Cannabinoid receptor ligands modulate fibrosis and inflammation in idiopathic pulmonary fibrosis: a preliminary study.

Background/aim: No specific pharmacological treatment regimen for idiopathic pulmonary fibrosis (IPF) exists. Therefore, new antiinflammatory therapeutic strategies are needed. Cannabinoids (CBs), known for their inflammation-modulating and antifibrotic effects, may be potential medication candidates for treating IPF.

A novel injectable nanotherapeutic platform increasing the bioavailability and anti-tumor efficacy of Arachidonylcyclopropylamide on an ectopic non-small cell lung cancer xenograft model: A randomized controlled trial.

Rapid progressing non-small cell lung adenocarcinoma (NSCLC) decreases treatment success. Cannabinoids emerge as drug candidates for NSCLC due to their anti-tumoral capabilities. We previously reported the controlled release of Arachidonylcyclopropylamide (ACPA) selectively targeting cannabinoid 1 (CB1) receptor in NSCLC cells in vitro.

2-AG-loaded and bone marrow-targeted PCL nanoparticles as nanoplatforms for hematopoietic cell line mobilization.

Background: The use of mobilizing agents for hematopoietic stem cell (HSC) transplantation is insufficient for an increasing number of patients. We previously reported lipid made endocannabinoid (eCB) ligands act on the human bone marrow (hBM) HSC migration in vitro, lacking long term stability to be therapeutic candidate. In this study, we hypothesized if a novel 2-AG-loaded polycaprolactone (PCL)-based nanoparticle delivery system that actively targets BM via phosphatidylserine (Ps) can be generated and validated.

Design of poly(vinyl pyrrolidone) and poly(ethylene glycol) microneedle arrays for delivering glycosaminoglycan, chondroitin sulfate, and hyaluronic acid.

Osteoarthritis (OA) is a prevalent joint disorder characterized by cartilage and bone degradation. Medical therapies like glucosaminoglycan (GAG), chondroitin sulfate (CS), and hyaluronic acid (HA) aim to preserve joint function and reduce inflammation but may cause side effects when administered orally or injection. Microneedle arrays (MNAs) offer a localized drug delivery method that reduces side effects.

Clinic-oriented injectable smart material for the treatment of diabetic wounds: Coordinating the release of GM-CSF and VEGF.

Chronic wounds are often caused by diabetes and present a challenging clinical problem due to vascular problems leading to ischemia. This inhibits proper wound healing by delaying inflammatory responses and angiogenesis. To address this problem, we have developed injectable particle-loaded hydrogels which sequentially release Granulocyte-macrophage- colony-stimulating-factor (GM-CSF) and Vascular endothelial growth factor (VEGF) encapsulated in polycaprolactone-lecithin-geleol mono-diglyceride hybrid particles.

Bone marrow mesenchymal stromal cells support regeneration of intestinal damage in a colitis mouse model, independent of their CXCR4 expression.

Inflammatory bowel disease (IBD) is characterized by a chronically dysregulated immune response in the gastrointestinal tract. Bone marrow multipotent mesenchymal stromal cells have an important immunomodulatory function and support regeneration of inflamed tissue by secretion of soluble factors as well as through direct local differentiation. CXCR4 is the receptor for CXCL12 (SDF-1, stromal-derived factor-1) and has been shown to be the main chemokine receptor, required for homing of MSCs.

The Evolutionary Route of in vitro Human Spermatogenesis: What is the Next Destination?

Malfunction in spermatogenesis due to genetic diseases, trauma, congenital disorders or gonadotoxic treatments results in infertility in approximately 7% of males. The behavior of spermatogonial stem cells (SSCs) within three-dimensional, multifactorial, and dynamic microenvironment implicates a niche that serves as a repository for fertility, since can serve as a source of mature and functional male germ cells. Current protocols enable reprogramming of mature somatic cells into induced pluripotent stem cells (iPSCs) and their limited differentiation to SSCs within the range of 0-5%.

Allogeneic bone marrow mesenchymal stem cell-derived exosomes alleviate human hypoxic AKI-on-a-Chip within a tight treatment window.

Background: Acute hypoxic proximal tubule (PT) injury and subsequent maladaptive repair present high mortality and increased risk of acute kidney injury (AKI) - chronic kidney disease (CKD) transition. Human bone marrow mesenchymal stem cell-derived exosomes (hBMMSC-Exos) as potential cell therapeutics can be translated into clinics if drawbacks on safety and efficacy are clarified. Here, we determined the real-time effective dose and treatment window of allogeneic hBMMSC-Exos, evaluated their performance on the structural and functional integrity of 3D microfluidic acute hypoxic PT injury platform.

Characterization of serum extracellular vesicles and their differential level of miR-197-3p in familial Mediterranean fever patients.

Objectives: The aim of this study was to analyze the existence of miRNAs derived from serum extracellular vesicles (EVs) in familial Mediterranean fever (FMF) patients. Our group has previously shown the association of certain miRNAs with FMF.

Methods: Serum samples of adult and pediatric FMF patients and their age matched controls were used in the study.

Dual Strategy with Adipose-Derived Stem Cells and l-arginine Recovered Cavernosal Functions in a Rat Model of Radical Prostatectomy.

As standard therapy for prostate cancer, radical prostatectomy causes cavernous nerve (CN) injury and increases fibrosis and hypoxia-induced penile structural alterations. This study aimed to determine the potential beneficial effects of adipose-derived stem cells (ADSCs) and l-arginine alone or in combination on the penile erection in a rat model of erectile dysfunction caused by bilateral cavernous nerve transection (CNT). Male rats ( = 35) were randomized into five groups: Sham-operated; CNT (4-weeks); CNT plus ADSCs (1 × 10 cells by intracavernosal injection); CNT plus l-arginine (4 weeks, 10 mg/kg/day, oral); and ADSCs combined with l-arginine in CNT.

Adrenomedullin has no effect on segmental bone defect healing but increases bone mineral density in rat model.

Objective: This study aimed to investigate the effect of adrenomedullin on the healing of the segmental bone defect in a rat model.

Methods: Thirty-six Wistar rats were randomly divided into 6 groups based on follow-up periods and administered a dose of adrenomedullin hormone. In each group, bilaterally, a 2-mm bone defect was created at the diaphysis of the radius.

Flow Cytometric and Immunohistochemical Follow-Up of Spermatogonial Lineage Commitment.

Flow cytometry and immunohistochemistry techniques both determine the target protein by immunolabeling. Flow cytometric analysis quantifies total number of fluorescent labeled cells and qualify sup-populations according to size and granularity. Immunohistochemistry is able to map immune-labeled cells and extracellular matrix components under light and electron microscope by enzyme or fluorescent molecules.

A pilot study: Nano-hydroxyapatite-PEG/PLA containing low dose rhBMP2 stimulates proliferation and osteogenic differentiation of human bone marrow derived mesenchymal stem cells.

Background: Bone morphogenetic protein 2 (BMP2) can enhance posterolateral spinal fusion (PLSF). The minimum effective dose that may stimulate mesenchymal stem cells however remains unknown. Nano-hydroxyapatite (nHAp) polyethylene glycol (PEG)/polylactic acid (PLA) was combined with recombinant human BMP2 (rhBMP2).

CB65 and novel CB65 liposomal system suppress MG63 and Saos-2 osteosarcoma cell growth .

Curable approaches for primary osteosarcoma are inadequate and urge investigation of novel therapeutic formulations. Cannabinoid ligands exert antiproliferative and apoptotic effect on osteosarcoma cells cannabinoid 2 (CB2) or transient receptor potential vanilloid type (TRPV1) receptors. In this study, we confirmed CB2 receptor expression in MG63 and Saos-2 osteosarcoma cells by qRT-PCR and flow cytometry (FCM), then reported the reduction effect of synthetic specific CB2 receptor agonist CB65 on the proliferation of osteosarcoma cells by WST-1 (water-soluble tetrazolium-1) and RTCA (real-time impedance-based proliferation).

A pumpless monolayer microfluidic device based on mesenchymal stem cell-conditioned medium promotes neonatal mouse in vitro spermatogenesis.

Background: Childhood cancer treatment-induced gonadotoxicity causes permanent infertility/sub-infertility in nearly half of males. The current clinical and experimental approaches are limited to cryopreservation of prepubertal testicular strips and in vitro spermatogenesis which are inadequate to achieve the expanded spermatogonial stem/progenitor cells and spermatogenesis in vitro. Recently, we reported the supportive effect of bone marrow-derived mesenchymal cell co-culture which is inadequate after 14 days of culture in static conditions in prepubertal mouse testis due to lack of microvascular flow and diffusion.

Detection of spermatogonial stem/progenitor cells in prepubertal mouse testis with deep learning.

Purpose: Rapid and easy detection of spermatogonial stem/progenitor cells (SSPCs) is crucial for clinicians dealing with male infertility caused by prepubertal testicular damage. Deep learning (DL) methods may offer visual tools for tracking SSPCs on testicular strips of prepubertal animal models. The purpose of this study is to detect and count the seminiferous tubules and SSPCs in newborn mouse testis sections using a DL method.

Comparative analysis of magnetically activated cell sorting and ultracentrifugation methods for exosome isolation.

Mesenchymal stem cell-derived exosomes regulate cell migration, proliferation, differentiation, and synthesis of the extracellular matrix, giving great potential for the treatment of different diseases. The ultracentrifugation method is the gold standard method for exosome isolation due to the simple protocol, and high yield, but presents low purity and requires specialized equipment. Amelioration of technical optimization is required for quick and reliable confinement of exosomes to translate them to the clinic as cell therapeutics In this study, we hypothesized that magnetically activated cell sorting may provide, an effective, reliable, and rapid tool for exosome isolation when compared to ultracentrifugation.

Synergistic Antitumor Potency of a Self-Assembling Cyclodextrin Nanoplex for the Co-Delivery of 5-Fluorouracil and Interleukin-2 in the Treatment of Colorectal Cancer.

Chemotherapy is the most used method after surgery in the treatment of colon cancer. Cancer cells escape the recognition mechanism of immune system cells to survive and develop chemoresistance. Therefore, the use of immunotherapy in combination with chemotherapy can increase the effectiveness of the treatment.

Effects of 5-fluorouracil released from different prosthetic meshes on post-operative adhesion formation in rats.

Objective: Post-operative adhesion is a common problem in abdominal surgery. Especially, foreign materials are strong stimulus for the development of adhesions. The aim of this study was to investigate whether drug release material coated prosthetic mesh decreases intra-abdominal adhesion formation or not.

Cannabinoids as Prospective Anti-Cancer Drugs: Mechanism of Action in Healthy and Cancer Cells.

Endogenous and exogenous cannabinoids modulate many physiological and pathological processes by binding classical cannabinoid receptors 1 (CB1) or 2 (CB2) or non-cannabinoid receptors. Cannabinoids are known to exert antiproliferative, apoptotic, anti-migratory and anti-invasive effect on cancer cells by inducing or inhibiting various signaling cascades. In this chapter, we specifically emphasize the latest research works about the alterations in endocannabinoid system (ECS) components in malignancies and cancer cell proliferation, migration, invasion, angiogenesis, autophagy, and death by cannabinoid administration, emphasizing their mechanism of action, and give a future perspective for clinical use.

Topical Intranasal Insulin Enhances Healing of Nasal Mucosa: An Experimental Animal Study.

Objective: Aim of this study was to evaluate the effect of topical intranasal insulin on healing of nasal mucosa in a rat model.

Methods: Forty-eight Wistar rats, weighing between 250 and 300 g and aged 10-12 weeks were used and randomized into two equal groups. 1.

Thioredoxin System and miR-21, miR-23a/b and let-7a as Potential Biomarkers for Brain Tumor Progression: Preliminary Case Data.

Background: The thioredoxin system and microRNAs (miRNAs) are potential targets for both cancer progression and treatment. However, the role of miRNAs and their relation with the expression profile of thioredoxin system in brain tumor progression remains unclear.

Methods: In this study, we aimed to determine the expression profiles of redox components Trx-1, TrxR-1 and PRDX-1, and oncogenic miR-21, miR-23a/b and let-7a and oncosuppressor miR-125 in different brain tumor tissues and their association with increasing tumor grade.

Vancomycin Containing PDLLA and PLGA/β-TCP Inhibit Biofilm Formation but Do Not Stimulate Osteogenic Transformation of Human Mesenchymal Stem Cells.

Aims: Chronic osteomyelitis, including implant-related prosthetic joint infection, is extremely difficult to cure. We develop vancomycin containing release systems from poly(d,l-lactide) (PDLLA) and poly(d,l-lactide-co-glycolide) (PLGA) composites with beta-tricalcium phosphate (β-TCP) to treat methicillin-resistant osteomyelitis. We ask whether vancomycin containing PDLLA/β-TCP and PLGA/β-TCP composites will prevent early biofilm formation, allow cell proliferation and osteogenic differentiation, and stimulate osteogenic signaling molecules in the absence of an osteogenic medium.

Mesenchymal stem cells promote spermatogonial stem/progenitor cell pool and spermatogenesis in neonatal mice in vitro.

Prepubertal cancer treatment leads to irreversible infertility in half of the male patients. Current in vitro spermatogenesis protocols and cryopreservation techniques are inadequate to expand spermatogonial stem/progenitor cells (SSPC) from testicles. Bone marrow derived mesenchymal stem cells (BM-MSC) bearing a close resemblance to Sertoli cells, improved spermatogenesis in animal models.

Comparison of total anastomosis time between four different combinations of suturing and knot tying techniques in microsurgical anastomosis.

Background: Various techniques have been described for performing microsurgical anastomosis with providing high patency rates. Although the total anastomotic time may not be an issue when dealing with a single set of anastomoses, using a faster technique may save significant amount of time in cases of transferring flaps with shorter critical ischemia time or where multiple anastomoses are required. This study compares the total anastomosis time between four different combinations of commonly used suturing and knot tying techniques.