Mechanism of Interleukin-17A Regulation of Mesenchymal Stroma/Stem Cell Osteogenic Differentiation.

The immune and musculoskeletal systems closely interplay in bone repair and regeneration. After bone injury, the body produces high levels of cytokines and signaling molecules to balance bone formation and resorption. Interleukin (IL)-17A, a cytokine expressed early in the inflammatory process, profoundly influences osteoprogenitor cell fate, thereby contributing to bone homeostasis.

An evaluation of the cytotoxic potential of medicinal mushrooms against human breast cancer cell lines.

Medicinal mushroom extracts, i.e. their dried biomass, have long been known as sources of bioactive compounds with positive effects on the human health.

Hydroxyurea inhibits proliferation and stimulates apoptosis through inducible nitric oxide synthase in erythroid cells.

Hydroxyurea (hydroxycarbamide, HU) arrests cells in the S-phase by inhibiting ribonucleotide reductase and DNA synthesis, significantly contributing to the release of nitric oxide (NO). We investigated the involvement of inducible NO synthase (NOS2) in the cytostatic effect of HU using in vitro shRNA-induced knockdown of the NOS2 transcript (NOS2) or a specific NOS2 inhibitor (1400W) in human erythroleukemic HEL92.1.

Development of Novel ROCK Inhibitors via 3D-QSAR and Molecular Docking Studies: A Framework for Multi-Target Drug Design.

Alterations in the actin cytoskeleton correlates to tumor progression and affect critical cellular processes such as adhesion, migration and invasion. Rho-associated coiled-coil-containing protein kinases (ROCK1 and ROCK2), important regulators of the actin cytoskeleton, are frequently overexpressed in various malignancies. The aim of this study was therefore to identify the key structural features of ROCK1/ROCK2 inhibitors using computer-aided drug design (CADD) approaches.

Multifaceted exploration of acylthiourea compounds: In vitro cytotoxicity, DFT calculations, molecular docking and dynamics simulation studies.

This study reports the synthesis and analysis of biologically active acylthiourea compounds (1 and 2) with a cyclohexyl moiety. The compounds were characterized using UV-Visible, FT-IR, H/C NMR, and elemental analysis. The crystal structure of 2 was solved, revealing intra- and inter-molecular hydrogen bonds.

Myeloid-derived suppressor cells: Implication in myeloid malignancies and immunotherapy.

Myeloid malignancies stem from a modified hematopoietic stem cell and predominantly include acute myeloid leukemia, myelodysplastic neoplasms, myeloproliferative malignancies, and chronic myelomonocytic leukemia. Myeloid-derived suppressor cells (MDSCs) exhibit immunoregulatory properties by governing the innate and adaptive immune systems, creating a permissive and supportive environment for neoplasm growth. This review examines the key characteristics of MDSCs in myeloid malignancies, highlighting that an increased MDSC count corresponds to heightened immunosuppressive capabilities, fostering an immune-tolerant neoplasm microenvironment.

A substituent-modified new salicylaldehyde-diphenyl-azine based AIEgen: A promising skeleton for copper ion sensor.

In this study, we have reported a novel 4-bromo-salicylaldehyde-diphenyl-azine (B-1), a new member of salicylaldehyde-diphenyl-azine (SDPA) family known for its excellent sensing properties. In contrast to the previously reported AIEgens, we found that the bromo-substitution at the 4th position of the salicylaldehyde moiety blue-shifted the emission by 10 and 15 nm as compared to the unsubstituted (Tong et.al 2017) and Bromo at the 5th position (Jain et.

Mesenchymal stromal cells in myeloid malignancies: Immunotherapeutic opportunities.

Myeloid malignancies are clonal disorders of the progenitor cells or hematopoietic stem cells, including acute myeloid leukemia, myelodysplastic syndromes, myeloproliferative malignancies, and chronic myelomonocytic leukemia. Myeloid neoplastic cells affect the proliferation and differentiation of other hematopoietic lineages in the bone marrow and peripheral blood, leading to severe and life-threatening complications. Mesenchymal stromal cells (MSCs) residing in the bone marrow exert immunosuppressive functions by suppressing innate and adaptive immune systems, thus creating a supportive and tolerant microenvironment for myeloid malignancy progression.

Host-guest interactions of coumarin-based 1,2-pyrazole using analytical and computational methods: Paper strip-based detection, live cell imaging, logic gates and keypad lock applications.

A novel Coumarin-based 1,2-pyrazole, HCPyTSC is synthesised and characterized. The chemosensor has been shown to have efficient colourimetric and fluorescence sensing capabilities for the quick and selective detection of fluoride and copper ions. At 376 and 430 nm, the HCPyTSC exhibits selective sensing for Cu and F ions.

Sex Differences and Cytokine Profiles among Patients Hospitalized for COVID-19 and during Their Recovery: The Predominance of Adhesion Molecules in Females and Oxidative Stress in Males.

The severity and mortality of coronavirus disease 2019 (COVID-19) are greater in males than in females, though the infection rate is the same in the two sexes. We investigated sex hormone differences associated with the hyperinflammatory immune response to SARS-CoV-2 on the basis of patients' cytokine profiles and vaccination statuses. Clinical and laboratory data of 117 patients with COVID-19 were collected to examine sex differences associated with oxidative stress markers, neutrophil extracellular traps (NETs), and plasma cytokine levels up to 5 months from hospital admission.

Transforming growth factor-beta superfamily regulates mesenchymal stem cell osteogenic differentiation: A microRNA linking.

The ability to differentiate into cells of different lineages, such as bone cells, is the principal value of adult mesenchymal stem cells (MSCs), which can be used with the final aim of regenerating damaged tissue. Due to its potential use and importance in regenerative medicine and tissue engineering, several questions have been raised regarding the molecular mechanisms of MSC differentiation. As one of the crucial mediators in organism development, the transforming growth factor-beta (TGF-β) superfamily directs MSCs' commitment to selecting differentiation pathways.

Current and Future Cancer Chemoprevention Strategies.

Cancer is a leading cause of death worldwide, accounting for nearly 10 million deaths in 2020 and ranking as the second-leading cause of death in economically developed countries [...

Transforming Growth Factor-β1 in Cancer Immunology: Opportunities for Immunotherapy.

Transforming growth factor-beta1 (TGF-β) regulates a plethora of cell-intrinsic processes that modulate tumor progression in a context-dependent manner. Thus, although TGF-β acts as a tumor suppressor in the early stages of tumorigenesis, in late stages, this factor promotes tumor progression and metastasis. In addition, TGF-β also impinges on the tumor microenvironment by modulating the immune system.

Increase in Frequency of Myeloid-Derived Suppressor Cells in the Bone Marrow of Myeloproliferative Neoplasm: Potential Implications in Myelofibrosis.

The Philadelphia-negative myeloproliferative neoplasms (MPNs), defined as clonal disorders of the hematopoietic stem cells, are characterized by the proliferation of mature myeloid cells in the bone marrow and a chronic inflammatory status impacting the initiation, progression, and symptomatology of the malignancies. There are three main entities defined as essential thrombocythemia (ET), polycythemia vera (PV), and primary myelofibrosis (PMF), and genetically classified by JAK2, CALR, or MPL mutations. In MPNs, due to the overproduction of inflammatory cytokines by the neoplastic cells and non-transformed immune cells, chronic inflammation may provoke the generation and expansion of myeloid-derived suppressors cells (MDSCs) that highly influence the adaptive immune response.

BMAL1 Regulates Glucokinase Expression Through E-Box Elements In Vitro.

The organization of a circadian system includes an endogenous pacemaker system, input pathways for environmental synchronizing (entraining) stimuli, and output pathways through which the clock regulates physiological and behavioral processes, for example, the glucose-sensing mechanism in the liver. The liver is the central regulator of metabolism and one of our peripherals clocks. In mammals, central to this pacemaker are the transcription factors Circadian Locomotor Output Cycles Kaput (CLOCK) and BMAL1 (Brain and Muscle ARNT-Like 1).

Appraisal of the Neuroprotective Effect of Dexmedetomidine: A Meta-Analysis.

Dexmedetomidine is an adrenergic receptor agonist that has been regarded as neuroprotective in several studies without an objective measure to it. Thus, the aim of this meta-analysis was to analyze and quantify the current evidence for the neuroprotective effects of dexmedetomidine in animals. The search was performed by querying the National Library of Medicine.

Effects of Adrenergic Receptor Stimulation on Human Hemostasis: A Systematic Review.

Catecholamine stimulation over adrenergic receptors results in a state of hypercoagulability. Chronic stress involves the release and increase in circulation of catecholamines and other stress related hormones. Numerous observational studies in human have related stressful scenarios to several coagulation variables, but controlled stimulation with agonists or antagonists to adrenergic receptors are scarce.

Effect of Dietary Supplements with ω-3 Fatty Acids, Ascorbic Acid, and Polyphenolic Antioxidant Flavonoid on Gene Expression, Organ Failure, and Mortality in Endotoxemia-Induced Septic Rats.

Sepsis syndrome develops through enhanced secretion of pro-inflammatory cytokines and the generation of reactive oxygen species (ROS). Sepsis syndrome is characterized by vascular hyperpermeability, hypotension, multiple organ dysfunction syndrome (MODS), and increased mortality, among others. Endotoxemia-derived sepsis is an important cause of sepsis syndrome.

Discovery of 1-Benzhydryl-Piperazine-Based HDAC Inhibitors with Anti-Breast Cancer Activity: Synthesis, Molecular Modeling, In Vitro and In Vivo Biological Evaluation.

Isoform-selective histone deacetylase (HDAC) inhibition is promoted as a rational strategy to develop safer anti-cancer drugs compared to non-selective HDAC inhibitors. Despite this presumed benefit, considerably more non-selective HDAC inhibitors have undergone clinical trials. In this report, we detail the design and discovery of potent HDAC inhibitors, with 1-benzhydryl piperazine as a surface recognition group, that differ in hydrocarbon linker.

and antitumor activity of tomatine in hepatocellular carcinoma.

There is abundant ethnopharmacological evidence the uses of regarding species as antitumor and anticancer agents. Glycoalkaloids are among the molecules with antiproliferative activity reported in these species. To evaluate the anticancer effect of the glycoalkaloid tomatine in hepatocellular carcinoma (HCC) (HepG2 cells) and models.

Inhibition of proinflammatory signaling impairs fibrosis of bone marrow mesenchymal stromal cells in myeloproliferative neoplasms.

Although bone marrow-derived mesenchymal stromal cells (BM-MSCs) have been identified as a major cellular source of fibrosis, the exact molecular mechanism and signaling pathways involved have not been identified thus far. Here, we show that BM-MSCs contribute to fibrosis in myeloproliferative neoplasms (MPNs) by differentiating into αSMA-positive myofibroblasts. These cells display a dysregulated extracellular matrix with increased FN1 production and secretion of profibrotic MMP9 compared to healthy donor cells.

Inflammation Promotes Oxidative and Nitrosative Stress in Chronic Myelogenous Leukemia.

Chronic inflammation is characterized by the production of reactive oxygen species (ROS), reactive nitrogen species, and inflammatory cytokines in myeloproliferative neoplasms (MPNs). In addition to these parameters, the aim of this study was to analyze the influence of ROS on the proliferation-related AKT/mTOR signaling pathway and the relationship with inflammatory factors in chronic myelogenous leukemia (CML). The activity of the antioxidant enzymes superoxide dismutase, glutathione peroxidase, and catalase is reduced in erythrocytes while levels of the oxidative stress markers malondialdehyde and protein carbonyl are elevated in the plasma of patients with CML.

How far are we from predicting multi-drug interactions during treatment for COVID-19 infection?

Seriously ill patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and hospitalized in intensive care units (ICUs) are commonly given a combination of drugs, a process known as multi-drug treatment. After extracting data on drug-drug interactions with clinical relevance from available online platforms, we hypothesize that an overall interaction map can be generated for all drugs administered. Furthermore, by combining this approach with simulations of cellular biochemical pathways, we may be able to explain the general clinical outcome.