Smart Cell Therapy: an industry perspective on macrophages as living drugs.

Macrophage-based cell therapies represent a cutting-edge frontier in immunotherapy, offering distinct advantages over conventional approaches like CAR-T. This review explores the potential of macrophages to orchestrate both innate and adaptive immune responses, enhancing the body's ability to combat diseases locally and systemically. Dubbed a "Smart Cell Therapy," macrophages can initiate and coordinate complex immunological cascades, leveraging multiple immune system components while also performing effector functions.

[Cholestasis, delirium and pulmonary nocardiosis in a man with systemic lupus erythematosus of late onset].

A case is presented of a 64-year-old male patient who was admitted because of delirium, jaundice, a pattern of cholestasis in the liver profile and a right lung mass in the context of a constitutional syndrome and weight loss in the last eight months. The lung mass was punctured and the culture of the obtained material developed white colonies, identified by mass spectrometry (MALDI-TOF) as Nocardia cyriacigeorgica. Regarding the clinical diagnosis, it was considered as systemic lupus erythematosus (SLE), on the basis of fulfilling 8 criteria according to SLICC 2012 group, and 24 points according to EULAR/ACR 2019.

Polypharmacy and Drug Interactions in the COVID-19 Pandemic.

The COVID-19 pandemic generated a great impact on health systems. We compared evolution, polypharmacy, and potential drug-drug interactions (P-DDIs) in COVID-19 and non-COVID-19 hospitalizations during first wave of pandemic. Prescriptions for hospitalized patients ≥ 18 years (COVID-19 and non-COVID-19 rooms) between April and September 2020 were included.

Corrigendum: Consistent long-term therapeutic efficacy of human umbilical cord matrix-derived mesenchymal stromal cells after myocardial infarction despite individual differences and transient engraftment.

[This corrects the article DOI: 10.3389/fcell.2021.

Exploring the Biological Properties of Zn(II) thiosemicarbazone Helicates.

The design of artificial helicoidal molecules derived from metal ions with biological properties is one of the objectives within metallosupramolecular chemistry. Herein, we report three zinc helicates derived from a family of thiosemicarbazone ligands with different terminal groups, Zn(L)∙2HO , Zn(L)∙2HO and Zn(L), obtained by an electrochemical methodology. These helicates have been fully characterized by different techniques, including X-ray diffraction.

Development and Implementation of the Hdc.DrApp.la and SIMDA Programs to Reduce Polypharmacy and Drug-drug Interactions in Patients Hospitalized in Internal Medicine.

Objectives: We evaluated polypharmacy and possible drug-drug interactions (p-DDIs) in hospitalized patients before and after using the SIMDA Computerized Medical Decision Support System (CMDSS).

Materials And Methods: We included the prescriptions of ≥ 18 years hospitalized patients in the internal medicine department. We developed and implemented the Hdc.

Could inhibition of metalloproteinases be used to block the process of metastasis?

Metastasis is a multisequential process that allows tumor cells to migrate to tissues distant from the primary tumor. Only a small number of cells escape from the primary tumor; however, the metastases generated are responsible for more than 90% of cancer deaths. Many metastatic processes initially require the total or partial start-up of a program for the transformation of tumor epithelial cells into mesenchymal cells (EMT).

Spectroscopic Characterization of Mitochondrial G-Quadruplexes.

Guanine quadruplexes (G4s) are highly polymorphic four-stranded structures formed within guanine-rich DNA and RNA sequences that play a crucial role in biological processes. The recent discovery of the first G4 structures within mitochondrial DNA has led to a small revolution in the field. In particular, the G-rich conserved sequence block II (CSB II) can form different types of G4s that are thought to play a crucial role in replication.

Pharmacological effects of ex vivo mesenchymal stem cell immunotherapy in patients with acute kidney injury and underlying systemic inflammation.

Mesenchymal stem cells (MSCs) have natural immunoregulatory functions that have been explored for medicinal use as a cell therapy with limited success. A phase Ib study was conducted to evaluate the safety and immunoregulatory mechanism of action of MSCs using a novel ex vivo product (SBI-101) to preserve cell activity in patients with severe acute kidney injury. Pharmacological data demonstrated MSC-secreted factor activity that was associated with anti-inflammatory signatures in the molecular and cellular profiling of patient blood.

Inhibition of glutathione reductase uncovers the activation of NADPH-inhibited glucose-6-phosphate dehydrogenase.

Eggleston and Krebs pointed to a paradox in glucose-6-phosphate dehydrogenase (G6PD) regulating process that has not yet been solved, and which originated the term "fine regulation" of G6PD and, therefore, of oxidative phase of pentose phosphate pathway (OPPP). The paradox is that, in basal-like conditions, the activity of G6PD evaluated "in vitro" is very low or nearly null because of the potent inhibiting effect exerted by NADPH, a coenzyme whose concentration in the cell is much higher than that of the substrate NADP . However, "in vivo," flow through OPPP occurs in basal conditions.

Consistent Long-Term Therapeutic Efficacy of Human Umbilical Cord Matrix-Derived Mesenchymal Stromal Cells After Myocardial Infarction Despite Individual Differences and Transient Engraftment.

Human mesenchymal stem cells gather special interest as a universal and feasible add-on therapy for myocardial infarction (MI). In particular, human umbilical cord matrix-derived mesenchymal stromal cells (UCM-MSC) are advantageous since can be easily obtained and display high expansion potential. Using isolation protocols compliant with cell therapy, we previously showed UCM-MSC preserved cardiac function and attenuated remodeling 2 weeks after MI.

Mesenchymal stromal cell delivery via an ex vivo bioreactor preclinical test system attenuates clot formation for intravascular application.

While mesenchymal stromal cells are an appealing therapeutic option for a range of clinical applications, their potential to induce clotting when used systemically remains a safety concern, particularly in hypercoagulable conditions, such as in patients with severe COVID-19, trauma, or cancers. Here, we tested a novel preclinical approach aimed at improving the safety of mesenchymal stromal cell (MSC) systemic administration by use of a bioreactor. In this system, MSCs are seeded on the exterior of a hollow-fiber filter, sequestering them behind a hemocompatible semipermeable membrane with defined pore-size and permeability to allow for a molecularly defined cross talk between the therapeutic cells and the whole blood environment, including blood cells and signaling molecules.

Type-I Cryoglobulinaemia Associated to Monoclonal Gammapathy of Undetermined Significance.

Cryoglobulins are immunoglobulins that undergo reversible precipitation at cold temperatures. Monoclonal type-I cryoglobulinaemia is the least frequent and is associated to hematological diseases such as multiple myeloma, Waldenström's macroglobulinaemia, chronic lymphocytic leukaemia and lymphoma. We describe the case of a 60-year-old female patient, who suffered from burning pain in her feet for ten months before her admission.

Author Correction: Mesenchymal Stromal Cell Bioreactor for Ex Vivo Reprogramming of Human Immune Cells.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Mesenchymal Stromal Cell Bioreactor for Ex Vivo Reprogramming of Human Immune Cells.

Bone marrow mesenchymal stromal cells (MSCs) have been studied for decades as potent immunomodulators. Clinically, they have shown some promise but with limited success. Here, we report the ability of a scalable hollow fiber bioreactor to effectively maintain ideal MSC function as a single population while also being able to impart an immunoregulatory effect when cultured in tandem with an inflamed lymphocyte population.

Structural, morphometric and immunohistochemical study of the rabbit accessory olfactory bulb.

The accessory olfactory bulb (AOB) is the first neural integrative centre of the vomeronasal system (VNS), which is associated primarily with the detection of semiochemicals. Although the rabbit is used as a model for the study of chemocommunication, these studies are hampered by the lack of knowledge regarding the topography, lamination, and neurochemical properties of the rabbit AOB. To fill this gap, we have employed histological stainings: lectin labelling with Ulex europaeus (UEA-I), Bandeiraea simplicifolia (BSI-B4), and Lycopersicon esculentum (LEA) agglutinins, and a range of immunohistochemical markers.

Convergence of Cell Pharmacology and Drug Delivery.

Cellular therapy is enabling new approaches to tackle significant unmet needs in areas such as regenerative medicine and immunotherapy. The pharmacology of cell therapeutics becomes of critical importance to assure that these new drugs work reproducibly and effectively. Cell pharmacology can benefit from adapting principles of classical molecular drug pharmacokinetics (PK) and pharmacodynamics (PD) to quantitatively understand rate-limiting constraints of cell fate after administration.

Biomanufacturing for clinically advanced cell therapies.

The achievements of cell-based therapeutics have galvanized efforts to bring cell therapies to the market. To address the demands of the clinical and eventual commercial-scale production of cells, and with the increasing generation of large clinical datasets from chimeric antigen receptor T-cell immunotherapy, from transplants of engineered haematopoietic stem cells and from other promising cell therapies, an emphasis on biomanufacturing requirements becomes necessary. Robust infrastructure should address current limitations in cell harvesting, expansion, manipulation, purification, preservation and formulation, ultimately leading to successful therapy administration to patients at an acceptable cost.

The Secretome Derived From 3D-Cultured Umbilical Cord Tissue MSCs Counteracts Manifestations Typifying Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is an autoimmune disorder whose treatment is mostly restricted to pain and symptom management and to the delay of joint destruction. Mesenchymal stem/stromal cells from the umbilical cord tissue (UC-MSCs) have previously been proven to be immunomodulatory and more efficient than bone marrow-derived MSCs in causing remission of local and systemic arthritic manifestations . Given the paracrine nature of UC-MSC activity, their application as active substances can be replaced by their secretome, thus avoiding allogeneic rejection and safety issues related to unwanted grafting.

[Chronic inflammatory demyelinating polyneuropathy in a diabetic patient with syphilis].

Chronic inflammatory demyelinating polyneuropathy (CIDP) is a disorder characterized by motor symptoms such as weakness in both proximal and distal muscles with globally diminished or absent reflexes. Insulin neuritis is referred as an acute pain in the extremities, due to the damage of peripheral nerves affecting mainly small fibers, in diabetic patients treated with insulin who achieved rapid glycemic control. Pain is unusual in classic CIDP.

Case Report: Penile Squamous Cell Carcinoma Associated With Severe Hypercalcemia and High Levels of Parathyroid Hormone-related Peptide Expressed in Metastatic Skin Tissue.

It is known that high levels of parathyroid hormone-related protein (PTHrP) correlate with a bad prognostic in malignancies. Here we present a patient with advanced penile cancer (PC) without antecedents of human papillomavirus infections and bone metastases but with severe hypercalcemia. By quantitative polymerase chain reaction, we observed high levels of PTHrP messenger RNA in metastatic cutaneous tissue.

[Association between diabetic ketoacidosis and acromegaly].

Diabetes mellitus occurs in nearly 10% of patients with acromegaly and is secondary to insulin resistance caused by high levels of growth hormone. Diabetes ketoacidosis has been described as a rare complication of acromegaly, resulting from a relative insulin deficiency caused by growth hormone excess. We described the case of a 38 year-old man who presented to the emergency room with a 6-week history of polydipsia, polyuria, polyphagia and weight loss.

Umbilical cord tissue-derived mesenchymal stromal cells maintain immunomodulatory and angiogenic potencies after cryopreservation and subsequent thawing.

Background Aims: The effect of cryopreservation on mesenchymal stromal cell (MSC) therapeutic properties has become highly controversial. However, data thus far have indiscriminately involved the assessment of different types of MSCs with distinct production processes. This study assumed that MSC-based products are affected differently depending on the tissue source and manufacturing process and analyzed the effect of cryopreservation on a specific population of umbilical cord tissue-derived MSCs (UC-MSCs), UCX.

Therapeutic angiogenesis induced by human umbilical cord tissue-derived mesenchymal stromal cells in a murine model of hindlimb ischemia.

Background: Mesenchymal stem cells derived from human umbilical cord tissue, termed UCX®, have the potential to promote a full range of events leading to tissue regeneration and homeostasis. The main goal of this work was to investigate UCX® action in experimentally induced hindlimb ischemia (HLI).

Methods: UCX®, obtained by using a proprietary technology developed by ECBio (Amadora, Portugal), were delivered via intramuscular injection to C57BL/6 females after unilateral HLI induction.