Direct Interaction Between CD34 Hematopoietic Stem Cells and Mesenchymal Stem Cells Reciprocally Preserves Stemness.

Background/objectives: A specialized microenvironment in the bone marrow, composed of stromal cells including mesenchymal stem cells (MSCs), supports hematopoietic stem cell (HSC) self-renewal, and differentiation bands play an important role in leukemia development and progression. The reciprocal direct interaction between MSCs and CD34 HSCs under physiological and pathological conditions is yet to be fully characterized.

Methods: Here, we established a direct co-culture model between MSCs and CD34 HSCs or MSCs and acute myeloid leukemia cells (THP-1, Molm-13, and primary cells from patients) to study heterocellular communication.

Uncovering the Molecular Pathways Implicated in the Anti-Cancer Activity of the Imidazoquinoxaline Derivative EAPB02303 Using a Model.

Imiqualines are analogues of the immunomodulatory drug imiquimod. EAPB02303, the lead of the second-generation imiqualines, is characterized by significant anti-tumor effects with IC50s in the nanomolar range. We used transgenic and mutant strains of two key signaling pathways (PI3K-Akt and Ras-MAPK) disrupted in human cancers to investigate the mode of action of EAPB02303.

Imiquimod Reverses Chronic Toxoplasmosis-Associated Behavioral and Neurocognitive Anomalies in a Rat Model.

is the etiologic agent of toxoplasmosis, a highly prevalent parasitosis. () transits in the brain from acute (AT) to chronic toxoplasmosis (CT), under host immune control. In immunocompromised patients, reactivation of CT is potentially life-threatening.

Identification of small molecule antivirals against HTLV-1 by targeting the hDLG1-Tax-1 protein-protein interaction.

Human T-cell leukemia virus type-1 (HTLV-1) is the first pathogenic retrovirus discovered in human. Although HTLV-1-induced diseases are well-characterized and linked to the encoded Tax-1 oncoprotein, there is currently no strategy to target Tax-1 functions with small molecules. Here, we analyzed the binding of Tax-1 to the human homolog of the drosophila discs large tumor suppressor (hDLG1/SAP97), a multi-domain scaffolding protein involved in Tax-1-transformation ability.

Ubiquitin-Related Modifier 1 (URM-1) Modulates Cx43 in Breast Cancer Cell Lines.

Gap-junction-forming connexins are exquisitely regulated by post-translational modifications (PTMs). In particular, the PTM of connexin 43 (Cx43), a tumor suppressor protein, regulates its turnover and activity. Here, we investigated the interaction of Cx43 with the ubiquitin-related modifier 1 (URM-1) protein and its impact on tumor progression in two breast cancer cell lines, highly metastatic triple-negative MDA-MB-231 and luminal breast cancer MCF-7 cell lines.

Invasion of bradyzoites: Molecular dissection of the moving junction proteins and effective vaccination targets.

Toxoplasmosis is a neglected parasitic disease necessitating public health control. Host cell invasion by occurs at different stages of the parasite's life cycle and is crucial for survival and establishment of infection. In tachyzoites, which are responsible for acute toxoplasmosis, invasion involves the formation of a molecular bridge between the parasite and host cell membranes, referred to as the moving junction (MJ).

Shelph, a Phosphatase Located in the Parasite Endoplasmic Reticulum, Is Required for Parasite Virulence.

Toxoplasma gondii is a single-celled parasitic eukaryote that evolved to successfully propagate in any nucleated cell. As with any other eukaryote, its life cycle is regulated by signaling pathways controlled by kinases and phosphatases. T.

HAS 1: A natural product from soil-isolated species with potent activity against cutaneous leishmaniasis caused by .

Cutaneous Leishmaniasis (CL) is a neglected tropical disease, classified by the World Health Organization (WHO) as one of the most unrestrained diseases. The Syrian war and the significant displacement of refugees aggravated the spread of this ailment into several neighboring countries in the Eastern Mediterranean Region (EMR). In Syria, is identified as one of the most aggressive and endemic identified species, causing localized or generalized lesions, often chronic or relapsing.

Development and Challenges of Synthetic Retinoid Formulations in Cancer.

Retinoids represent a class of chemical compounds derived from or structurally and functionally related to vitamin A. Retinoids play crucial roles in regulating a range of crucial biological processes spanning embryonic development to adult life. These include regulation of cell proliferation, differentiation, and cell death.

Interplay between innate immunity and the viral oncoproteins Tax and HBZ in the pathogenesis and therapeutic response of HTLV-1 associated adult T cell leukemia.

The Human T-cell Leukemia virus type 1 (HTLV-1) causes an array of pathologies, the most aggressive of which is adult T-cell leukemia (ATL), a fatal blood malignancy with dismal prognosis. The progression of these diseases is partly ascribed to the failure of the immune system in controlling the spread of virally infected cells. HTLV-1 infected subjects, whether asymptomatic carriers or symptomatic patients are prone to opportunistic infections.

Avoiding post mastectomy lateral "Dog Ears" by an L incision and lipoaspiration: The Paris Breast Center technique.

Background: Lateral dog ear after mastectomy in overweight or large breasted patients is a source for patient discomfort and is aesthetically unpleasing. Although many different techniques have been proposed, none of them have emerged as standard. In 2012, the authors published their mastectomy technique based on an inverted L-scar incision and closure with a lateral skin flap advanced supero-medially onto the chest wall.

Updates on the Epidemiology of the Human T-Cell Leukemia Virus Type 1 Infection in the Countries of the Eastern Mediterranean Regional Office of the World Health Organization with Special Emphasis on the Situation in Iran.

Background: The epidemiology and prevalence of the Human T-cell leukemia virus type-1 (HTLV-1) infection represent a recommended priority by global health agencies. An in-depth revision to update the status of this infection in countries including those of the Eastern Mediterranean Regional Office (EMRO) of the World Health Organization is hence required.

Methods: Ninety-seven studies evaluating the HTLV-1 infection in low- and high-risk populations in EMRO countries were retrieved from the international electronic databases and were used to assess the epidemiological status of the infection in these countries.

EAPB0503, an Imidazoquinoxaline Derivative Modulates SENP3/ARF Mediated SUMOylation, and Induces NPM1c Degradation in NPM1 Mutant AML.

Nucleophosmin-1 (NPM1) is a pleiotropic protein involved in numerous cellular processes. NPM1 shuttles between the nucleus and the cytoplasm, but exhibits a predominant nucleolar localization, where its fate and functions are exquisitely controlled by dynamic post-translational modifications (PTM). Sentrin/SUMO Specific Peptidase 3 (SENP3) and ARF are two nucleolar proteins involved in NPM1 PTMs.

A Novel Approach for Tuberous Breast Correction Using Power-Assisted Liposuction, Loops, and Lipofilling (PALLL).

Background: Autologous fat grafting has recently gained popularity in breast and reconstructive procedures.

Objectives: The aim of this paper was to describe a tricomposite tuberous breast reconstruction that comprises matrix dissociation through extensive tunnelization, tissue recruitment with loops, and autologous fat transfer. This approach, called "matrix modeling," was implemented by the power-assisted liposuction, loops, and lipofilling (PALLL) technique as a method to expand the lower pole, reshape the breast, and increase breast volume.

Toxoplasmosis: Current and Emerging Parasite Druggable Targets.

Toxoplasmosis is a prevalent disease affecting a wide range of hosts including approximately one-third of the human population. It is caused by the sporozoan parasite (), which instigates a range of symptoms, manifesting as acute and chronic forms and varying from ocular to deleterious congenital or neuro-toxoplasmosis. Toxoplasmosis may cause serious health problems in fetuses, newborns, and immunocompromised patients.

Comprehensive Overview of -Induced and Associated Diseases.

() is a prevalent protozoan parasite of medical and veterinary significance. It is the etiologic agent of toxoplasmosis, a neglected disease in which incidence and symptoms differ between patients and regions. In immunocompetent patients, toxoplasmosis manifests as acute and chronic forms.

Adult T-Cell Leukemia: a Comprehensive Overview on Current and Promising Treatment Modalities.

Purpose Of The Review: Adult T-cell leukemia (ATL) is an aggressive chemo-resistant malignancy secondary to HTLV-1 retrovirus. Prognosis of ATL remains dismal. Herein, we emphasized on the current ATL treatment modalities and their drawbacks, and opened up on promising targeted therapies with special focus on the HTLV-1 regulatory proteins Tax and HBZ.

Actinomycin D Targets NPM1c-Primed Mitochondria to Restore PML-Driven Senescence in AML Therapy.

Unlabelled: Acute myeloid leukemia (AML) pathogenesis often involves a mutation in the NPM1 nucleolar chaperone, but the bases for its transforming properties and overall association with favorable therapeutic responses remain incompletely understood. Here we demonstrate that an oncogenic mutant form of NPM1 (NPM1c) impairs mitochondrial function. NPM1c also hampers formation of promyelocytic leukemia (PML) nuclear bodies (NB), which are regulators of mitochondrial fitness and key senescence effectors.

P18 (SRS35/TgSAG4) Plays a Role in the Invasion and Virulence of .

Toxoplasmosis is a prevalent parasitic disease caused by (). Under the control of the host immune system, persists as latent bradyzoite cysts. Immunosuppression leads to their reactivation, a potentially life-threatening condition.

A Pin1/PML/P53 axis activated by retinoic acid in acute myeloid leukemia.

Retinoic acid (RA) was proposed to increase survival of chemotherapy- treated patients with nucleophosmin-1 (NPM-1c)-mutated acute myeloid leukemia. We reported that, ex vivo, RA triggers NPM-1c degradation, P53 activation and growth arrest. PML organizes domains that control senescence or proteolysis.

Corrigendum to: A New Suturing Method for Optimal Wound Healing: Technique and Experience.

[This corrects the article DOI: 10.1093/asjof/ojaa008.].

Imiquimod Targets Toxoplasmosis Through Modulating Host Toll-Like Receptor-MyD88 Signaling.

is a prevalent parasite of medical and veterinary importance. Tachyzoïtes and bradyzoïtes are responsible for acute and chronic toxoplasmosis (AT and CT), respectively. In immunocompetent hosts, AT evolves into a persistent CT, which can reactivate in immunocompromised patients with dire consequences.

Loss of interleukin-10 activates innate immunity to eradicate adult T-cell leukemia-initiating cells.

Adult T cell leukemia/lymphoma (ATL) is associated to chronic human T cell leukemia virus type 1 (HTLV-1) infection and carries a poor prognosis. Arsenic trioxide (AS) and interferon-alpha (IFNα) together selectively trigger Tax viral oncoprotein degradation and cure Tax-driven murine ATL. AS/IFNα/zidovudine treatment achieves a high response rate in patients with chronic ATL.

Scarless Composite Breast Reconstruction Utilizing an Advancement Skin Flap, Loops, and Lipofilling.

Background: Autologous fat grafting has gained popularity in breast reconstructive surgery. To further increase the breast volume and provide a reliable breast shape, a skin flap can be advanced from the upper abdomen and lateral thorax to the breast.

Objectives: The aim of this study was to propose a method of breast reconstruction utilizing the principles of power-assisted liposuction and lipofilling (PALL) for breast matrix dissociation applied through infiltration, tunnelization, extensive undermining and lipofilling, in combination with loops (PALLL) to recruit a vascularized flap to reshape the breast.