Assessing Health Risks Associated with Heavy Metals in Food: A Bibliometric Analysis.

Bibliometric analysis is an effective method used to identify research trends based on historical publications that involves combining different frameworks, tools and methods, leading to the creation of different metrics. This study employed bibliometric analysis to investigate the global health risk assessment of heavy metals in food from 2000 to 2022 using Web of Science and VOSviewer. We explore publication trends, affiliations, countries, journals, citations, keywords and author collaborations. Of the 573 publications on this topic, there has been a notable increase in recent years. The Ministry of Agriculture and Rural Affairs (China) and Shahid Beheshti University of Medical Sciences (Iran) are the most prolific affiliations. Environmental Science and Pollution Research is the top journal. Notably, "heavy metals", "risk assessment", "cadmium", "lead", and "trace elements" are frequently used keywords. A study by Miraglia et al. in 2009 received the most citations. Amin Mousavi Khaneghah (Poland) is the most prolific author, with 24 papers. Articles mainly focus on contamination levels in fish, seafood, cereals, dairy, meat, and fruit/vegetables. Some studies highlight potential risks, necessitating stricter food product controls for consumer safety.

Plackett-Burman design in the biosynthesis of silver nanoparticles with Mutisia acuminatta (Chinchircoma) and preliminary evaluation of its antibacterial activity.

Background: The aim of this study was to synthesize silver nanoparticles (AgNPs) using the methanolic fraction of Mutisia acuminatta leaves using Plackett-Burman design to optimize process parameters and to evaluate its antibacterial effect. Methods: For the separation of Mutisia acuminatta phytoconstituents, chromatographic techniques were used. For characterization and identification, UV - VIS spectrophotometry, FTIR spectrophotometry, Dynamic Light Scattering (DLS) and transmission electron microscopy (TEM) were used. The Plackett-Burman design used polynomial regression statistical analysis to determine the most influential variables. Results: UV-VIS spectroscopy reported an absorbance concerning surface plasmon resonance between 410-420 nm wavelength for the AgNPs. FTIR spectrophotometry reported characteristic peaks in the biosynthesized AgNPs, observing the disappearance of spectral peaks between 1000-1500 cm -1. By UHPLC-MS, caffeic acid derivatives, coumarins, flavonoids, lignans, disaccharide and a complex formed between silver and the solvent (AgCH3CN+) were identified. Using DLS, the AgNPs presented an average hydrodynamic size of 45.91 nm. TEM determined the spherical shape of the AgNPs, presenting diameters in the range of 30 to 60 nm. The biosynthesized AgNPs showed higher antibacterial activity against Escherichia coli and Staphylococcus aureus than the total extract, the methanolic fraction and pure methanol. The polynomial model in the biosynthesis was validated with an adequate fitting representing the experimental data of the process. The most significant variables for the model obtained were the reaction pH (X 2) and the concentration of the precursor salt AgNO 3 (X 6). Conclusions: The synthesized AgNPs offer a viable option for further development due to the presence of bioactive compounds, adequate characterization and antibacterial activity.

Evidence of Partial Seniority Conservation in the πg_{9/2} Shell for the N=50 Isotones.

The reduced transition probabilities for the 4_{1}^{+}→2_{1}^{+} and 2_{1}^{+}→0_{1}^{+} transitions in ^{92}Mo and ^{94}Ru and for the 4_{1}^{+}→2_{1}^{+} and 6_{1}^{+}→4_{1}^{+} transitions in ^{90}Zr have been determined in this experiment making use of a multinucleon transfer reaction. These results have been interpreted on the basis of realistic shell-model calculations in the f_{5/2}, p_{3/2}, p_{1/2}, and g_{9/2} proton valence space. Only the combination of extensive lifetime information and large scale shell-model calculations allowed the extent of the seniority conservation in the N=50 g_{9/2} orbital to be understood. The conclusion is that seniority is largely conserved in the first πg_{9/2} orbital.

The Biota orientalis, oil extract Epiitalis®, is efficacious at reducing the symptoms of knee osteoarthritis: a pilot, multi-site, dose-ranging, randomized, blinded, placebo-controlled trial.

OBJECTIVE: To explore the safety, and efficacy of a proprietary hydrolyzed oil extract from seeds of Biota orientalis (hBO/Epiitalis®, Interpath Pty Ltd) in patients with knee pain due to osteoarthritis (OA). METHODS: Patients aged 40-65 with X-ray diagnosed knee OA and knee pain ≥ 60 on a 100-point VAS (visual analog scale) were enrolled and randomized into four groups to receive daily hBO for 56 days as high (hBO-HD, 640 mg), mid (hBO-MD, 320 mg) or low (hBO-LD, 160 mg) doses, or a matched placebo oil. The primary outcome was change in VAS knee pain from baseline to 56 days in the mITT (modified intention to treat) population. Exploratory outcomes were the mWOMAC (modified Western Ontario and McMaster Universities Arthritis Index), and the SF-36 QoL (quality of life) questionnaire. The OMERACT-OARSI (Outcome Measures in Arthritis Clinical Trials-Osteoarthritis Research Society International) responder index was also calculated. RESULTS: 223 patients were included in the mITT population. Reductions in VAS scores between baseline and day 56 [Least square mean (LS mean) and 95% confidence interval (CI) of LS mean] were 36.4 (31.7-41.0), 37.9 (33.2-42.7), 35.7 (31.2-40.1) and 9.8 (14.5-15.2) for the hBO-HD, hBO-MD, hBO-LD, and placebo groups respectively. The VAS changes in all hBO groups were significantly different (p < 0.0001) vs. changes in the placebo group. hBO treatment led to similar quantitative beneficial changes in mWOMAC, SF-36 and OMERACT-OARSI responder index. There were no SAEs and no adverse events ascribed to the intervention. CONCLUSION: In a 56-day trial, hBO was safe, and was efficacious at reducing symptoms in patients with knee OA. REGISTRATION: NCT04117490; Oct 7, 2019.

Clonal cutaneous and neurosyphilis: A pitfall in pseudolymphoma diagnosis.

Syphilis is a sexually transmitted infectious disease caused by the bacterium Treponema pallidum and can cause a wide variety of cutaneous manifestations, most commonly, a papulosquamous eruption of the trunk and extremities. Treatment with penicillin is curative. We report a case of a 69-year-old man who presented with recent onset of blurry vision and a nonpainful, nonpruritic eruption of pink-to-violaceous dermal nodules on his upper trunk and upper extremities. Biopsies of two separate locations revealed a dense superficial and deep perivascular atypical lymphocytic infiltrate with admixed plasma cells, histiocytes, and eosinophils. Some scattered cells expressed CD30, PD1, BCL-6, and ICOS. T-cell receptor (TCR)-rearrangement showed an identical TCR-gamma clone between both biopsy specimens. The patient was subsequently seen by ophthalmology and diagnosed with acute anterior uveitis. Rapid plasma reagin was reactive and cerebrospinal fluid studies showed findings consistent with a diagnosis of neurosyphilis. A T. pallidum immunostain of the skin biopsies was performed upon re-review, and was diffusely positive for spirochetes at the dermal-epidermal junction and within injured vessels. The patient was treated with penicillin G with near-resolution of his skin lesions. This case highlights the unusual ability of syphilis to mimic a T-cell lymphoma with matching clones across two different biopsy sites.

Primary cutaneous mucormycosis in a premature neonate treated conservatively with amphotericin B.

Cutaneous mucormycosis is a rare, often fatal fungal infection that most commonly affects patients with underlying immunosuppression but also can occur in premature neonates. We report the case of an extremely premature boy (<25 weeks) who developed primary cutaneous mucormycosis shortly after birth. Although surgical debridement has been a mainstay of treatment in combination with antifungal therapy, our patient was successfully treated with amphotericin B alone-the management only reported in three other cases to date. We present this case to highlight that prompt initiation of treatment with amphotericin B alone may be an appropriate alternative to surgical intervention, particularly in patients with non-angioinvasive disease who are poor surgical candidates.

Effects of virtual reality-based motor rehabilitation: a systematic review of fMRI studies.

Background.The use of virtual reality (VR) as a rehabilitation tool has been shown to induce motor and cognitive improvements in different populations. Functional magnetic resonance imaging (fMRI) has been used to investigate neuroplasticity resulting from these treatments. We hypothesize that VR rehabilitation induces functional improvement and brain changes that can be detected by fMRI.Objective.To systematically review the effects of VR intervention on the cortical reorganization measured by fMRI and associated with functional improvement.Approach.We performed a systematic review of studies published between 2005 and 2021. Papers were retrieved from six databases using the following keywords: 'motor rehabilitation', 'fMRI' and 'virtual reality'. Case studies, pre-post studies, cross-sectional studies, and randomized controlled trials published were included. Manuscripts were assessed by The National Institutes of Health study quality assessment tools to determine their quality.Main results.Twenty-three articles met our eligibility criteria: 18 about VR rehabilitation in stroke and five on other clinical conditions (older adults, cerebral palsy, and Parkinson's disease). Changes in neural patterns of activation and reorganization were revealed in both the ipsilesional and the contralesional hemispheres. Results were located mainly in the primary motor cortex, sensorimotor cortex and supplementary motor area in post-stroke patients in the acute, subacute, and chronic rehabilitation phases, and were associated with functional improvement after VR intervention. Similar effects were observed in older adults and in patients with other neurological diseases with improved performance.Significance.Most stroke-related studies showed either restoration to normal or increase of activation patterns or relateralization at/to the ipsilesional hemisphere, with some also reporting a decrease in activity or extent of activation after VR therapy. In general, VR intervention demonstrated evidence of efficacy both in neurological rehabilitation and in performance improvement of older adults, accompanied by fMRI evidence of brain reorganization.

Morphological diversity and discrimination tools of the non-marine ostracod Cypridopsis silvestrii across temporal and spatial scales from Patagonia.

Geometric morphometric methods are powerful tools to discriminate between closely related ostracods taxa as well as to study the relationship between their morphological variations, taxonomy and paleoecology. In this study, valve outline analysis allows the discrimination between the non-marine ostracod C. silvestrii and R. whatleyi juveniles, pointing out differences in the posterior valve area and surface ornamentation. Modern female specimens of C. silvestrii from 23 sites located in a spatial transect (41 to 51 °S) exhibited extensive morphological variability, on the basis of which three morphotypes (acuminated, transitional, subtruncated) were determined. Multivariate analyses showed that acuminated and transitional shapes are not arranged in groups but the subtruncated morphotype, previously described as E. cecryphalium, seems to be associated with low water conductivity (372 µS cm-1), dominant cold (5 ºC) and windy (8.6 m s-1) climatic conditions. The fossil cluster which included nine cores spanning the last 15.6 kyr, only covered acuminated and transitional shapes, which may indicate that these lineages might be older than the subtruncated morphotype. In addition, morphological differences between reproduction modes suggested that parthenogenetic females exhibit de posterior margin more acuminate than sexual females. These results set the ground for more precise ecological and paleoenvironmental studies in Patagonia.

Extracellular Vesicles Derived From Adult and Fetal Bone Marrow Mesenchymal Stromal Cells Differentially Promote ex vivo Expansion of Hematopoietic Stem and Progenitor Cells.

Recently, we and others have illustrated that extracellular vesicles (EVs) have the potential to support hematopoietic stem and progenitor cell (HSPC) expansion; however, the mechanism and processes responsible for the intercellular communication by EVs are still unknown. In the current study, we investigate whether primary human bone marrow derived mesenchymal stromal cells (BMSC) EVs isolated from two different origins, fetal (fEV) and adult (aEV) tissue, can increase the relative low number of HSPCs found in umbilical cord blood (UCB) and which EV-derived components are responsible for ex vivo HSPC expansion. Interestingly, aEVs and to a lesser extent fEVs, showed supportive ex vivo expansion capacity of UCB-HSPCs. Taking advantage of the two BMSC sources with different supportive effects, we analyzed the EV cargo and investigated how gene expression is modulated in HSPCs after incubation with aEVs and fEVs. Proteomics analyses of the protein cargo composition of the supportive aEV vs. the less-supportive fEV identified 90% of the Top100 exosome proteins present in the ExoCarta database. Gene Ontology (GO) analyses illustrated that the proteins overrepresented in aEVs were annotated to oxidation-reduction process, mitochondrial ATP synthesis coupled proton transport, or protein folding. In contrast, the proteins overrepresented in fEVs were annotated to extracellular matrix organization positive regulation of cell migration or transforming growth factor beta receptor (TGFBR) signaling pathway. Small RNA sequencing identified different molecular signatures between aEVs and fEVs. Interestingly, the microRNA cluster miR-99b/let-7e/miR-125a, previously identified to increase the number of HSPCs by targeting multiple pro-apoptotic genes, was highly and significantly enriched in aEVs. Although we identified significant differences in the supportive effects of aEVs and fEVs, RNAseq analyses of the 24 h treated HSPCs indicated that a limited set of genes was differentially regulated when compared to cells that were treated with cytokines only. Together, our study provides novel insights into the complex biological role of EVs and illustrates that aEVs and fEVs differentially support ex vivo expansion capacity of UCB-HSPCs. Together opening new means for the application of EVs in the discovery of therapeutics for more efficient ex vivo HSPC expansion.

Identification of osteolineage cell-derived extracellular vesicle cargo implicated in hematopoietic support.

Osteolineage cell-derived extracellular vesicles (EVs) play a regulatory role in hematopoiesis and have been shown to promote the ex vivo expansion of human hematopoietic stem and progenitor cells (HSPCs). Here, we demonstrate that EVs from different human osteolineage sources do not have the same HSPC expansion promoting potential. Comparison of stimulatory and non-stimulatory osteolineage EVs by next-generation sequencing and mass spectrometry analyses revealed distinct microRNA and protein signatures identifying EV-derived candidate regulators of ex vivo HSPC expansion. Accordingly, the treatment of umbilical cord blood-derived CD34+ HSPCs with stimulatory EVs-altered HSPC transcriptome, including genes with known roles in cell proliferation. An integrative bioinformatics approach, which connects the HSPC gene expression data with the candidate cargo in stimulatory EVs, delineated the potentially targeted biological functions and pathways during hematopoietic cell expansion and development. In conclusion, our study gives novel insights into the complex biological role of EVs in osteolineage cell-HSPC crosstalk and promotes the utility of EVs and their cargo as therapeutic agents in regenerative medicine.

Taxonomic revision of Cypridopsis silvestrii comb. nov. (Ostracoda, Crustacea) from Patagonia, Argentina with morphometric analysis of their intraspecific shape variability and sexual dimorphism.

In this study we redescribe an ostracod species belonging to the subfamily Cypridopsinae Kaufmann, 1900, sampled in seven localities of northern and southern Patagonia, Argentina. A new taxonomical combination is proposed, Cypridopsis silvestrii comb. nov., based on detailed description of females and the first descriptions of males. Cypridopsis silvestrii occurred on a wide geographical distribution range, from 40º to 48º S latitude, as well as broad environmental tolerance ranges. We evaluated morphological variations in two populations of C. silvestrii from northern (El Toro lake) and southern (El Sello lake) Patagonia, with contrasting limnological conditions. El Toro is a small shallow lake with high salinity waters and El Sello is a large deep lake with lower salinity. Based on morphometric analysis, our results showed intraspecific variation in valve shape and size between populations. Sexual dimorphism in El Toro population was identified through morphometric analyses. Additionally, comparison of valve outlines in living and subfossil individuals from El Toro lake allowed specimens previously described as juveniles of Eucypris fontana (Graf, 1931) to be identified as adults of C. silvestrii comb. nov. The present contribution increases knowledge of the taxonomic identity, the ecological requirements and the geographical distribution of C. silvestrii, and shows that morphometric analyses are a feasible and useful tool for exploring intraspecific shape differences and assisting in taxonomic identification. Furthermore, the results presented herein provide tools for C. silvestrii identification in paleolimnological studies, and emphasize the usefulness of studying living representatives for clarification of the taxonomic status of species widely distributed in Quaternary sediments.

Semi-automatic combustion of environmental and biological samples on Oxidizer M307 and equivalents: New solutions for background reduction.

The aim is to introduce and characterize a new experimental demonstrative model contributing to the increase of measurement accuracy, in terms of minimum detectable activity (MDA) and background reduction, for the analysis of samples having low concentrations in tritium and radiocarbon on Quantulus 1220. The clue is related to the qualitative and quantitative differences between tritium and carbon-14 inventories of the pulp used to manufacture the cups involved in noncatalytic combustion of samples by flame oxidation method. The quality of the experimental results depends on the temporal origin of the wood from which the pulp/cellulose was extracted/purified, the specific inventory contributing to the threshold level of the MDA for the beta-emitting radionuclide to be investigated. Finally, the aim is to create and to use such a 100% old cellulose combustion cups for determining low concentrations of these radionuclides. It may be obtained by an adapted technology following the literature data and may be recommended for routine analyses of environmental samples coming from areas with no nuclear or minor nuclear influences, and also for low-level biological samples. This first attempt resulted in improvement of measurement performances up to 400% for carbon-14 and by approximately 50% for tritium.

Inactivation of CREBBP expands the germinal center B cell compartment, down-regulates MHCII expression and promotes DLBCL growth.

The genes encoding the histone acetyl-transferases (HATs) CREB binding protein (CREBBP) and EP300 are recurrently mutated in the activated B cell-like and germinal center (GC) B cell-like subtypes of diffuse large B cell lymphoma (DLBCL). Here, we introduced a patient mutation into a human DLBCL cell line using CRISPR and deleted Crebbp and Ep300 in the GC B cell compartment of mice. CREBBP-mutant DLBCL clones exhibited reduced histone H3 acetylation, expressed significantly less MHCII, and grew faster than wild-type clones in s.c. and orthotopic xenograft models. Mice lacking Crebbp in GC B cells exhibited hyperproliferation of their GC compartment upon immunization, had reduced MHCII surface expression on GC cells, and developed accelerated MYC-driven lymphomas. Ep300 inactivation reproduced some, but not all, consequences of Crebbp inactivation. MHCII deficiency phenocopied the effects of CREBBP loss in spontaneous and serial transplantation models of MYC-driven lymphomagenesis, supporting the idea that the mutational inactivation of CREBBP promotes immune evasion. Indeed, the depletion of CD4+ T cells greatly facilitated the engraftment of lymphoma cells in serial transplantation models. In summary, we provide evidence that both HATs are bona fide tumor suppressors that control MHCII expression and promote tumor immune control; mutational inactivation of CREBBP, but not of EP300, has additional cell-intrinsic engraftment and growth-promoting effects.

Couple relationship education: A randomized controlled trial of professional contact and self-directed tools.

The aim of this randomized controlled trial was to examine the efficacy of an evidence-based relationship distress prevention program, the Couples Coping Enhancement Training (CCET), in dual well-earning couples and to investigate whether effects vary by (a) hours of professional contact and (b) mode of delivery (face to face vs. self-learning DVD). N = 159 couples were randomly assigned to 1 of 4 intervention conditions: (1) standard CCET (15 hours face to face), (2) compact CCET (12 hr face to face), (3) short CCET (self-learning DVD + 8 hr face to face), or (4) wait-list control group. Relationship satisfaction and dyadic coping skills were assessed by means of questionnaires completed prior to and 2 weeks after completion of the treatment, at 3-month follow-up, and at 6-month follow-up. Baseline latent change models for 2 factors showed that the CCET enhanced relationship satisfaction and dyadic coping skills in couples relative to the wait-list control group, albeit effects were small. The standard format of the CCET was not more effective than the compact or the short format indicating that reduced amount of professional contact did not decrease the treatment's efficacy and that the self-learning DVD successfully replaced the psycho-educational part of the program. Since dual earner couples usually face multiple stressors, it is a promising finding that they can strengthen their relationship with a relatively short time investment. (PsycINFO Database Record

Dilatation and Dysfunction of the Neo-aortic Root and in 76 Patients After the Ross Procedure.

Pulmonary autograft replacement (Ross procedure) is used as an alternative to prosthetic aortic valve replacement patients with aortic valve disease. There are limited data on incidence and risk factors for dilatation and dysfunction of the neo-aortic after the Ross procedure. Ross procedure was performed in 100 patients at our institution between 1993 and 2011. In 76 patients, complete follow-up data were available. Their median age at surgery was 16 (0.4-58) years (76 % males; 95 % with congenital aortic valve disease). Median follow-up duration was 5.2 years (0.3-16.0 years). We analyzed their clinical and echocardiographic follow-up to identify possible risk factors for neo-aortic root dilatation and dysfunction. Ross procedure included reduction plasty of the native ascending aorta in 25 % of patients. During follow-up, 21 patients (28 %) developed neo-aortic root dilatation, 38 patients (50 %) dilatation oft the native ascending aorta and 7 patients (9 %) at least moderate neo-aortic regurgitation. Univariate risk factors for neo-aortic root dilatation were preoperative aortic regurgitation (p = 0.04), concomitant reduction plasty of the ascending aorta (p = 0.009) and a longer duration of follow-up (p = 0.005). Younger age at surgery was associated with dilatation of the ascending aorta (p = 0.03). Reoperation on the neo-aortic root because of severe dilatation was necessary in 6 patients (8 %), where 2 patients had at least moderate neo-aortic root regurgitation. Neo-aortic root and aortic dilatation are common after the Ross procedure. This is often combined with neo-aortic valve dysfunction. Close follow-up of these patients is mandatory.

Influencing chondrogenic differentiation of human mesenchymal stromal cells in scaffolds displaying a structural gradient in pore size.

UNLABELLED: Articular cartilage lesions have a limited ability to heal by themselves. Yet, golden standard treatments for cartilage repair such as drilling, microfracture and mosaicplasty provide further damage and an unstable solution that degenerates into fibrocartilage in time. Articular cartilage presents a number of gradients in cell number and size along with structural gradients in extra cellular matrix (ECM) composition. Therefore, creating scaffolds that display a structural gradient can be an appealing strategy for cartilage tissue regeneration treatments. In the present study, a scaffold with an in-built discrete gradient in pore size was produced by additive manufacturing. Human mesenchymal stromal cells (hMSCs) were seeded within the gradient scaffolds and their proliferation, differentiation and ECM deposition was evaluated with respect to 2 non-gradient scaffolds. Glycosaminoglycan (GAG) deposition was significantly higher in gradient scaffolds and non-gradient scaffolds with the smallest pore size compared to non-gradient scaffolds with the largest pore size. A gradual increase of chondrogenic markers was observed within the gradient structures with decreasing pore size, which was also accompanied by an increasingly compact ECM formation. Therefore, scaffolds displaying a structural gradient in pore size seem to be a promising strategy to aid in the process of hMSC chondrogenic differentiation and could be considered for improved cartilage tissue regeneration applications. STATEMENT OF SIGNIFICANCE: We present the development of a novel hierarchical scaffold obtained by additive manufacturing. Structural hierarchy is obtained by changing pore size within the pore network characterizing the fabricated scaffolds and proves to be a functional element in the scaffold to influence adult stem cell differentiation in the chondrogenic lineage. Specifically, in regions of the scaffolds presenting smaller pores an increasing differentiation of stem cells toward the chondrogenic differentiation is displayed. Taking inspiration from the zonal organization of articular cartilage tissue, pore size gradients could, therefore, be considered as a new and important element in designing 3D scaffolds for regenerative medicine applications, in particular for all those tissues where gradient physical properties are present.

The hematopoietic oncoprotein FOXP1 promotes tumor cell survival in diffuse large B-cell lymphoma by repressing S1PR2 signaling.

Aberrant expression of the oncogenic transcription factor forkhead box protein 1 (FOXP1) is a common feature of diffuse large B-cell lymphoma (DLBCL). We have combined chromatin immunoprecipitation and gene expression profiling after FOXP1 depletion with functional screening to identify targets of FOXP1 contributing to tumor cell survival. We find that the sphingosine-1-phosphate receptor 2 (S1PR2) is repressed by FOXP1 in activated B-cell (ABC) and germinal center B-cell (GCB) DLBCL cell lines with aberrantly high FOXP1 levels; S1PR2 expression is further inversely correlated with FOXP1 expression in 3 patient cohorts. Ectopic expression of wild-type S1PR2, but not a point mutant incapable of activating downstream signaling pathways, induces apoptosis in DLBCL cells and restricts tumor growth in subcutaneous and orthotopic models of the disease. The proapoptotic effects of S1PR2 are phenocopied by ectopic expression of the small G protein Gα13 but are independent of AKT signaling. We further show that low S1PR2 expression is a strong negative prognosticator of patient survival, alone and especially in combination with high FOXP1 expression. The S1PR2 locus has previously been demonstrated to be recurrently mutated in GCB DLBCL; the transcriptional silencing of S1PR2 by FOXP1 represents an alternative mechanism leading to inactivation of this important hematopoietic tumor suppressor.

Cross-Talk Between Human Tenocytes and Bone Marrow Stromal Cells Potentiates Extracellular Matrix Remodeling In Vitro.

Tendon and ligament (T/L) pathologies account for a significant portion of musculoskeletal injuries and disorders. Tissue engineering has emerged as a promising solution in the regeneration of both tissues. Specifically, the use of multipotent human mesenchymal stromal cells (hMSC) has shown great promise to serve as both a suitable cell source for tenogenic regeneration and a source of trophic factors to induce tenogenesis. Using four donor sets, we investigated the bidirectional paracrine tenogenic response between human hamstring tenocytes (hHT) and bone marrow-derived hMSC. Cell metabolic assays showed that only one hHT donor experienced sustained notable increases in cell metabolic activity during co-culture. Histological staining confirmed that co-culture induced elevated collagen protein levels in both cell types at varying time-points in two of four donor sets assessed. Gene expression analysis using qPCR showed the varied up-regulation of anabolic and catabolic markers involved in extracellular matrix maintenance for hMSC and hHT. Furthermore, analysis of hMSC/hHT co-culture secretome using a reporter cell line for TGF-ß, a potent inducer of tenogenesis, revealed a trend of higher TGF-ß bioactivity in hMSC secretome compared to hHT. Finally, hHT cytoskeletal immunostaining confirmed that both cell types released soluble factors capable of inducing favorable tenogenic morphology, comparable to control levels of soluble TGF-ß1. These results suggest a potential for TGF-ß-mediated signaling mechanism that is involved during the paracrine interplay between the two cell types that is reminiscent of T/L matrix remodeling/turnover. These findings have significant implications in the clinical use of hMSC for common T/L pathologies.