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Clinical Science (London, England :... Jun 2024Our previous studies indicated that there is overexpression of MIAT in fibroids and MIAT is a sponge for the miR-29 family in these tumors. The objective of the present...
Our previous studies indicated that there is overexpression of MIAT in fibroids and MIAT is a sponge for the miR-29 family in these tumors. The objective of the present study was to determine if the knockdown of MIAT in fibroid xenografts will increase miR-29 levels and reduce the expression of genes targeted by this miRNA such as collagen and cell cycle regulatory proteins in a mouse model for fibroids. Ovariectomized CB-17 SCID/Beige mice bearing estrogen/progesterone pellets were implanted subcutaneously in the flank with equal weight of fibroid explants which had been transduced by lentivirus for either control (empty vector) or MIAT knockdown for four weeks (n=7). Knockdown of MIAT in fibroid xenografts resulted in a 30% reduction of tumor weight and a marked increase in miR-29a, -b, and -c levels in the xenografts. There was reduced cell proliferation and expression of cell cycle regulatory genes CCND1, CDK2, and E2F1 and no significant changes in apoptosis. The xenografts with MIAT knockdown expressed lower mRNA and protein levels of FN1, COL3A1, and TGF-β3, and total collagen protein. Targeting MIAT, which sponges the pro-fibrotic miR-29 family, is an effective therapy for fibroids by reducing cell proliferation and thereby, tumor growth and accumulation of ECM, which is a hallmark of these benign gynecologic tumors.
Topics: Animals; Leiomyoma; Female; RNA, Long Noncoding; MicroRNAs; Humans; Cell Proliferation; Uterine Neoplasms; Mice, SCID; Gene Expression Regulation, Neoplastic; Disease Models, Animal; Mice; Gene Knockdown Techniques; Xenograft Model Antitumor Assays; Apoptosis
PubMed: 38817011
DOI: 10.1042/CS20240190 -
ACS Applied Materials & Interfaces Jun 2024In the present work, we explored Lewis acid catalysis, via FeCl, for the heterogeneous surface functionalization of cellulose nanofibrils (CNFs). This approach,...
In the present work, we explored Lewis acid catalysis, via FeCl, for the heterogeneous surface functionalization of cellulose nanofibrils (CNFs). This approach, characterized by its simplicity and efficiency, facilitates the amidation of nonactivated carboxylic acids in carboxymethylated cellulose nanofibrils (c-CNF). Following the optimization of reaction conditions, we successfully introduced amine-containing polymers, such as polyethylenimine and Jeffamine, onto nanofibers. This introduction significantly enhanced the physicochemical properties of the CNF-based materials, resulting in improved characteristics such as adhesiveness and thermal stability. Reaction mechanistic investigations suggested that endocyclic oxygen of cellulose finely stabilizes the transition state required for further functionalization. Notably, a nanocomposite, containing CNF and a branched low molecular weight polyethylenimine (CNF-PEI 800), was synthesized using the catalytic reaction. The composite CNF-PEI 800 was thoroughly characterized having in mind its potential application as coating biomaterial for medical implants. The resulting CNF-PEI 800 hydrogel exhibits adhesive properties, which complement the established antibacterial qualities of polyethylenimine. Furthermore, CNF-PEI 800 demonstrates its ability to support the proliferation and differentiation of primary human osteoblasts over a period of 7 days.
Topics: Cellulose; Nanocomposites; Humans; Catalysis; Nanofibers; Chlorides; Ferric Compounds; Osteoblasts; Polyethyleneimine; Prostheses and Implants; Biocompatible Materials
PubMed: 38816917
DOI: 10.1021/acsami.4c04351 -
Scientific Reports May 2024Bone graft granules implanted in bone defects come into physical contact with the host bone and form interconnected porous structure. However, there exists an accidental...
Bone graft granules implanted in bone defects come into physical contact with the host bone and form interconnected porous structure. However, there exists an accidental displacement of granules to unintended locations and leakage of granules from bone defects. Although covering the defect with a barrier membrane prevents granule emanation, this procedure is troublesome. To resolve these problems, we fabricated bioresorbable mesh cages (BRMc) in this study. Bone graft granules composed of carbonate apatite alone (Gr) and bioresorbable mesh cages (BRMc/Gr) introduced the bone graft granules and were implanted into the bone defect in the rabbit femur. Micro-computed tomography and histological analysis were conducted at 4 and 12 weeks after implantation. Osteoprogenitors in the bloodstream from the host bone passed through the pores of BRMc, penetrated the porous structure of graft granules, and might interact with individual granules. Then bone remodeling could progress actively and new bone was formed. The new bone formation was similar to the host bone at 12 weeks and there were minimal signs of local tissue inflammation. BRMc/Gr could reduce the risk of unwanted new bone formation occurring due to loss of granules from the bone defects compared with Gr because BRMc enclosed granules and prevent granules leakage from bone defects and BRMc could not induce unfavorable effects to forme new bone. Additionally, BRMc/Gr could keep granules assembled in one place, avoid displacement of granules to unintended locations, and carry easily. These results demonstrated that BRMc/Gr was effective in bone regeneration and improved clinical handling.
Topics: Animals; Rabbits; Femur; Bone Transplantation; X-Ray Microtomography; Absorbable Implants; Bone Regeneration; Osteogenesis
PubMed: 38816454
DOI: 10.1038/s41598-024-63067-y -
Poultry Science Jul 2024The capacity of combinations of feed enzymes, natural betaine and a probiotic, combined with alternative plant-based ingredients, to totally replace soybean meal (SBM)...
Total replacement of soybean meal with alternative plant-based ingredients and a combination of feed additives in broiler diets from 1 day of age during the whole growing period.
The capacity of combinations of feed enzymes, natural betaine and a probiotic, combined with alternative plant-based ingredients, to totally replace soybean meal (SBM) in a broiler diet was evaluated. Day-old Ross 308 males (2,574) were assigned to 9 treatments (13 pens/treatment, 22 birds/pen) in a completely randomized design. All diets were pelleted and fed ad libitum in 4 phases: starter, grower, finisher 1, finisher 2 (0-10, 10-21, 21-35, and 35-42 d of age, respectively). Treatments included: 1) control diet containing SBM (SBM control), supplemented with phytase (PhyG), at 2,000, 1,500, 1000 and 1,000 FTU/kg in each phase and xylanase (X) at 750 U/kg, [crude protein (CP): 23.5%, 22.0%, 20.2% and 19.3% in each phase]; 2) to 5), alternative (ALT), SBM-free diets, containing the same CP level as the control ("CP high"), supplemented with PhyG as in the control, protease (P, 800 U/kg) and in 2) xylanase (750 U/kg) (ALT+PhyG+P+X), 3) xylanase-β-glucanase (XB, 1,200 U/kg and 152 U/kg) (Alt+PhyG+P+XB), 4) XB plus betaine (800 g/ton) (ALT+PhyG+P+XB+Bet), and 5) XB plus a probiotic [150,000 colony forming units (CFU)/g] (ALT+PhyG+P+XB+Prob); 6) to 9) as treatments 2) to 5) but with CP reduced by -2.0 to -1.5% points vs. control ('CP low'). Final (d 42) BW and overall (d 0-42) feed conversion ratio (FCR) of birds fed the SBM control exceeded breeder objectives (+3.8% and -1.9%, respectively). Overall FCR was reduced and d 42 BW increased in birds fed "low" vs. "high" CP (P < 0.01). Overall FCR and feed intake were not different in ALT+PhyG+XB+P+Bet and ALT+PhyG+XB+P+Prob vs. the control, whereas final BW was reduced (P < 0.05) in all ALT treatments but close to breeder objectives (98.3%) in ALT+PhyG+XB+P+Prob. Feed costs of this treatment were similar to the control. Total replacement of SBM with alternative plant-based ingredients in a CP-low diet supplemented with hydrolytic enzymes and probiotics can achieve growth performance outcomes close to commercial breeder objectives.
Topics: Animals; Animal Feed; Chickens; Male; Diet; Dietary Supplements; Betaine; Glycine max; Animal Nutritional Physiological Phenomena; Probiotics; Random Allocation; 6-Phytase; Endo-1,4-beta Xylanases
PubMed: 38815497
DOI: 10.1016/j.psj.2024.103854 -
Carbohydrate Research Jul 2024Triacedimannose (TADM) is a synthetic trivalent acetylated glycocluster comprising β-1,2-linked mannobioses that in humans induces TNF in vitro and in vivo. The purpose...
Triacedimannose (TADM) is a synthetic trivalent acetylated glycocluster comprising β-1,2-linked mannobioses that in humans induces TNF in vitro and in vivo. The purpose of this study was to analyze whether uptake of acetylated glycoclusters of such β-1,2-linked mannobioses by human macrophages is dependent on the mannose receptor (CD206) or if it is mediated by transmembrane activation. In mannose receptor blocking assays, monocyte-derived polarized macrophages were incubated with carbohydrate test-compounds and their binding to the mannose receptor was demonstrated as inhibition of FITC-Dextran binding. For 1H NMR spectroscopy, macrophages were incubated with TADM. The cells were collected at 6 and 24 h of incubation, centrifuged and washed twice with PBS. We found dose-dependent blocking of the mannose receptor in macrophage carbohydrate constructs containing free hydroxyl groups, but not by the trivalent acetylated glycocluster molecules. NMR spectroscopic analyses demonstrated that TADM was found in washed cellular pellets after 6-h co-culture, while after 24-h co-culture TADM was no more detectable, suggesting cleavage of the acetyl groups in vitro. The Type 1 immune response enhancing effects of TADM and other, stereochemically and structurally similar, trivalent acetylated glycoclusters may be due to transmembrane uptake of macrophages independent of the mannose receptor.
Topics: Mannose Receptor; Lectins, C-Type; Macrophages; Receptors, Cell Surface; Mannose-Binding Lectins; Humans; Adjuvants, Immunologic; Acetylation
PubMed: 38815341
DOI: 10.1016/j.carres.2024.109166 -
Acta Pharmaceutica (Zagreb, Croatia) Jun 2024In the past, the administration of medicines for children mainly involved changes to adult dosage forms, such as crushing tablets or opening capsules. However, these... (Review)
Review
In the past, the administration of medicines for children mainly involved changes to adult dosage forms, such as crushing tablets or opening capsules. However, these methods often led to inconsistent dosing, resulting in under- or overdosing. To address this problem and promote adherence, numerous initiatives, and regulatory frameworks have been developed to develop more child-friendly dosage forms. In recent years, multiparticulate dosage forms such as mini-tablets, pellets, and granules have gained popularity. However, a major challenge that persists is effectively masking the bitter taste of drugs in such formulations. This review therefore provides a brief overview of the current state of the art in taste masking techniques, with a particular focus on taste masking by film coating. Methods for evaluating the effectiveness of taste masking are also discussed and commented on. Another important issue that arises frequently in this area is achieving sufficient dissolution of poorly water-soluble drugs. Since the simultaneous combination of sufficient dissolution and taste masking is particularly challenging, the second objective of this review is to provide a critical summary of studies dealing with multiparticulate formulations that are tackling both of these issues.
Topics: Taste; Solubility; Humans; Drug Compounding; Pharmaceutical Preparations; Dosage Forms; Chemistry, Pharmaceutical; Tablets; Administration, Oral; Child; Excipients; Drug Liberation
PubMed: 38815202
DOI: 10.2478/acph-2024-0015 -
Scientific Reports May 2024Calcification of aortic valve leaflets is a growing mortality threat for the 18 million human lives claimed globally each year by heart disease. Extensive research has...
Calcification of aortic valve leaflets is a growing mortality threat for the 18 million human lives claimed globally each year by heart disease. Extensive research has focused on the cellular and molecular pathophysiology associated with calcification, yet the detailed composition, structure, distribution and etiological history of mineral deposition remains unknown. Here transdisciplinary geology, biology and medicine (GeoBioMed) approaches prove that leaflet calcification is driven by amorphous calcium phosphate (ACP), ACP at the threshold of transformation toward hydroxyapatite (HAP) and cholesterol biomineralization. A paragenetic sequence of events is observed that includes: (1) original formation of unaltered leaflet tissues: (2) individual and coalescing 100's nm- to 1 μm-scale ACP spherules and cholesterol crystals biomineralizing collagen fibers and smooth muscle cell myofilaments; (3) osteopontin coatings that stabilize ACP and collagen containment of nodules preventing exposure to the solution chemistry and water content of pumping blood, which combine to slow transformation to HAP; (4) mm-scale nodule growth via ACP spherule coalescence, diagenetic incorporation of altered collagen and aggregation with other ACP nodules; and (5) leaflet diastole and systole flexure causing nodules to twist, fold their encasing collagen fibers and increase stiffness. These in vivo mechanisms combine to slow leaflet calcification and establish previously unexplored hypotheses for testing novel drug therapies and clinical interventions as viable alternatives to current reliance on surgical/percutaneous valve implants.
Topics: Calcium Phosphates; Humans; Aortic Valve; Osteopontin; Calcinosis; Collagen; Durapatite; Aortic Valve Stenosis; Cholesterol
PubMed: 38806601
DOI: 10.1038/s41598-024-62962-8 -
Scientific Reports May 2024Extracellular vesicles (EVs) are lipid-membrane enclosed structures that are associated with several diseases, including those of genitourinary tract. Urine contains EVs...
Extracellular vesicles (EVs) are lipid-membrane enclosed structures that are associated with several diseases, including those of genitourinary tract. Urine contains EVs derived from urinary tract cells. Owing to its non-invasive collection, urine represents a promising source of biomarkers for genitourinary disorders, including cancer. The most used method for urinary EVs separation is differential ultracentrifugation (UC), but current protocols lead to a significant loss of EVs hampering its efficiency. Moreover, UC protocols are labor-intensive, further limiting clinical application. Herein, we sought to optimize an UC protocol, reducing the time spent and improving small EVs (SEVs) yield. By testing different ultracentrifugation times at 200,000g to pellet SEVs, we found that 48 min and 60 min enabled increased SEVs recovery compared to 25 min. A step for pelleting large EVs (LEVs) was also evaluated and compared with filtering of the urine supernatant. We found that urine supernatant filtering resulted in a 1.7-fold increase on SEVs recovery, whereas washing steps resulted in a 0.5 fold-decrease on SEVs yield. Globally, the optimized UC protocol was shown to be more time efficient, recovering higher numbers of SEVs than Exoquick-TC (EXO). Furthermore, the optimized UC protocol preserved RNA quality and quantity, while reducing SEVs separation time.
Topics: Ultracentrifugation; Humans; Extracellular Vesicles; Biomarkers; Urine; Female
PubMed: 38806574
DOI: 10.1038/s41598-024-62783-9 -
Minerva Cardiology and Angiology Aug 2024The latest generation ultrathin Supraflex Cruz (Sahajanand Medical Technologies Limited, Surat, India) sirolimus-eluting stent (SES) has shown early healing properties...
Safety and efficacy of the latest generation biodegradable polymer-coated ultrathin sirolimus-eluting stent in the treatment of coronary artery disease in a European all-comer population with or without high bleeding risk: The Cruz HBR Registry.
BACKGROUND
The latest generation ultrathin Supraflex Cruz (Sahajanand Medical Technologies Limited, Surat, India) sirolimus-eluting stent (SES) has shown early healing properties and represents an attractive percutaneous coronary intervention (PCI) device in a high bleeding risk (HBR) population. The aim of this Cruz HBR registry was to assess safety and efficacy of the Supraflex Cruz SES in a large cohort of all-comer patients, of whom about one third were patients at HBR.
METHODS
Patients undergoing PCI were enrolled in this prospective, multi-centre, open label registry and stratified into non-HBR and HBR groups. The primary endpoint was a device-oriented composite endpoint (DOCE), a composite of cardiovascular death, myocardial infarction not clearly attributable to a non-target vessel and clinically driven target lesion revascularization within 12 months after PCI. The predefined aims were to show non-inferiority of the non-HBR group to the Supraflex arm of the TALENT Trial, and of the HBR group to polymer-free biolimus-coated stent arm of LEADERS FREE Trial.
RESULTS
A total of 1203 patients were enrolled across 26 European centers, including a significant proportion (38.7%; N.=466) of HBR patients. A total of 1745 lesions were treated in 1203 patients and 2235 stents were implanted. The DOCE occurred within the total cohort in 5.8% of patients with a significant difference between HBR patients and non-HBR patients (8.1% vs. 4.4%; P<0.001). All-cause mortality at 12 months was significantly (P<0.0001) different among HBR (9.0%) and non-HBR patients (1.7%), respectively. At 12 months, the overall incidence of definite and probable stent thrombosis was 1.0%. Major bleeding occurred in 5.9% patients of the HBR group. These results met the non-inferiority criteria with respect to the TALENT trial for the non-HBR group (P<0.0001), and the LEADERS FREE trial for the HBR group (P<0.0001).
CONCLUSIONS
The Cruz HBR registry confirms that PCI with the Supraflex Cruz SES is associated with a favorable clinical outcome in an all-comer population, including complex patients with HBR.
Topics: Humans; Drug-Eluting Stents; Sirolimus; Male; Registries; Female; Coronary Artery Disease; Prospective Studies; Percutaneous Coronary Intervention; Aged; Middle Aged; Polymers; Hemorrhage; Treatment Outcome; Europe; Absorbable Implants; Prosthesis Design; Risk Factors
PubMed: 38804621
DOI: 10.23736/S2724-5683.24.06462-7 -
International Journal of Nanomedicine 2024There is an ongoing need for improved healing response and expedited osseointegration on the Ti implants in acetabular fracture sites. To achieve adequate bonding and...
INTRODUCTION
There is an ongoing need for improved healing response and expedited osseointegration on the Ti implants in acetabular fracture sites. To achieve adequate bonding and mechanical stability between the implant surface and the acetabular fracture, a new coating technology must be developed to promote bone integration and prevent bacterial growth.
METHODS
A cylindrical Ti substrate mounted on a rotating specimen holder was used to implant Ca, P, and Sr ions at energies of 100 KeV, 75 KeV and 180 KeV, respectively, using a low-energy accelerator to synthesize strontium-substituted hydroxyapatite at varying conditions. Ag ions of energy 100 KeV were subsequently implanted on the as-formed surface at the near-surface region to provide anti-bacterial properties to the as-formed specimen.
RESULTS
The properties of the as-formed ion-implanted specimen were compared with the SrHA-Ag synthesized specimens by cathodic deposition and low-temperature high-speed collision technique. The adhesion strength of the ion-implanted specimen was 43 ± 2.3 MPa, which is well above the ASTM standard for Ca-P coating on Ti. Live/dead cell analysis showed higher osteoblast activity on the ion-implanted specimen than the other two. Ag in the SrHA implanted Ti by ion implantation process showed superior antibacterial activity.
DISCUSSION
In the ion implantation technique, nano-topography patterned surfaces are not concealed after implantation, and their efficacy in interacting with the osteoblasts is retained. Although all three studies examined the antibacterial effects of Ag ions and the ability to promote bone tissue formation by MC3T3-E1 cells on SrHA-Ag/Ti surfaces, ion implantation techniques demonstrated superior ability. The synthesized specimen can be used as an effective implant in acetabular fracture sites based on their mechanical and biological properties.
Topics: Titanium; Silver; Strontium; Anti-Bacterial Agents; Acetabulum; Animals; Coated Materials, Biocompatible; Osseointegration; Mice; Surface Properties; Fractures, Bone; Durapatite; Osteoblasts; Hydroxyapatites; Prostheses and Implants; Ions; Humans; Cell Line
PubMed: 38803996
DOI: 10.2147/IJN.S464905