Sappanone A ameliorates acute lung injury through inhibiting the activation of the NF-κB signaling pathway.

Acute lung injury (ALI) is a serious respiratory disease characterized by diffuse alveolar injury, and it has emerged as a major concern in clinical practice due to limited treatments. This study aimed to explore the pharmacological effects and regulatory mechanism of sappanone A (SA) on ALI. In vivo, mice were administered with SA followed by intratracheal injection of lipopolysaccharide (LPS) to establish an animal model of ALI.

The Protective Effects of Ruscogenin Against Lipopolysaccharide-Induced Myocardial Injury in Septic Mice.

Sepsis-induced myocardial dysfunction commonly occurs in individuals with sepsis and is a severe complication with high morbidity and mortality rates. This study aimed to investigate the effects and potential mechanisms of the natural steroidal sapogenin ruscogenin (RUS) against lipopolysaccharide (LPS)-induced myocardial injury in septic mice. We found that RUS effectively alleviated myocardial pathological damage, normalized cardiac function, and increased survival in septic mice.

Lung Ultrasound Score as a Predictor of Failure to Wean COVID-19 Elderly Patients off Mechanical Ventilation: A Prospective Observational Study.

Background: The lung ultrasound score was developed for rapidly assessing the extent of lung ventilation, and it can predict failure to wean various types of patients off mechanical ventilation. Whether it is also effective for COVID-19 patients is unclear.

Methods: This single-center, prospective, observational study was conducted to assess the ability of the 12-region lung ultrasound score to predict failure to wean COVID-19 patients off ventilation.

Pattern Recognition Analysis of Metabolites in Escherichia coli Based on ESI-Orbitrap Mass Spectrometry.

To achieve rapid detection of carbapenem-resistant Escherichia coli strains, a pattern recognition method based on electrospray ionization Orbitrap mass spectrometry (ESI-Orbitrap MS) was used for the analysis of drug-resistant, and sensitive strains of metabolites were analyzed. Results of five clustering methods applied to analytical data of metabolites were evaluated using iso-phenotypic coefficients. The effectiveness of three methods, principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA) and orthogonal partial least squares discriminant analysis (OPLS-DA), was compared.

CircNFIX stimulates the proliferation, invasion, and stemness properties of ovarian cancer cells by enhancing SH3RF3 mRNA stability via binding LIN28B.

We aimed to study the regulatory roles and mechanism of circular nuclear factor IX (circNFIX) in cancer growth and stemness properties of ovarian cancer (OC). CircNFIX and SH3RF3 levels in OC tissues and cells were tested by quantitative real-time PCR. RNase R treatment quantified circNFIX RNA stability.

Exosomal circNFIX promotes angiogenesis in ovarian cancer via miR-518a-3p/TRIM44 axis.

Ovarian cancer (OC) is a gynecological cancer with high mortality. OC-derived exosomal circRNAs can regulate angiogenesis. This study aims to explore the role and mechanism of exosomal circRNA nuclear factor I X (CircNFIX) derived from OC cells in angiogenesis.

[Clear Cell Carcinoma of Cervix in a 12-Year-Old Girl: A Case Report].

The 12-year-old patient was admitted to the hospital on September 19, 2019 for "vaginal bleeding for 2 months and pelvic mass to be diagnosed". The patient and her family explicitly denied any previous history of diethylstilbestrol exposure. After admission, relevant examinations were conducted and hysteroscopic exploration was performed under general anesthesia.

Phosphorylation of Akt at Thr308 regulates p-eNOS Ser1177 during physiological conditions.

Endothelial nitric oxide synthase (eNOS)-derived nitric oxide (NO) plays a crucial role in maintaining vascular homeostasis. As a hallmark of eNOS activation, phosphorylation of eNOS at Ser1177 induced by activated protein kinase B (PKB/Akt) is pivotal for NO production. The complete activation of Akt requires its phosphorylation of both Thr308 and Ser473.

Insight into molecular characteristics of a Chinese coal via separation, characterization, and data processing.

Dayan lignite was subjected to thermal dissolution sequentially with cyclohexane, acetone, and methanol. Each thermal dissolution extract was subjected to further separation/enrichment using column chromatography, which was sequentially eluted with petroleum ether, a mixture of ethyl acetate and petroleum ether (vol:vol = 1:1), and ethyl acetate. The three thermal dissolution extracts and nine enrichment subfractions were characterized by an Orbitrap mass spectrometry equipped with an atmospheric pressure chemical ionization ion source.

N/O co-doped porous interconnected carbon nanosheets from the co-hydrothermal treatment of soybean stalk and nickel nitrate for high-performance supercapacitors.

Porous interconnected carbon nanosheets (PICNs) with high electrochemical performance were prepared by doping urea and a co-hydrothermal precursor derived from soybean stalk (SS) and nickel nitrate. The specific surface area and average pore diameter of the as-synthesized PICNs are 2226.29 m g and 1.

Proteomic Profiling of Signaling Networks Modulated by G-CSF/Plerixafor/Busulfan-Fludarabine Conditioning in Acute Myeloid Leukemia Patients in Remission or with Active Disease prior to Allogeneic Stem Cell Transplantation.

To characterize intracellular signaling in peripheral blood (PB) cells of acute myeloid leukemia (AML) patients undergoing pretransplant conditioning with CXCR4 inhibitor plerixafor, granulocyte colony-stimulating factor (G-CSF), and busulfan plus fludarabine (Bu+Flu) chemotherapy, we profiled 153 proteins in 33 functional groups using reverse phase protein array. CXCR4 inhibition mobilized AML progenitors and clonal AML cells, and this was associated with molecular markers of cell cycle progression. G-CSF/plerixafor and G-CSF/plerixafor/Bu+Flu modulated distinct signaling networks in AML blasts of patients undergoing conditioning with active disease compared to nonleukemic PB cells of patients in remission.

Distinct protein signatures of acute myeloid leukemia bone marrow-derived stromal cells are prognostic for patient survival.

Mesenchymal stromal cells (MSC) support acute myeloid leukemia (AML) cell survival in the bone marrow (BM) microenvironment. Protein expression profiles of AML-derived MSC are unknown. Reverse phase protein array analysis was performed to compare expression of 151 proteins from AML-MSC (n=106) with MSC from healthy donors (n=71).

Anti-leukemia activity of NSC-743380 in SULT1A1-expressing acute myeloid leukemia cells is associated with inhibitions of cFLIP expression and PI3K/AKT/mTOR activities.

Our recent study showed that acute myeloid leukemia (AML) cells expressing SULT1A1 are highly sensitive to NSC-743380, a small molecule that inhibits STAT3 activity and induces SULT1A1-dependent apoptosis of various cancer cell lines. In this study, we characterized the molecular mechanisms of NSC-743380-mediated anti-leukemia activity in AML cell lines and antileukemia activity of NSC-743380 in patient-derived primary leukemia cells from AML patients. Our results showed that treatment with NSC-743380 triggered robust apoptosis in SULT1A1-positive AML cells.

Tumor status and genotype affect the bone marrow microenvironment in acute myeloid leukemia.

The genetic heterogeneity of acute myeloid leukemia (AML) and the variable responses of individual patients to therapy suggest that different AML genotypes may influence the bone marrow (BM) microenvironment in different ways. We performed gene expression profiling of bone marrow mesenchymal stromal cells (BM-MSC) isolated from normal C57BL/6 mice or mice inoculated with syngeneic murine leukemia cells carrying different human AML genotypes, developed in mice with wild-type or nullgenetic backgrounds. We identified a set of genes whose expression in BM-MSC was modulated by all four AML genotypes tested.

A novel pH-controlled hydrogen sulfide donor protects gastric mucosa from aspirin-induced injury.

Hydrogen sulphide (H S) serves as a vital gastric mucosal defence under acid condition. Non-steroidal anti-inflammatory drugs (NSAIDs) are among widely prescribed medications with effects of antipyresis, analgesia and anti-inflammation. However, their inappropriate use causes gastric lesions and endogenous H S deficiency.

MLN0128, a novel mTOR kinase inhibitor, disrupts survival signaling and triggers apoptosis in AML and AML stem/ progenitor cells.

mTOR activation leads to enhanced survival signaling in acute myeloid leukemia (AML) cells. The active-site mTOR inhibitors (asTORi) represent a promising new approach to targeting mTOR in AKT/mTOR signaling. MLN0128 is an orally-administered, second-generation asTORi, currently in clinical development.

Leukemia cell mobilization with G-CSF plus plerixafor during busulfan-fludarabine conditioning for allogeneic stem cell transplantation.

We hypothesized that during conditioning chemotherapy for allogeneic stem cell transplant (allo-SCT), the disruption of stromal-leukemia interactions using G-CSF in combination with the CXCR4-specific inhibitor, plerixafor, may promote the release of leukemic cells from the niche and increase tumor elimination. In a phase 1/2 investigation, we treated 45 AML/myelodysplastic syndrome (MDS)/CML patients (34 AML, 7 MDS and 4 CML) with G-CSF (10 μg/kg daily for 6 days starting on day -9) plus plerixafor (doses of 0, 80, 160 or 240 μg/kg daily for 4 days starting on day -7) along with the busulfan-fludarabine (Bu-Flu) conditioning regimen. In the phase 1 part, we determined that G-CSF plus plerixafor is safe in this setting.

Clinicopathologic and prognostic relevance of ARID1A protein loss in colorectal cancer.

Aim: To explore the association between AT-rich interactive domain 1A (ARID1A) protein loss by immunohistochemistry and both clinicopathologic characteristics and prognosis in patients with colorectal cancer.

Methods: We retrospectively collected clinicopathologic data and archived paraffin-embedded primary colorectal cancer samples from 209 patients, including 111 patients with colon cancer and 98 patients with rectal cancer. The tumor stage ranged from stage I to stage IV according to the 7(th) edition of the American Joint Committee on Cancer tumor-node-metastasis (TNM) staging system.

Expression of sulfotransferase SULT1A1 in cancer cells predicts susceptibility to the novel anticancer agent NSC-743380.

The small molecule anticancer agent NSC-743380 modulates functions of multiple cancer-related pathways and is highly active in a subset of cancer cell lines in the NCI-60 cell line panel. It also has promising in vivo anticancer activity. However, the mechanisms underlying NSC-743380's selective anticancer activity remain uncharacterized.

SL-401 and SL-501, targeted therapeutics directed at the interleukin-3 receptor, inhibit the growth of leukaemic cells and stem cells in advanced phase chronic myeloid leukaemia.

While imatinib and other tyrosine kinase inhibitors (TKIs) are highly efficacious in the treatment of chronic myeloid leukaemia (CML), some patients become refractory to these therapies. After confirming that interleukin-3 receptor (IL3R, CD123) is highly expressed on CD34(+) /CD38(-) BCR-ABL1(+) CML stem cells, we investigated whether targeting IL3R with diphtheria toxin (DT)-IL3 fusion proteins SL-401 (DT388 -IL3) and SL-501 (DT388 -IL3[K116W]) could eradicate these stem cells. SL-401 and SL-501 inhibited cell growth and induced apoptosis in the KBM5 cell line and its TKI-resistant KBM5-STI subline.

PI3K inhibitor GDC-0941 enhances apoptotic effects of BH-3 mimetic ABT-737 in AML cells in the hypoxic bone marrow microenvironment.

Unlabelled: Both phosphatidylinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin signaling and antiapoptotic Bcl-2 family members are critical for survival of acute myeloid leukemia (AML) cells. Here, we demonstrate the antileukemic effects of simultaneous inhibition of PI3K by the selective class I PI3K inhibitor GDC-0941 and of Bcl-2 family members by the BH3 mimetic ABT-737 in the context of the bone marrow microenvironment, where hypoxia and interactions with bone marrow stromal cells promote AML cell survival and chemoresistance. The combination of GDC-0941 and ABT-737 profoundly downregulated antiapoptotic Mcl-1 expression levels, activated BAX, and induced mitochondrial apoptosis in AML cells co-cultured with bone marrow stromal cells under hypoxic conditions.

Ganglioside GD2 identifies breast cancer stem cells and promotes tumorigenesis.

Cancer stem cells (CSCs) are a small subpopulation of cancer cells that have increased resistance to conventional therapies and are capable of establishing metastasis. However, only a few biomarkers of CSCs have been identified. Here, we report that ganglioside GD2 (a glycosphingolipid) identifies a small fraction of cells in human breast cancer cell lines and patient samples that are capable of forming mammospheres and initiating tumors with as few as 10 GD2+ cells.