Value of deep learning reconstruction of chest low-dose CT for image quality improvement and lung parenchyma assessment on lung window.

OBJECTIVES: To explore the performance of low-dose computed tomography (LDCT) with deep learning reconstruction (DLR) for the improvement of image quality and assessment of lung parenchyma. METHODS: Sixty patients underwent chest regular-dose CT (RDCT) followed by LDCT during the same examination. RDCT images were reconstructed with hybrid iterative reconstruction (HIR) and LDCT images were reconstructed with HIR and DLR, both using lung algorithm. Radiation exposure was recorded. Image noise, signal-to-noise ratio, and subjective image quality of normal and abnormal CT features were evaluated and compared using the Kruskal-Wallis test with Bonferroni correction. RESULTS: The effective radiation dose of LDCT was significantly lower than that of RDCT (0.29 ± 0.03 vs 2.05 ± 0.65 mSv, p < 0.001). The mean image noise ± standard deviation was 33.9 ± 4.7, 39.6 ± 4.3, and 31.1 ± 3.2 HU in RDCT, LDCT HIR-Strong, and LDCT DLR-Strong, respectively (p < 0.001). The overall image quality of LDCT DLR-Strong was significantly better than that of LDCT HIR-Strong (p < 0.001) and comparable to that of RDCT (p > 0.05). LDCT DLR-Strong was comparable to RDCT in evaluating solid nodules, increased attenuation, linear opacity, and airway lesions (all p > 0.05). The visualization of subsolid nodules and decreased attenuation was better with DLR than with HIR in LDCT but inferior to RDCT (all p < 0.05). CONCLUSION: LDCT DLR can effectively reduce image noise and improve image quality. LDCT DLR provides good performance for evaluating pulmonary lesions, except for subsolid nodules and decreased lung attenuation, compared to RDCT-HIR. CLINICAL RELEVANCE STATEMENT: The study prospectively evaluated the contribution of DLR applied to chest low-dose CT for image quality improvement and lung parenchyma assessment. DLR can be used to reduce radiation dose and keep image quality for several indications. KEY POINTS: • DLR enables LDCT maintaining image quality even with very low radiation doses. • Chest LDCT with DLR can be used to evaluate lung parenchymal lesions except for subsolid nodules and decreased lung attenuation. • Diagnosis of pulmonary emphysema or subsolid nodules may require higher radiation doses.

A comparative analysis of deep learning and hybrid iterative reconstruction algorithms with contrast-enhancement-boost post-processing on the image quality of indirect computed tomography venography of the lower extremities.

PURPOSE: To examine whether there is a significant difference in image quality between the deep learning reconstruction (DLR [AiCE, Advanced Intelligent Clear-IQ Engine]) and hybrid iterative reconstruction (HIR [AIDR 3D, adaptive iterative dose reduction three dimensional]) algorithms on the conventional enhanced and CE-boost (contrast-enhancement-boost) images of indirect computed tomography venography (CTV) of lower extremities. MATERIALS AND METHODS: In this retrospective study, seventy patients who underwent CTV from June 2021 to October 2022 to assess deep vein thrombosis and varicose veins were included. Unenhanced and enhanced images were reconstructed for AIDR 3D and AiCE, AIDR 3D-boost and AiCE-boost images were obtained using subtraction software. Objective and subjective image qualities were assessed, and radiation doses were recorded. RESULTS: The CT values of the inferior vena cava (IVC), femoral vein ( FV), and popliteal vein (PV) in the CE-boost images were approximately 1.3 (1.31-1.36) times higher than in those of the enhanced images. There were no significant differences in mean CT values of IVC, FV, and PV between AIDR 3D and AiCE, AIDR 3D-boost and AiCE-boost images. Noise in AiCE, AiCE-boost images was significantly lower than in AIDR 3D and AIDR 3D-boost images ( P < 0.05). The SNR (signal-to-noise ratio), CNR (contrast-to-noise ratio), and subjective scores of AiCE-boost images were the highest among 4 groups, surpassing AiCE, AIDR 3D, and AIDR 3D-boost images (all P < 0.05). CONCLUSION: In indirect CTV of the lower extremities images, DLR with the CE-boost technique could decrease the image noise and improve the CT values, SNR, CNR, and subjective image scores. AiCE-boost images received the highest subjective image quality score and were more readily accepted by radiologists.

Curcumol alleviates liver fibrosis through inducing autophagy and ferroptosis in hepatic stellate cells.

To explore the effect of curcumol on autophagy and ferroptosis of hepatic stellate cells, and to clarify the molecular mechanism of its anti-hepatic fibrosis. In the present study, we report that curcumol promotes the death of activated HSCs and reduces the deposition of extracellular matrix. Interestingly, curcumol treatment can trigger ferroptosis to eliminate activated HSCs characterized by iron overload, lipid ROS accumulation, glutathione depletion, and lipid peroxidation. Curcumol promotes HSC autophagy, which may be the key mechanism for its induction of ferroptosis. It is worth noting that the upregulation of nuclear receptor coactivator 4 (NCOA4) may play a key molecular mechanism. NCOA4 mediates the release of iron ions and induces the occurrence of ferroptosis. Overall, curcumol promotes autophagy in hepatic stellate cells, mediates the degradation of NCOA4 and FTH1 complexes, releases iron ions, leads to iron overload, and induces ferroptosis, which may be an important mechanism for its anti-hepatic fibrosis effect.

2-(Naphthalene-2-thio)-5,8-dimethoxy-1,4-naphthoquinone induces apoptosis via ROS-mediated MAPK, AKT, and STAT3 signaling pathways in HepG2 human hepatocellular carcinoma cells.

1,4-naphthoquinone and its derivatives have attracted widespread attention due to their multiple biological activities, such as induction of cancer cell apoptosis; however, most of these compounds have high cytotoxicity. In this study, in order to reduce their toxicity and increase their potential anti-tumor effects, we synthesized a novel 1,4-naphthoquinone derivative named 2-(naphthalene-2-thio)-5,8-dimethoxy-1,4-naphthoquinone (NTDMNQ), and investigated its apoptotic effects and underlying mechanism. Our results showed that NTDMNQ inhibited the viability of HepG2, Hep3B, and Huh7 human hepatocellular carcinoma (HCC) cells. It also increased the accumulation of cells in the G0/G1 phase of the cell cycle by increasing the expression levels of p-p53, p21 and p27, while decreasing the levels of Cyclin D1, Cyclin E, Cyclin-dependent kinase 2 (CDK2), CDK4, and CDK6. Inhibition of reactive oxygen species (ROS) by the ROS scavenger N-acetyl-L-cysteine (NAC) decreased apoptosis in NTDMNQ-treated cells. Western blot analysis showed that NTDMNQ increased the phosphorylation of p38 and c-Jun N-terminal kinase (JNK), and decreased the phosphorylation of extracellular signal-regulated kinase (ERK), AKT, and signal transducer and activator of transcription-3 (STAT3); these effects were blocked by NAC. Both the JNK inhibitor (SP600125) and p38 inhibitor (SB203580) reversed the phosphorylation of STAT3, and the ERK inhibitor (FR180204) and AKT inhibitor (LY294002) reduced the expression of STAT3. Taken together, these findings suggest that NTDMNQ induces apoptosis via ROS-mediated MAPK, AKT and STAT3 signaling pathways in HepG2 cells, and may be a potent anticancer agent.

Molecular biomarker-guided anti-angiogenic targeted therapy for malignant glioma.

Despite aggressive multimodality treatment, the prognosis of glioma, especially malignant glioma, remains very poor. After decades of effort, anti-angiogenic therapy has become an important method of cancer treatment in addition to surgery, radiotherapy and chemotherapy. Although the performance of anti-angiogenic therapy in colorectal cancer is good, its performance in malignant glioma remains unsatisfactory. Several phase III clinical trials showed no overall survival benefits. To solve this problem, the division of patients into groups based on their molecular biomarkers is an important step. This paper provides current insights into anti-angiogenic drugs undergoing clinical trials and discusses the potential of molecular biomarkers to guide glioma diagnosis.

The design of 1,4-naphthoquinone derivatives and mechanisms underlying apoptosis induction through ROS-dependent MAPK/Akt/STAT3 pathways in human lung cancer cells.

The natural compound 1,4-naphthoquinone has potent anti-tumor activity. However, the clinical application of 1,4-naphthoquinone and its derivatives has been limited by their side effects. In this study, we attempted to reduce the toxicity of 1,4-naphthoquinone by synthesizing two derivatives: 2,3-dihydro-2,3-epoxy-2-propylsulfonyl-5,8-dimethoxy-1,4-naphthoquinone (EPDMNQ) and 2,3-dihydro-2,3-epoxy-2-nonylsulfonyl-5,8-dimethoxy-1,4-naphthoquinone (ENDMNQ). Then we evaluated the cytotoxicity and molecular mechanisms of these compounds in lung cancer cells. EPDMNQ and ENDMNQ significantly inhibited the viabilities of three lung cancer cell lines and induced A549 cell cycle arrest at the G1 phase. In addition, they induced the apoptosis of A549 lung cancer cells by increasing the phosphorylation of p38 and c-Jun N-terminal kinase (p-JNK), and decreasing the phosphorylation of extracellular signal-related kinase (p-ERK), protein kinase B (Akt), and signal transducer and activator of transcription 3 (STAT3). Furthermore, they increased reactive oxygen species (ROS) levels in A549 cells; however, pretreatment with the ROS inhibitor N-acetyl-l-cysteine significantly inhibited EPDMNQ- and ENDMNQ-mediated apoptosis and reversed apoptotic proteins expression. In conclusion, EPDMNQ and ENDMNQ induced G1 phase cell cycle arrest and apoptosis in A549 cells via the ROS-mediated activation of mitogen activated protein kinase (MAPK), Akt and STAT3 signaling pathways.

Quinalizarin induces cycle arrest and apoptosis via reactive oxygen species-mediated signaling pathways in human melanoma A375 cells.

Quinalizarin, a bioactive and highly selective compound, is known to promote apoptosis in colon and lung cancer cells. However, studies evaluating quinalizarin-induced apoptosis in melanoma cells have not been conducted. In the present study, we investigated the underlying mechanisms of antimelanoma activity of quinalizarin in human melanoma A375 cells. The MTT assay and Trypan blue staining were used to evaluate the cell viability. The flow cytometry was used to detect cell cycle, apoptosis and reactive oxygen species (ROS). Western blot was used to detect the expression of cell cycle and apoptosis-related proteins, MAPK, and STAT3. The results revealed a significant dose and time dependent effect of quinalizarin on inhibiting proliferation in three kinds of human melanoma cells, and had no significant toxic effects on normal cells. Moreover, quinalizarin triggered G2/M phase cell arrest by modulating the protein expression levels of CDK 1/2, cyclin A, cyclin B, p21 and p27, and induced apoptosis by down-regulating the antiapoptotic protein Bcl-2 and upregulating the proapoptotic protein BAD, leading to the activation of caspase-3 and PARP in the caspase cascade in A375 cells. Quinalizarin treatment led to apoptosis of A375 cells via activation of MAPK and inhibition of STAT3 signaling pathways. In addition, quinalizarin increased the level of ROS, but ROS scavenger NAC inhibited quinalizarin-induced apoptosis by regulating MAPK and STAT3 signaling pathways. In summary, quinalizarin induces cell cycle arrest and apoptosis via ROS-mediated MAPK and STAT3 signaling pathways in human melanoma A375 cells, and quinalizarin may be used as a novel and effective antimelanoma therapeutic.

Glycitein induces reactive oxygen species-dependent apoptosis and G0/G1 cell cycle arrest through the MAPK/STAT3/NF-κB pathway in human gastric cancer cells.

Glycitein is an isoflavone that reportedly inhibits the proliferation of human breast cancer and prostate cancer cells. However, its anti-cancer molecular mechanisms in human gastric cancer remain to be defined. This study evaluated the antitumor effects of glycitein on human gastric cancer cells and investigated the underlying mechanisms. We used MTT assay, flow cytometry and western blotting to investigate its molecular mechanisms with focus on reactive oxygen species (ROS) production. Our results showed that glycitein had significant cytotoxic effects on human gastric cancer cells. Glycitein markedly decreased mitochondrial transmembrane potential (ΔΨm) and increased AGS cells mitochondrial-related apoptosis, and caused G0/G1 cell cycle arrest by regulating cycle-related protein. Mechanistically, accompanying ROS, glycitein can activate mitogen-activated protein kinase (MAPK) and inhibited the signal transducer and activator of transcription 3 (STAT3) and nuclear factor-kappaB (NF-κB) signaling pathways. Furthermore, the MAPK signaling pathway regulated the expression levels of STAT3 and NF-κB upon treatment with MAPK inhibitor and N-acetyl-L-cysteine (NAC). These findings suggested that glycitein induced AGS cell apoptosis and G0/G1 phase cell cycle arrest via ROS-related MAPK/STAT3/NF-κB signaling pathways. Thus, glycitein has the potential to a novel targeted therapeutic agent for human gastric cancer.

Mechanisms underlying isoliquiritigenin-induced apoptosis and cell cycle arrest via ROS-mediated MAPK/STAT3/NF-κB pathways in human hepatocellular carcinoma cells.

Isoliquiritigenin (ISL), a natural flavonoid isolated from plant licorice, has various pharmacological properties, including anticancer, anti-inflammatory, and antiviral effects. However, the underlying mechanisms and signaling pathways of ISL in human hepatocellular carcinoma (HCC) cells remain unknown. In this study, we evaluated the effects of ISL on the apoptosis of human HCC cells with a focus on reactive oxygen species (ROS) production. Our results showed that ISL exhibited cytotoxic effects on two human liver cancer cells in a dose-dependent manner. ISL significantly induced mitochondrial-related apoptosis and cell cycle arrest at the G2/M phase, which was accompanied by ROS accumulation in HepG2 cells. However, pretreatment with an ROS scavenger, N-acetyl-l-cysteine (NAC), inhibited ISL-induced apoptosis. In addition, ISL increased the phosphorylation levels of c-Jun N-terminal kinase (JNK), p38 kinase and inhibitor of NF-κB (IκB), and decreased the phosphorylation levels of extracellular signal-regulated kinase (ERK), signal transducer and activator of transcription 3 (STAT3), nuclear factor-kappa B (NF-κB), these effects were blocked by NAC and mitogen-activated protein kinase (MAPK) inhibitors. Taken together, the findings of this study indicate that ISL induced HepG2 cell apoptosis via ROS-mediated MAPK, STAT3, and NF-κB signaling pathways. Therefore, ISL may be a potential treatment for human HCC, as well as other cancer types.

Quinalizarin Induces Apoptosis through Reactive Oxygen Species (ROS)-Mediated Mitogen-Activated Protein Kinase (MAPK) and Signal Transducer and Activator of Transcription 3 (STAT3) Signaling Pathways in Colorectal Cancer Cells.

BACKGROUND Quinalizarin (1,2,5,8-tetrahydroxyanthraquinone) exhibits potentially useful anticancer effects by inducing apoptosis in several types of cancer, but its underlying mechanism of action remains unknown. The present study examined the effects of quinalizarin on the induction of cell cycle arrest, apoptosis, the generation of reactive oxygen species (ROS), other underlying mechanisms, and its role in modifying colorectal cancer cell lines. MATERIAL AND METHODS The MTT assay was used to evaluate the viability of SW480 and HCT-116 cells that had been treated with quinalizarin and 5-fluorouracil (5-FU). Cell cycle arrest and apoptosis were analyzed by flow cytometry. Western blotting was used to investigate the mitochondrial pathway; Akt, MAPK, and STAT3 signaling pathways were also investigated. The relationship between ROS generation and apoptosis was analyzed by flow cytometry and western blotting. RESULTS The results indicated that quinalizarin significantly inhibits the viability of SW480 and HCT-116 cells in a dose-dependent manner. Quinalizarin induced SW480 cell cycle arrest at G2/M by regulating cyclin B1 and CDK1/2. The apoptosis-related protein expression levels of p-p53, Bad, cleaved caspase-3, cleaved PARP and p-JNK were increased in quinalizarin-treated cells, while protein expression levels Bcl-2, p-Akt, p-ERK, and p-STAT3 were decreased. Quinalizarin induced apoptosis in colorectal cancer cells by regulating MAPK and STAT3 signaling pathways via ROS generation. CONCLUSIONS Quinalizarin induces apoptosis via ROS-mediated MAPK/STAT3 signaling pathways.

The compound 2-(naphthalene-2-thio)-5,8-dimethoxy-1,4-naphthoquinone induces apoptosis via reactive oxygen species-regulated mitogen-activated protein kinase, protein kinase B, and signal transducer and activator of transcription 3 signaling in human gastric cancer cells.

Hit, Lead & Candidate Discovery It is reported that 1,4-naphthoquinones and their derivatives have potent antitumor activity in various cancers, although their clinical application is limited by observed side effects. To improve the therapeutic efficacy of naphthoquinones in the treatment of cancer and to reduce side effects, we synthesized a novel naphthoquinone derivative, 2-(naphthalene-2-thio)-5,8-dimethoxy-1,4-naphthoquinone (NTDMNQ). In this study, we explored the effects of NTDMNQ on apoptosis in gastric cancer cells with a focus on reactive oxygen species (ROS) production. Our results demonstrated that NTDMNQ exhibited the cytotoxic effects on gastric cancer cells in a dose-dependent manner. NTDMNQ significantly induced mitochondrial-related apoptosis in AGS cells and increased the accumulation of ROS. However, pre-treatment with N-acetyl-L-cysteine (NAC), an ROS scavenger, inhibited the NTDMNQ-induced apoptosis. In addition, NTDMNQ increased the phosphorylation of p38 kinase and c-Jun N-terminal kinase (JNK) and decreased the phosphorylation of extracellular signal-regulated kinase (ERK), protein kinase B (Akt), and Signal Transducer and Activator of Transcription 3 (STAT3); these effects were blocked by mitogen-activated protein kinase (MAPK) inhibitor and NAC. Taken together, the present findings indicate that NTDMNQ-induced gastric cancer cell apoptosis via ROS-mediated regulation of the MAPK, Akt, and STAT3 signaling pathways. Therefore, NTDMNQ may be a potential treatment for gastric cancer as well as other tumor types.

Modulation of the HIF-1α-NCOA4-FTH1 Signaling Axis Regulating Ferroptosis-induced Hepatic Stellate Cell Senescence to Explore the Anti-hepatic Fibrosis Mechanism of Curcumol.

INTRODUCTION: Senescence of activated hepatic stellate cells (HSC) reduces extracellular matrix expression to reverse liver fibrosis. Ferroptosis is closely related to cellular senescence, but its regulatory mechanisms need to be further investigated. The iron ions weakly bound to ferritin in the cell are called labile iron pool (LIP), and together with ferritin, they maintain cellular iron homeostasis and regulate the cell's sensitivity to ferroptosis. METHODS: We used lipopolysaccharide (LPS) to construct a pathological model group and divided the hepatic stellate cells into a blank group, a model group, and a curcumol 12.5 mg/L group, a curcumol 25 mg/L group, and a curcumol 50 mg/L group. HIF-1α-NCOA4- FTH1 signalling axis, ferroptosis and cellular senescence were detected by various cellular molecular biology experiments. RESULT: We found that curcumol could induce hepatic stellate cell senescence by promoting iron death in hepatic stellate cells. Curcumol induced massive deposition of iron ions in hepatic stellate cells by activating the HIF-1α-NCOA4-FTH1 signalling axis, which further led to iron overload and lipid peroxidation-induced ferroptosis. Interestingly, our knockdown of HIF-1α rescued curcumol-induced LIP and iron deposition in hepatic stellate cells, suggesting that HIF-1α is a key target of curcumol in regulating iron metabolism and ferroptosis. We were able to rescue curcumol-induced hepatic stellate cell senescence when we reduced LIP and iron ion deposition using iron chelators. CONCLUSION: Overall, curcumol induces ferroptosis and cellular senescence by increasing HIF-1α expression and increasing NCOA4 interaction with FTH1, leading to massive deposition of LIP and iron ions, which may be the molecular biological mechanism of its anti-liver fibrosis.

Diagnosis of a Familial Psittacosis Outbreak with Clinical Analysis and Metagenomic Next-Generation Sequencing Under COVID-19: A Case Series.

Purpose: To explore the clinical characteristics, diagnosis, and treatment of family outbreak of psittacosis and to improve the success rate of treatment. Patients and Methods: The clinical characteristics, diagnosis, treatment, and outcome of family outbreak of psittacosis, which consists three patients, diagnosed by clinical analysis and metagenomic next-generation sequencing (mNGS) in our hospital were analyzed retrospectively. Results: We report on three instances of clustered atypical pneumonia, which were caused by Chlamydia psittaci during the COVID-19 pandemic. All patients exhibited symptoms of fever and cough, while one patient also experienced gastrointestinal symptoms such as nausea, vomiting, and diarrhea. Laboratory tests indicated no significant increase in leukocytes and neutrophils, but a mild increase in C-reactive protein was observed in all three patients. Chest computed tomography (CT) scans revealed a consolidation shadow in a unilateral lung lobe in all three patients. Both patients were treated with empirical moxifloxacin, yielding unsatisfactory outcomes. mNGS was conducted on sputum samples from one adult patient, revealing the presence of Chlamydia psittaci. Additional doxycycline was prescribed immediately, and then the patients' temperatures were stabilized, and the lesion in chest CT was absorbed. The pediatric patient exhibited less severe symptoms compared to the adult patients and exhibited a favorable response to azithromycin administration. Conclusion: This study reports a cluster of a family outbreak of atypical pneumonia caused by C. psittaci in China. The occurrence of a family outbreak during the COVID-19 pandemic may be attributed to familial aggregation resulting from the epidemic. The three cases reported in this study did not experience severe complications, which can be attributed to the prompt medical intervention and swift diagnosis. This finding implies the need to enhance patients' awareness and vigilance towards their health. Additionally, mNGS emerges as a valuable technique for accurately identifying pathogens causing pulmonary infections.

Gut microbiota combined with metabolomics reveal the mechanism of curcumol on liver fibrosis in mice.

OBJECTIVE: Liver fibrosis is a reversible pathological process, and its prevention and treatment hold great significance for patients with chronic liver disease. This study combined 16S rRNA analysis of gut microbiota and serum metabolomics to explore the mechanism of curcumol's effect on liver fibrosis in mice. The results clarified the relationship between the gut microbiota and metabolites in the process of liver fibrosis. MATERIALS AND METHODS: In this study, we randomly divided mice into a control group, a model group, and a curcumol treatment group to analyze the pathological changes in the liver tissue as well as the activities of the toll-like receptor 4 (TLR4)/nuclear factory kappa B (NF-κB) signaling pathway and inflammatory factors, such as tumor necrosis factor (TNF), interleukin 6 (IL-6), and IL-8. The gut microbiota were analyzed by 16 S rRNA sequencing, and serum metabolites were examined by liquid chromatography-mass spectrometry (LC-MS) metabolomic analysis. RESULTS: Molecular biological testing found that curcumol could significantly improve the pathological changes of the liver tissue and inhibit the occurrence of liver inflammation. Intestinal flora testing found that curcumol could significantly change the abundances of Veillonellaceae, Prerotella_oulorum, and Alistipes_finegoldii. Metabolomics analysis found that curcumol's antihepatic fibrosis effect may be related to its regulation of arachidonic acid metabolism. Correlation analysis suggested that curcumol regulated the abundances of Bacteroidota and Bacteroides and participated in the metabolism of Prostaglandin B2. CONCLUSIONS: When liver fibrosis occurs, the intestinal flora and metabolic network are altered. The effect of curcumol on liver fibrosis may be related to its regulation of intestinal flora and the resulting interference with metabolic pathways, thereby reducing liver inflammation.

Copper enhances genotoxic drug resistance via ATOX1 activated DNA damage repair.

Copper is involved in various biochemical and physiological processes. The absorbed copper ions are transported to the intracellular destination via copper chaperones, such as ATOX1. Previous studies have demonstrated that neoplastic cells have a high demand for copper; however, its role in cancer cells has not been fully elucidated. Here, we reveal that the high level of copper contributes to drug resistance and repair of damaged DNA in cancer cells at least partially via ATOX1-induced expression of MDC1, a crucial protein involved in double-strand DNA damage repair. Specifically, ATOX1 enters into nuclear to target MDC1 promoter after treatments of various genotoxic agents, thus promoting the transcription of MDC1 in a copper-dependent manner. Therefore, knockout or blockage of ATOX1 conferred sensitivity to Gemcitabine in transplanted tumor mouse models. Together, our findings gain new insight into the role of copper in DNA damage repair and provide a novel strategy for clinical cancer therapy of drug-resistance cancers.

Modulation of the VEGF/AKT/eNOS signaling pathway to regulate liver angiogenesis to explore the anti-hepatic fibrosis mechanism of curcumol.

ETHNOPHARMACOLOGICAL RELEVANCE: Curcuma is a common Chinese herbal medicine that is used in the clinical treatment of chronic liver disease. Studies have found that curcumol is the main active ingredient of curcuma and has good hepatoprotective and anti-inflammatory effects. However, there are few reports on the molecular mechanism underlying the anti-liver fibrosis effect of curcumol. AIM: To explore the effect of curcumol on liver angiogenesis, and to reveal the mechanism of curcumol against liver fibrosis. MATERIALS AND METHODS: We used liver collagenase perfusion combined with Percoll density gradient sedimentation to separate primary liver sinusoidal endothelial cells, and then applied a leptin-activated cell pathological model. The cells were divided into four treatment groups as follows: blank group, model group, curcumol group, and solafini group. MTT was used to detect the cell proliferation rate in each group, and RT-PCR and western blotting were used to detect the expressions of VEGF, AKT, eNOS, CD31, and vWF. A fluorescent probe was used to detect NO expression, and scanning electron microscopy was used to observe changes in the cell fenestration structure. Angiogenesis assays were used to observe blood vessel formation in each group. RESULTS: The results of the MTT test found that the proliferation rate of each group was higher. The results of the molecular biology tests found that curcumol inhibited the activity of the VEGF/AKT/eNOS pathway, thereby increasing fenestration of sinusoidal endothelial cells and inhibiting liver angiogenesis. These differences were statistically significant compared with the model group. CONCLUSIONS: Curcumol inhibits the activity of the VEGF/AKT/eNOS signaling pathway, regulates the structure of hepatic sinusoidal endothelial cells, and inhibits liver angiogenesis, which together may explain its anti-liver fibrosis mechanism.

Association of a novel PKHD1 mutation in a family with autosomal dominant polycystic liver disease.

BACKGROUND: Autosomal dominant polycystic liver disease (ADPLD) is characterized by multiple cysts in the liver without (or only occasional) renal cysts. At least seven genes are associated with high risk for developing ADPLD; however, clear genetic involvement is undetermined in more than 50% of ADPLD patients. METHODS: To identify additional ADPLD-associated genes, we collected 18 unrelated Chinese ADPLD cases, and performed whole exome sequencing on all the participants. After filtering the sequencing data against the human gene mutation database (HGMD) professional edition, we identified new mutations. We then sequenced this gene in family members of the patient. RESULTS: Among the 18 ADPLD cases analyzed by whole exome sequencing, we found 2 cases with a PRKCSH mutation (~11.1%), 2 cases with a PKD2 mutation (~11.1%), 1 case with both PKHD1 and PKD1 mutations (~5.6%), 1 case with GANAB mutation (~5.6%), 1 case with PKHD1 mutation (~5.6%), and 1 case with PKD1 mutations (~5.6%). We identified a new PKHD1 missense mutation in an ADPLD family, in which both patients showed innumerable small hepatic cysts, as reported previously. Additionally, we found that PRKCSH and SEC63 mutation frequencies were lower in the Chinese population compared with those in European and American populations. CONCLUSIONS: We report a family with ADPLD associated with a novel PKHD1 mutation (G1210R). The genetic profile of ADPLD in the Chinese population is different from that in European and American populations, suggesting that further genetic research on genetic mutation of ADPLD in the Chinese population is warranted.

Vascular Diameters as Predictive Factors of Recanalization Surgery Outcomes in Internal Carotid Artery Occlusion.

Background: Revascularization surgery sometimes can achieve recanalization in patients with internal carotid artery occlusion (ICAO). High-resolution vessel wall magnetic resonance imaging (HRVWI) is a feasible technique to give detailed characteristics of the vessel wall, which may help to identify patients that carry higher success rates and more suitable for revascularization surgery. Objective: To examine the association between HRVWI characteristics of ICAO and the success rate of revascularization surgery in ICAO patients. Methods: We conducted a retrospective analysis of 31 ICAO recanalization patients enrolled from October 2017 to May 2019. The clinical data of patients and lesions were collected and analyzed. Results: A total of 31 ICAO patients were enrolled in this study. No significant differences were found between recanalization success and recanalization failure groups with regard to occlusion length, distal end of the occluded segment, and the treatment applied. The ipsilateral-to-contralateral diameter ratios (I/C ratios) of C1 or C2 and the diameter of C7 were positively related to recanalization success. A two-factor predictive model was constructed, and the I/C ratio of C2 < 0.86 and the diameter of C7 < 1.75mm were separately assigned 1 point. The ICAO patients who scored 0, 1, or 2 points had a risk of 5.6% (1/18), 55.6% (5/9), or 100% (4/4) to fail in the recanalization. Conclusions: The I/C ratios of C1 or C2 and the diameter of C7 are predictive factors of a revascularization surgery success in ICAO patients. A risk stratification model involving C2 and C7 was constructed for future clinical applications.

Establishment of a specific in vivo Cu(â ) reporting system based on metallothionein screening.

Copper is one of the indispensable trace metal elements in organisms, but excess copper means cytotoxicity. Cells protect themselves by storing excess copper in copper-binding proteins. Metallothioneins (MTs) are a group of low-molecular-weight, cysteine-rich proteins, which are well known for sensing and binding the overcharged Zn(Ⅱ), Cd(Ⅱ), and Cu(Ⅰ) in cells. However, there are only few reports on MTs that can specifically respond to intracellular copper ions in mammals in real-time. Here, we screened copper-response MTs in pancreatic cancer cells through data-mining, RNA-seq, and qPCR analysis. We found that MT1E, MT1F, and MT1X mRNA were significantly upregulated after exogenous copper ion induction. By constructing the stable cell lines with MT1E, MT1F, or MT1X promoter-driven EGFP as reporters, we found that only PMT1F-EGFP could specifically and stably report the intracellular Cu(Ⅰ) changes in multiple cell lines including Panc-1, 8988T, 293T, HepG2, and normal hepatic cells, indicating that PMT1F-EGFP is an ideal in vivo Cu(Ⅰ) reporter. Using the PMT1F-EGFP reporter, we found that MEK inhibitors (U0126) and Astragaloside IV could significantly increase intracellular copper ions. According to these results, PMT1F-EGFP reporter can sense intracellular copper change and can be used to screen copper-target drugs and study copper-related cellular physiology and pathology.

Effect of Curcumol on the Fenestrae of Liver Sinusoidal Endothelial Cells Based on NF-κB Signaling Pathway.

OBJECTIVE: To study the effect of curcumol on liver sinusoidal endothelial cells (LSECs) and to analyze the mechanism of antihepatic fibrosis. METHODS: The effects of drug intervention on cell proliferation rates were detected by MTT assay. The expression of NF-κB was detected by RT-PCR and WB. The NF-κB expression and entry into the nucleus were detected by immunofluorescence; scanning electron microscopy was used to observe the changes of LSECs fenestrae. RESULTS: MTT results showed that the interference of cell proliferation in each group was small. RT-PCR showed that the expression of NF-κB in the curcumol intervention group was significantly lower than that in the positive control group (P < 0.05). The WB detection found that, in the curcumol intervention group, the expression of pNF-κB in the NF-κB signaling pathway was significantly lower than that in the positive control group (P < 0.05). Scanning electron microscopy showed that the LSEC fenestrae were significantly improved compared with the positive control group. CONCLUSION: Curcumol may be one of the mechanisms of antihepatic fibrosis by inhibiting the activity of the NF-κB signaling pathway and increasing the fenestrae of LSECs.