Organoids derived from patients provide a new opportunity for research and individualized treatment of malignant peritoneal mesothelioma.

BACKGROUND: Malignant peritoneal mesothelioma (MPM) is an extremely rare and highly invasive tumor. Due to the lack of accurate models that reflect the biological characteristics of primary tumors, studying MPM remains challenging and is associated with an exceedingly unfavorable prognosis. This study was aimed to establish a new potential preclinical model for MPM using patient-derived MPM organoids (MPMOs) and to comprehensively evaluate the practicality of this model in medical research and its feasibility in guiding individualized patient treatment. METHODS: MPMOs were constructed using tumor tissue from MPM patients. Histopathological analysis and whole genome sequencing (WGS) were employed to determine the ability of MPMOs to replicate the original tumor's genetic and histological characteristics. The subcutaneous and orthotopic xenograft models were employed to assess the feasibility of establishing an in vivo model of MPM. MPMOs were also used to conduct drug screening and compare the results with retrospective analysis of patients after treatment, in order to evaluate the potential of MPMOs in predicting the effectiveness of drugs in MPM patients. RESULTS: We successfully established a culture method for human MPM organoids using tumor tissue from MPM patients and provided a comprehensive description of the necessary medium components for MPMOs. Pathological examination and WGS revealed that MPMOs accurately represented the histological characteristics and genomic heterogeneity of the original tumors. In terms of application, the success rate of creating subcutaneous and orthotopic xenograft models using MPMOs was 88% and 100% respectively. Drug sensitivity assays demonstrated that MPMOs have different medication responses, and these differences were compatible with the real situation of the patients. CONCLUSION: This study presents a method for generating human MPM organoids, which can serve as a valuable research tool and contribute to the advancement of MPM research. Additionally, these organoids can be utilized as a means to evaluate the effectiveness of drug treatments for MPM patients, offering a model for personalized treatment approaches.

Circ_0007429/miR-637/TRIM71/Ago2 axis participates in the regulation of proliferation, migration, invasion, apoptosis, and aerobic glycolysis of HCC.

CircRNAs play an important role in the progression of hepatocellular carcinoma (HCC), however, the role of circ_0007429 in HCC remains unknown. Using bioinformatics tools, we selected circ_0007429 that was most highly expressed in HCC tissues and investigated its role in HCC progression. Immunohistochemistry, plasmid transfection, real-time quantitative PCR, and western blot analysis were used to identify the relationship between circ_0007429 and its potential target, miR-637, and TRIM71. The regulatory effect of circ_0007429 on miR-637/TRIM71/Ago2 signaling and its key role in HCC progression were studied in vitro. A nude mouse xenograft model was used to examine tumor growth in vivo. Circ_0007429 and TRIM71 expression were upregulated, while miR-637 expression was downregulated in HCC tissues and cells compared with their expression in control groups. Knockdown of circ_0007429 enhanced apoptosis in HCC cells, while impeded proliferation, migration, invasion, and aerobic glycolysis, which were reversed by miR-637 inhibitor. High levels of circ_0007429 correlated with a poor survival rate of HCC patients. Additionally, circ_0007429 interfering inhibited tumor growth in vivo. TRIM71 directly bound to miR-637 and inhibited Ago2 expression. Moreover, circ_0007429 promotes aerobic glycolysis in HCC cells through the miR/TRIM71/Ago2 axis. Circ_0007429 promotes HCC progression by promoting cell proliferation, migration, invasion, and aerobic glycolysis and by inhibiting cell apoptosis through the miR/TRIM71/Ago2 axis. These results provide molecular insights into the mechanism of HCC and suggest that circ_0007429 could be a therapeutic target for HCC.

Epigenetically regulated gene expression profiles reveal four molecular subtypes with prognostic and therapeutic implications in colorectal cancer.

Transcriptomic deregulation by epigenetic mechanisms plays a crucial role in the heterogeneous progression of colorectal cancer (CRC). Herein, we first demonstrated that the frequencies of the aberrancies of DNA methylation-correlated (METcor) and microRNA (miRNA)-correlated (MIRcor) genes were significantly co-regulated. Next, through integrative clustering of the expression profiles of METcor and MIRcor genes, four molecular subtypes were identified in CRC patients from The Cancer Genome Atlas and then validated in four independent datasets. More importantly, the four subtypes were well characterized and showed distinct clinical and molecular features: (i) S-I: high metabolic activity, sensitive to 5-fluorouracil-based chemotherapy and good prognosis; (ii) S-II: moderate metabolic activity, marked proliferation, frequent KRAS mutation and intermediate prognosis; (iii) S-III: moderate metabolic activity, marked proliferation, promoter DNA hypermethylation, high mutation burden, frequent BRAF and EGFR mutations, moderate levels of epithelial-mesenchymal transition (EMT) and transforming growth factor ß (TGFß) signals, immune-inflamed phenotype, sensitive to cetuximab and death protein-1 inhibitor treatment and relatively poor prognosis and (iv) S-IV: miRNA overexpression, stem/serrated/mesenchymal-like properties, hypoxia, high levels of EMT and TGFß signals, immune-excluded phenotype and poor prognosis. Overall, this study established a molecular classification based on epigenetically regulated gene expression profiles, thereby providing a better understanding of the epigenetic mechanisms underlying CRC heterogeneity.

Quantitative proteomics identified 3 oxidative phosphorylation genes with clinical prognostic significance in gastric cancer.

The aim of the present study was to explore the underlying mechanisms involved in gastric cancer (GC) formation using data-independent acquisition (DIA) quantitative proteomics analysis. We identified the differences in protein expression and related functions involved in biological metabolic processes in GC. Totally, 745 differentially expressed proteins (DEPs) were found in GC tissues vs. gastric normal tissues. Despite enormous complexity in the details of the underlying regulatory network, we find that clusters of proteins from the DEPs were mainly involved in 38 pathways. All of the identified DEPs involved in oxidative phosphorylation were down-regulated. Moreover, GC possesses significantly altered biological metabolic processes, such as NADH dehydrogenase complex assembly and tricarboxylic acid cycle, which is mostly consistent with that in KEGG analysis. Furthermore the higher expression of UQCRQ, NDUFB7 and UQCRC2 were positively correlated with a better prognosis, implicating these proteins may as novel candidate diagnostic and prognostic biomarkers.

Aurora kinase A mediates c-Myc's oncogenic effects in hepatocellular carcinoma.

Dysregulation of c-Myc (Myc) has been shown to contribute to progression of hepatocellular carcinoma, however, the detailed molecular mechanism remains poorly understood. Here, we report that Myc binds to the Aurora kinase A (Aurka) promoter and induces expression of Aurka in HCC cells. Increased expression of Aurka correlates with that of Myc in HCC. Nuclear accumulation of Aurka was confirmed by subcellular protein fractionation and immunoblot experiments in HCC cells. Myc inhibition decreases the nuclear accumulation of Aurka in HCC cells. Also Aurka accumulating in the nucleus up-regulates Myc transcription by binding the Myc promoter containing the highly conserved CCCTCCCCA in the NHE region of the CpG islands. Inhibition of Myc or Aurka diminishes the malignant phenotypes of HCC cells by down-regulating some common target genes. Also Aurka and Myc mediates the effects of each other, at least partially, on proliferation, anchorage-independent soft agar growth, and ATP production. Blocking Aurka in an orthotopic model significantly impairs tumor growth in mice. These results identify a Myc-Aurka feedback loop in which Myc and Aurka regulate expression of each other at the transcriptional level and both play an important role in hepatocarcinogenesis.

The global burden, trends, and inequalities of individuals with developmental and intellectual disabilities attributable to iodine deficiency from 1990 to 2019 and its prediction up to 2030.

Objective: The objective of this study was to assess the global burden of disease for developmental and intellectual disabilities caused by iodine deficiency from 1990 to 2019. Methods: Using data from the global burden of disease (GBD) 2019, we conducted a cross-country inequity analysis to examine the worldwide burden of developmental and intellectual disabilities caused by the issue of iodine deficiency from 1990 to 2019. Absolute and relative inequality were assessed by the slope index of inequality and the concentration index, respectively. After summarising the latest evidence, we also projected the age-standardized prevalence and years lived with disability (YLD) rates up to 2030 using the BAPC and INLA packages in R statistical software. Results: In 2019, the global age-standardized prevalence and YLD rates for developmental and intellectual disabilities due to iodine deficiency were 22.54 per 100,000 population (95% UI 14.47 to 29.23) and 4.12 per 100,000 population (95% UI 2.25 to 6.4), respectively. From 1990 to 2019, the age-standardized prevalence and YLD rates of developmental and intellectual disabilities due to iodine deficiency decreased significantly. Geographic distribution showed that areas with lower socio-demographic indices (SDI) were the most affected. The correlation between higher SDI and lower prevalence highlights the role of economic and social factors in the prevalence of the disease. Cross-national inequity analysis shows that disparities persist despite improvements in health inequalities. In addition, projections suggest that the disease burden may decline until 2030. Conclusion: This research underscores the necessity for targeted interventions, such as enhancing iodine supplementation and nutritional education, especially in areas with lower SDI. We aim to provide a foundation for policymakers further to research effective preventative and potential alternative treatment strategies.

Vaccination with plasmid DNA encoding a mutant toxic shock syndrome toxin-1 ameliorates toxin-induced lethal shock in mice.

Staphylococcal toxic shock syndrome toxin-1 (TSST-1), a superantigenic toxin produced by Staphylococcus (S.) aureus, is a major cause of septic shock and toxic shock syndrome. To investigate whether vaccination with a plasmid DNA encoding a non-toxic mutant TSST-1 (mTSST-1) can protect mice against wild-type TSST-1-induced lethal shock, the mice were intranasally immunized with the plasmid DNA (named pcDNA-mTSST-1) plus a mucosal adjuvant, a non-toxic mutant labile toxin (mLT). After the immunization, the mice were challenged with TSST-1 and lipopolysaccharide (LPS). The survival rate of mice immunized with pcDNA-mTSST-1 plus mLT was higher than that of the control mice immunized with PBS alone, mLT alone, pcDNA-mTSST-1 alone, or a parent plasmid plus mLT. The titers of interferon-γ (IFN-γ) in the sera of mice immunized with pcDNA-mTSST-1 plus mLT were significantly lower than those of the mLT control mice. Immunization with pcDNA-mTSST-1 plus mLT increased the serum levels of TSST-1-specific antibodies, especially immunoglobulin G1 (IgG1) and IgG2a subclasses. Furthermore, the sera obtained from mice immunized with pcDNA-mTSST-1 plus mLT significantly inhibited the TSST-1-induced secretion of IFN-γ and tumor necrosis factor-α (TNF-α) in murine spleen cells in vitro. These results indicate that immunization with pcDNA-mTSST-1 plus mLT provides protection against the lethal toxic shock of mice induced by wild-type TSST-1. The protective effect could be due to TSST-1-specific neutralizing antibodies as well as the inhibition of IFN-γ and TNF-α secretions. Since TSST-1 is commonly released by invasive S. aureus, the pcDNA-mTSST-1 should be useful in preventing toxin-induced shock resulting from S. aureus infection.

Regulation of mild cognitive impairment associated with liver disease by humoral factors derived from the gastrointestinal tract and MRI research progress: a literature review.

Patients with liver disease are prone to various cognitive impairments. It is undeniable that cognitive impairment is often regulated by both the nervous system and the immune system. In this review our research focused on the regulation of mild cognitive impairment associated with liver disease by humoral factors derived from the gastrointestinal tract, and revealed that its mechanisms may be involved with hyperammonemia, neuroinflammation, brain energy and neurotransmitter metabolic disorders, and liver-derived factors. In addition, we share the emerging research progress in magnetic resonance imaging techniques of the brain during mild cognitive impairment associated with liver disease, in order to provide ideas for the prevention and treatment of mild cognitive impairment in liver disease.

Optimum cycles of induction chemotherapy in concurrent chemo-radiotherapy management of unresectable stage III non-small cell lung cancer: Results from a single institutional database.

Induction chemotherapy (IC) prior to concurrent chemo-radiotherapy is the recommended treatment for unresectable stage III non-small cell lung cancer (NSCLC). However, the optimum number of IC cycles for improved survival outcomes is still not known. Here, we assessed the efficacy of 2 or more cycles of IC for unresectable stage III NSCLC patients from our hospital. Data on unresectable stage III NSCLC patients treated with IC + concurrent chemo-radiotherapy at our hospital between 2018 and 2022 were retrieved and analyzed, and survival outcomes compared between IC = 2 and IC > 2 patients. Univariate and multivariate Cox regression, and Chi-square or Fisher exact test were used to assess prognosis and acute toxicity profiles. One hundred twenty-six patients were recruited; 90 for IC = 2 and 36 for IC > 2. Median follow-up time was 26 months [IQR 16-38]. Three-year overall survival was not statistically significant between the 2 groups (77.8% vs 75.0%, P = .453). Distant metastasis free survival, loco-regional recurrence free survival and progression free survival were also not significant, (90.0% vs 86.1%, P = .068), 97.8% vs 97.2%, P = .056), and (73.3% vs 66.7%, P = .446) respectively. Univariate and multivariate Cox regression analysis revealed smoking, T_stage, N_stage, and IC_regimen as independent prognostic factor for overall survival, while drinking and T_stage were risk factors for progression free survival. In summary, 2 cycles of platinum-based IC was effective for stage III unresectable NSCLC and adding more than 2 cycles did not offer extra survival benefits.

Experience and coping strategies of bowel dysfunction in postoperative patients with rectal cancer: a systematic review of qualitative evidence.

Aim: Due to the changes of bowel physiological structure and functional disorders after rectal cancer surgery, patients will face many bowel dysfunction for a long time, which will greatly affect their quality of life. The purpose of this review is to integrate the qualitative research on the experience of bowel dysfunction and coping strategies in postoperative patients with rectal cancer. Methods: Systematic retrieval of PubMed, EMbase, Cochrane Library, CINAHL, Web of Sciences, PsycINFO, Willey and other databases was carried out by using the method of subject words and keywords. The Critical Appraisal Skill Programme (CASP) Qualitative Studies Checklist was used for Qualitative assessment. The findings were extracted from the included study and synthesized into the final themes, which was evaluated strictly in accordance with the ConQual process. Results: Nine studies involving 345 participants were included and two main themes were extracted: "Experience a series of changes caused by bowel dysfunction" and "nmet needs and coping strategies facing bowel dysfunction". The changes of rectal cancer patients who experience bowel dysfunction after operation mainly include three parts: bowel dysfunction is more than just a bowel reaction, which covers the bowel symptoms themselves and the subsequent body-related symptoms. The interruption of a normal life, mainly reflected in personal, family, and social life. Complex psychological reactions to bowel dysfunction, psychological changes have a dual nature, showing a positive and negative intertwined. There are two main aspects of unmet needs and coping strategies: the demand is mainly manifested in the need for information and support from medical professionals, while the coping strategy mainly includes diet, activity and drug management. Conclusion: Rectal cancer patient often experience persistent bowel dysfunction after operation, which has a certain physical and mental effects. A series of new needs of postoperative patients are often not fully met, and patients often rely on their own empirical attempts to seek balance, less can get professional support. Future studies need to focus on how to provide continuous information support for postoperative rectal cancer patients, especially professional care from health care staff.

WIPF1 promotes gastric cancer progression by regulating PI3K/Akt signaling in a myocardin-dependent manner.

Wiskott-Aldrich syndrome protein-interacting protein family member 1 (WIPF1) is associated with malignant tumor progression. However, molecular links between WIPF1 and gastric cancer (GC) remain elusive. The expression of WIPF1 was detected in GC tissues and cells. WIPF1 was overexpressed in GC tissues and cells and high expression of WIPF1 was an independent risk factor for a poor prognosis in patients with GC. Further experiments indicated that WIPF1 promoted the proliferation, invasion, and migration of GC cells in vivo and in vitro. WIPF1-regulated genes were closely related to cell proliferation and migration in GC, and silencing WIPF1 significantly repressed PI3K/AKT signaling pathway activation. WIPF1 was activated by myocardin (MYOCD) translation. Rescue experiments confirmed that MYOCD promotes the proliferation, invasion, and migration of GC cells in a WIPF1-dependent manner and activates the PI3K/AKT signaling pathway. MYOCD may transactivate WIPF1 and facilitate GC cell growth and metastasis by activating the PI3K/AKT signaling pathway.

Spinal cord injury: global burden from 1990 to 2019 and projections up to 2030 using Bayesian age-period-cohort analysis.

Background: Spinal cord injuries, often resulting from spine fractures, can lead to severe lifelong symptoms such as paraplegia and even mortality. Over the past few decades, there has been a concerning increase in the annual incidence and mortality rates of spinal cord injuries, which has also placed a growing financial strain on healthcare systems. This review aims to offer a comprehensive overview of spinal cord injuries by estimating their global incidence, prevalence, and the impact in terms of years lived with disability, using data obtained from the 2019 Global Burden of Disease Study. Method: In this study, we utilized data from the 2019 Global Burden of Disease Study, a widely recognized source for global health data. Our methodology involved estimating the global incidence and prevalence of spinal cord injuries while also assessing the impact on years lived with a disability. We analyzed this data comprehensively to identify patterns and trends and made predictions. Finding: This research delved into the evolving trends in the global burden of spinal cord injuries, identified key risk factors, and examined variations in incidence and disability across different Socio-demographic Index (SDI) levels and age groups. Briefly, in 2019, the global incidence and burden of YLDs of SCI significantly increased compared to 1990. While males had higher incidence rates compared to females. Falls were identified as the primary cause of SCI. Trend projections up to 2030 revealed a slight decrease in ASIR for males, an upward trend in age-specific incidence rates for both sexes and a similar pattern in age-standardized YLD rates. Additionally, our findings provided crucial groundwork for shaping future policies and healthcare initiatives, with the goal of mitigating the burden of spinal cord injuries, enhancing patient outcomes, and fortifying prevention efforts. Interpretation: Understanding the global burden of spinal cord injuries is essential for designing effective healthcare policies and prevention strategies. With the alarming increase in prevalence rates and their significant impact on individuals and healthcare systems, this research contributes vital insights to guide future efforts in reducing the incidence of spinal cord injuries, improving the quality of life for affected individuals, and reducing the economic burden on healthcare systems worldwide.

GSPT1 Functions as a Tumor Promoter in Human Liver Cancer.

OBJECTIVE: This study analyzed the role of G1 to S phase transition 1 protein (GSPT1) in promoting progression of liver cancer cells. METHODS: A bioinformatics database was used to analyze the expression levels of GSPT1 in liver cancer tissues and the prognosis of patients. Subsequently, Western blotting and quantitative PCR were used to verify the expression levels of GSPT1 between normal hepatocytes and hepatoma cells. We used a CRISPR/Cas9 system to construct knockouts of GSPT1 in HepG2 and HCCLM9 liver cancer cells. The effect of GSPT1 on liver cancer cell migration and invasion was analyzed using flow cytometry, migration, and tumor formation assays. RESULTS: The Cancer Genome Atlas Liver Hepatocellular Carcinoma dataset indicated that GSPT1 expression was upregulated in liver cancer cell lines, and patients with liver cancer had poor prognosis. Knockout of GSPT1 in cells significantly inhibited tumor proliferation, cell migration, and growth in vivo. CONCLUSION: In this study, we found that GSPT1 promotes the migration and invasion of liver cancer cells.

Nerve regeneration in transplanted organs and tracer imaging studies: A review.

The technique of organ transplantation is well established and after transplantation the patient might be faced with the problem of nerve regeneration of the transplanted organ. Transplanted organs are innervated by the sympathetic, parasympathetic, and visceral sensory plexuses, but there is a lack of clarity regarding the neural influences on the heart, liver and kidneys and the mechanisms of their innervation. Although there has been considerable recent work exploring the potential mechanisms of nerve regeneration in organ transplantation, there remains much that is unknown about the heterogeneity and individual variability in the reinnervation of organ transplantation. The widespread availability of radioactive nerve tracers has also made a significant contribution to organ transplantation and has helped to investigate nerve recovery after transplantation, as well as providing a direction for future organ transplantation research. In this review we focused on neural tracer imaging techniques in humans and provide some conceptual insights into theories that can effectively support our choice of radionuclide tracers. This also facilitates the development of nuclear medicine techniques and promotes the development of modern medical technologies and computer tools. We described the knowledge of neural regeneration after heart transplantation, liver transplantation and kidney transplantation and apply them to various imaging techniques to quantify the uptake of radionuclide tracers to assess the prognosis of organ transplantation. We noted that the aim of this review is both to provide clinicians and nuclear medicine researchers with theories and insights into nerve regeneration in organ transplantation and to advance imaging techniques and radiotracers as a major step forward in clinical research. Moreover, we aimed to further promote the clinical and research applications of imaging techniques and provide clinicians and research technology developers with the theory and knowledge of the nerve.

DNMBP-AS1 Regulates NHLRC3 Expression by Sponging miR-93-5p/17-5p to Inhibit Colon Cancer Progression.

Long non-coding RNAs (LncRNAs) act as competing endogenous RNAs (ceRNAs) in colon cancer (CC) progression, via binding microRNAs (miRNAs) to regulate the expression of corresponding messenger RNAs (mRNAs). This article aims to explore the detailed molecular mechanism of ceRNA in CC. Top mad 5000 lncRNAs and top mad 5000 mRNAs were used to perform weighted gene co-expression network analysis (WGCNA), and key modules were selected. We used 405 lncRNAs in the red module and 145 mRNAs in the purple module to build the original ceRNA network by online databases. The original ceRNA network included 50 target lncRNAs, 41 target miRNAs, and 34 target mRNAs. Fifty target lncRNAs were used to establish a prognostic risk model by univariate and least absolute shrinkage and selection operator (LASSO) Cox regression analyses. LncRNAs in the risk model were used to build the secondary ceRNA network, which contained 9 lncRNAs in the risk model, 35 miRNAs, and 29 mRNAs. Survival analyses of 29 mRNAs in the secondary ceRNA network have shown HOXA10 and NHLRC3 were identified as crucial prognostic factors. Finally, we constructed the last ceRNA network including 5 lncRNAs in the risk model, 8 miRNAs, and 2 mRNAs related to prognosis. Quantitative real-time polymerase chain reaction (qRT-PCR) results revealed that DNMBP-AS1 and FAM87A were down-regulated in CC cells and tissues. Function assays showed that over-expression of DNMBP-AS1 and FAM87A inhibited CC cells proliferation and migration. Mechanism study showed that DNMBP-AS1 served as miR-93-5p/17-5p sponges and relieved the suppression effect of miR-93-5p/17-5p on their target NHLRC3. Our study suggested that DNMBP-AS1 inhibited the progression of colon cancer through the miR-93-5p/17-5p/NHLRC3 axis, which could be potential therapeutic targets for CC.

Superior cervical ganglionectomy alters gut microbiota in rats.

The diversity and complexity of sympathetic function highlight the importance of fundamental research. Little is known about the interaction of superior cervical sympathetic ganglion (SCG) and gut microbiota. In this study, the engagement of the sympathetic ganglia with gut microbiota was investigated. Bilateral superior cervical ganglionectomy (SCGx) significantly altered the microbiota composition in rats 14 days post-surgery, and these microbiotas may participate in several biological pathways in the host, suggesting the vital role of the cervical sympathetic ganglion in regulating the microbiome-brain axis, and further confirming that the sympathetic nervous system (SNS) regulates the microbiome-brain axis.

Neurotrophin3 promotes hepatocellular carcinoma apoptosis through the JNK and P38 MAPK pathways.

Although liver cancer is a malignant tumor with the highest mortality across the world, its pathogenesis and therapeutic targets remain unclear. Apoptosis, a natural cell death mechanism, is an important target of anticancer therapy. The discovery of effective apoptotic regulators can lead to the identification of novel therapeutic targets for treating cancer. Neurotrophin 3 (NTF3) is a member of the nerve growth factor (NGF) family that is involved in the progression of various cancers, including medulloblastoma, primitive neuroectodermal brain tumors, and breast cancer. NTF3 is under-expressed in human hepatocellular carcinoma (HCC), albeit its specific effects and the action mechanism have not been elucidated. Here, we confirmed that NTF3 expression was significantly low in HCC with reference to the GSEA database. By collecting patient data from our center and performing qRT-PCR analysis, we found that NTF3 expression was significantly downregulated in 74 patients with HCC. Low NTF3 expression was associated with a shorter overall survival (OS), recurrence-free survival (RFS), progression-free survival (PFS), and disease-specific survival (DSS). Both in vivo and in vitro experiments revealed that NTF3 considerably inhibited the progression of HCC cells. We found that the ligand NTF3 is regulated by c-Jun and binds to the p75 neurotrophin receptor (p75NTR) and then activates the JNK and P38 MAPK pathways to induce apoptosis. Entinostat (the target of HDAC1/HDAC3) can activate the NTF3/p75NTR pathway. These results indicate that NTF3 is a tumor suppressor, and that its low expression can help in predict poor clinical outcomes in HCC. Therefore, NTF3 can be used as a potential treatment molecule for HCC.

The connectome from the cerebral cortex to skeletal muscle using viral transneuronal tracers: a review.

Connectomics has developed from an initial observation under an electron microscope to the present well-known medical imaging research approach. The emergence of the most popular transneuronal tracers has further advanced connectomics research. Researchers use the virus trans-nerve tracing method to trace the whole brain, mark the brain nerve circuit and nerve connection structure, and construct a complete nerve conduction pathway. This review assesses current methods of studying cortical to muscle connections using viral neuronal tracers and demonstrates their application in disease diagnosis and prognosis.

TGF-ß1/Smad3 upregulates UCA1 to promote liver fibrosis through DKK1 and miR18a.

TGF-ß1 is the strongest cytokine known to promote liver fibrosis. It has been previously demonstrated that the activation of TGF-ß1 initiates a temporary collagen accumulation program, which is important for wound repair in several organs. Furthermore, temporary extracellular matrix enhancement often leads to progressive fibrosis, which is accountable for cases of severe morbidity and mortality worldwide. However, its action mechanism has not been fully explored. It was previously reported that UCA1 could promote its occurrence and development in various tumors. Importantly, it was reported that TGF-ß1 could activate the expression of UCA1 in liver cancer, gastric cancer, and breast cancer. However, the role of UCA1 in organ fibrosis, including liver fibrosis, remains unreported. The present study reported for the first time that TGF-ß1/Smad3 could promote liver fibrosis by upregulating UCA1, which further affected DKK1 and collagen, such as COL1A1, COL1A2, and COL3A1. Meanwhile, UCA1 could competitively bind with miR18a to stabilize Smad3 to constitute a positive feedback pathway, which played a significant role in the promotion of liver fibrosis. Altogether, the present study provides a theoretical basis for devising promising treatment strategies for liver fibrosis. KEY MESSAGES : UCA1 was found to promote the progression of liver fibrosis in vitro. UCA1 is regulated by TGF-ß1 and promotes liver fibrosis through the canonical Smad pathway. UCA1 can competitively bind with miR18a, promote liver fibrosis by stabilizing Smad3, and form a UCA1-miR18a/Smad3 positive feedback. UCA1 binds EZH2 to inhibit the DKK1 expression and promote liver fibrosis.

Bioinformatics Analysis and Identification of Potential Genes Associated with Pathogenesis and Prognosis of Gastric Cancer.

OBJECTIVE: Gastric cancer (GC) is a deadly cancer and a challenging public health problem globally. This study aimed to analyze potential genes associated with pathogenesis and prognosis of gastric cancer. METHODS: This work selected the overlapping differentially expressed genes (DEGs) in GC from four datasets, the GSE29272, GSE29998, GSE54129 and GSE118916 Gene Expression Omnibus databases. These DEGs were used to carry out comprehensive bioinformatic analysis to analyze the related functions and pathways enriched, the relative expression levels and immune infiltrates, the prognostic characteristics and the interaction network. RESULTS: In total, 55 DEGs increased while 98 decreased in their expression levels. For those DEGs with increased expression, they were mostly concentrated on "focal adhesion" and "ECM-receptor interaction", whereas DEGs with decreased expression were mostly associated with "gastric acid secretion" and "drug metabolism cytochrome P450". MCODE and ClueGO results were then integrated to screen 10 hub genes, which were FN1, COL1A1, COL3A1, BGN, TIMP1, COL1A2, LUM, VCAN, COL5A2 and SPP1. Survival analysis revealed that higher expression of the ten hub genes significantly predicted lower overall survival of GC patients. TIMP1 was most significantly related to neutrophils, CD8+ T cells, as well as dendritic cells, while LUM was most significantly related to macrophages. CONCLUSION: Immunohistochemistry results and functional testing showed that the expression of COL5A2 was elevated in GC and that it might be a key gene in GC tumorigenesis.