Hydrogen sulfide coordinates glucose metabolism switch through destabilizing tetrameric pyruvate kinase M2.

Most cancer cells reprogram their glucose metabolic pathway from oxidative phosphorylation to aerobic glycolysis for energy production. By reducing enzyme activity of pyruvate kinase M2 (PKM2), cancer cells attain a greater fraction of glycolytic metabolites for macromolecule synthesis needed for rapid proliferation. Here we demonstrate that hydrogen sulfide (HS) destabilizes the PKM2 tetramer into monomer/dimer through sulfhydration at cysteines, notably at C326, leading to reduced PKM2 enzyme activity and increased PKM2-mediated transcriptional activation.

Cep57 regulates human centrosomes through multivalent interactions.

Human Cep57 is a coiled-coil scaffold at the pericentriolar matrix (PCM), controlling centriole duplication and centrosome maturation for faithful cell division. Genetic truncation mutations of Cep57 are associated with the mosaic-variegated aneuploidy (MVA) syndrome. During interphase, Cep57 forms a complex with Cep63 and Cep152, serving as regulators for centrosome maturation.

Online citizen sciences reveal natural enemies and new occurrence data of Fujie, Shimizu & Maeto, 2021 (Hymenoptera, Braconidae, Euphorinae).

Background: Citizen science is a research approach that involves collaboration between professional scientists and non-professional volunteers. The utilisation of recent online citizen-science platforms (e.g.

Re-evaluation of the taxonomic confusion of the metallic-blue Pimpla Fabricius, 1804 (Hymenoptera: Ichneumonidae: Pimplinae) species in the Oriental region.

The metallic-blue body coloration is a distinct characteristic found in seven species of the cosmopolitan genus Pimpla Fabricius, 1804. In this study, we focus on two externally similar species, namely P. cyanator Morley, 1914 in India and P.

Combating breast cancer progression through combination therapy with hypomethylating agent and glucocorticoid.

Breast cancer is the leading cause of cancer-related death in women. Among breast cancer types, triple-negative breast cancer (TNBC) accounts for 15% of all breast cancers with aggressive tumor behavior. By using bioinformatic approaches, we observed that the microRNA-708 promoter is highly methylated in breast carcinomas, and this methylation is linked to a poor prognosis.

MicroRNA-708 emerges as a potential candidate to target undruggable NRAS.

RAS, the most frequently mutated oncogene that drives tumorigenesis by promoting cell proliferation, survival, and motility, has been perceived as undruggable for the past three decades. However, intense research in the past has mainly focused on KRAS mutations, and targeted therapy for NRAS mutations remains an unmet medical need. NRAS mutation is frequently observed in several cancer types, including melanoma (15-20%), leukemia (10%), and occasionally other cancer types.

DNA Sequencing from Subcritical Concentration of Cell-Free DNA Extracted from Electrowetting-on-Dielectric Platform.

Electro-Wetting-On-Dielectric (EWOD) based digital operations have demonstrated outstanding potential in actuating and manipulating liquid droplets. Here, we adapted the EWOD for extracting femtogram quantities of cell-free DNA (cf-DNA) from 1 μL of KSOM mouse embryo culture medium. Our group extracted the femtogram quantity of cf-DNA from 1 μL of mouse embryo culture medium in our previous work.

Lack of social touch alters anxiety-like and social behaviors in male mice.

The importance of social interactions has been reported in a variety of animal species. In human and rodent models, social isolation is known to alter social behaviors and change anxiety or depression levels. During the coronavirus pandemic, although people could communicate with each other through other sensory cues, social touch was mostly prohibited under different levels of physical distancing policies.

BARD1 is an ATPase activating protein for OLA1.

OLA1 is a P-loop ATPase, implicated in centrosome duplication through the interactions with tumor suppressors BRCA1 and BARD1. Disruption of the interaction of OLA1 with BARD1 results in centrosome amplification. However, the molecular interplay and mechanism of the OLA1-BARD1 complex remain elusive.

Monocytes secrete CXCL7 to promote breast cancer progression.

Certain immune cells and inflammatory cytokines are essential components in the tumor microenvironment to promote breast cancer progression. To identify key immune players in the tumor microenvironment, we applied highly invasive MDA-MB-231 breast cancer cell lines to co-culture with human monocyte THP-1 cells and identified CXCL7 by cytokine array as one of the increasingly secreted cytokines by THP-1 cells. Further investigations indicated that upon co-culturing, breast cancer cells secreted CSF1 to induce expression and release of CXCL7 from monocytes, which in turn acted on cancer cells to promote FAK activation, MMP13 expression, migration, and invasion.

The Hidden Role of Hydrogen Sulfide Metabolism in Cancer.

Hydrogen Sulfide (HS), an endogenously produced gasotransmitter, is involved in various important physiological and disease conditions, including vasodilation, stimulation of cellular bioenergetics, anti-inflammation, and pro-angiogenesis. In cancer, aberrant up-regulation of HS-producing enzymes is frequently observed in different cancer types. The recognition that tumor-derived HS plays various roles during cancer development reveals opportunities to target HS-mediated signaling pathways in cancer therapy.

Effects of synthetic glucocorticoids on breast cancer progression.

Glucocorticoids (GCs) are widely prescribed as adjuvant therapy for breast cancer patients. Unlike other steroid hormone receptors, the GC receptor is not considered an oncogene. Research in the past few years has revealed the complexity of GC-mediated signaling, but it remains puzzling whether GCs promote or inhibit tumor progression in different cancer types.

Extraction of Cell-free Dna from An Embryo-culture Medium Using Micro-scale Bio-reagents on Ewod.

As scientific and technical knowledge advances, research on biomedical micro-electromechanical systems (bio-MEMS) is also developing towards lab-on-a-chip (LOC) devices. A digital microfluidic (DMF) system specialized for an electrowetting- on-dielectric (EWOD) mechanism is a promising technique for such point-of-care systems. EWOD microfluidic biochemical analytical systems provide applications over a broad range in the lab-on-a-chip field.

Dysregulation of cystathionine γ-lyase promotes prostate cancer progression and metastasis.

Hydrogen sulfide (H S), an endogenous signaling gaseous molecule, is involved in various physiological activities, including vessel relaxation, regulation of cellular bioenergetics, inflammation, and angiogenesis. By using xenograft orthotopic implantation of prostate cancer PC3 cells and subsequently comparing bone metastatic with primary tumor-derived cancer cells, we find that H S-producing enzyme cystathionine γ-lyase (CTH) is upregulated in bone-metastatic PC3 cells. Clinical data further reveal that the expression of CTH is elevated in late-stage prostate cancer patients, and higher CTH expression correlates with poor survival from The Cancer Genome Atlas (TCGA) prostate cancer RNA-seq datasets.

Wild-type p53 upregulates an early onset breast cancer-associated gene GAS7 to suppress metastasis via GAS7-CYFIP1-mediated signaling pathway.

The early onset breast cancer patients (age ≤ 40) often display higher incidence of axillary lymph node metastasis, and poorer five-year survival than the late-onset patients. To identify the genes and molecules associated with poor prognosis of early onset breast cancer, we examined gene expression profiles from paired breast normal/tumor tissues, and coupled with Gene Ontology and public data base analysis. Our data showed that the expression of GAS7b gene was lower in the early onset breast cancer patients as compared to the elder patients.

Low-dose glucocorticoids suppresses ovarian tumor growth and metastasis in an immunocompetent syngeneic mouse model.

Ovarian cancer has the highest mortality rate among gynecologic malignancies. Despite chemotherapy and surgical debulking options, ovarian cancer recurs and disseminates frequently with a poor prognosis. We previously reported a novel role of glucocorticoids (GCs) in metastatic ovarian cancer by upregulating microRNA-708.

New dimension of glucocorticoids in cancer treatment.

Glucocorticoids have been used in clinical oncology for over half a century. The clinical applications of glucocorticoids in oncology are mainly dependent on their pro-apoptotic action to treat lymphoproliferative disorders, and also on alleviating side effects induced by chemotherapy or radiotherapy in non-hematologic cancer types. Researches in the past few years have begun to unveil the profound complexity of glucocorticoids signaling and have contributed remarkably on therapeutic strategies.

Glucocorticoids mediate induction of microRNA-708 to suppress ovarian cancer metastasis through targeting Rap1B.

Glucocorticoids are widely used in conjunction with chemotherapy for ovarian cancer to prevent hypersensitivity reactions. Here we reveal a novel role for glucocorticoids in the inhibition of ovarian cancer metastasis. Glucocorticoid treatments induce the expression of miR-708, leading to the suppression of Rap1B, which result in the reduction of integrin-mediated focal adhesion formation, inhibition of ovarian cancer cell migration/invasion and impaired abdominal metastasis in an orthotopic xenograft mouse model.

Rapamycin by itself and additively in combination with carboplatin inhibits the growth of ovarian cancer cells.

Objective: The current standard treatment for ovarian carcinoma, consisting of surgery followed by chemotherapy with carboplatin and paclitaxel, is fraught with a high rate of recurrences. We hypothesized that targeted inhibition of specific signaling pathways in combination with conventional drugs may increase chemotherapeutic efficacy.

Methods: We analyzed the expression and activation profiles of various signaling pathways in nine established ovarian cancer cell lines (CAOV-3, ES2, PA-1, SKOV-3, NIHOVCAR3, OV90, TOV112D, A1847, A2780) and 24 freshly procured human ovarian tumors.

Ephrin-B2-induced cleavage of EphB2 receptor is mediated by matrix metalloproteinases to trigger cell repulsion.

EphB receptors provide crucial adhesive and repulsive signals during cell migration and axon guidance, but it is unclear how they switch between these opposing responses. Here we provide evidence of an important role for matrix metalloproteinases (MMPs) in repulsive EphB2 signaling. We found that EphB2 is cleaved by MMPs both in vitro and in vivo, and that this cleavage is induced by interaction with its ligand ephrin-B2.

The WW domain-containing proteins interact with the early spliceosome and participate in pre-mRNA splicing in vivo.

A growing body of evidence supports the coordination of mRNA synthesis and its subsequent processing events. Nuclear proteins harboring both WW and FF protein interaction modules bind to splicing factors as well as RNA polymerase II and may serve to link transcription with splicing. To understand how WW domains coordinate the assembly of splicing complexes, we used glutathione S-transferase fusions containing WW domains from CA150 or FBP11 in pull-down experiments with HeLa cell nuclear extract.

Antioxidant properties and phytochemical characteristics of extracts from Lactuca indica.

Lactuca indica (Compositae) is an edible wild vegetable, used as a folk medicine in anti-inflammatory, antibacterial, and other medications in Asia. This is the first scientific evaluation of the chemopreventive therapeutic properties of L. indica using five antioxidation assay systems.