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It has been a big challenge to distinguish synchronous multiple primary lung cancer (sMPLC) from primary lung cancer with intrapulmonary metastases (IPM). We aimed to assess the clinical application of dynamic 18F-FDG PET/CT in patients with multiple lung cancer nodules. We enrolled patients with multiple pulmonary nodules who had undergone dynamic 18F-FDG PET/CT and divided them into sMPLC and IPM groups based on comprehensive features. The SUVmax, fitted K i value based on dynamic scanning, and corresponding maximum diameter ( D max ) from the two largest tumors were determined in each patient. We determined the absolute between-tumor difference of SU V max / D max and K i / D max (Δ SU V max / D max ; Δ K i / D max ) and assessed the between-group differences. Further, the diagnostic accuracy was evaluated by ROC analysis and the correlation between Δ SU V max / D max and Δ K i / D max from all groups was determined. There was no significant difference for Δ SU V max / D max between the IPM and sMPLC groups, while the IPM group had a significantly higher Δ K i / D max than the sMPLC group. The AUC of Δ K i / D max for differentiating sMPLC from IPM was 0.80 (cut-off value of K i = 0.0059 , sensitivity 79%, specificity 75%, p < 0.001). There was a good correlation (Pearson r = 0.91 , 95% CI: 0.79-0.96, p < 0.0001) between Δ SU V max / D max and Δ K i / D max in the IPM group but not in the sMPLC group (Pearson r = 0.45 , p > 0.05). Dynamic 18F-FDG PET/CT could be a useful tool for distinguishing sMPLC from IPM. K i calculation based on Patlak graphic analysis could be more sensitive than SUVmax in discriminating IPM from sMPLC in patients with multiple lung cancer nodules. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is a common neurodegenerative disease in middle-aged and older adults. Abnormal proteins such as α-synuclein are essential factors in PD's pathogenesis. Autophagy is the main participant in the clearance of abnormal proteins. The overactive or low function of autophagy leads to autophagy stress. Not only is it difficult to clear abnormal proteins but also it can cause damage to neurons. In this article, the effects of natural products ingredients, such as salidroside, paeoniflorin, curcumin, resveratrol, corynoxine, and baicalein, on regulating autophagy and protecting neurons were discussed in detail to provide a reference for the research and development of drugs for the treatment of PD. [ABSTRACT FROM AUTHOR]

It has been a big challenge to distinguish synchronous multiple primary lung cancer (sMPLC) from primary lung cancer with intrapulmonary metastases (IPM). We aimed to assess the clinical application of dynamic 18F-FDG PET/CT in patients with multiple lung cancer nodules. We enrolled patients with multiple pulmonary nodules who had undergone dynamic 18F-FDG PET/CT and divided them into sMPLC and IPM groups based on comprehensive features. The SUVmax, fitted K i value based on dynamic scanning, and corresponding maximum diameter ( D max ) from the two largest tumors were determined in each patient. We determined the absolute between-tumor difference of SU V max / D max and K i / D max (Δ SU V max / D max ; Δ K i / D max ) and assessed the between-group differences. Further, the diagnostic accuracy was evaluated by ROC analysis and the correlation between Δ SU V max / D max and Δ K i / D max from all groups was determined. There was no significant difference for Δ SU V max / D max between the IPM and sMPLC groups, while the IPM group had a significantly higher Δ K i / D max than the sMPLC group. The AUC of Δ K i / D max for differentiating sMPLC from IPM was 0.80 (cut-off value of K i = 0.0059 , sensitivity 79%, specificity 75%, p < 0.001). There was a good correlation (Pearson r = 0.91 , 95% CI: 0.79-0.96, p < 0.0001) between Δ SU V max / D max and Δ K i / D max in the IPM group but not in the sMPLC group (Pearson r = 0.45 , p > 0.05). Dynamic 18F-FDG PET/CT could be a useful tool for distinguishing sMPLC from IPM. K i calculation based on Patlak graphic analysis could be more sensitive than SUVmax in discriminating IPM from sMPLC in patients with multiple lung cancer nodules. [ABSTRACT FROM AUTHOR]

Ischemic stroke is often associated with a large disease burden. The existence of ischemia-reperfusion injury brings great challenges to the treatment of ischemic stroke. The purpose of this study was to explore the differences of metabolites in different parts of the brain induced by Shuxuetong injection against cerebral ischemia-reperfusion and to extend the corresponding mechanism. The rats were modeled by transient middle cerebral artery occlusion (t-MCAO) operation, and the success of modeling was determined by neurological function score and TTC staining. UPLC-Q/TOF-MS metabolomics technique and multivariate statistical analysis were used to analyze the changes and differences of metabolites in the cortex and hippocampus of cerebral ischemia-reperfusion rats. Compared with the model group, the neurological function score and cerebral infarction volume of the Shuxuetong treatment group were significantly different. There were differences and changes in the metabolic distribution of the cortex and hippocampus in each group, the distribution within the group was relatively concentrated. The separation trend between the groups was obvious, and the distribution of the Shuxuetong treatment group was similar to that of the sham operation group. We identified 13 metabolites that were differentially expressed in the cortex, including glutamine, dihydroorotic acid, and glyceric acid. We also found five differentially expressed metabolites in the hippocampus, including glutamic acid and fumaric acid. The common metabolic pathways of Shuxuetong on the cortex and hippocampus were D-glutamine and D-glutamate metabolism and nitrogen metabolism, which showed inhibition of cortical glutamine and promotion of hippocampal glutamic acid. Specific pathways of Shuxuetong enriched in the cortex included glyoxylate and dicarboxylate metabolism and pyrimidine metabolism, which showed inhibition of glyceric acid and dihydroorotic acid. Specific pathways of Shuxuetong enriched in the hippocampus include arginine biosynthesis and citrate cycle (TCA cycle), which promotes fumaric acid. Shuxuetong injection can restore and adjust the metabolic disorder of the cortex and hippocampus in cerebral ischemia-reperfusion rats. The expression of Shuxuetong in different parts of the brain is different and correlated. [ABSTRACT FROM AUTHOR]

Objective. To observe the therapeutic effect of Carvacrol on oral squamous cell carcinoma (OSCC) and dissect underlying molecular mechanisms. Methods. Keap1/Nrf2, NALP3, Vimentin, and E-cadherin expression was detected in OSCC and normal oral mucosa (NOM) tissues using immunofluorescence or western blot. When treated with Carvacrol or tert-butylhydroquinone (TBHQ) that activates Nrf2, the expression of Keap1/Nrf2/HO-1, epithelial-mesenchymal transition- (EMT-) related proteins, and NALP3 was examined in OSCC cells. Nrf2 was silenced by treatment with sh-Nrf2 or ML385. After silencing Nrf2 or Carvacrol treatment, cell proliferation and migration were assessed by clone formation and scratch and transwell tests in OSCC cells. Moreover, the expression of Keap1/Nrf2/HO-1, EMT-related proteins, and NALP3 was detected. Results. Keap1/Nrf2, NALP3, Vimentin, and E-cadherin proteins were all significantly upregulated in OSCC than NOM tissues. Carvacrol significantly suppressed Keap1/Nrf2/HO-1 activation. Carvacrol or silencing Nrf2 markedly inhibited the expression of Keap1/Nrf2/HO-1, EMT-related proteins, and NALP3 inflammasome in OSCC cells. Furthermore, clone formation and migration capacities were suppressed following treatment with Carvacrol or Nrf2 depletion. The opposite results were found when there is overexpression of Nrf2. However, Carvacrol distinctly improved the cancer-promoting effect induced by Nrf2 overexpression. Conclusion. Our findings suggested that Carvacrol ameliorated inflammation, proliferation, and migration for OSCC, which was related to inhibition of the Nrf2/Keap1 pathway. [ABSTRACT FROM AUTHOR]

Objective. To clarify the role and molecular mechanism of mitochondrial calcium uniporter (MCU) in the malignant biological behaviors of oral squamous cell carcinoma (OSCC) cells through clinical and cellular experiments. Methods. Immunohistochemistry and qRT-PCR techniques were used to observe the expression of MCU, nuclear factor erythroid 2-related factor 2 (Nrf2), mitochondrial calcium uptake 1 (MICU1), and MICU2 in OSCC and normal tissues. After treatment with si-MCU, spermine, and/or sh-Nrf2, malignant biological behaviors of OSCC cells including proliferation, migration, and apoptosis were detected by clone formation, migration, and mitochondrial membrane potential (MMP) assays. Furthermore, MCU, MICU1, MICU2, Nrf2, and other proteins related to malignant biological behaviors were examined using western blot, immunohistochemistry, and immunofluorescence assays. Results. MCU, Nrf2, and MICU1 were strongly expressed in OSCC as compared to normal tissues, while MICU2 was relatively weakly expressed in OSCC tissues. Knockdown of MCU distinctly weakened proliferation and migration and lowered MMP level in CAL 27 cells. Conversely, its activation reinforced migrated capacity and increased MMP level in CAL 27 cells, which was reversed after cotransfection with sh-Nrf2. After treatment with si-MCU or spermine, Nrf2 expression was not affected in CAL 27 cells. However, MCU expression was distinctly suppressed in CAL 27 cells transfected with sh-Nrf2. Furthermore, knockdown of Nrf2 significantly reversed the increase in expression of MICU1 and MICU2 induced by MCU activation in CAL 27 cells. Conclusion. MCU, as a novel oncogene of OSCC, augments malignant biological behaviors of OSCC cells, which could be transcriptionally regulated by Nrf2. [ABSTRACT FROM AUTHOR]

Accumulating statistics have shown that liver cancer causes the second highest mortality rate of cancer-related deaths worldwide, of which 80% is hepatocellular carcinoma (HCC). Given the underlying molecular mechanism of HCC pathology is not fully understood yet, identification of reliable predictive biomarkers is more applicable to improve patients' outcomes. The results of principal component analysis (PCA) showed that the grouped data from 1557 samples in Gene Expression Omnibus (GEO) came from different populations, and the mean tumor purity of tumor tissues was 0.765 through the estimate package in R software. After integrating the differentially expressed genes (DEGs), we finally got 266 genes. Then, the protein-protein interaction (PPI) network was established based on these DEGs, which contained 240 nodes and 1747 edges. FOXM1 was the core gene in module 1 and highly associated with FOXM1 transcription factor network pathway, while FTCD was the core gene in module 2 and was enriched in the metabolism of amino acids and derivatives. The expression levels of hub genes were in line with The Cancer Genome Atlas (TCGA) database. Meanwhile, there were certain correlations among the top ten genes in the up- and downregulated DEGs. Finally, Kaplan–Meier curves and receiver operating characteristic (ROC) curves were plotted for the top five genes in PPI. Apart from CDKN3, the others were closely concerned with overall survival. In this study, we detected the potential biomarkers and their involved biological processes, which would provide a new train of thought for clinical diagnosis and treatment. [ABSTRACT FROM AUTHOR]

The traditional Chinese medicine decoction FuFangChangTai (FFCT) has been used in the therapy of colon cancer clinically, yielding alleviated toxicity and enhanced immunity. In our previous study, FFCT exerted its antitumor activity not only by inducing apoptosis but also by activating autophagy to eliminate tumor cells. However, its mechanism is not well understood. The purpose of this study was to investigate the relationship between macrophages activation and FFCT-induced autophagy. Results showed that FFCT could induce autophagy in colon cancer, as demonstrated by increased level of intracellular autophagy marker LC3 II in CT26.WT cells by fluorescence microscope and western blot assay. FFCT also facilitated numbers of vesicular bodies with bilayer membrane in CT26.WT cells, which were indicative of autophagosomes formation. Autophagosomes secreted by FFCT-treated CT26.WT cells can activate M1 type macrophages, accompanied with increased expression of costimulatory molecules CD86 and CD40 on the surface of RAW264.7 cells, and more inflammatory cytokines secretion, such as TNF-α, IL-6, MCP-1, and IL-1β. mRNA expressions of M2 macrophages markers, such as IL-10, CD206, Arg-1, and FIZZ-1, were downregulated. And this process helps regulate the polarization of macrophages and promote the immune response. These findings support a mechanism of FFCT-induced autophagy and provide novel evidence demonstrating that macrophages are involved in FFCT-induced autophagy progression. [ABSTRACT FROM AUTHOR]