PPIH as a poor prognostic factor increases cell proliferation and m6A RNA methylation in hepatocellular carcinoma.

RNA-binding proteins (RBPs) play a crucial role in the biological processes of liver hepatocellular carcinoma (LIHC). Peptidyl-prolyl cis-trans isomerase H (PPIH), an RBP, possesses prolyl isomerase activity and functions as a protein chaperone. The relationship between PPIH and LIHC has not yet been fully elucidated. This study elucidated potential mechanisms through which PPIH affects the prognosis of LIHC. Bioinformatics analysis and in vitro experiments revealed that PPIH expression was higher in LIHC tissues than in normal tissues. PPIH was identified as an independent prognostic factor, with high PPIH expression being associated with worse prognoses. Moreover, PPIH increased the m6A RNA methylation level and promoted cell proliferation by modulating DNA replication and the expression of cell cycle-related genes in LIHC cells. Bioinformatics analysis also revealed that PPIH expression increased immune cell infiltration and the expression of immune checkpoint proteins. Collectively, these findings indicate that PPIH might promote LIHC progression by enhancing the m6A RNA methylation level, increasing cell proliferation, and altering the tumor immune microenvironment. Our study demonstrates that PPIH, as a poor prognostic factor, may lead to LIHC malignancy through multiple pathways. Further in-depth research on this topic is warranted.

TBC1D10B promotes tumor progression in colon cancer via PAK4­mediated promotion of the PI3K/AKT/mTOR pathway.

This study aimed to explore the expression, function, and mechanisms of TBC1D10B in colon cancer, as well as its potential applications in the diagnosis and treatment of the disease.The expression levels of TBC1D10B in colon cancer were assessed by analyzing the TCGA and CCLE databases. Immunohistochemistry analysis was conducted using tumor and adjacent non-tumor tissues from 68 colon cancer patients. Lentiviral infection techniques were employed to silence and overexpress TBC1D10B in colon cancer cells. The effects on cell proliferation, migration, and invasion were evaluated using CCK-8, EDU, wound healing, and Transwell invasion assays. Additionally, GSEA enrichment analysis was used to explore the association of TBC1D10B with biological pathways related to colon cancer. TBC1D10B was significantly upregulated in colon cancer and closely associated with patient prognosis. Silencing of TBC1D10B notably inhibited proliferation, migration, and invasion of colon cancer cells and promoted apoptosis. Conversely, overexpression of TBC1D10B enhanced these cellular functions. GSEA analysis revealed that TBC1D10B is enriched in the AKT/PI3K/mTOR signaling pathway and highly correlated with PAK4. The high expression of TBC1D10B in colon cancer is associated with poor prognosis. It influences cancer progression by regulating the proliferation, migration, and invasion capabilities of colon cancer cells, potentially acting through the AKT/PI3K/mTOR signaling pathway. These findings provide new targets and therapeutic strategies for the treatment of colon cancer.

Nicotine improves DSS-induced colitis by inhibiting NLRP3 and altering gut microbiota.

Ulcerative colitis (UC) is a chronic recurrent inflammatory disease affecting the rectum and colon. Numerous epidemiological studies have identified smoking as a protective factor for UC. Dysbiosis of intestinal microbiota and release of inflammatory factors are well-established characteristics associated with UC. Therefore, we have observed that nicotine exhibits the potential to ameliorate colitis symptoms in UC mice. Additionally, it exerts a regulatory effect on colonic microbiota dysbiosis by promoting the growth of beneficial bacteria while suppressing harmful bacteria. Combined in vivo and in vitro investigations demonstrate that nicotine primarily impedes the assembly of NLRP3, subsequently inhibiting downstream IL-1ß secretion.

CD206 modulates the role of M2 macrophages in the origin of metastatic tumors.

Tumor metastasis is a key factor affecting the life of patients with malignant tumors. For the past hundred years, scientists have focused on how to kill cancer cells and inhibit their metastasis in vivo, but few breakthroughs have been made. Here we hypothesized a novel mode for cancer metastasis. We show that the phagocytosis of apoptotic tumor cells by macrophages leads to their polarization into the M2 phenotype, and that the expression of stem cell related as well as drug resistance related genes was induced. Therefore, it appears that M2 macrophages have "defected" and have been transformed into the initial "metastatic cancer cells", and thus are the source, at least in part, of the distal tissue tumor metastasis. This assumption is supported by the presence of fused cells with characteristics of both macrophage and tumor cell observed in the peripheral blood and ascites of patients with ovarian cancer. By eliminating the expression of CD206 in M2 macrophages using siRNA, we show that the growth and metastasis of tumors was suppressed using both in vitro cell line and with experimental in vivo mouse models. In summary, we show that M2 macrophages in the blood circulation underwent a "change of loyalty" to become "cancer cells" that transformed into distal tissue metastasis, which could be suppressed by the knockdown of CD206 expression.

PET/CT Examination of Teratomas after Stem Cell Transplantation for a Spinal Cord Injury: A Case Report.

BACKGROUND: In clinical practice, stem cell transplantation has become an effective method for treating spinal cord nerve injury. Up to now, there has been no report on teratoma caused by transplanted stem cell's abnormal differentiation in the clinic, especially in the analysis of imaging manifestations. Therefore, this article aims to analyze the PET/CT imaging manifestations of teratoma caused by stem cell transplantation to improve the imaging diagnosing capability. CASE PRESENTATION: A patient with a spinal cord injury who had received a stem cell transplant was examined by PET/CT on September 10th, 2020. The PET/CT images of the lesion showed irregular mixed low density on the right side of the erector spinae muscle area at the level of the cervical 3-5 vertebral body, with a maximum cross-section of 9.1×3.9 cm. The 18F-FDG metabolism of the lesion was increased, and the maximum standard uptake value (SUVmax) was 10.7. The boundary was unclear with the third cervical vertebra and cervical 3 and 4-level vertebral plates. Based on the patient's medical history, the lesion was diagnosed as an abnormal proliferative tumor, which was consistent with the pathological examination results. CONCLUSION: To date, there have been no clinical reports on teratomas caused by stem cell transplantation for spinal cord injury at home or abroad. This case report enhances the knowledge of the diagnosis and treatment methods of this type of disease and confirms the diagnostic value of PET/CT examination.

Significance of platelet adhesion-related genes in colon cancer based on non-negative matrix factorization-based clustering algorithm.

Background: Although surgical methods are the most effective treatments for colon adenocarcinoma (COAD), the cure rates remain low, and recurrence rates remain high. Furthermore, platelet adhesion-related genes are gaining attention as potential regulators of tumorigenesis. Therefore, identifying the mechanisms responsible for the regulation of these genes in patients with COAD has become important. The present study aims to investigate the underlying mechanisms of platelet adhesion-related genes in COAD patients. Methods: The present study was an experimental study. Initially, the effects of platelet number and related genomic alteration on survival were explored using real-world data and the cBioPortal database, respectively. Then, the differentially expressed platelet adhesion-related genes of COAD were analyzed using the TCGA database, and patients were further classified by employing the non-negative matrix factorization (NMF) analysis method. Afterward, some of the clinical and expression characteristics were analyzed between clusters. Finally, least absolute shrinkage and selection operator regression analysis was used to establish the prognostic nomogram. All data analyses were performed using the R package. Results: High platelet counts are associated with worse survival in real-world patients, and alternations to platelet adhesion-related genes have resulted in poorer prognoses, based on online data. Based on platelet adhesion-related genes, patients with COAD were classified into two clusters by NMF-based clustering analysis. Cluster2 had a better overall survival, when compared to Cluster1. The gene copy number and enrichment analysis results revealed that two pathways were differentially enriched. In addition, the differentially expressed genes between these two clusters were enriched for POU6F1 in the transcription factor signaling pathway, and for MATN3 in the ceRNA network. Finally, a prognostic nomogram, which included the ALOX12 and ACTG1 genes, was established based on the platelet adhesion-related genes, with a concordance (C) index of 0.879 (0.848-0.910). Conclusion: The mRNA expression-based NMF was used to reveal the potential role of platelet adhesion-related genes in COAD. The series of experiments revealed the feasibility of targeting platelet adhesion-associated gene therapy.

TRIM69: a marker of metastasis and potential sensitizer to 5-Fluorouracil and PD-1 blockers in colon adenocarcinoma.

BACKGROUND: Several proteins in the tripartite-motif (TRIM) family are associated with the development of colorectal cancer (CRC), but research on the role of TRIM69 was lacking. The present study examined the correlation between TRIM69 expression and colon adenocarcinoma (COAD). METHODS: mRNA sequencing data for COAD patients was extracted from The Cancer Genome Atlas to analyze correlations between TRIM69 expression and patients' clinical features as well as survival. Potential associations with immune cells and chemosensitivity also were predicted using various algorithms in the TIMER, Limma, clusterProfiler, GeneMANIA, and Gene Set Cancer Analysis platforms. Subsequently, polymerase chain reaction analysis and immunohistochemical staining were used to detect TRIM69 expression in COAD tissue samples from real-world patients. RESULTS: TRIM69 expression was lower in COAD tissues than in normal tissues and correlated with the pathologic stage and metastasis (M category). Additionally, TRIM69 was found to be involved in several immune-related pathways, notably the NOD-like signaling pathway. These results suggest that high TRIM69 expression has the potential to enhance tumor sensitivity to 5-fluorouracil and programmed cell death protein 1 (PD-1) blockers. CONCLUSIONS: From our findings that TRIM69 expression was significantly reduced in COAD compared with non-cancer tissues and associated with pathologic stage and metastasis, we conclude that increasing TRIM69 expression and/or activity may help to improve therapeutic outcomes. Accordingly, TRIM69 represents a potentially valuable marker of metastasis and target for adjuvant therapy in COAD.

Genomic full-length sequence of the HLA-B*13:64 allele was identified in a Chinese bone marrow donor.

Genomic full-length sequence of HLA-B*13:64 was identified in a Chinese individual by sequence-based typing.

LEARN algorithm: a novel option for predicting non-alcoholic steatohepatitis.

Background: There is an unmet need for accurate non-invasive methods to diagnose non-alcoholic steatohepatitis (NASH). Since impedance-based measurements of body composition are simple, repeatable and have a strong association with non-alcoholic fatty liver disease (NAFLD) severity, we aimed to develop a novel and fully automatic machine learning algorithm, consisting of a deep neural network based on impedance-based measurements of body composition to identify NASH [the bioeLectrical impEdance Analysis foR Nash (LEARN) algorithm]. Methods: A total of 1,259 consecutive subjects with suspected NAFLD were screened from six medical centers across China, of which 766 patients with biopsy-proven NAFLD were included in final analysis. These patients were randomly subdivided into the training and validation groups, in a ratio of 4:1. The LEARN algorithm was developed in the training group to identify NASH, and subsequently, tested in the validation group. Results: The LEARN algorithm utilizing impedance-based measurements of body composition along with age, sex, pre-existing hypertension and diabetes, was able to predict the likelihood of having NASH. This algorithm showed good discriminatory ability for identifying NASH in both the training and validation groups [area under the receiver operating characteristics (AUROC): 0.81, 95% CI: 0.77-0.84 and AUROC: 0.80, 95% CI: 0.73-0.87, respectively]. This algorithm also performed better than serum cytokeratin-18 neoepitope M30 (CK-18 M30) level or other non-invasive NASH scores (including HAIR, ION, NICE) for identifying NASH (P value <0.001). Additionally, the LEARN algorithm performed well in identifying NASH in different patient subgroups, as well as in subjects with partial missing body composition data. Conclusions: The LEARN algorithm, utilizing simple easily obtained measures, provides a fully automated, simple, non-invasive method for identifying NASH.

Combining nanotechnology with monoclonal antibody drugs for rheumatoid arthritis treatments.

Rheumatoid arthritis (RA) is a systemic immune disease characterized by synovial inflammation. Patients with RA commonly experience significant damage to their hand and foot joints, which can lead to joint deformities and even disability. Traditional treatments have several clinical drawbacks, including unclear pharmacological mechanisms and serious side effects. However, the emergence of antibody drugs offers a promising approach to overcome these limitations by specifically targeting interleukin-1 (IL-1), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and other cytokines that are closely related to the onset of RA. This approach reduces the incidence of adverse effects and contributes to significant therapeutic outcomes. Furthermore, combining these antibody drugs with drug delivery nanosystems (DDSs) can improve their tissue accumulation and bioavailability.Herein, we provide a summary of the pathogenesis of RA, the available antibody drugs and DDSs that improve the efficacy of these drugs. However, several challenges need to be addressed in their clinical applications, including patient compliance, stability, immunogenicity, immunosupression, target and synergistic effects. We propose strategies to overcome these limitations. In summary, we are optimistic about the prospects of treating RA with antibody drugs, given their specific targeting mechanisms and the potential benefits of combining them with DDSs.

Small molecule RAF265 as an antiviral therapy acts against HSV-1 by regulating cytoskeleton rearrangement and cellular translation machinery.

Host-targeting antivirals (HTAs) have received increasing attention for their potential as broad-spectrum antivirals that pose relatively low risk of developing drug resistance. The repurposing of pharmaceutical drugs for use as antivirals is emerging as a cost- and time- efficient approach to developing HTAs for the treatment of a variety of viral infections. In this study, we used a virus titer method to screen 30 small molecules for antiviral activity against Herpes simplex virus-1 (HSV-1). We found that the small molecule RAF265, an anticancer drug that has been shown to be a potent inhibitor of B-RAF V600E, reduced viral loads of HSV-1 by 4 orders of magnitude in Vero cells and reduced virus proliferation in vivo. RAF265 mediated cytoskeleton rearrangement and targeted the host cell's translation machinery, which suggests that the antiviral activity of RAF265 may be attributed to a dual inhibition strategy. This study offers a starting point for further advances toward clinical development of antivirals against HSV-1.

A primary cardiac schwannoma of the right ventricle: a case report and literature review.

BACKGROUND: Primary cardiac schwannoma remains extremely rare and difficult to distinguish from other myocardial tumours. We report a case of cardiac schwannoma that occurred in the lateral wall of the right ventricle and grew in the myocardial walls. It is the third case of schwannoma that occurred in the free wall of the right ventricle. Moreover, we reviewed and summarised the literature for cases involving benign cardiac schwannomas. CASE PRESENTATION: We present a case of a 64-year-old woman who presented to our centre with syncope for 1-2 min. Echocardiogram and contrast-enhanced computed tomography subsequently revealed a 2.9 × 1.9 cm homogeneous mass originating from the anterior wall of the right ventricle. The patient underwent thoracotomy to resect the mass, which was pathologically verified as Schwann cell tumour. CONCLUSIONS: This is a rare case added to the limited existing literature on cardiac schwannoma. Comprehensive analysis of various imaging examinations is helpful to determine the extent of the tumour. Complete surgical resection is recommended for similar cases involving cardiac schwannomas, especially when the patient has related symptoms. Patients generally have a good prognosis. The pathogenesis of cardiac schwannoma needs further research in order to prevent and manage this rare lesion.

Scorpion venom heat-resistant synthetic peptide protects dopamine neurons against 6-hydroxydopamine neurotoxicity in C. elegans.

Parkinson's disease (PD) is a common neurodegenerative disease. The main pathological feature is the degeneration and loss of dopaminergic neurons in the substantia nigra, which leads to the significant decrease of dopamine content in the striatum. Our recent studies have shown that scorpion venom heat-resistant synthetic peptide (SVHRSP) have protective effects on neuroinflammation. In this study, using C. elegans induced by 6-hydroxydopamine (6-OHDA) as neurodegenerative model, we investigated the effect of SVHRSP on dopaminergic neurons neurotoxicity. Our results implied that SVHRSP treatment could improve the motor capacity in 6-OHDA-induced C. elegans and improve dopaminergic neuron mediated food sensitivity behavior. After SVHRSP treatment, dopaminergic neuron degeneration induced by 6-OHDA was significantly prevented along with a decreased α-synuclein aggregation and restored lipid deposition in C. elegans induced by 6-OHDA. We also observed the reduced levels of reactive oxygen species (ROS) after SVHRSP treatment in model-building C. elegans. In addition, the genes related to apoptosis, oxidative stress, like ctl-1, egl-1and cat-2 in C. elegans induced by 6-OHDA upregulated after treatment with SVHRSP. In conclusion, SVHRSP may impose anti-PD effect through its neuroprotective action on dopaminergic neurons. This study elucidates the effect and related mechanism of SVHRSP on PD and provides evidences for the therapeutic treatment of PD.

Impact of Metabolic Dysfunction Associated Fatty Liver Disease on the Prognosis of Patients with Hepatitis B Virus-Related Hepatocellular Carcinoma Based on Propensity Score Matching Analysis.

Purpose: Both metabolic dysfunction-associated fatty liver disease (MAFLD) and hepatitis B virus (HBV) are risk factors for hepatocellular carcinoma (HCC). Although concurrent MAFLD is common in patients with HBV-related HCC, whether MAFLD increases the risk of poor prognosis in patients with HBV-related HCC remains unclear. This study aimed to investigate the impact of MAFLD on prognosis in patients with HBV-related HCC. Patients and Methods: In this retrospective cohort study, 549 patients with HBV-related HCC were enrolled from January 2010 to April 2020 in Guangdong Provincial Hospital of Chinese Medicine, including 169 patients with MAFLD (MAFLD group) and 380 patients without MAFLD (Non-MAFLD group). Propensity score matching (PSM) analysis was performed to balance the baseline characteristics. Kaplan-Meier survival curves were performed to compare the prognosis between the two matched groups. A multivariate Cox proportional hazards model was used to determine the risk factors for poor prognosis. Results: The median follow-up time for all patients was 20 (interquartile range 8-40) months. We found concurrent MAFLD was associated with a significantly decreased PFS rate before and after PSM analysis. The 1-year, 2-year, and 3-year PFS rates for the MAFLD and Non-MAFLD groups after PSM were 61.3% and 70.8%, 43.9% and 54.5%, 31.1% and 41.8%, respectively. Cox multivariable analysis showed that concurrent MAFLD was an independent risk factor for poor prognosis (death or progression) (HR = 1.49, P = 0.001). More interestingly, the risk of poor prognosis was significantly higher in the MAFLD subtype with metabolic components ≥2 compared to those with metabolic components <2 (HR = 1.97, P < 0.001). Conclusion: Concurrent MAFLD was associated with a higher risk of poor prognosis in patients with HBV-related HCC, especially MAFLD with metabolic components ≥2.

Disturbance of serum lipid metabolites and potential biomarkers in the Bleomycin model of pulmonary fibrosis in young mice.

BACKGROUND: Altered metabolic pathways have recently been considered as potential drivers of idiopathic pulmonary fibrosis (IPF) for the study of drug therapeutic targets. However, our understanding of the metabolite profile during IPF formation is lacking. METHODS: To comprehensively characterize the metabolic disorders of IPF, a mouse IPF model was constructed by intratracheal injection of bleomycin into C57BL/6J male mice, and lung tissues from IPF mice at 7 days, 14 days, and controls were analyzed by pathology, immunohistochemistry, and Western Blots. Meanwhile, serum metabolite detections were conducted in IPF mice using LC-ESI-MS/MS, KEGG metabolic pathway analysis was applied to the differential metabolites, and biomarkers were screened using machine learning algorithms. RESULTS: We analyzed the levels of 1465 metabolites and found that more than one-third of the metabolites were altered during IPF formation. There were 504 and 565 metabolites that differed between M7 and M14 and controls, respectively, while 201 differential metabolites were found between M7 and M14. In IPF mouse sera, about 80% of differential metabolite expression was downregulated. Lipids accounted for more than 80% of the differential metabolite species with down-regulated expression. The KEGG pathway enrichment analysis of differential metabolites was mainly enriched to pathways such as the metabolism of glycerolipids and glycerophospholipids. Eight metabolites were screened by a machine learning random forest model, and receiver operating characteristic curves (ROC) assessed them as ideal diagnostic tools. CONCLUSIONS: In conclusion, we have identified disturbances in serum lipid metabolism associated with the formation of pulmonary fibrosis, contributing to the understanding of the pathogenesis of pulmonary fibrosis.

A novel radiomics signature based on T2-weighted imaging accurately predicts hepatic inflammation in individuals with biopsy-proven nonalcoholic fatty liver disease: a derivation and independent validation study.

Background: Currently, there are no effective methods for assessing hepatic inflammation without resorting to histological examination of liver tissue obtained by biopsy. T2-weighted images (T2WI) are routinely obtained from liver magnetic resonance imaging (MRI) scan sequences. We aimed to establish a radiomics signature based on T2WI (T2-RS) for assessment of hepatic inflammation in people with nonalcoholic fatty liver disease (NAFLD). Methods: A total of 203 individuals with biopsy-confirmed NAFLD from two independent Chinese cohorts with liver MRI examination were enrolled in this study. The hepatic inflammatory activity score (IAS) was calculated by the unweighted sum of the histologic scores for lobular inflammation and ballooning. One thousand and thirty-two radiomics features were extracted from the localized region of interest (ROI) in the right liver lobe of T2WI and, subsequently, selected by minimum redundancy maximum relevance and least absolute shrinkage and selection operator (LASSO) methods. The T2-RS was calculated by adding the selected features weighted by their coefficients. Results: Eighteen radiomics features from Laplacian of Gaussian, wavelet, and original images were selected for establishing T2-RS. The T2-RS value differed significantly between groups with increasing grades of hepatic inflammation (P<0.01). The T2-RS yielded an area under the receiver operating characteristic (ROC) curve (AUROC) of 0.80 [95% confidence interval (CI): 0.71-0.89] for predicting hepatic inflammation in the training cohort with excellent calibration. The AUROCs of T2-RS in the internal cohort and external validation cohorts were 0.77 (0.61-0.93) and 0.75 (0.63-0.84), respectively. Conclusions: The T2-RS derived from radiomics analysis of T2WI shows promising utility for predicting hepatic inflammation in individuals with NAFLD.

Efficacy and safety of AnluoHuaxian pills on chronic hepatitis B with normal or minimally elevated alanine transaminase and early liver fibrosis: A randomized controlled trial.

ETHNOPHARMACOLOGICAL RELEVANCE: The AnluoHuaxian pill (AHP) is a widely used patented medicine for chronic hepatitis B (CHB) patients with advanced fibrosis or cirrhosis that has been used in China for more than 15 years. However, data are lacking on whether monotherapy with AHP can be effective in CHB patients with alanine aminotransferase (ALT) levels less than 2 times the upper limit of normal (ALT<2ULN) and early liver fibrosis (F ≤ 2). AIM OF THE STUDY: We aimed to investigate whether monotherapy with AHP improves liver histology in these patients. MATERIALS AND METHODS: In this double-blind, randomized, placebo-controlled trial, 270 CHB patients with ALT<2ULN and F ≤ 2 were treated in 12 hospitals in China. The patients were randomly assigned to an intervention (AHP) group and a placebo group at a ratio of 2:1. Of these 270 enrolled patients, 147 had paired liver biopsies. The primary end point was histological change after 48 weeks of treatment. RESULTS: Per-protocol analysis revealed that the rate of histologic improvement in liver fibrosis patients in the AHP group was significantly higher than that in the placebo group (37.7% vs. 19.5%, P = 0.035) after 48 weeks of treatment, which was consistent with results from intention-to-treat and sensitivity analyses. Moreover, after adjusting for baseline characteristics, AHP was superior to placebo with respect to improving liver fibrosis (odds ratio [OR] = 2.58, 95% confidence interval [CI]: (1.01, 6.63),P = 0.049) and liver histology (OR = 3.62, 95% CI: (1.42, 9.20),P = 0.007). In noninvasive measurement of liver fibrosis (FibroScan®), the level of liver stiffness measurement (LSM) had decreased significantly at 48 weeks (5.1 kPa) compared with that at baseline (5.7 kPa) (P = 0.008) in the AHP group, whereas it did not decrease significantly in the placebo group. Cirrhosis developed in one patient in the placebo group but in no patients in the AHP group. No serious side effects occurred in the AHP-treated patients. CONCLUSIONS: Treatment of CHB patients who had ALT<2ULN and F ≤ 2 with the traditional Chinese medicine AHP for 48 weeks improves liver fibrosis. However, due to the short duration of treatment and the limited sample size of liver pathology, the long-term benefits of AHP in reducing fibrosis and the risk of cirrhosis and hepatocellular carcinoma in these patients need to be further studied in the future.

Time-Specific Pattern of Iron Deposition in Different Regions in Parkinson's Disease Measured by Quantitative Susceptibility Mapping.

Studies have shown the spatial specificity of cranial iron deposition in different regions in Parkinson's disease (PD). However, the time-specific patterns of iron deposition are not yet clear. The purpose of this study was to investigate the time pattern of iron variations and its clinical relevance in multiple gray matter nuclei in PD using quantitative susceptibility mapping (QSM). Thirty controls and 33 PD patients were enrolled, namely, 11 cases of early stage of PD (ESP) and 22 cases of advanced stage of PD (ASP) according to the Hoehn-Yahr stages. The iron content in the subcortical nuclei covering substantia nigra (SN), red nucleus (RN), head of the caudate nucleus (CN), globus pallidus (GP), and putamen (PT) was measured using QSM, and the clinical symptoms of PD were evaluated by various rating scales. The QSM values in SN, RN, GP, and PT significantly increased in PD patients compared with the controls. Further subgroup comparison with the controls indicated that the iron content in SN and GP (paleostriatum) gradually elevated in the whole disease duration and was related to clinical features. While the iron content in RN and PT (neostriatum) only elevated significantly in ESP patients, further iron deposition was not obvious in ASP patients. Our study confirmed that QSM could be used as a disease biomarker and could be suitable for longitudinal monitoring. However, considering the temporal characteristics of iron deposition in neostriatum, iron deposition in the neostriatum should be paid more attention in the early stage of the disease, even in the preclinical stage, in future research.

Mangiferin Inhibits Human Lung Adenocarcinoma by Suppressing MiR-27b and MiR-92a.

Lung adenocarcinoma (LUAD) is one of the most prevalent malignancies. However, its mechanism and therapeutic strategy remain to be clarified. Mangiferin is a flavonoid derived from the leaves of mango trees of the lacquer family that has many pharmacological and physiological effects. This research aimed to elucidate the biological effect of mangiferin in LUAD cell lines and clarify the in vitro mechanism of mangiferin. Mangiferin was shown to significantly restrain the proliferation of LUAD cells (A549, H1299, and H2030 cells) in a dose- and time-dependent manner. Furthermore, mangiferin was capable of stimulating apoptosis, and more cells were blocked in G1 and S phase in the mangiferin-treated cells than in those not treated with mangiferin. Microarrays and micro-RNA sequencing data suggested that there is a higher level of miR-27b and miR-92a in LUAD tissues than in non-LUAD tissues. Additional experiments indicated that mangiferin may be related to the downregulated levels of miR-92a and miR-27b. In conclusion, mangiferin likely regulates proliferation and apoptosis in LUAD cells by reducing the expression levels of miR-92a and miR-27b.