Mechanistic Aspects of Biphenyl Urea-Based Analogues in Triple-Negative Breast Cancer Cell Lines.

Triple-negative breast cancer (TNBC) poses significant challenges due to its aggressive nature and limited treatment options. In this study, we investigated the impact of urea-based compounds on TNBC cells to uncover their mechanisms of action and therapeutic potential. Notably, polypharmacology urea analogues were found to work via p53-related pathways, and their cytotoxic effects were amplified by the modulation of oxidative phosphorylation pathways in the mitochondria of cancer cells.

Secretome of Dental Pulp-Derived Stem Cells Reduces Inflammation and Proliferation of Glioblastoma Cells by Deactivating Mapk-Akt Pathway.

Background: Dental pulp-derived stem cells (DPSC) is a promising therapy as they modulate the immune response, so we evaluated the inhibitory effect of DPSC secretome (DPSC) on the proliferation and inflammation in human glioblastoma (GBM) cells (U-87 MG) and elucidated the concomitant mechanisms involved.

Methods: The U87-MG cells were cultured with DPSC for 24 h and assessed the expression of inflammatory molecules using quantitative reverse transcription-polymerase chain reaction (qRT-PCR), generation of reactive oxygen species (ROS), and mitochondrial functionality using a seahorse flux analyzer. MTT (3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide) assay and cell cycle analysis were performed to evaluate the proliferation and cell cycle.

Secretory products of DPSC mitigate inflammatory effects in microglial cells by targeting MAPK pathway.

Activated microglial cells in the central nervous system (CNS) are the main contributors to neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease. Inhibiting their activation will help in reducing inflammation and oxidative stress during pathogenesis, potentially limiting the progression of the diseases. The immunomodulation properties of dental pulp-derived stem cells (DPSC) make it a promising therapy for neurodegenerative disorders.

KLF2 Regulates Neural Differentiation of Dental Pulp-derived Stem Cells by Modulating Autophagy and Mitophagy.

Background: Transplantation of stem cells for treating neurodegenerative disorders is a promising future therapeutic approach. However, the molecular mechanism underlying the neuronal differentiation of dental pulp-derived stem cells (DPSC) remains inadequately explored. The current study aims to define the regulatory role of KLF2 (Kruppel-like factor 2) during the neural differentiation (ND) of DPSC.

Impact of sequential herbicides application on crop productivity, weed and nutrient dynamics in soybean under conservation agriculture in Vertisols of Central India.

Adoption of conservation agriculture (CA) is very slow due to weed infestations. The application of herbicides is the only viable option to deal with problem of weed management to adhere with basic principles of CA. A field experiment was carried out for three years to evaluate the expediency of different herbicides and their sequential applications under CA.

Interactive effect of tillage and crop residue management on weed dynamics, root characteristics, crop productivity, profitability and nutrient uptake in chickpea (Cicer arietinum L.) under Vertisol of Central India.

Tillage and crop residue management play an imperative role in soil physico-chemical properties that eventually affects crop productivity. The objective of the study to find out a compatible combination of tillage and crop residue management for achieving sustainable food production by improving soil properties, providing favorable environment to crop plants. Secondly, managing crop residues effectively to reduce environmental pollution arising due to crop residue burning.

Polyphenolic Compounds Inhibit Osteoclast Differentiation While Reducing Autophagy through Limiting ROS and the Mitochondrial Membrane Potential.

Polyphenolic compounds are a diverse group of natural compounds that interact with various cellular proteins responsible for cell survival, differentiation, and apoptosis. However, it is yet to be established how these compounds interact in myeloid cells during their differentiation and the molecular and intracellular mechanisms involved. Osteoclasts are multinucleated cells that originate from myeloid cells.

Dental Pulp-Derived Stem Cells Reduce Inflammation, Accelerate Wound Healing and Mediate M2 Polarization of Myeloid Cells.

This work aimed to validate the potential use of dental pulp-derived stem cells (DPSCs) for the treatment of inflammation by defining their mechanisms of action. We planned to investigate whether priming of DPSC with proinflammatory molecules had any impact on their behavior and function. In the first step of our validation in vitro, we showed that priming of DPSCs with the bioactive agents LPS, TNF-α, or IFN-γ altered DPSCs' immunologic properties by increasing their expression levels of IL-10, HGF, IDO, and IL-4 and by decreasing their mitochondrial functions.

Evaluation of Urea-Based Inhibitors of the Dopamine Transporter Using the Experimental Autoimmune Encephalomyelitis Model of Multiple Sclerosis.

The dopaminergic system is involved in the regulation of immune responses in various homeostatic and disease conditions. For conditions such as Parkinson's disease and multiple sclerosis (MS), pharmacological modulation of dopamine (DA) system activity is thought to have therapeutic relevance, providing the basis for using dopaminergic agents as a treatment of relevant states. In particular, it was proposed that restoration of DA levels may inhibit neuroinflammation.

Corneal Epithelial Stem Cell Supernatant in the Treatment of Severe Dry Eye Disease: A Pilot Study.

Purpose: To report the subjective assessment of topical self-administered, cadaver-derived corneal epithelial stem cell supernatant for treatment of severe dry eye disease (DED).

Methods: Thirty-four eyes of 17 patients with advanced DED as defined by Standardized Patient Evaluation of Eye Dryness (SPEED) questionnaire ≥14, Ocular Surface Disease Index (OSDI©) score ≥40 and documented attempt of at least six conventional dry eye therapies were enrolled into a prospective clinical trial at a single private practice institution. Treatment consisted of patient self-administered topical instillation of the corneal epithelial stem cell-derived product four times daily in both eyes for 12 weeks.

Dental pulp-derived stem cells inhibit osteoclast differentiation by secreting osteoprotegerin and deactivating AKT signalling in myeloid cells.

Osteoclasts (OCs) differentiate from the monocyte/macrophage lineage, critically regulate bone resorption and remodelling in both homeostasis and pathology. Various immune and non-immune cells help initiating activation of myeloid cells for differentiation, whereas hyper-activation leads to pathogenesis, and mechanisms are yet to be completely understood. Herein, we show the efficacy of dental pulp-derived stem cells (DPSCs) in limiting RAW 264.

Generation of Myocardial Ischemic Wounds and Healing with Stem Cells.

Myocardial ischemia is a common manifestation of cardiovascular diseases (CVD) that affects the health and lives of millions of people worldwide. While numerous treatment options exist that address cardiac damage after ischemic injury, none of these can repair damaged cardiac tissue. Stem cell-mediated therapy is an emerging approach for cardiac tissue regeneration that has shown promise in preclinical models and in clinical studies.

Generation of Acute Hind Limb Ischemia in NOD/SCID Mice and Treatment with Nanofiber-Expanded CD34 Hematopoietic Stem Cells.

Critical limb ischemia (CLI) is primarily associated with a high risk of major amputation, cardiovascular events, and death. The current therapy involves direct endovascular intervention and is associated with long-term recurrence. However, patients with significant comorbidities are not eligible for this therapy.

Cutaneous Wound Generation in Diabetic NOD/SCID Mice and the Use of Nanofiber-Expanded Hematopoietic Stem Cell Therapy.

Despite significant advances in diabetic wound management, diabetic wounds remain a significant global problem that decreases patient's quality of life, and chronic wounds may lead to amputation and death to the patients. To develop a potential regenerative therapy, a xenogeneic transplantation compatible laboratory model needs to be developed. This procedure demonstrates how to isolate hematopoietic stem cells (CD133) from human umbilical cord blood, expand CD34 stem cells using a nanofiber scaffold (polyether sulfone-coated and amino group-treated), induce diabetes in immunocompromised (NOD/SCID) mice, induce a cutaneous wound in mice, and how to treat the wound with the nanofiber-expanded CD34 stem cells.

Development of Cutaneous Wound in Diabetic Immunocompromised Mice and Use of Dental Pulp-Derived Stem Cell Product for Healing.

Chronic nonhealing wounds impact nearly 15% of Medicare beneficiaries (8.2 million) in the United States costing $28-$32 billion annually. Despite advancement in wound management, approximately 8% of diabetic Medicare beneficiaries have a foot ulcer and 1.

KLF2 regulates dental pulp-derived stem cell differentiation through the induction of mitophagy and altering mitochondrial metabolism.

To define the regulatory role of Kruppel-like factor 2 (KLF2) during osteoblast (OB) differentiation of dental pulp-derived stem cell (DPSC)s, herein, we show that the levels of KLF2 and autophagy-related molecules were significantly increased in differentiated cells. Gain-of-function and loss-of-function approaches of KLF2 confirmed that KLF2 modulated autophagic and OB differentiation-related molecules. In addition, knockdown of the autophagic molecule (ATG7 or BECN1) in DPSCs resulted in reduced levels of KLF2 and OB differentiation-related molecules.

Transcriptional Regulation of Osteoclastogenesis: The Emerging Role of KLF2.

Dysregulation of osteoclastic differentiation and its activity is a hallmark of various musculoskeletal disease states. In this review, the complex molecular factors underlying osteoclastic differentiation and function are evaluated. The emerging role of KLF2 in regulation of osteoclastic differentiation is examined, specifically in the context of rheumatoid arthritis in which it has been most extensively studied among the musculoskeletal diseases.