The establishment of lipid profiles reference ranges during pregnancy: a systematic review and meta-analysis.

Background: Maternal lipid levels, which are crucial for both foetal development and maternal health, exhibit significant physiological changes during pregnancy. Current reference ranges for lipids that are based on common adults may inadequately assess the appropriate lipid levels during pregnancy and fail to predict potential risks. Therefore, it is necessary to establish trimester-specific reference intervals (TSRIs) for pregnant women during pregnancy.

The impacts of vitamin D supplementation on serum levels of thyroid autoantibodies in patients with autoimmune thyroid disease: a meta-analysis.

Background: Although vitamin D (VitD) deficiency had been found with close relationship with autoimmune thyroid disorders (AITD), the findings about the impacts of VitD supplementation on the production of anti-thyroid peroxidase (TPOAb) and anti-thyroglobulin antibodies (TgAb) remained inconsistent. Thus, a systemic meta-analysis was conducted to figure out the exact effects of VitD intervention on the production of TPOAb and TgAb in AITD patients.

Methods: We searched PubMed, Web of Science, Embase and The Cochrane Library databases for all clinical studies up to May 2023, which evaluated the changes in serum TPOAb and TgAb titers of AITD patients after VitD intervention.

Optimization of 1-Methyl-3-(pyridin-3-yl)-1-indol Derivatives as ROR1 Inhibitors with Improved Activity and Selectivity.

ROR1 has garnered significant attention as a therapeutic target in oncology due to its critical involvement in cancer malignancy. Several biologics targeting ROR1 have advanced to clinical trials, but the development of selective small-molecule inhibitors remains limited. In our previous work, we identified the indole-based as a novel ROR1 inhibitor with promising antitumor efficacy.

Structure-directing optimization of N-(2,3-dihydrobenzo[b] [1,4]dioxin-6-yl)benzamide derivatives as selective receptor tyrosine kinase-like orphan receptor 1 (ROR1) inhibitors for cancer therapy.

Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is an attractive therapeutic target for various cancers, including leukemia and lung cancer. Although some biological agents have entered clinical trials and several small-molecule inhibitors have been developed, selective ROR1 inhibitors remain underexplored. In our previous studies, we identified LDR102, an indole derivative, as a ROR1 inhibitor with favorable binding affinity and potent antitumor efficacy.

Mechanism of LINC01018/miR-182-5p/Rab27B in the immune escape through PD-L1-mediated CD8 T cell suppression in glioma.

Background: Glioma is a malignant tumor associated with poorer prognosis. This study aims to elucidate the mechanism of LINC01018/miR-182-5p/Rab27B axis in PD-L1-mediated CD8 T cell suppression in the progression of gliomas.

Methods: LINC01018, miR-182-5p, and Rab27B expression levels in glioblastoma tissues were measured.

The development of thyroid autoimmunity is potentially associated with the deficiency of vitamin D3 rather than vitamin D2 in euthyroid men.

Objective: Vitamin D(VitD) deficiency has been found prevalent among patients with thyroid autoimmunity (TAI). This study aimed to investigate whether low VitD2 or VitD3 potentially contributed to the development of TAI in euthyroid male patients, which had not been reported before.

Methods: A total of 2882 euthyroid male petroleum workers were recruited from those participants in the healthcare program at the second affiliated hospital of Dalian Medical University in 2021, whose serum VitD levels, thyroid functions, and autoantibody titers were all examined at the same time.

The Dynamic Changes in Maternal Thyroid Parameters Across the Three Trimesters and Their Differential Effects on the Occurrence of Adverse Obstetric Outcomes.

Objective: Thyroid parameters undergo significant dynamic changes during pregnancy. This study aimed to comprehensively analyze the impact of abnormal thyroid parameters in each trimester on the incidence of common adverse obstetric outcomes.

Methods: Blood samples drawn for thyroid parameters in each trimester during the antenatal period were determined after the participants gave birth.

Rational Design, Synthesis, and Biological Evaluation of Novel c-Met Degraders for Lung Cancer Therapy.

Cellular-mesenchymal epithelial transition factor (c-Met) is an attractive target for treating multiple cancers. Despite plentiful c-Met inhibitors have been developed, some issues, including the acquired drug resistance to c-Met inhibitors, have emerged to hamper their application in clinical treatment. Degradation of c-Met offers an opportunity to solve these issues.

Prognostic signature detects homologous recombination deficient in glioblastoma.

Background: Glioblastoma (GBM) is a frequent malignant tumor in neurosurgery characterized by a high degree of heterogeneity and genetic instability. DNA double-strand breaks generated by homologous recombination deficiency (HRD) are a well-known contributor to genomic instability, which can encourage tumor development. It is unknown, however, whether the molecular characteristics linked with HRD have a predictive role in GBM.

Targeting oncogenic transcriptional factor c-myc by oligonucleotide PROTAC for the treatment of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death, but effective therapeutic strategies are limited. Transcriptional factor c-Myc plays an oncogenic role in tumorigenesis and is an attractive target for HCC treatment. However, targeted therapy against c-Myc remains challenging.

Regulation of a novel circATP8B4/miR-31-5p/nestin ceRNA crosstalk in proliferation, motility, invasion and radiosensitivity of human glioma cells.

Deregulation of circular RNAs (circRNAs) is frequent in human glioma. Although circRNA ATPase phospholipid transporting 8B4 (circATP8B4) is highly expressed in glioma, its precise action in glioma development is still not fully understood. The relationship of microRNA (miR)-31-5p and circATP8B4 or nestin (NES) was predicted by bioinformatic analysis and confirmed by RNA pull-down and Dual-luciferase reporter assays.

Genomics and proteomics to determine novel molecular subtypes and predict the response to immunotherapy and the effect of bevacizumab in glioblastoma.

Glioblastoma (GBM) is a highly aggressive, infiltrative malignancy that cannot be completely cured by current treatment modalities, and therefore requires more precise molecular subtype signatures to predict treatment response for personalized precision therapy. Expression subtypes of GBM samples from the Cancer Genome Atlas (TCGA) were identified using BayesNM and compared with existing molecular subtypes of GBM. Biological features of the subtypes were determined by single-sample gene set enrichment analysis.

Discovery of Novel Receptor Tyrosine Kinase-like Orphan Receptor 1 (ROR1) Inhibitors for Cancer Treatment.

Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is an oncogenic membrane protein in several malignancies and has been considered an attractive target for the treatment of human cancers. In this study, structure-based virtual screening and structure optimization were conducted to identify novel ROR1 inhibitors. Based on hit compound , 45 novel ROR1 inhibitors were designed and synthesized, and the detailed structure-activity relationship was investigated.

Screening of Cross-Reactive Aptamers for the Detection of 24 Quinolones by Using a Liebig's Law-Guided Parallel-Series Strategy.

Quinolones, a widely used class of antibiotics, present significant environmental and health concerns if they excessively remain in the environment and in food. Aptamers specific to quinolones can be applied as bioreceptors for the detection of quinolone residues in the environment and food. The quinolone family contains dozens of different individuals that share the same core structure coupled with various substituents at six different positions.

An overview of sphingosine-1-phosphate receptor 2: Structure, biological function, and small-molecule modulators.

Over the past decade, there has been a notable increase in research on sphingosine-1-phosphate receptor 2 (S1PR2), which is a type of G-protein-coupled receptor. Upon activation by S1P or other ligands, S1PR2 initiates downstream signaling pathways such as phosphoinositide 3-kinase (PI3K), Mitogen-activated protein kinase (MAPK), Rho/Rho-associated coiled-coil containing kinases (ROCK), and others, contributing to the diverse biological functions of S1PR2 and playing a pivotal role in various physiological processes and disease progressions, such as multiple sclerosis, fibrosis, inflammation, and tumors. Due to the extensive biological functions of S1PR2, many S1PR2 modulators, including agonists and antagonists, have been developed and discovered by pharmaceutical companies (e.

Novel ProTide prodrugs of 5-fluoro-2'-deoxyuridine for the treatment of liver cancer.

ProTide prodrug technology has emerged as a promising way for the development of anti-viral and anti-tumor drugs, whereas, there are fewer applications for the treatment of liver cancer. Herein, a series of distinct 3'-ester ProTide prodrugs of 5-fluoro-2'-deoxyuridine (FdUR) were synthesized and evaluated for their anti-liver cancer activity. The most efficient prodrug 11b reached a sub-micromolar activity (IC = 0.

Design, synthesis, and evaluation of JTE-013 derivatives as novel potent S1PR2 antagonists for recovering the sensitivity of colorectal cancer to 5-fluorouracil.

Targeting sphingosine-1-phosphate receptor 2 (S1PR2) has been proved as a promising strategy to reverse 5-fluorouracil (5-FU) resistance. Here, we report the discovery of the novel JTE-013 derivative compound 37 h as a more effective S1PR2 antagonist to reverse 5-FU resistance in SW620/5-FU and HCT116 cells than JTE-013 and previously reported compound 5. Compound 37 h could effectively bind S1PR2 and reduce its expression, thus leading to decreased expression of JMJD3 and dihydropyrimidine dehydrogenase (DPD), while also increasing the level of H3K27me3 to decrease the degradation of 5-FU and thereby increase its intracellular concentration in SW620/5-FU, HCT116, and L02 cells.

Rational Design, Synthesis, and Biological Evaluation of Novel S1PR2 Antagonists for Reversing 5-FU-Resistance in Colorectal Cancer.

Resistance to 5-FU reduces its clinical efficacy for the treatment of colorectal cancer. Sphingosine-1-phosphate receptor 2 (S1PR2) has emerged as a potential target to reverse 5-FU-resistance by inhibiting the expression of dihydropyrimidine dehydrogenase (DPD). In this study, 38 novel S1PR2 antagonists based on aryl urea structure were designed and synthesized, and the structure-activity relationship was investigated based on the S1PR2 binding assay.

Long non-coding RNA LINC01018 inhibits human glioma cell proliferation and metastasis by directly targeting miRNA-182-5p.

Aim: Accumulating evidence suggests that lncRNAs are potential biomarkers and key regulators of tumor development and progression. However, the precise function of most lncRNAs in glioma remains unknown. In this study, we explored the role of long intergenic non-protein coding RNA 1018 (LINC01018) in human glioma.

Correlations Between Iron Status and Body Composition in Patients With Type 2 Diabetes Mellitus.

Background: Our study aimed to investigate the association between iron metabolism and body composition in patients with type 2 diabetes mellitus (T2DM).

Methods: A total of 824 patients with T2DM were enrolled. Measurements of body composition were obtained by dual-energy X-ray absorptiometry.

Long Chain Non Coding RNA Targeting miR Signal Axis Regulates the Mechanism of Apoptosis and Invasion and Migration of Glioma U251 Cells.

The occurrence of glioma is gradually promoted by various factors, and it has gone through multiple stages of development, involving abnormal expression of multiple genes. One of the important reasons for the development of gliomas is the interaction of genetic factors and the environment. Non-coding transcripts can also form this high-level structure, and the formation of binding sites for interactions between lncRNA and proteins, DNA, and other RNA molecules may be related to their structural diversity.

Policy Uncertainty, Official Social Capital, and the Effective Corporate Tax Rate-Evidence From Chinese Firms.

The political environment has a significant impact on the sustainable development of enterprises. This manuscript aims to investigate the effect of policy uncertainty and official social capital on enterprises' effective tax rate (ETR) due to the change of officials. Based on the panel data from the Chinese Industrial Enterprise Database from 1998 to 2009, it is shown that the policy uncertainty caused by the change of local government officials significantly increases the ETR of enterprises.

Syringic Acid Suppressed Proliferation, Invasion, and Migration via Inhibition of Matrix Metalloproteinases Expression on Glioblastoma Cells by Promoting Apoptosis.

Background: Human brain tumor glioblastoma (GBM) is the most hostile malignancy, currently lacking a successful cure and good prognosis.

Objective: To examine the anticancer effects of syringic acid (SA) on human cancer GBM cells.

Methodology: The different doses of SA were added to GBM cells to study its effect on viability, invasion, relocation, apoptosis, and mRNA and protein levels.

Novel 5-fluorouracil sensitizers for colorectal cancer therapy: Design and synthesis of S1P receptor 2 (S1PR2) antagonists.

Sphingosine-1-phosphate receptor 2 (S1PR2) has been identified as a brand-new GPCR target for designing antagonists to reverse 5-FU resistance. We herein report the structural optimization and structure-activity relationship of JTE-013 derivatives as S1PR2 antagonists. Compound 9d was the most potent S1PR2 antagonist (K = 34.