Scoparone inhibits the development of hepatocellular carcinoma by modulating the p38 MAPK/Akt/NF-κB signaling in nonalcoholic fatty liver disease mice.

BACKGROUND AND STUDY AIM: The mechanisms underlying the progression of non-alcoholic fatty liver disease (NAFLD) into hepatocellular carcinoma (HCC) remains confusing and the therapeutics approaches are also challenging. Here, we aimed to investigate the effects of scoparone on the treatment of HCC stemmed from NAFLD and the underlying mechanisms. MATERIALS AND METHODS: A model of NAFLD-HCC was created in mice, and these mice were treated with scoparone. Biochemical assays were conducted to assess the levels of biochemical markers. Tumors were evaluated through morphological examination. Histopathological analyses were performed using oil red O, Hematoxylin and Eosin, and Masson coloration assays. Immunohistochemistry (IHC) and RT-PCR were performed to analyze protein expression and measure mRNA expression levels, respectively. RESULTS: Scoparone could ameliorate the pathological alterations observed in NAFLD-HCC mouse model. IHC analysis indicated an upregulation of NF-κB p65 expression in both NAFLD and NAFLD-HCC models, which was subsequently reverted by scoparone administration. Furthermore, scoparone treatment resulted in a reversal of the increased mRNA expression levels of NF-κB target genes, including TNF-α, MCP-1, iNOS, COX-2, NF-κB, and MMP-9, which were originally elevated in the NAFLD-HCC condition. Additionally, scoparone exhibited a capacity to counteract the activation of the MAPK/Akt signaling in the NAFLD-HCC model. CONCLUSION: These findings suggest that scoparone holds promise as a potential therapeutic agent for NAFLD-associated HCC, and its model of action may involve the regulation of inflammatory pathways governed by the MAPK/Akt/NF-κB signaling cascade.

MRI measurements of brain hippocampus volume in relation to mild cognitive impairment and Alzheimer disease: A systematic review and meta-analysis.

BACKGROUND: This is the first meta-analysis conducted to compare the hippocampal volume measured by magnetic resonance imaging (MRI) in healthy normal subjects, mild cognitive impairment (MCI) and Alzheimer disease (AD), and to analyze the relationship between hippocampal volume changes and MCI and AD. METHODS: English literatures published from January 2004 to December 2006 were extracted from PubMed, Embase, Wanfang Medical, and China National Knowledge Infrastructure databases. Statistical analysis was carried out with Stata/SE 16.0 software. RESULTS: The smaller the volume of the hippocampus measured by MRI, the more severe the cognitive impairment or AD. Different MRI post-measurement correction methods have different measurement results: Left hippocampal volume measured by MRI Raw volume method is negatively correlated with MCI and AD (OR [odds ratio] = 0.58, 95%CI [confidence interval]: 0.42, 0.75) right hippocampal volume measured was not associated with MCI OR AD (OR = 0.87, 95%CI: 0.56, 1.18); left hippocampal volume measured by MRI total intracranial volume (TIV) Correction was not associated with MCI and AD (OR = 0.90, 95%CI: 0.62, 1.19), measured right hippocampal volume was not associated with MCI OR AD (OR = 0.81, 95%CI: 0.49, 1.12); left hippocampal volume measured by MRI TIV Correction was not associated with MCI and AD (OR = 0.90, 95%CI: 0.62, 1.19), measured right hippocampus volume was negatively associated with MCI and AD (OR = 0.49, 95%CI: 0.35, 0.62). CONCLUSION: The shrinkage of hippocampus volume is closely related to MCI and AD. MRI measurement of hippocampus volume is not only an auxiliary diagnostic tool for MCI and AD, but also a good prognosis assessment tool.

The relationship between vitamin D deficiency and diabetic foot ulcer: A meta-analysis.

A meta-analysis investigation to measure the relationship between vitamin D deficiency (VDD) and diabetic foot ulcer (DFU). A comprehensive literature inspection till February 2023 was applied and 1765 interrelated investigations were reviewed. The 15 chosen investigations enclosed 2648 individuals with diabetes mellitus in the chosen investigations' starting point, 1413 of them were with DFUs, and 1235 were without DFUs. Odds ratio (OR) in addition to 95% confidence intervals (CIs) were used to compute the value of the relationship between VDD and DFU by the dichotomous and continuous approaches and a fixed or random model. Individuals with DFUs had significantly lower vitamin D levels (VDL) (MD, -7.14; 95% CI, -8.83 to -5.44, P < 0.001) compared to those without DFU individuals. Individuals with DFUs had a significantly higher number of VDD individuals (OR, 2.27; 95% CI, 1.63-3.16, P < 0.001) compared to those without DFU individuals. Individuals with DFU had significantly lower VDL and a significantly higher number of VDD individuals compared to those without DFU individuals. However, caused of the small sample sizes of several chosen investigations for this meta-analysis, care must be exercised when dealing with its values.

Alisol B 23-Acetate Increases the Antitumor Effect of Bufalin on Liver Cancer through Inactivating Wnt/ß-Catenin Axis.

Objective: Liver cancer seriously threatens the health of people. Meanwhile, it has been reported that bufalin could act as an inhibitor in liver cancer. In addition, alisol B 23-acetate is a natural product derived from Alisma plantago-aquatica Linn which has an antitumor effect. In this study, we aimed to explore whether alisol B 23-acetate could increase the antitumor effect of bufalin on liver cancer. Methods: In order to detect the effect of alisol B 23-acetate in combination with bufalin on liver cancer, human liver cancer SMMC-7721 and MHCC97 cells were used as subjects. Bufalin and alisol B 23-acetate were performed on cells. Cell viability was tested by MTT assay. In addition, flow cytometry was performed to assess the cell apoptosis. Autophagy-related protein levels were tested by western blotting. Results: The data revealed that bufalin significantly decreased the viability of liver cancer cells, and the inhibitory effect was further increased by alisol B 23-acetate. In addition, alisol B 23-acetate notably enhanced the apoptotic effect of bufalin on liver cancer cells through mediation of Mcl-1, Bax, Bcl-2, and cleaved caspase-3. Meanwhile, alisol B 23-acetate in combination with bufalin induced the autophagy in liver cancer cells through mediation of Beclin-1 and p62. Furthermore, alisol B 23-acetate in combination with bufalin significantly downregulated the level of GSK-3ß and increased the expression of ß-catenin in liver cancer cells. Conclusion: In summary, these findings provide the first evidence that alisol B 23-acetate improves the anticancer activity of bufalin on liver cancer through activation of the Wnt/ß-catenin axis, and these outcomes might shed new lights on exploring the new methods against liver cancer.

Prediction of tumor response via a pretreatment MRI radiomics-based nomogram in HCC treated with TACE.

OBJECTIVES: To develop and validate a pre-transcatheter arterial chemoembolization (TACE) MRI-based radiomics model for predicting tumor response in intermediate-advanced hepatocellular carcinoma (HCC) patients. MATERIALS: Ninety-nine intermediate-advanced HCC patients (69 for training, 30 for validation) treated with TACE were enrolled. MRI examinations were performed before TACE, and the efficacy was evaluated according to the mRECIST criterion 3 months after TACE. A total of 396 radiomics features were extracted from T2-weighted pre-TACE images, and least absolute shrinkage and selection operator (LASSO) regression was applied to feature selection and model construction. The performance of the model was evaluated by receiver operating characteristic (ROC) curves, calibration curves, and decision curves. RESULTS: The AFP value, Child-Pugh score, and BCLC stage showed a significant difference between the TACE response (TR) and non-TACE response (nTR) patients. Six radiomics features were selected by LASSO and the radiomics score (Rad-score) was calculated as the sum of each feature multiplied by the non-zero coefficient from LASSO. The AUCs of the ROC curve based on Rad-score were 0.812 and 0.866 in the training and validation cohorts, respectively. To improve the diagnostic efficiency, the Rad-score was further integrated with the above clinical indicators to form a novel predictive nomogram. Results suggested that the AUC increased to 0.861 and 0.884 in the training and validation cohorts, respectively. Decision curve analysis showed that the radiomics nomogram was clinically useful. CONCLUSION: The radiomics and clinical indicator-based predictive nomogram can well predict TR in intermediate-advanced HCC and can further be applied for auxiliary diagnosis of clinical prognosis. KEY POINTS: • The therapeutic outcome of TACE varies greatly even for patients with the same clinicopathologic features. • Radiomics showed excellent performance in predicting the TACE response. • Decision curves demonstrated that the novel predictive model based on the radiomics signature and clinical indicators has great clinical utility.

Alleviation of non-alcoholic fatty liver disease by Huazhi Fugan Granules is associated with suppression of TLR4/NF-κB signaling pathway.

INTRODUCTION: In parallel with the improvement of living standard, Non-alcoholic fatty liver disease (NAFLD) becomes the most common liver disease around the world. Huazhi Fugan Granules (HZFGG) is a formula which is used to treating of fatty liver, Based on the data we studied, HZFGG may have potential as a therapeutic formula for the alleviation of NAFLD. OBJECTIVES: The aim of our study was to identifying the improvement of HZFGG on NAFLD and exploring the potential mechanisms. METHODS: MCD diet fed C57BL/6 mice once a day for 4 weeks to induce NAFLD model, HZFGG (10, 15, 20g/kg) orally administered simultaneously. The serum levels of TC, TG, ALT, AST were detected. H&E and Oil Red O staining were used to observed the liver sections. TNF-α, IL-1ß and Gpx were also detected. The expression levels of TLR4, MyD88, p-NF-κB, NF-κB, p-IκBa were measured by western blotting assay. The apoptosis of the liver tissues were detected by TUNEL assay. RESULTS: HZFGG decreased the serum levels of TC, TG, ALT, AST in MCD-diet mice. HZFGG alleviated inflammation by decreasing the levels of TNF-α and IL-1ß and ameliorated oxidative stress through increased the level of Gpx. HZFGG Attenuates MCD-induced liver steatosis and injury in mice. Hepatocyte apoptosis was decreased after HZFGG treatment. Furthermore, HZFGG also suppressed the expression levels of TLR4 and MyD88, subsequently, inhibited the phosphorylation of NF-κB and IκBa. CONCLUSION: HZFGG can improved MCD induced hepatic injury through inhibited TLR4/NF-κB signaling pathway in NAFLD model.

Fuyuan Xingnao Decoction Promotes Angiogenesis Through the Rab1/AT1R Pathway in Diabetes Mellitus Complicated With Cerebral Infarction.

Fuyuan Xingnao decoction (FYXN), a traditional Chinese formula comprised of seven herbs, has been utilized to treat diabetes mellitus complicated with cerebral infarction (DMCI) for years. Yet, its protective and regulatory mechanism is poorly understood. The aim of the study is to investigate the effects of FYXN on DMCI in vitro and in vivo, as well as its mechanism in angiogenesis. For in vivo experiments, FYXN was administered to DMCI rats with streptozotocin (STZ) injection-induced diabetes. Then middle cerebral artery occlusion (MCAO) was conducted and the cerebral cortex sections of the rats were obtained. The ultrastructure of cerebral microvessels and new vessel density of ischemic penumbra were evaluated by the transmission electron microscopy (TEM) assay and immunohistochemistry, respectively. Protein and mRNA expression levels of Rab1/AT1R in cortex were assayed by Western blotting and real-time fluorescence quantitative real-time polymerase chain reaction (RT-qPCR). In vitro, FYXN serum was produced in rats on the fourth day 2 h after the last FYXN administration. Green fluorescence was observed after transfection with lentivirus packaged Rab1-WT or siRNA for 24 h. The activity of brain microvascular endothelial cells (BMECs) treated with sera from these rats was tested by MTT assay and Transwell assays, respectively. The expression of AT1R on the cell membrane and endoplasmic reticulum of BMECs was evaluated by immunofluorescence staining. Protein expression levels of signaling molecules in the Rab1/AT1R pathways were also detected. Results showed that in vivo, FYXN treatment significantly intensified CD31 staining in the cortical areas and enhanced the mRNA and protein levels of AT1R, Ang II, Rab1a, Rab1b and VEGF expression in ischemic cerebral cortex tissues. In vitro, the expression levels of AT1R, Ang II, Rab1a, Rab1b and VEGF in the cerebral infarction model group were significantly higher than those in the control group, with further increases after administration of FYXN drug serum. FYXN promoted the proliferation and migration of BMECs by activating the Rab1/AT1R signaling pathway. In conclusion, FYXN exerts a protective effect against DMCI by promoting angiogenesis via the Rab1/AT1R pathway, which provides strong evidence for the therapeutic effect of FYXN on DMCI.

Treatment of hospital-acquired pneumonia with multi-drug resistant organism by Buzhong Yiqi decoction based on Fuzheng Quxie classical prescription: study protocol for a randomized controlled trial.

BACKGROUND: Drug resistance in China is becoming a more and more serious issue. Infection by drug-resistant bacteria has become a major disease that seriously threatens the health of Chinese people and affects national medical finance. Therefore, it is of great scientific and clinical significance to actively carry out research on the prevention and treatment of infections by multi-drug resistant organisms (MDRO). Previous studies by the authors suggested that patients with hospital-acquired pneumonia caused by MDRO mostly showed the pathological state of "insufficient healthy Qi and internal accumulation of pathogenic Qi" and "acute deficiency syndrome" mainly characterized by Qi deficiency. Buzhong Yiqi decoction is a famous classic prescription in traditional Chinese medicine (TCM) for treating internal damage fever. This study intends to provide an evidence-based rationale for Buzhong Yiqi decoction in treating MDRO hospital-acquired pneumonia by conducting a multi-center randomized controlled clinical study. METHODS/DESIGN: This study is designed to be a multi-center randomized controlled study in which patients are assigned randomly into control (standard therapy) and trial (standard therapy plus Buzhong Yiqi decoction) groups. The patients will be selected from the emergency department and the ICU inpatient department of five study sites and will all be diagnosed with MDRO hospital-acquired pneumonia and meet the inclusion criteria. Forty patients are to be enrolled in each study site, resulting in a total of 200 patients in the study. The treatment course is 28 days. DISCUSSION: In this study: (1) the theory of "acute Qi deficiency" in MDRO hospital-acquired pneumonia is put forward for the first time, and the basic theories of TCM are further improved; (2) a multi-center randomized controlled clinical study will be performed for the first time with Buzhong Yiqi decoction, the classic prescription for reinforcing healthy Qi and eliminating pathogenic Qi, providing a reliable evidence-based rationale for the treatment of MDRO pulmonary infection with TCM; (3) the clinical application and modern disease spectrum of Buzhong Yiqi decoction is expanded, and the scientific notion of "treating different diseases with the same method" is enriched further. TRIAL REGISTRATION: China Clinical Trial Registry, ChiCTR1900022429. Registered on April 11, 2019. http://www.chictr.org.cn/listbycreater.aspx.