Tumor tissue includes cancer cells and their associated stromal cells, such as adipocytes, myocytes, and immune cells. Obesity modulates tumor microenvironment through the secretion of several inflammatory mediators by inducing adipogenesis and myogenesis. Previously, we indicated that tumor growth is promoted by a transcription factor nuclear factor erythroid 2-related factor 3 (NRF3) in human cancer cells. However, the impact of obesity on NRF3-mediated tumorigenesis remains unknown. Here we show that obesity reprograms the tumorigenic to the antitumorigenic function of Nrf3 using a diet-induced obese mouse model. Nrf3 knockdown decreased tumor growth in mice fed a normal diet (ND), whereas it reversely increased tumor growth in mice fed a high-fat diet (HFD). Then, the tumor tissues derived from Nrf3 knockdown or control cancer cells in ND- or HFD-fed mice were subjected to a DNA microarray-based analysis. Similar to the tumor formation results, the expressions of genes related to adipogenesis, myogenesis, and interferon-alpha response were reversed by obesity, implying an increase or recruitment (or both combined) of adipocytes, myocytes, and immune cells. Among these gene sets, we focused on adipocytes. We showed that Nrf3 knockdown reduced cancer cell growth in the preadipocyte culture medium, while the growth inhibitory effect of Nrf3 knockdown on cancer cells was abolished in the adipocyte culture medium. These results suggest the possibility that cancer-associated adipocytes secrete the potential reprogramming factor from the tumorigenic to the antitumorigenic function of Nrf3 in cancer cells.

This study aimed to investigate the serum plasmacytoma variant translocation 1 (PVT1) level in pregnant women with gestational hypertension and pre-eclampsia and its diagnostic value for diseases and its influence on pregnancy outcome. Serum PVT1 levels in 72 pregnant women with gestational hypertension, 72 pregnant women with pre-eclampsia and 71 healthy pregnant women were evaluated by RT-qPCR, and the diagnostic significance of PVT1 for gestational hypertension was verified by receiver operator characteristic (ROC) curve. The correlation between PVT1 and clinical indicators were evaluated by Pearson correlation coefficient method. Logistic regression analysis evaluated the influencing factors in the development process of gestational hypertension to pre-eclampsia. The effect of PVT1 level on pregnancy outcome was evaluated by prognostic analysis. Results showed that PVT1 level was down-regulated in gestational hypertension group compared with healthy control group, whereas PVT1 level was down-regulated more significantly in pre-eclampsia group than in gestational hypertension group. ROC curve showed that PVT1 had high diagnostic accuracy for gestational hypertension. Pearson correlation coefficient and multiple linear regression analysis showed that PVT1 was correlated with systolic blood pressure, diastolic blood pressure, interleukin (IL)-6 and tumor necrosis factor-α. Logistic regression analysis revealed that IL-6 and PVT1 were the influencing factors of gestational hypertension to pre-eclampsia transition. Moreover, prognostic analysis manifested that the incidence of fetal growth restriction in low PVT1 expression group was significantly higher than that in high PVT1 expression group. The expression level of PVT1 has a high diagnostic accuracy for gestational hypertension, and the low PVT1 expression group is more prone to fetal growth restriction.

The genome sequences of severe acute respiratory syndrome (SARS)-related coronaviruses (sarbecoviruses) have been reported to include many long and complex insertions/deletions (indels) in specific genomic regions, including open reading frame 1a (ORF1a), S1 domain of the spike, and ORF8 genes. These indel hotspots incorporate various non-classical, long, and complex indels with uncertain developmental processes. A possible explanation for these complex and diversified indels at the hotspots is genetic recombination. To determine the possible association between recombination events and development of indel hotspots, this study investigated the genome sequences of many sarbecoviruses from different countries and hosts and compared the distributions of the indel hotspots and recombination sites by performing multiple sequence alignments and recombination analyses. The genomes of 19 SARS-related coronaviruses (15 coronaviruses that infect bats, two that infect humans, one that infects pangolins, and one that infects civets), including human-infecting SARS-CoV and SARS-CoV-2, were evaluated. Hotspots of complex indels with diverse RNA sequences around gaps were clustered in non-structural protein 2 (Nsp2) and Nsp3 of ORF1a, S1, and ORF8. Phylogenetic reconstructions revealed different structures of the inferred phylogenetic trees between genomic regions, and recombination analyses identified multiple recombination sites across ORF1ab and S genes. However, the nucleotide positions of the indel hotspots were not identical with the identified recombination sites in the recombinant viruses, suggesting the involvement of different developmental processes of indel hotspots and genetic recombination. Further research is required to elucidate the developmental mechanisms underpinning clustered complex indels and recombination events in the evolutionary history of sarbecoviruses.

Prostate cancer has a high incidence rate. Many articles reported its usefulness with the advent of robotic surgery in 2001. However, epidural analgesia is declining due to the spread of minimally invasive treatment. There have been no studies using nationwide databases on the impact of epidural analgesia use on length of hospital stay and medical costs. Therefore, we used a Japanese national inpatient database from April 2016 to March 2020. The study population included 46,166 patients. We compared a postoperative analgesia management group using epidural analgesia [Epidural Analgesia Group (EA Group): 5,354] and a group not using epidural analgesia [non-Epidural Analgesia Group (non-EA Group): 40,812]. We found significant differences among the two groups regarding the length of stay, days from surgery to discharge, and inpatient cost of surgery to discharge. Hospital length of stay and postoperative hospital stay was statistically shorter in the EA group than in the non-EA group (11.3 ± 2.8 days vs. 12.1 ± 3.1 days, p < 0.001 and 8.9 ± 2.5 days vs. 9.3 ± 2.7 days, p < 0.001), respectively, and medical costs were also significantly lower in the EA group (84,566 JPY vs. 294,277 JPY, p < 0.001). Also, the activities of daily living (ADL) assessment at discharge determined a considerably higher score in the EA group than in the non-EA groups. Epidural analgesia for postoperative pain management largely depends on each medical institution’s treatment policy. However, epidural analgesia is declining due to the spread of minimally invasive treatment. Therefore, epidural analgesia should be reconsidered because it can reduce hospital stays and hospitalization costs.

Zhibaidihuang Decoction (ZBDHD) is a traditional Chinese medicine with immense potential to treat IgA nephropathy. However, its core ingredients and representative mechanism remain unclear. In this study, we uncovered the key component and underlying mechanisms of ZBDHD for IgA nephropathy by applying network pharmacology and molecular docking approaches. This was done by first identifying the active ingredients and, subsequently, their corresponding gene targets in ZBDHD with the help of the Traditional Chinese Medicine Systems Pharmacology and analysis platform (TCMSP) database, thereby constructing the drug-compound-target network. The IgA nephropathy-associated genes were then identified using GeneCards, Drugbank, and OMIM databases. The overlapped targets were later obtained to establish Protein-Protein Interaction (PPI) networks, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Finally, we performed molecular docking among active compounds and hub genes, and thereby verified the key compound of ZBDHD. The drug-compound-gene network consisted of 289 nodes and 1,113 edges. The top four active ingredients were beta-sitosterol, kaempferol, quercetin and stigmasterol. The top five hub genes in the PPI network were AKT1, ILB1, IL-6, TNF, and TP53. Molecular docking results could demonstrate that there was high affinity among active compounds and the core targets, while quercetin may possibly be the key compound of ZBDHD. We first identified the positive compound and the candidate molecular mechanisms of ZBDHD in an IgA nephropathy treatment and discovered that quercetin might be the core compound of ZBDHD in the treatment of IgA nephropathy.

This study aimed to investigate whether fecal microbiota transplantation (FMT) provides protection for stroke injury in obese patients. Rats were fed high-fat diet (HFD) for 4 weeks and subjected to middle cerebral artery occlusion (MCAO). After FMT for 30 days, body weight, serum total cholesterol and triglyceride levels, neurological score, brain water content, and cerebral infarction volume were measured. Brain reactive oxygen species, superoxide dismutase and malondialdehyde were detected and the levels of Bcl-2, Bax and cleaved caspase-3 were examined. Rats fed with HFD had higher body weight and higher serum total cholesterol and triglyceride levels. Neurological score was lower, brain water content and cerebral infarction volume were higher in obese rats following MCAO, but FMT improved neurological deficit. Moreover, oxidative stress was enhanced in obese rats following MCAO, but FMT attenuated oxidative stress. Brain Bcl-2 level was lower while Bax and cleaved caspase-3 levels were higher in obese rats following MCAO, but FMT increased brain Bcl-2 level and decreased Bax and cleaved caspase-3 levels. In conclusion, FMT attenuated cerebral ischemic injury in obese rats and the beneficial effects of FMT may be mediated by the attenuation of oxidative stress and apoptosis in the brain.

This study aimed to investigate the correlation between Leishmania infection and dendritic cell infiltration and explore the underlying molecular mechanism how Leishmania infection regulates dendritic cell infiltration. Three datasets, GSE63931, GSE80008 and GSE77528 were combined and their batch effects were removed by Combat function in sva R package. Immune cell infiltrations were estimated using the Microenvironment Cell Populations-counter (MCP-counter) R package. Statistical results were verified by Student’s t test. The differential expression of metadherin (MTDH) was identified by Limma R package. The correlation between MTDH expression and dendritic cell infiltration was estimated by Pearson’s product moment correlation coefficient. GDS5086 was used to explore MTDH expression pattern in dendritic cells infected with Leishmania. Compared with normal samples, 5 types of immune cells showed differential infiltration in leishmaniasis samples, including T cells, CD8⁺ T cells, dendritic cells, cytotoxic lymphocytes and B lineage cells. Among these, only DCs were significantly suppressed in leishmaniasis samples. Notably, MTDH expression was differential between leishmaniasis and normal samples. There was a significant correlation between MTDH expression and dendritic cell infiltration. In conclusion, these results demonstrate that Leishmania infection leads to the downregulation of MTDH expression and the suppression of dendritic cell infiltration.

Imaging features of the lung in postmortem computed tomography (CT) scans have been reported in drowning cases. However, it is difficult for forensic pathologists with limited experience to distinguish subtle differences in CT images. In this study, artificial intelligence (AI) with deep learning capability was used to diagnose drowning in postmortem CT images, and its performance was evaluated. The samples consisted of high-resolution CT images of the chest of 153 drowned and 160 non-drowned bodies captured by an 8- or 64-row multislice CT system. The images were captured with an image slice thickness of 1.0 mm and spacing of 30 mm, and 28 images were typically captured. A modified AlexNet was used as the AI architecture. The output result was the drowning probability for each component image. To evaluate the performance of the proposed model, the area under the receiver operating characteristic curve (AUC) was analyzed, and the AUC value of 0.95 was obtained. This indicates that the proposed AI architecture is a useful and powerful complementary testing approach for diagnosing drowning in postmortem CT images. Notably, the accuracy was 81% (62/77) for cases in which resuscitation was performed, and 92% (216/236) for cases in which resuscitation was not attempted. Therefore, the proposed AI method should not be used to diagnose the cause of death when aggressive cardiopulmonary resuscitation was performed. Additionally, because honeycomb lungs are likely to exhibit different morphologies, emphysema cases should also be treated with caution when the proposed AI method is used to diagnose drowning.

The long noncoding RNAs (lncRNAs) are widely involved in the progression of various malignant tumors. The current study investigated the role and mechanism of lncRNA melanoma highly expressed noncoding RNA (MHENCR) in colorectal carcinoma. The expression of MHENCR was measured by real-time quantitative reverse transcription PCR (RT-qPCR). The chi-square analysis was used to analyze the correlation between MHECNR and miR-532-3p. Kaplan-Meier curve and multivariate Cox regression analysis were conducted to assess the significance of MHENCR in clinic. The interaction of MHENCR and miR-532-3p was probed using Pearson analysis and dual-luciferase reporter assay. Cellular experiments were implemented to explore the effects of MHENCR/miR-532-3p on colorectal carcinoma cells. Compared with para-cancerous tissues, MHENCR expression was increased and miR-532-3p expression was decreased in tumor tissues. High expression of MHENCR exhibited shorter overall survival. Interfering of MHENCR suppressed cellular activities while the silence of miR-532-3p diminished the decreased cellular behaviors in colorectal carcinoma cells. Interfering with MHENCR expression represses colorectal carcinoma cell proliferation, migration, and invasion by regulating miR-532-3p. MHENCR may act as a novel prognostic marker in colorectal carcinoma and MHENCR/miR-532-3p may serve as a potential target for treating colorectal carcinoma.

This study aimed to investigate the effects of listening to Wolfgang Amadeus Mozart’s “Sonata for two pianos in D major, K448” and Johann Sebastian Bach’s “Brandenburg concerto No. 4 in G major, BWV1049” on the heart rate, blood pressure, and autonomic nervous activity. Seventeen healthy young adults were recruited as participants. All participants underwent a 10-minute rest, a 10-minute load test, and a triplicate 8-minute music listening process. Electrocardiograms were continuously measured from the measurement onset to completion. Moreover, the high-frequency (HF) component was extracted from the heart rate variability analysis as a measure of the parasympathetic nervous activity and the ratio of low frequency (LF) to HF as a measure of the sympathetic nervous activity. Blood pressure was also measured. There was a significant decrease in the heart rate after listening to both K448 and BWV1049, as well as in the silence state. Blood pressure did not significantly change in either case. Further, the LF/HF ratio significantly decreased after listening to BWV1049. Nevertheless, HF did not change after listening to either music. In conclusion, this study suggests that listening to K448 does not affect the heart rate, blood pressure, or autonomic nervous activity, whereas listening to BWV1049 may suppress the sympathetic nervous activity in healthy adults.