Monochasma savatieri Franch. protects against acute lung injury via α7nAChR-TLR4/NF-κB p65 signaling pathway based on integrated pharmacology analysis.

Ethnopharmacological Relevance: Acute lung injury (ALI) is a life-threatening condition with high morbidity and mortality, underscoring the urgent need for novel treatments. Monochasma savatieri Franch. (LRC) is commonly used clinically to treat wind-heat cold, bronchitis, acute pneumonia and acute gastroenteritis.

Identification of memory B-cell-associated miRNA signature to establish a prognostic model in gastric adenocarcinoma.

Background: Memory B cells and microRNAs (miRNAs) play important roles in the progression of gastric adenocarcinoma (GAC), also known as stomach adenocarcinoma (STAD). However, few studies have investigated the use of memory B-cell-associated miRNAs in predicting the prognosis of STAD.

Methods: We identified the marker genes of memory B cells by single-cell RNA sequencing (scRNA-seq) and identified the miRNAs associated with memory B cells by constructing an mRNA‒miRNA coexpression network.

SSELM-neg: spherical search-based extreme learning machine for drug-target interaction prediction.

Background: The experimental verification of a drug discovery process is expensive and time-consuming. Therefore, efficiently and effectively identifying drug-target interactions (DTIs) has been the focus of research. At present, many machine learning algorithms are used for predicting DTIs.

Reciprocal positive regulation between BRD4 and YAP in GNAQ-mutant uveal melanoma cells confers sensitivity to BET inhibitors.

Uveal melanoma (UM) is the most common intraocular cancer in adults. UMs are usually initiated by a mutation in GNAQ or GNA11 (encoding Gq or G11, respectively), unlike cutaneous melanomas (CMs), which usually carry a BRAF or NRAS mutation. Currently, there are no clinically effective targeted therapies for UM carrying Gq/11 mutations.

Identification of active compounds and molecular mechanisms of Dalbergia tsoi Merr.et Chun to accelerate wound healing.

As a traditional Chinese medicine, Dalbergia tsoi Merr.et Chun (JZX) has been used for the treatment of wounds since ancient times. However, the active compounds and molecular mechanisms of JZX in the acceleration of wound healing are still unknown.

PTEN loss confers sensitivity to rapalogs in clear cell renal cell carcinoma.

Rapalogs (everolimus and temsirolimus) are allosteric mTORC1 inhibitors and approved agents for advanced clear cell renal cell carcinoma (ccRCC), although only a subset of patients derive clinical benefit. Progress in genomic characterization has made it possible to generate comprehensive profiles of genetic alterations in ccRCC; however, the correlations between recurrent somatic mutations and rapalog efficacy remain unclear. Here, we demonstrate by using multiple patient-derived ccRCC cell lines that compared to PTEN-proficient cells, PTEN-deficient cells exhibit hypersensitivity to rapalogs.

Systematic discovery of signaling pathways linking immune activation to schizophrenia.

Immune activation has been shown to play a critical role in the development of schizophrenia; however its underlying mechanism remains unknown. Our report demonstrates a high-quality protein interaction network for schizophrenia (SCZ Network), constructed using our "neighborhood walk" approach in combination with "random walk with restart". The spatiotemporal expression pattern of the genes in this disease network revealed two developmental stages sensitive to perturbation by immune activation: mid-to late gestation, and adolescence.

BAP1 loss augments sensitivity to BET inhibitors in cancer cells.

The tumor suppressor gene BAP1 encodes a widely expressed deubiquitinase for histone H2A. Both hereditary and acquired mutations are associated with multiple cancer types, including cutaneous melanoma (CM), uveal melanoma (UM), and clear cell renal cell carcinoma (ccRCC). However, there is no personalized therapy for BAP1-mutant cancers.

Co-occurrence of BAP1 and SF3B1 mutations in uveal melanoma induces cellular senescence.

Uveal melanoma (UM) is the most common intraocular tumor in adults. Recurrent mutations in BRCA1-associated protein 1 (BAP1) and splicing factor 3B subunit 1 (SF3B1) display a mutually exclusive pattern in UM, but the underlying mechanism is unknown. We show that combined BAP1 deficiency and SF3B1 hotspot mutation lead to senescence and growth arrest in human UM cells.

Spliceosome-regulated RSRP1-dependent NF-κB activation promotes the glioblastoma mesenchymal phenotype.

Background: The glioblastoma (GBM) mesenchymal (MES) phenotype, induced by NF-κB activation, is characterized by aggressive tumor progression and poor clinical outcomes. Our previous analysis indicated that MES GBM has a unique alternative splicing (AS) pattern; however, the underlying mechanism remains obscure. We aimed to reveal how splicing regulation contributes to MES phenotype promotion in GBM.

Distinct placental molecular processes associated with early-onset and late-onset preeclampsia.

Patients with preeclampsia display a spectrum of onset time and severity of clinical presentation, yet the underlying molecular bases for the early-onset and late-onset clinical subtypes are not known. Although several transcriptome studies have been done on placentae from PE patients, only a small number of differentially expressed genes have been identified due to very small sample sizes and no distinguishing of clinical subtypes. We carried out RNA-seq on 65 high-quality placenta samples, including 33 from 30 patients and 32 from 30 control subjects, to search for dysregulated genes and the molecular network and pathways they are involved in.

Construction and Analysis of Survival-Associated Competing Endogenous RNA Network in Lung Adenocarcinoma.

Increasing evidence has shown that noncoding RNAs play significant roles in the initiation, progression, and metastasis of tumours via participating in competing endogenous RNA (ceRNA) networks. However, the survival-associated ceRNA in lung adenocarcinoma (LUAD) remains poorly understood. In this study, we aimed to investigate the regulatory mechanisms underlying ceRNA in LUAD to identify novel prognostic factors.

BAP1 deletion abrogates growth and metastasis of murine cutaneous melanoma.

Although germline mutations in BRCA-associated protein-1 (BAP1) predispose to cutaneous melanoma (CM), BAP1 is rarely mutated in primary CM outside the familial context. The role of BAP1 in the pathogenesis of CM remains obscure. Here, we discovered an unexpected role of BAP1 in suppressing CM growth and metastasis.

Preeclampsia-Associated lncRNA Regulates the Proliferation, Invasion, and Migration of Placental Trophoblast Cells.

Preeclampsia is believed to be caused by impaired placentation with insufficient trophoblast invasion, leading to impaired uterine spiral artery remodeling and angiogenesis. However, the underlying molecular mechanism remains unknown. We recently carried out transcriptome profiling of placental long noncoding RNAs (lncRNAs) and identified 383 differentially expressed lncRNAs in early-onset severe preeclampsia.

Association of lncRNA SH3PXD2A-AS1 with preeclampsia and its function in invasion and migration of placental trophoblast cells.

Accumulating evidence suggests that the pathogenesis of preeclampsia involves poor placentation caused by insufficient trophoblast invasion and impaired uterine spiral artery remodeling, yet the underlying molecular mechanism remains unclear. We carried out transcriptome profiling on placentae from preeclamptic patients and normal subjects, and identified about four hundred long non-coding RNAs differentially expressed in placentae of patients with early-onset severe preeclampsia. Here, we report our identification of lncRNA SH3PXD2A-AS1 as a potential causal factor for this disease and its downstream pathways involved in placentation.

Landscape of Dysregulated Placental RNA Editing Associated With Preeclampsia.

Dysregulated RNA editing is well documented in several diseases, such as cancer and neurodegenerative diseases. The extent to which RNA editing might be involved in diseases originated in the placenta remains unknown. Here, we have systematically profiled RNA editome on the placentae, 9 from patients with early-onset severe preeclampsia (EOSPE) and 32 from normal subjects, and a widespread RNA editing dysregulation in EOSPE has been identified.

Whole-Genome Promoter Profiling of Plasma DNA Exhibits Diagnostic Value for Placenta-Origin Pregnancy Complications.

Placenta-origin pregnancy complications, including preeclampsia (PE), gestational diabetes mellitus (GDM), fetal growth restriction (FGR), and macrosomia (MA) are common occurrences in pregnancy, resulting in significant morbidity and mortality for both mother and fetus. However, despite their frequency, there are no reliable methods for the early diagnosis of these complications. Since cfDNA is mainly derived from placental trophoblasts and maternal hematopoietic cells, it might have information for gene expression which can be used for disease prediction.

Gene Selection for the Discrimination of Colorectal Cancer.

Background: Colorectal cancer (CRC) is the third most common cancer worldwide. Cancer discrimination is a typical application of gene expression analysis using a microarray technique. However, microarray data suffer from the curse of dimensionality and usual imbalanced class distribution between the majority (tumor samples) and minority (normal samples) classes.

Classification of glioma based on prognostic alternative splicing.

Background: Previously developed classifications of glioma have provided enormous advantages for the diagnosis and treatment of glioma. Although the role of alternative splicing (AS) in cancer, especially in glioma, has been validated, a comprehensive analysis of AS in glioma has not yet been conducted. In this study, we aimed at classifying glioma based on prognostic AS.

An Integrated Approach for Identifying Molecular Subtypes in Human Colon Cancer Using Gene Expression Data.

Identifying molecular subtypes of colorectal cancer (CRC) may allow for more rational, patient-specific treatment. Various studies have identified molecular subtypes for CRC using gene expression data, but they are inconsistent and further research is necessary. From a methodological point of view, a progressive approach is needed to identify molecular subtypes in human colon cancer using gene expression data.

Conservative site-specific and single-copy transgenesis in human LINE-1 elements.

Genome engineering of human cells plays an important role in biotechnology and molecular medicine. In particular, insertions of functional multi-transgene cassettes into suitable endogenous sequences will lead to novel applications. Although several tools have been exploited in this context, safety issues such as cytotoxicity, insertional mutagenesis and off-target cleavage together with limitations in cargo size/expression often compromise utility.

Identifying molecular subtypes in human colon cancer using gene expression and DNA methylation microarray data.

Identifying colon cancer subtypes based on molecular signatures may allow for a more rational, patient-specific approach to therapy in the future. Classifications using gene expression data have been attempted before with little concordance between the different studies carried out. In this study we aimed to uncover subtypes of colon cancer that have distinct biological characteristics and identify a set of novel biomarkers which could best reflect the clinical and/or biological characteristics of each subtype.

AGE/RAGE/Akt pathway contributes to prostate cancer cell proliferation by promoting Rb phosphorylation and degradation.

Metabolomic research has revealed that metabolites play an important role in prostate cancer development and progression. Previous studies have suggested that prostate cancer cell proliferation is induced by advanced glycation end products (AGEs) exposure, but the mechanism of this induction remains unknown. This study investigated the molecular mechanisms underlying the proliferative response of prostate cancer cell to the interaction of AGEs and the receptor for advanced glycation end products (RAGE).

Probing into the biological processes influenced by ESC factor and oncoprotein HMGA2 using iPSCs.

Induced pluripotent stem cells (iPSCs) are rapidly evolving into an important research tool due to their close resemblance with pluripotent embryonic stem cells (ESCs). Of particular interest at this point are iPSC applications in disease modeling and drug discovery/testing. The high mobility group AT-hook 2 (HMGA2) protein is a nonhistone chromatin factor normally expressed in ESCs and during early developmental stages.