappa, Delta, Delta-plus, and Lambda variants, is reported. Vnarbody 20G6 and 17F6 have broad neutralizing activities against all these SARS-CoV-2 viruses as well as other sarbecoviruses, including Pangolin coronavirus and Bat coronavirus. Intranasal administration of 20G6 effectively protects mice from the challenges of SARS-CoV-2 Wuhan and Beta variants. 20G6 and 17F6 contain a unique "WXGY" motif in the complementary determining region 3 that binds to a hidden epitope on RBD, which is highly conserved in sarbecoviruses through a novel ß-sheet interaction. It is found that the S375F mutation on Omicron RBD disrupts the structure of ß-strand, thus impair the binding with 20G6. The study demonstrates that shark-derived vnarbodies offer a prophylactic and therapeutic option against most SARS-CoV-2 variants and provide insights into antibody evasion by the Omicron variant.

Celastrol Inhibits the Proliferation and Induces Apoptosis of Colorectal Cancer Cells via Downregulating NF-κB/COX-2 Signaling Pathways.

BACKGROUND: Colorectal cancer (CRC) is the third-ranked malignant tumor in the world that contributes to the death of a major population of the world. Celastrol, a bioactive natural product isolated from the medicinal plant Tripterygium wilfordii Hook F, has been proved to be an effective anti-tumor inhibitor for multiple tumors. OBJECTIVE: To reveal the therapeutic effect and underlying mechanisms of celastrol on CRC cells. METHODS: CCK-8 and clonogenic assay were used to analyze the cell proliferation in CRC cells. Flow cytometry analysis was conducted to assess the cell cycle and cell apoptosis. Wound-healing and cell invasion assay were used to evaluate the migrating and invasion capability of CRC cells. The potential antitumor mechanism of celastrol was investigated by qPCR, western blot, and confocal immunofluorescence analyses. RESULTS: Celastrol effectively inhibited CRC cell proliferation by activating caspase-dependent cell apoptosis and facilitating G1 cell cycle arrest in a dose-dependent manner, as well as cell migration and invasion by downregulating the MMP2 and MMP9. Mechanistic protein expression revealed that celastrol suppressed the expression of COX-2 by inhibiting the phosphorylation of NF-κB p65 and subsequently leading to cytoplasmic retention of p65 protein, thereby inhibiting its nuclear translocation and transcription activities. CONCLUSION: These findings indicate that celastrol is an effective inhibitor for CRC, regulating the NF-κB/COX-2 pathway, leading to the inhibition of cell proliferation characterized by cell cycle arrest and caspase-dependent apoptosis, providing a potential alternative therapeutic agent for CRC patients.

Micheliolide suppresses the viability, migration and invasion of U251MG cells via the NF-κB signaling pathway.

Micheliolide (MCL), a sesquiterpene lactone isolated from Michelia compressa and Michelia champaca, has been used previously to inhibit the NF-κB signaling pathway. MCL has exerted various therapeutic effects in numerous types of disease, such as inflammatory and cancer. However, to the best of our knowledge, its underlying anticancer mechanism remains to be understood. The present study aimed to investigate the effects of MCL on human glioma U251MG cells and to determine the potential anticancer mechanism of action of MCL. From Cell Counting Kit-8, colony formation assay, apoptosis assay and Confocal immunofluorescence imaging analysis, the results revealed that MCL significantly inhibited cell viability in vitro and induced cell apoptosis via activation of the cytochrome c/caspase-dependent apoptotic pathway. In addition, MCL also suppressed cell invasion and metastasis via the wound healing and Transwell invasion assays. Furthermore, western blot and reverse transcription PCR analyses demonstrated that MCL significantly downregulated cyclooxygenase-2 (COX-2) expression levels, which may have partially occurred through the inactivation of the NF-κB signaling pathway. In conclusion, the results of the present study indicated that MCL may inhibit glioma carcinoma growth by downregulating the NF-κB/COX-2 signaling pathway, which suggested that MCL may be a novel and alternative antitumor agent for the treatment of human glioma carcinoma.

NACHT, LRR, and PYD domains-containing Protein 3 and LL-37: prognostic value of new biomarkers in community-acquired pneumonia. / Proteína 3 contendo um domínio NACHT, porção C-terminal rica em repetições de leucina e de domínio pirina e LL-37: valor prognóstico de novos biomarcadores em pneumonia adquirida na comunidade.

OBJECTIVE: This study aimed to determine the serum levels of NACHT, Leucine-rich repeat (LRR), and Pyrin (PYD) domains-containing Protein 3 (NLRP3) and cathelicidin LL-37, and investigate their prognostic significance in community-acquired pneumonia (CAP). METHODS: The sample of this prospective study was composed of 76 consecutive patients with CAP. Demographic data and clinical characteristics were collected. Serum levels of NLRP3 and LL-37 were determined by ELISA. Spearman's analysis was used to evaluate the correlation between NLRP3 and LL-37. Association of NLRP3 and LL-37 with 30-day survival and mortality rates was assessed using the Kaplan-Meier curve and logistic regression analysis. RESULTS: Serum NLRP3 significantly increased whereas serum LL-37 significantly decreased in patients with severe CAP. Significant correlation was observed between serum NLRP3 and LL-37 in CAP patients. Patients with higher levels of NLRP3 and lower levels of LL-37 showed lower 30-day survival rate and higher mortality compared with those with lower NLRP3 and higher LL-37 levels. CONCLUSION: Severe CAP patients tend to present higher serum NLRP3 and lower serum LL-37, which might serve as potential biomarkers for CAP prognosis.

OBJETIVO: Este estudo teve como objetivo determinar os níveis séricos de proteína 3 contendo um domínio NACHT, porção C-terminal rica em repetições de leucina e de domínio pirina (NLRP3) e catelicidina LL-37, bem como investigar sua importância prognóstica em pneumonia adquirida na comunidade (PAC). MÉTODOS: Este estudo prospectivo incluiu 76 pacientes com PAC. Foram obtidos dados demográficos e características clínicas. Os níveis séricos de NLRP3 e LL-37 foram determinados por meio do teste ELISA. A correlação entre NLRP3 e LL-37 foi estimada por intermédio da análise de Spearman. A associação entre NLRP3 e LL-37 com 30 dias de taxa de sobrevida e de mortalidade foi avaliada pela curva de Kaplan-Meier e análise de regressão logística. RESULTADOS: Os níveis séricos de NLRP3 estavam elevados, enquanto os níveis de LL-37 apresentaram redução significativa em pacientes com PAC grave. Observou-se correlação significativa entre os níveis séricos de NLRP3 e LL-37 em pacientes com PAC. Pacientes com níveis elevados de NLRP3 e níveis reduzidos de LL-37 exibiram maior taxa de sobrevida em 30 dias e de mortalidade quando comparados com aqueles com níveis inferiores de NLRP3 e LL-37. CONCLUSÕES: Pacientes com PAC grave tendem a apresentar níveis séricos elevados de NLRP3 e níveis reduzidos de LL-37, o que pode ser utilizado como um potencial biomarcador prognóstico.

Neuronal EphA4 Regulates OGD/R-Induced Apoptosis by Promoting Alternative Activation of Microglia.

Accumulating evidence indicates that post-injury inflammation characterized by activated microglia contributes much to the neuropathology of ischemic injury. Several studies have demonstrated that microglia exhibit two entirely different functional activation states, referred to as classically activated (M1) and alternatively activated (M2) phenotype. Promoting microglial phenotype to switch from M1 dominant to M2 dominant might be a promising approach for handling ischemic injury. However, the comprehensive mechanism that underlines microglia polarization in ischemic brain remains unclear. Neuronal erythropoietin-producing human hepatocellular carcinoma cell receptor 4 (EphA4), the richest Eph receptor in the central nervous system (CNS), upregulate after ischemia and may have the potential to regulate microglia activation. We hypothesized that modulating EphA4/ephrin signaling could affect ischemic injury through controlling microglia polarization. We therefore knocked down neuronal EphA4 with short hairpin RNA (shRNA) and determined the role of EphA4/ephrin signaling in oxygen-glucose deprivation and reperfusion (OGD/R)-induced injury. We found that EphA4 shRNA treatment attenuated OGD/R-induced apoptosis and microglia proliferation. Neuronal EphA4 knockdown also promoted microglial M2 polarization, which reduced pro-inflammatory mediators and released anti-inflammatory cytokines as well as neurotrophic factors. We further revealed that EphA4 shRNA treatment functioned through RhoA/Rho-associated kinase 2 (ROCK2) signaling, a key mediator of microglia alternative activation. Together, these data suggested that blockage of EphA4/ephrin signaling between neuron and microglia decreased OGD/R-induced injury by promoting alternative activation of microglia via RhoA/ROCK2 signaling.

Retracted: Epigallocatechin gallate ameliorates morphological changes of pancreatic islets in diabetic mice and downregulates blood sugar level by inhibiting the accumulation of AGE-RAGE.

This study aimed to elucidate the key mechanisms and effects of the functional component of green tea, epigallocatechin gallate (EGCG) on a diabetic mouse model. The detected relationship between compounds and genes recorded in the STITCH database highlighted an interaction network between the direct target genes of EGCG and the known diabetes-related genes, which was made apparent through the analysis of gene-gene interactions and signaling pathways, revealing that a key AGE-RAGE signaling pathway in diabetes was enriched in the network. By means of systematic supplementary analyses on diabetic mice, provided evidence suggested that EGCG could significantly enhance the morphology of pancreatic tissues in diabetic mice and downregulate the blood glucose level in a clear dose effect manner, and increased insulin receptor (IR), insulin receptor substrate (IRS1 and IRS2) expression in the liver. Through the detection of protein expression, EGCG was observed to possess the ability to downregulate the accumulation of AGE-RAGE in pancreatic tissues as well as in the transcription factor nuclear factor-κB (NF-κB), which represents a potentially significant method by which EGCG influences diabetes. The results of this study provided evidence indicating that EGCG can effectively improve the morphology of pancreatic tissues, but notably reduce blood glucose levels in diabetic mice, which may be related to its inhibition of AGE-RAGE signaling pathway and activation of transcription factor NF-κB pathway.

Proteína 3 contendo um domínio NACHT, porção C-terminal rica em repetições de leucina e de domínio pirina e LL-37: valor prognóstico de novos biomarcadores em pneumonia adquirida na comunidade / NACHT, LRR, and PYD domains-containing Protein 3 and LL-37: prognostic value of new biomarkers in community-acquired pneumonia

RESUMO Objetivo Este estudo teve como objetivo determinar os níveis séricos de proteína 3 contendo um domínio NACHT, porção C-terminal rica em repetições de leucina e de domínio pirina (NLRP3) e catelicidina LL-37, bem como investigar sua importância prognóstica em pneumonia adquirida na comunidade (PAC). Métodos Este estudo prospectivo incluiu 76 pacientes com PAC. Foram obtidos dados demográficos e características clínicas. Os níveis séricos de NLRP3 e LL-37 foram determinados por meio do teste ELISA. A correlação entre NLRP3 e LL-37 foi estimada por intermédio da análise de Spearman. A associação entre NLRP3 e LL-37 com 30 dias de taxa de sobrevida e de mortalidade foi avaliada pela curva de Kaplan-Meier e análise de regressão logística. Resultados Os níveis séricos de NLRP3 estavam elevados, enquanto os níveis de LL-37 apresentaram redução significativa em pacientes com PAC grave. Observou-se correlação significativa entre os níveis séricos de NLRP3 e LL-37 em pacientes com PAC. Pacientes com níveis elevados de NLRP3 e níveis reduzidos de LL-37 exibiram maior taxa de sobrevida em 30 dias e de mortalidade quando comparados com aqueles com níveis inferiores de NLRP3 e LL-37. Conclusões Pacientes com PAC grave tendem a apresentar níveis séricos elevados de NLRP3 e níveis reduzidos de LL-37, o que pode ser utilizado como um potencial biomarcador prognóstico.

ABSTRACT Objective This study aimed to determine the serum levels of NACHT, Leucine-rich repeat (LRR), and Pyrin (PYD) domains-containing Protein 3 (NLRP3) and cathelicidin LL-37, and investigate their prognostic significance in community-acquired pneumonia (CAP). Methods The sample of this prospective study was composed of 76 consecutive patients with CAP. Demographic data and clinical characteristics were collected. Serum levels of NLRP3 and LL-37 were determined by ELISA. Spearman's analysis was used to evaluate the correlation between NLRP3 and LL-37. Association of NLRP3 and LL-37 with 30-day survival and mortality rates was assessed using the Kaplan-Meier curve and logistic regression analysis. Results Serum NLRP3 significantly increased whereas serum LL-37 significantly decreased in patients with severe CAP. Significant correlation was observed between serum NLRP3 and LL-37 in CAP patients. Patients with higher levels of NLRP3 and lower levels of LL-37 showed lower 30-day survival rate and higher mortality compared with those with lower NLRP3 and higher LL-37 levels. Conclusion Severe CAP patients tend to present higher serum NLRP3 and lower serum LL-37, which might serve as potential biomarkers for CAP prognosis.

Expression of miR-30c and miR-29b in prostate cancer and its diagnostic significance.

This study aimed to investigate the expression of miR-30c and miR-29b in prostate cancer (PCa) and its clinical significance. The expression of miR-30c and miR-29b was detected by RT-qPCR in 187 cases of PCa and their adjacent tissues. Combined with clinical information, the correlation between the expression of miR-29b and miR-30c and the clinical features of PCa was analyzed, and ROC curve was plotted. The expression of miR-30c and miR-29b detected by RT-qPCR showed that the expression of miR-29b and miR-30c in PCa tissues was significantly lower than that in adjacent cancerous tissues (p<0.05). By comparing the expression and clinical data of miR-29b and miR-30c in the cancer tissues of PCa patients, it was observed that age, smoking, and TNM staging were not related to miR-29b and miR-30c expression (p>0.05), while lymph node metastasis, bone metastasis, and Gleason score were related to the expression of miR-29b and miR-30c (p<0.01). The ROC curve showed that miR-29b AUC, 0.924; 95% CI, 0.824-0.967, and miR-30c AUC, 0.944; 95% CI, 0.798-0.972. miR-30c and miR-29b are clinically relevant to PCa. In conclusion, detecting the expression of miR-30c and miR-29b not only can differentiate between PCa and paracancerous tissues, but it is also anticipated to become a new biomarker for the diagnosis of PCa.

Epoxymicheliolide, a novelguaiane-type sesquiterpene lactone, inhibits NF­κB/COX­2 signaling pathways by targeting leucine 281 and leucine 25 in IKKß in renal cell carcinoma.

Parthenolide (PTL) is a sesquiterpene lactone compound obtained from Tanacetum parthenium (feverfew) and inhibits the activation of nuclear factor (NF)-κB. Epoxymicheliolide (EMCL) is a compound which is structurally related to PTL; however, EMCL is more stable under acidic and alkaline conditions. As a biologically active molecule, the detailed mechanism by which EMCL inhibits tumor activity remains to be elucidated. The present study evaluated the effect of EMCL on renal cell carcinoma (RCC) cells and identified the underlying mechanisms. It was found that treatment with EMCL significantly inhibited the proliferation of RCC cells in vitro and increased the induction of apoptosis by activating the mitochondria- and caspase-dependent pathway. Simultaneously, EMCL suppressed cell invasion and metastasis by inhibiting epithelial-mesenchymal transition, as observed in a microfluidic chip assay. Furthermore, using immunofluorescence analysis, an electrophoretic mobility shift assay and a dual-luciferase reporter assay, it was shown that treatment with EMCL significantly suppressed the expression of cyclooxygenase­2 by inhibiting the translocation of NF­κB p50/p65 and the activity of NF­κB. Collectively, the results indicated that EMCL suppressed tumor growth by inhibiting the activation of NF­κB and suggested that EMCL may be a novel anticancer agent in the treatment of RCC.

Curcumin potentiates the potent antitumor activity of ACNU against glioblastoma by suppressing the PI3K/AKT and NF-κB/COX-2 signaling pathways.

Glioblastoma (GBM) is a highly invasive and challenging primary tumor of the central nervous system (CNS), and currently available treatments provide limited benefits to patients with this disease. Therefore, the development of novel therapeutic targets and effective treatment strategies is essential. Nimustine hydrochloride (ACNU) is widely used as the standard chemotherapeutic agent and is frequently administered together with other chemotherapeutic agents in clinical studies. Curcumin, a natural polyphenolic compound, could potentially be combined with chemotherapeutics for cancer treatment; however, there are no reports of studies where ACNU and curcumin were combined for GBM treatment, and the mechanisms underlying their activity remain poorly understood. In the present study, we investigated the effects of combined treatment with curcumin and ACNU on GBM cells and found that it significantly enhanced the inhibition of cell proliferation, colony formation, migration, and invasion. In addition, co-treatment with curcumin increased ACNU-induced apoptosis through enhancing the release of cytochrome c from the mitochondrial intermembrane space into the cytosol. Further, curcumin and ACNU acted synergistically in their antitumor effects by targeting N-cadherin/MMP2/9, PI3K/AKT, and NF-κB/COX-2 signaling. These results indicate that curcumin can enhance the anti-proliferation, anti-migration, and proapoptotic activities of ACNU against GBM, and provide strong evidence that combined treatment with curcumin and ACNU has the potential to be an effective therapeutic option for GBM.