Human Bone Research Articles

BCG vaccination alters the epigenetic landscape of progenitor cells in human bone marrow to influence innate immune responses

Although the Bacille-Calmette-Guérin (BCG) vaccine is used to prevent tuberculosis, it also offers protection against a diverse range of non-mycobacterial infections. However, the underlying protective mechanisms in humans are not yet fully understood. Here, we surveyed at single-cell resolution the gene expression and chromatin landscape of human bone marrow, aspirated before and 90days after BCG vaccination or placebo. We showed that BCG alters both the gene expression and epigenetic profiles of human hematopoietic stem and progenitor cells (HSPCs). Changes in gene expression occurred primarily within uncommitted stem cells. By contrast, changes in chromatin accessibility were most prevalent within differentiated progenitor cells at sites influenced by Kruppel-like factor (KLF) and early growth response (EGR) transcription factors and were highly correlated (r>0.8) with the interleukin (IL)-1β secretion capacity of paired peripheral blood mononuclear cells (PBMCs). Our findings shed light on BCG vaccination's profound and lasting effects on HSPCs and its influence on innate immune responses and trained immunity.

Morphometry of the Suprascapular Notch and the Incidence of Ossification of Superior Transverse Scapular Ligament in an Adult Human Scapulae Bone of South Indian Population

Morphometry of the Suprascapular Notch and the Incidence of Ossification of Superior Transverse Scapular Ligament in an Adult Human Scapulae Bone of South Indian Population

The comparison of extracellular vesicles with matrix vesicles derived from human vascular smooth muscle versus bone osteoblastic and osteosarcoma cells

The comparison of extracellular vesicles with matrix vesicles derived from human vascular smooth muscle versus bone osteoblastic and osteosarcoma cells

Phase Transformation and Mechanical Optimization of Eggshell-Derived Hydroxyapatite across a Wide Sintering Temperature Range.

Calcium phosphate, particularly hydroxyapatite (HA), bears a close resemblance to human bones, rendering it a prevalent material in biomedical applications. This study focuses on the successful preparation of HA using a precipitation method with eggshell as a raw material. Subsequently, the HA powder was press-formed and sintered at various temperatures to investigate the impact of sintering temperature on the mechanical properties, including hardness, compressive strength, and fracture toughness, of the sintered HA samples (E-HA). Statistical analyses, including one-way ANOVA and Tukey's post-hoc test, were conducted to determine significant differences in these properties at different sintering temperatures. Experimental findings revealed that as the sintering temperature increased, HA partially transformed into β-TCP between 800 and 1300 °C, with α-TCP observed at 1400 °C. The elimination of pores led to an increase in relative density, with a maximum relative density of 94.5% achieved at 1200 and 1300 °C. E-HA sintered at 1200 °C exhibited the highest hardness (5.08 GPa), compressive strength (255.79 MPa), and fracture toughness (1.21 MPa·m0.5). However, at 1400 °C, a slight decrease in apparent density (2.90 g/cm3) was noted due to the presence of α-TCP, along with significant grain growth. This study's objective is clearly aligned with the study design, incorporating detailed statistical analyses to validate the findings. Furthermore, bacterial culture experiments were conducted using sintered E-HA, Chem-HA (HA synthesized from reagent-grade calcium carbonate), and Comm-HA (commercial HA). Streptococcus mutans was cultured on the surfaces of sintered E-HA, Chem-HA, and Comm-HA samples for 20 h. After culturing, the OD values for all samples were below 0.2, indicating significant antibacterial efficacy. The comparable OD values and bacterial counts (p > 0.05) suggest that the source of HA does not impact its antibacterial properties. This underscores the potential of eggshell-derived HA as an effective material for biomedical applications.

3D osteocyte lacunar morphometry of human bone biopsies with high resolution microCT: From monoclonal gammopathy to newly diagnosed multiple myeloma

Osteocytes are mechanosensitive, bone-embedded cells which are connected via dendrites in a lacuno-canalicular network and regulate bone resorption and formation balance. Alterations in osteocyte lacunar volume, shape and density have been identified in conditions of aging, osteoporosis and osteolytic bone metastasis, indicating patterns of impaired bone remodeling, osteolysis and disease progression. Osteolytic bone disease is a hallmark of the hematologic malignancy multiple myeloma (MM), in which monoclonal plasma cells in the bone marrow disrupt the bone homeostasis and induce excessive resorption at local and distant sites. Qualitative and quantitative changes in the 3D osteocyte lacunar morphometry have not yet been evaluated in MM, nor in the precursor conditions monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM). In this study, we characterized the osteocyte lacunar morphology in trabecular bone of the iliac crest at the ultrastructural level using high resolution microCT in human bone biopsy samples of three MGUS, two SMM and six newly diagnosed MM. In MGUS, SMM and MM we found a trend for lower lacunar density and a shift towards larger lacunae with disease progression (higher 50 % cutoff of the lacunar volume cumulative distribution) in the small osteocyte lacunae 20–900 μm3 range compared to control samples. In the larger lacunae 900–3000 μm3 range, we detected significantly higher lacunar density and microporosity in the MM group compared to the MGUS/SMM group. Regarding the shape distribution, the MGUS/SMM group showed a trend for flatter, more elongated and anisotropic osteocyte lacunae compared to the control group. Altogether, our findings suggest that osteocytes in human MM bone disease undergo changes in their lacunae density, volume and shape, which could be an indicator for osteolysis and disease progression. Future studies are needed to understand whether alterations of the lacunae architecture affect the mechanoresponsiveness of osteocytes, and ultimately bone adaptation and fracture resistance in MM and its precursors conditions.

Preparation and Characterization of Hydroxyapatite Using Precursor Extracted from Cockle Shell Waste

Hydroxyapatite (HAP) is a widely used biomaterial due to its excellent bioactivity, biocompatibility, and structural similarity to the mineral component of human bone and teeth. However, the synthesis of HAP typically relies on expensive and non-renewable precursors, which can limit its widespread applications. This study investigates the extraction and purification of HAP from cockle shells, which are a readily available and renewable source of calcium carbonate. The extraction and purification of hydroxyapatite (HAP) from cockle shells, which are rich in calcium carbonate, is a promising method for producing HAP for biomedical applications due to its bioactivity and biocompatibility. This study investigates the use of a calcination process and wet slurry precipitation technique to produce HAP from seashells, focusing on the effect of reaction time of phosphate source (KH2PO4) and calcium oxide (CaO) on HAP production. EDX reported Ca/P ratio of 1.61 for HAP synthesized by chemical precipitation for 2 hours of reaction. Meanwhile, the XRD results indicate that a 4-hour reaction time produces more crystalline HAP than shorter reaction times, highlighting the importance of reaction time in HAP synthesis. This research demonstrates the potential of utilizing seashell waste as a valuable natural resource for applications in healthcare and waste management.

Assessment of Novel Surgical Procedures Using Bone Morphogenic Protein-7 Infused Into Decellularised Muscle and Bioactive Ceramic: A Histological Analysis.

Reconstruction of critical bone defects is considered a challenge due to vascular reperfusion injury that may occur. The present study hypothesized that the use of decellularized muscle scaffold (DMS) and bone morphogenic protein-7 (BMP-7), along with resorbable bioactive ceramic silica calcium phosphate cement (SCPC) seeded with human bone marrow stromal cells, can expedite bone formation and maturation. Surgical bone defects were created in 20 nude transgenic mice. In experimental group 1 (n = 10), a critical-size (4mm) calvarial defect was made and grafted with DMS-BMP-7/SCPC. In situ human bone marrow stromal cells [human mesenchymal stromal cells (hMSC)] were seeded thereafter. As a control, group 2 (n = 10) was treated with DMS/SCPC seeded with hMSCs. After 8 weeks, bone regeneration was evaluated using histology and histomorphometry for both groups. Histological examination showed bone regeneration crossing the gap (experimental group 1), bone regeneration was noted at the defect periphery, and scattered islands of bone at the canters of the defects (control group 2). New bone formation and maturation were superior in the groups treated with the DMS/BMP-7/SCPC/hMSC constructs. The quantitative histological assessment revealed that the average bone surface area was 255 ± 25mm2, which was 1.5 times the surface area of group 2, which was reported at 170 ± 35mm2. The reported difference was considered statistically significant (P < 0.05). The DMS-BMP-7/SCPC scaffold induced bone regeneration and neovascularization in critical-size defects.

Dihydromyricetin-loaded oxidized polysaccharide/L-arginine chitosan adhesive hydrogel promotes bone regeneration by regulating PI3K/AKT signaling pathway and MAPK signaling pathway

Bone defects caused by trauma, infection and congenital diseases still face great challenges. Dihydromyricetin (DHM) is a kind of flavone extracted from Ampelopsis grossedentata, a traditional Chinese medicine. DHM can enhance the osteogenic differentiation of human bone marrow mesenchymal stem cells with the potential to promote bone regeneration. Hydrogel can be used as a carrier of DHM to promote bone regeneration due to its unique biochemical characteristics and three-dimensional structure. In this study, oxidized phellinus igniarius polysaccharides (OP) and L-arginine chitosan (CA) are used to develop hydrogel. The pore size and gel strength of the hydrogel can be changed by adjusting the oxidation degree of oxidized phellinus igniarius polysaccharides. The addition of DHM further reduce the pore size of the hydrogel (213 μm), increase the mechanical properties of the hydrogel, and increase the antioxidant and antibacterial activities of the hydrogel. The scavenging rate of DPPH are 72.30 ± 0.33 %, and the inhibition rate of E.coli and S.aureus are 93.12 ± 0.38 % and 94.49 ± 1.57 %, respectively. In addition, PCAD has good adhesion and biocompatibility, and its extract can effectively promote the osteogenic differentiation of MC3T3-E1 cells. Network pharmacology and molecular docking show that the promoting effect of DHM on osteogenesis may be achieved by activating the PI3K/AKT and MAPK signaling pathways. This is confirmed through in vitro cell experiments and in vivo animal experiments.

Formulation and characterization of a novel anti-human bone cancer supplement from silver nanoparticles green-synthesized using Allium sativum l. Leaf aqueous extract

Several studies have recently uncovered the ability of plants to enhance the therapeutic efficacies of Ag NPs on various carcinoma cells, particularly those associated with human bone tumors. Developing and formulating novel chemotherapy supplements or medications for the management of bone tumors in humans is a top research focus for both developing and developed nations. Our current study involved the development of a contemporary chemotherapeutic medication utilizing silver nanoparticles (AgNPs) combined with an aqueous extract of Allium sativum L. for the purpose of treating bone tumors in humans. AgNPs were characterized using XRD, TEM, UV–Vis, and FE-SEM. The peaks detected at 2θ values of 77.4, 65.1, and 37.8 were associated with the crystal planes 311, 220, and 111, respectively. To examine the antioxidant characteristics of AgNPs, the DPPH assay was employed with BHT serving as the positive control. The MTT assay was employed to examine the anti-human bone tumor and cytotoxicity properties of AgNPs on bone cancer cells, including A-673 and HS-729 (rhabdomyosarcoma), MHH-ES1 and CADO-ES1 (Ewing’s sarcoma), MG-63 and HOS (osteosarcoma), as well as CH-3573 and SW-1353 (chondrosarcoma). The DPPH assay demonstrated comparable antioxidant capacities among AgNPs, and butylated hydroxytoluene. The anti-human bone tumor properties and cell viability of silver nanoparticles exhibited a dose-dependent decrease against CH-3573, SW-1353, MG-63, HOS, MHH-ES1, CADO-ES1, HS-729, and A-673 cells, while showing no cytotoxic effects on the normal cell line. The viability of the cells and their response to the nanoparticles varied based on the dosage administered. The silver nanoparticles exhibited IC50 values of 154, 67, 129, 110, 124, 107, 70, and 81 µg/ml against H-3573, SW-1353, MG-63, HOS, MHH-ES1, CADO-ES1, HS-729, and A-673 cell lines, respectively. The HOS revealed the most effective outcome regarding anti-human bone tumor efficacies when treated with AgNPs, surpassing the results observed in other cell lines. Based on the aforementioned results, it is possible to utilize the silver nanoparticles with A. sativum extract for the management of various human bone tumors, particularly human bone rhabdomyosarcoma, human bone chondrosarcoma, human bone osteosarcoma, and human bone Ewing’s sarcoma.

Recyclable thermo-responsive elastin-based adhesives with tough underwater adhesion and rapid hemostasis ability

Protein-based underwater adhesives have attracted tremendous attention due to their excellent biocompatibility compared to adhesives prepared with synthetic polymers. However, the fabrication of protein-based adhesives always requires multiple successive steps, and their underwater adhesion is quite limited. Inspired by the human elastic fibers, bone matrix, and marine adhesive proteins, a thermo-responsive underwater adhesive was fabricated through a facial one-step complexation of elastin (ELN), hydroxyapatite (HAP), and tannic acid (TA) based on multiple non-covalent molecular interactions. During underwater adhesion, the adhesive can perform sufficient flowability to adhere seamlessly and strongly to the substrates upon heating at 37 ℃ and then significantly increase its cohesion through cooling down to 25 ℃ to sustain adhesion. The regulation of the balance between adhesion and cohesion in response to temperature change enables the adhesive to exhibit a robust underwater adhesion ranging from 0.3 to 1.1 MPa to the substrates with low, medium, or high surface energy, outperforming most protein-based adhesives. Importantly, the adhesive can be further processed into powders with well-maintained underwater adhesion by a simple drying and grinding method, facilitating adhesion onto irregular-shaped target sites, reusability, and closed-loop recycling. The adhesive powder also possesses a rapid in vivo hemostatic property, suggesting a potential biomedical application.

A nomogram and risk stratification system for predicting survival in T1-2N0-1 breast cancer patients with liver metastasis in females: a population-based study

PurposeLiver was one of the most common distant metastatic sites in breast cancer. Patients with distant metastasis were identified as American Joint Committee on Cancer (AJCC) stage IV indicating poor prognosis. However, few studies have predicted the survival in females with T1-2N0-1 breast cancer who developed liver metastasis. This study aimed to explore the clinical features of these patients and establish a nomogram to predict their overall survival.Results1923 patients were randomly divided into training (n = 1154) and validation (n = 769) cohorts. Univariate and multivariate analysis showed that age, marital status, race, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER2), chemotherapy, surgery and bone metastasis, brain metastasis were considered the independent prognostic indicators. We developed a nomogram according to these ten parameters. The consistency index (c-index) was 0.72 (95% confidence interval CI 0.70–0.74) in the training cohort, 0.72 (95% CI 0.69–0.74) in the validation cohort. Calibration plots indicated that the nomogram-predicted survival was consistent with the recorded 1-, 3- and 5-year prognoses. Decision curve analysis curves in both the training and validation cohorts demonstrated that the nomogram showed better prediction than the AJCC TNM (8th) staging system. Kaplan Meier curve based on the risk stratification system showed that the low-risk group had a better prognosis than the high-risk group (P < 0.001).ConclusionsA predictive nomogram and risk stratification system were constructed to assess prognosis in T1-2N0-1 breast cancer patients with liver metastasis in females. The risk model established in this study had good predictive performance and could provide personalized clinical decision-making for future clinical work.

Developing a risk score to inform the use of rhBMP-2 in adult spinal deformity surgery.

Recombinant human bone morphogenetic protein-2 (rhBMP-2) has not shown superior benefit overall in cost-effectiveness during adult spinal deformity (ASD) surgery. Retrospective PURPOSE: Generate a risk score for pseudarthrosis to inform the utilization of rhBMP-2, balancing costs against quality of life and complications. ASD patients with 3-year data were included. Quality of life gained was calculated from ODI to SF-6D and translated to quality-adjusted life years (QALYs). Cost was calculated using the PearlDiver database and CMS definitions for complications and comorbidities. Established weights were generated for predictive variables via logistic regression to yield a predictive risk score for pseudarthrosis that accounted for frailty, diabetes, depression, ASA grade, thoracolumbar kyphosis and three-column osteotomy use. Risk score categories, established via conditional inference tree (CIT)-derived thresholds were tested for cost-utility of rhBMP-2 usage, controlling for age, prior fusion, and baseline deformity and disability. 64% of ASD patients received rhBMP-2 (308/481). There were 17 (3.5%) patients that developed pseudarthrosis. rhBMP-2 use overall did not lower pseudarthrosis rates (OR: 0.5, [0.2-1.3]). Pseudarthrosis rates for each risk category were: No Risk (NoR) 0%; Low-Risk (LowR) 1.6%; Moderate Risk (ModR) 9.3%; High-Risk (HighR) 24.3%. Patients receiving rhBMP-2 had similar QALYs overall to those that did not (0.163 vs. 0.171, p = .65). rhBMP-2 usage had worse cost-utility in the LowR cohort (p < .001). In ModR patients, rhBMP-2 usage had equivocal cost-utility ($53,398 vs. $61,581, p = .232). In the HighR cohort, the cost-utility was reduced via rhBMP-2 usage ($98,328 vs. $211,091, p < .001). Our study shows rhBMP-2 demonstrates effective cost-utility for individuals at high risk for developing pseudarthrosis. The generated score can aid spine surgeons in the assessment of risk and enhance justification for the strategic use of rhBMP-2 in the appropriate clinical contexts. III.

Atranorin is a novel potential candidate drug for treating myelodysplastic syndrome

This work is devoted to the study of biocompatibility, cyto- and genotoxicity, mechanism of action and prospects for the use of atranorin, which is an AKT kinase inhibitor, for the treatment of myelodysplastic syndrome. Atranorin was isolated by preparative flash chromatography; identification was carried out by UV, IR, and NMR spectroscopy, mass spectrometry, and elemental analysis. Biocompatibility studies included studies of haemocompatibility, genotoxicity, antioxidant activity, cytotoxicity against ECV340 and HEK293 cell lines. Computer modelling of the interaction of atranorin with AKT kinase was carried out using docking followed by molecular dynamics of the resulting complexes; the ADMET properties of atranorin were also calculated. Flow cytometry included analysis of the expression level of PD-L1 and TIM-3 in the presence of atranorin on THP-1, Mono-Mac-1 and KG-1 cell lines, as well as human bone marrow cells.

Outcomes of Birmingham Hip Resurfacing Based on Clinical Aspects and Retrieval Analysis of Failed Prosthesis.

This research aims to identify the prevalence of failure for Birmingham Hip Prosthesis (BHR) in total hip arthroplasty and to analyze its reasons from biomaterials and biofunctional perspectives. We present our current analysis and tests on a series of different BHR-retrieved prostheses after premature failure. Relevant clinical data, such as X-ray investigations and intraoperative images for clinical case studies, were analyzed to better understand all factors involved in BHR prosthesis failure. A detailed analysis of the failures highlighted uneven cement distribution, overloading in certain areas, and void formation in the material. A closer investigation using microscopical techniques revealed the presence of a crack originating from the gap between the cement mantle and human bone. Additionally, scanning electron microscopy analyses were conducted as part of the investigation to examine bone cement morphology in detail and better understand the interactions at the interfaces between implant, cement, and bone. In conclusion, this research emphasizes the importance of surgical technique planning and the cementation procedure in the success rate of BHR prostheses. It also underscores the need to carefully evaluate patient characteristics and bone quality to minimize the risk of BHR prosthesis failure. The cementation procedure seems to be essential for the long-term functionality of the BHR prosthesis.

Comparing the Corrosion Behavior and Microstructure of a WE43 Mg Alloy in Simulated Body Fluids Under Different CO2 Conditions

With the low density and high specific strength, magnesium (Mg) alloys are lightweight alloys with various applications. In addition, combined with biocompatibility, similar mechanical properties to human bones, and unique biodegradability, Mg alloys are promising biodegradable implant materials for orthopedic surgeries. However, the degradation rates of Mg alloys are too fast in physiological environments, which limits the clinical applications of Mg implants. Therefore, understanding the corrosion behavior in physiological environments is crucial for developing biodegradable Mg alloys.During Mg alloy degradation, hydroxide (OH-) ions are generated, and the pH near the alloy surface increases. Since carbonate-bicarbonate (CO3 2--HCO3 -) is a vital pH buffer system in the human body, the corrosion behavior of Mg alloys would be affected by the CO2 concentrations of the test environments. In this study, we performed electrochemical and corrosion tests of a solution heat-treated WE43 (Mg-4 wt%Y-3 wt%Nd) alloy in Hanks’ balanced salt solutions (HBSS) at 37°C. By performing the tests in air and in an incubator maintained at 5% CO2, the effect of carbonate-bicarbonate pH buffering on the corrosion behavior and corrosion microstructure of the WE43 Mg alloy was investigated.When testing the WE43 Mg alloy in air, a general corrosion morphology was observed during the 24-hour immersion. In contrast, WE43 Mg alloy tested in the incubator shows a more active surface potential and localized corrosion initiates on the alloy surface in the early stages of immersion. Electrochemical impedance spectroscopy (EIS) analysis shows that WE43 Mg alloy tested in air has better corrosion resistance than in the incubator. Furthermore, the corrosion resistance of the alloy tested in air increases with immersion time but decreases when tested in the incubator. Potentiodynamic polarization curves after 24-hour immersion confirm that the corrosion current density (i corr) of the WE43 Mg alloy tested in the incubator is higher than that when tested in air. The difference in corrosion behavior is owing to the carbonate-bicarbonate pH buffering effect and will be discussed based on corrosion microstructure characterizations. Figure 1

An enzymatically crosslinked collagen type II/hyaluronic acid hybrid hydrogel: A biomimetic cell delivery system for cartilage tissue engineering

This study presents new injectable hydrogels based on hyaluronic acid and collagen type II that mimic the polysaccharide-protein structure of natural cartilage. After collagen isolation from chicken sternal cartilage, tyramine-grafted hyaluronic acid and collagen type II (HA-Tyr and COL-II-Tyr) were synthesized. Hybrid hydrogels were prepared with different ratios of HA-Tyr/COL-II-Tyr using horseradish peroxidase and noncytotoxic concentrations of hydrogen peroxide to encapsulate human bone marrow-derived mesenchymal stromal cells (hBM-MSCs). The findings showed that a higher HA-Tyr content resulted in a higher storage modulus and a lower hydrogel shrinkage, resulting in hydrogel swelling. Incorporating COL-II-Tyr into HA-Tyr hydrogels induced a more favorable microenvironment for hBM-MSCs chondrogenic differentiation. Compared to HA-Tyr alone, the hybrid HA-Tyr/COL-II-Tyr hydrogel promoted enhanced chondrocyte adhesion, spreading, proliferation, and upregulation of cartilage-related gene expression. These results highlight the promising potential of injectable HA-Tyr/COL-II-Tyr hybrid hydrogels to deliver cells for cartilage regeneration.

Synthetic or Natural (Bio-Based) Hydroxyapatite? A Systematic Comparison between Biomimetic Nanostructured Coatings Produced by Ionized Jet Deposition.

Calcium phosphate (CaP)-based materials are largely explored in orthopedics, to increase osseointegration of the prostheses and specifically in spine surgery, to permit better fusion. To address these aims, nanostructured biogenic apatite coatings are emerging, since they better mimic the characteristics of the host tissue, thus potentially being better candidates compared to their synthetic counterpart. Here, we compare hydroxyapatite (HA) nanostructured coatings, obtained by ionized jet deposition, starting from synthetic and natural sources. The starting materials and the corresponding films are characterized and compared from a compositional and morphological point of view, then their stability is studied after post-treatment annealing. Although all the films are formed by globular aggregates and show morphological features at different scales (from nano to micro), significant differences are found in composition between the synthetic and naturally derived HA in terms of magnesium and sodium content, carbonate substitution and Ca/P ratio, while differences between the coatings obtained by the different natural HA sources are minor. In addition, the shape of the aggregates is also target-dependent. All coatings have a good stability after over 14 days of immersion in medium, with natural apatite coatings showing a better behavior, as no cracking and detachments are observed during immersion. Based on these results, both synthetic and naturally derived apatitic materials appear promising for applications in spine surgery, with coatings from natural sources possessing physiochemical properties more similar to the mineral phase of the human bone tissue.

Mesenchymal vs. epithelial extracellular vesicles in corneal epithelial repair, apoptosis, and immunomodulation: An in vitro study

Corneal injuries often lead to epithelial damage, apoptosis, and inflammation which impact visual function. Effective epithelial healing is critical for optimal vision and functioning of the cornea. Mesenchymal stem/stromal cells (MSCs)-derived extracellular vesicles (EVs) present promising avenues for cell-free therapy, however, evaluation of their specific roles in corneal epithelial injury requires further investigations with due consideration to the endogenous human corneal epithelial cell-derived EVs (HCEC-EVs). This study aims to isolate and characterize the EVs from a commonly available human corneal epithelial cell line (HCE-2 [50. B1], ATCC) and evaluate their corneal epithelial repair, anti-apoptotic, and immunomodulatory potential in comparison with human bone marrow mesenchymal stem cell-derived EVs (BM-MSC-EVs) in vitro. Both the BM-MSC- and HCEC-EVs exhibited similar morphology with a diameter <150 nm. However, the yield of EVs from HCECs was higher than that of BM-MSCs. Nanoparticle tracking analysis revealed an average EV size of ∼120 nm, while western blotting confirmed the presence of CD63, CD81, and TSG101, whereas Calnexin could not be detected in the BM-MSC- and HCEC-EVs. The corneal epithelial repair was monitored through in vitro wound healing assay, whereas apoptosis was studied through flow cytometry-based Propidium iodide staining in H2O2-treated cells. IL-1β-stimulated HCECs were treated with BM-MSC- and HCEC-EVs for 24 h and expression of pro- (IL-6 and TNF-α) and anti-inflammatory (IL-10 and TGF-β) cytokines was evaluated through ELISA. Our results, limited to in vitro investigations, suggest that compared with HCEC-EVs, BM-MSC-EVs showed: i) accelerated corneal epithelial healing, ii) enhanced anti-apoptotic potential, and iii) improved anti-inflammatory properties, in cultured HCECs.

ARCHAEOMETRIC analysis of pigments from archaeological contexts in the upper DELTA of the PARANÁ river (ARGENTINA)

AbstractThis research delves into ancient pigment practices among the Goya‐Malabrigo societies in the Upper Delta of the Paraná River during the Late Holocene. Utilising Raman microspectroscopy and X‐ray diffraction, we analysed 33 samples from six archaeological sites and four natural outcrops. Our discoveries uncovered hematite in red pigments across diverse materials (potsherds, shells, human bones, and sediments), anatase adorning ceramics with whitish tones, and charcoal creating darker shades. These findings not only contribute to the understanding of the mineral composition of ancient colours used by Indigenous people in domestic and funerary contexts but also set the first stage for forthcoming provenance research, integrating multiple archaeometric techniques to unravel the origins of these compelling pigments.

A model of long-term population growth with an application to Central West Argentina.

We propose an Ideal Specialization Model to help explain the diversity of population growth trajectories exhibited across archaeological regions over thousands of years. The model provides a general set of expectations useful for guiding empirical research, and we provide a concrete example by conducting a preliminary evaluation of three expectations in Central West Argentina. We use kernel density estimates of archaeological radiocarbon, estimates of paleoclimate, and human bone stable isotopes from archaeological remains to evaluate three expectations drawn from the model's dynamics. Based on our results, we suggest that innovations in the production of food and social organization drove demographic transitions and population expansion in the region. The consistency of population expansion in the region positively associates with changes in diet and, potentially, innovations in settlement and social integration.