Exosomal mRNA Cargo are biomarkers of tumor and immune cell populations in pediatric osteosarcoma.

Osteosarcoma is the commonest malignant bone tumor of children and adolescents and is characterized by a high risk of recurrence despite multimodal therapy, especially in metastatic disease. This suggests the presence of clinically undetected cancer cells that persist, leading to cancer recurrence. We sought to evaluate the utility of peripheral blood exosomes as a more sensitive yet minimally invasive blood test that could aid in evaluating treatment response and surveillance for potential disease recurrence. We extracted exosomes from the blood of pediatric osteosarcoma patients at diagnosis (n=7) and after neoadjuvant chemotherapy (n=5 subset), as well as from age-matched cancer-free controls (n=3). We also obtained matched tumor biopsy samples (n=7) from the cases. Exosome isolation was verified by CD9 immunoblot and characterized on electron microscopy. Profiles of 780 cancer-related transcripts were analysed in mRNA from exosomes of osteosarcoma patients at diagnosis and control patients, matched post-chemotherapy samples, and matched primary tumor samples. Peripheral blood exosomes of osteosarcoma patients at diagnosis were significantly smaller than those of controls and overexpressed extracellular matrix protein gene THBS1 and B cell markers MS4A1 and TCL1A. Immunohistochemical staining of corresponding tumor samples verified the expression of THBS1 on tumor cells and osteoid matrix, and its persistence in a treatment-refractory patient, as well as the B cell origin of the latter. These hold potential as liquid biopsy biomarkers of disease burden and host immune response in osteosarcoma. Our findings suggest that exosomes may provide novel and clinically-important insights into the pathophysiology of cancers such as osteosarcoma.

A Retrospective Review of Secondary Hemophagocytic Lymphohistiocytosis (HLH) and Dengue-associated HLH from a Teaching Hospital in Singapore.

Real-world data on the outcome of Asian patients with secondary hemophagocytic lymphohistiocytosis (HLH), especially on dengue-associated HLH, are limited to small case series. This is a retrospective records review of adult patients with secondary HLH between 2015 and 2020. Thirty-two adult patients were followed up for a median of 6.6 months (range 0.1 - 75 months). 15 had underlying lymphomas, and 12 had viral infections. Hemophagocytosis was seen in 28 of 29 patients with a bone marrow biopsy. 100% and 76.5% of patients with and without an underlying malignancy required HLH-directed therapy and blood product transfusion. 12 of 15 patients with lymphomas were treated with additional chemotherapy. Patients with malignancy-associated HLH had poorer survival than non-malignancy-associated HLH (median overall survival (OS) 1.5 months versus not reached, p-value 0.003). The 1-year survival rates of patients with malignancy-associated HLH, HLH with unknown etiologies, and infection-associated HLH were 0.133 (95% CI: 0.036 - 0.484), 0.400 (95% CI: 0.137 - 1.000) and 0.833 (95% CI: 0.647 - 1.000), respectively. Malignancy significantly increased the risk of death compared to infection-associated HLH (HR 9.37, p-value 0.003). Eight patients were diagnosed with dengue-associated HLH with a median HSCORE of 240 (98-99% probability of HLH). Their mean ferritin was 34,740 ng/mL. Three patients required blood product transfusion, 5 required corticosteroids and/or etoposide, with a median duration of treatment of 31 days. Their overall survival rate was 87.5%. Our study highlights the stark contrast in the survival of secondary HLH patients with and without an underlying malignancy. We also present one of the world's most extensive case series of dengue-associated HLH.

The neglected perioperative population of undiagnosed diabetics - a retrospective cohort study.

BACKGROUND: Diabetes is known to increase morbidity and 30-day mortality in adults undergoing non-cardiac surgery, but longer term outcomes are less studied. This study was done to explore how undiagnosed and known diabetes affect 30-day and one-year morbidity and mortality outcomes. The secondary aim was to study the prevalence of undiagnosed diabetics in our perioperative Asian surgical population. METHODS: A retrospective cohort study of 2106 patients aged > 45 years undergoing non-cardiac surgery in a single tertiary hospital was performed. Undiagnosed diabetics were identified (HbA1c ≥6.5% or fasting blood glucose ≥126 mg/dL) and relevant demographic, clinical and surgical data were analyzed to elicit the relationship to adverse outcomes. Univariate analysis was first performed to identify significant variables with p-values ≤0.1, which were then analyzed using multiple logistic regression to calculate the adjusted odds ratio. RESULTS: The prevalence of undiagnosed diabetes was 7.4%. The mean and median HbA1c of known diabetics were 7.9 and 7.5%, while the mean and median HbA1c for undiagnosed diabetics were 7.2 and 6.8% respectively. 36.4% of known diabetics and 20.5% of undiagnosed diabetics respectively had a random blood glucose > 200 mg/dL. Undiagnosed diabetics had a three-fold increase in 1-year mortality compared to non-diabetics (adjusted OR 3.46(1.80-6.49) p < 0.001) but this relationship was not significant between known and non-diabetics. Compared to non-diabetics, known diabetics were at increased risks of new-onset atrial fibrillation (aOR 2.48(1.01-6.25) p = 0.047), infection (aOR 1.49(1.07-2.07) p = 0.017), 30-day readmission (aOR 1.62(1.17-2.25) p = 0.004) and 30-day mortality (aOR 3.11(1.16-8.56) p = 0.025). CONCLUSIONS: Although undiagnosed diabetics have biochemically less severe disease compared to known diabetics at the point of testing, they are at a one-year mortality disadvantage which is not seen among known diabetics. This worrying trend highlights the importance of identifying and treating diabetes. Congruent to previous studies, known diabetics have higher morbidity and 30-day mortality compared to non-diabetics.

[Clinical outcomes of opening coronary chronic total occlusion lesions with the assistance of BridgePoint devices].

Objective: To investigate the safety, efficacy and prognosis of antegrade dissection re-entry (ADR) with the assistance of BridgePoint devices in opening coronary chronic total occlusion (CTO). Methods: A total of 87 consecutive patients, who underwent percutaneous coronary intervention using BridgePoint devices from April 2016 to December 2018 in Xijing Hospital, were included in this study. General information of the selected patients, features of CTO lesions and intraoperative parameters were recorded. Short-term outcomes including technical success rate (defined as achieving TIMI 3 blood flow with residual stenosis<30%), surgical success rate (defined as no major adverse cardiovascular events (MACE) occured while hospitalized), complications, and MACE during hospitalization were observed. MACE included death, recurrent myocardial infarction, target vascular reconstruction (TVR) and cardiac tamponade. Patients were followed up by outpatient or telephone visits at 30 days and 6, 12, 24 and 36 months after discharge. Results: Eighty-seven patients, aged (61±10) years with J-CTO scores (2.49±0.52) were included, and 75(86%) were male. Six patients underwent direct ADR with BridgePoint system, and all were successful. Eighty-one patients underwent rescue ADR using BridgePoint devices, and 62 of them were successful. The success rate of ADR with BridgePoint devices was 78.2% (68/87). Nine out of the 19 failed cases succeeded after the application of rescue antegrade/retrograde technique. The technical success rate was 88.5% (77/87). Coronary perforation occurred in 2 cases (2.3%), one case was treated with covered stent and the other case with tamponade was treated with pericardiocentesis. One patient developed periprocedural myocardial infarction, and one patient suffered from sudden death, and one patient had cardiac tamponade. In-hospital MACE occurred in 3 (3.4%) patients. The surgical success rate was 85.1% (74/87).The procedure time was (175±72)minutes and the amount of contrast used was (449±155)ml. During a follow-up of 17(11, 26) months, the incidence of MACE within 30 days was 4.7% (4/86), while 10.5% (9/86) within 6 months, 17.4% (15/86) within 17 months. Conclusion: Opening CTO with the assistance of BridgePoint devices is feasible and safe, with high success rate and satisfactory outcome.

[Imaging diagnosis of 95 cases of moderate and severe acute carbon monoxide poisoning].

Objective: To explore the difference of radiological imaging features of delayed encephalopathy after carbon monoxide poisoning (DECMP) and acute carbon monoxide poisoning (ACMP) , and the correlation between the imaging findings and clinical prognosis of the disease. Methods: The correlation between imaging findings and clinical manifestations and prognosis of 95 patients with moderate and severe acute carbon monoxide poisoning were retrospectively analyzed. In the above 95 cases, there were 62 cases of ACMP and 33 cases of DEACMP. All patients underwent conventional CT, MRI and magnetic resonance diffusion tensor imaging (DTI) . Circular regions of interest (ROI) measurement was used for analysis of average diffusion coefficient (ADC) value and fractional anisotropy (FA) value of the MRI and DTI imaging manifestations in different brain regions. Results: The main clinical manifestation of moderate acute carbon monoxide poisoning was consciousness disorder and fatigue; Severe poisoning patients showed deep coma as the main clinical manifestations; The most prominent clinical manifestations of DEACMP were mental disorders and neurological impairment in the extrapyramidal system. A total of 95 cases with moderate or severe CO poisoning showed unilateral or bilateral cerebral cortex, bilateral basal ganglia (white ball) , cerebral white matter around bilateral ventricles or bilateral centrum semiovale, around bilateral ventricles cerebral white matter around bilateral ventricles and bilateral centrum semiovale, cerebral cortex and subcortical involvement. CT showed normal or low density shadow.MRI showed that the lesion T(1)WI presented slightly low or equal signal, T(2)WI and FLAIR sequences showed equal, a slightly higher or high signal; DWI sequence showed slightly higher or high signal. ADC value and FA value in different brain white matter regions of DEACMP group was significantly lower than those of ACMP group (P<0.05) , especially for those around semi oval center and lateral ventricles of the brain white matter (P<0.01) ; The ADC values increased significantly, FA value decreased significantly in the nerve nucleus (P<0.05) , especially for ADC values in globus pallidus (P<0.01) . Conclusion: DTI can evaluate the brain tissue damage in patients with DEACMP more early and more accurately.

Reduction Levels and the Effects of High-Molecular-Weight Adiponectin via AMPK/eNOS in Chinese Type 2 Diabetes.

Aim: This study was to investigate the change of high-molecula-weight (HMW) adiponectin (APN) isoform, the association between type 2 diabetes mellitus (T2DM) and HMW APN isoform, the variation of Disulfide-bond A oxidoreductase-like protein (DsbA-L), the effect of HMW APN isoform on AMP-dependent protein kinase (AMPK) and endothelial nitric oxide synthase (eNOS) in Chinese T2DM. Method: 169 patients aged at (48.7±9.4) years and 107 healthy control subjects aged at (42.6±7.8) years took part in this study. Anthropometric measures of the characters were assayed and different APN isoforms, DsbA-L, AMPK and eNOS levels were determined. Results: Ln(sRAGE) and Ln(Adiponectin) were significantly lower and significantly higher for the other characteristics in T2DM. Ln(Adiponectin) was negatively and significantly correlated with WHR, Ln(triglycerides), fasting plasma glucose, HbA1c (%) in control subjects and T2DM patients. Plasma and adipose tissue total APN and HMW APN were significantly reduced in newly diagnosed T2DM patients. DsbA-L was markedly down-regulated in diabetic adipose tissue. HMW APN caused significant decreases in AMPK and eNOS phosphorylation levels of human umbilical vein endothelial cells (HUVECs). Conclusions: Our results demonstrated that total APN levels was closely related to the risk of T2DM and HMW APN reduction was involved in the diabetic vascular AMPK/eNOS signal pathway. The findings will provide insight into novel therapeutic approaches for reducing the elevated cardiovascular risk associated with T2DM.

Elevation of cortical C26:0 due to the decline of peroxisomal ß-oxidation potentiates amyloid ß generation and spatial memory deficits via oxidative stress in diabetic rats.

Diabetes mellitus correlates with subsequent development of Alzheimer's disease (AD). An accumulation of very long chain fatty acids (VLCFAs) was observed in AD brains. We found previously that inhibiting peroxisomal ß-oxidation by an inhibitor caused increases in VLCFA and ß-amyloid peptide (Aß) in the cortex and primary cultured neurons of rats. Therefore, we investigated whether there was an impaired peroxisomal ß-oxidation and elevated VLCFA related to the increased Aß in the diabetic brain. This study was conducted in a type 2 diabetic rat model induced by a high-fat diet and low-dose streptozotocin. A decrease in peroxisomal ß-oxidation activity caused by down-regulated thiolase expression and a consequent increase in C26:0 were observed. Meanwhile, decreases in eicosapentenoic acid (EPA) and increases in oxidative stress [indicated by levels of malondialdehyde (MDA), and the protein expression of NOX4, p47(phox) and HO-1], Aß, and the expression of AßPP and BACE1, two proteins involved in Aß production, were observed. C26:0 levels were positively correlated with Aß and MDA. This work suggests that in addition to decreases in EPA, increases in C26:0 by impaired peroxisomal ß-oxidation can be a potential risk factor contributing to the progression of AD in diabetic brains via inducing oxidative stress.

Rapamycin reduces severity of senile osteoporosis by activating osteocyte autophagy.

SUMMARY: Osteocyte is the orchestrator of bone remolding and decline in osteocyte autophagy is involved in senile osteoporosis. Our results suggested that rapamycin, at least in part by activating osteocyte autophagy, reduced the severity of age-related bone changes in trabecular bone of old male rats. INTRODUCTION: Previous literatures have showed that osteocyte is the orchestrator of bone remolding and age-related decline in osteocyte number is associated with senile osteoporosis. Autophagy is an important cellular protective mechanism which can preserve osteocyte viability and failure of autophagy in osteocyte with age has been linked to senile osteoporosis. The purpose of this study was to explore whether rapamycin, one activator of autophagy, has protective effects on senile osteoporosis through inducing osteocyte autophagy. METHODS: Fifty-two 24-month-old male Sprague-Dawley (SD) rats were randomly divided into two groups. Rapamycin (1 mg/kg weight/day) or DMSO vehicle control was administered intraperitoneally for 12 weeks. BMD and bone microstructure were determined by Micro-CT. Fluorochrome labeling of the bones was performed to measure the mineral apposition rate (MAR). TRAP staining was performed to evaluate osteoclast number. The plasma levels of bone turnover markers were also analyzed. The effects of rapamycin on osteocyte autophagy were determined by immunohistochemistry, Western blot, and q-PCR. TUNEL was used to determine the prevalence of osteocyte apoptosis. RESULTS: Micro-CT evaluation demonstrated that rapamycin had a protective effect on age-related bone loss in trabecular bone. Besides, rapamycin resulted in an obvious increase of MAR and a decrease of osteoclast number in contrast to the control group. Furthermore, rapamycin also induced autophagy in osteocyte demonstrated by increased LC3-positive osteocyte and increased LC3 turnover. In addition, rats treated with rapamycin exhibited decreased apoptosis of osteocyte determined by TUNEL. CONCLUSIONS: These results suggested that rapamycin, at least in part by activating osteocyte autophagy, reduced the severity of age-related bone changes in trabecular bone of old male rats. Therefore, rapamycin might be a feasible therapeutic approach for senile osteoporosis.

Irisin improves fatty acid oxidation and glucose utilization in type 2 diabetes by regulating the AMPK signaling pathway.

BACKGROUND/OBJECTIVES: It has been reported that irisin regulated exercise-mediated adipocyte browning; however, the systematical effects of irisin on the metabolism of glucose and lipid in diabetes are largely unknown. In the present study, we investigated the role and underlying mechanism of irisin in glucose utilization and lipid metabolism in diabetic mice. METHODS: A mouse model of diabetes was established by feeding C57BL/6 mice with high-fat diet. The diabetic mice were then treated with irisin. To mimic type 2 diabetes in vitro, myocytes and hepatocytes were cultured in a medium of high glucose and high fat. Glucose uptake, fatty acid oxidation and the expression of related protein were evaluated. RESULTS: Irisin improved glucose tolerance and glucose uptake as evidenced by increased (18)F-FDG accumulation and GLUT4 translocation in diabetic skeletal muscle. Irisin also increased glucose uptake in myocytes cultured in high glucose/high fatty acid medium. In contrast, irisin reduced the expression of PEPCK and G6Pase, which are involved in gluconeogenesis, in diabetic liver. Consistently, irisin reduced fat weight and serum total cholesterol and triglyceride levels in diabetic mice, but increased acetyl coenzyme A carboxylase-ß phosphorylation in muscle tissue and uncoupling protein 1 expression in fat tissue. In addition, irisin increased the oxidation of fatty acid in myocytes. Knockdown of the adenosine monophosphate (AMP)-activated protein kinase (AMPK) attenuated the effects of irisin on glucose uptake and fatty acid ß-oxidation in myocytes. Similarly, inhibition of AMPK by a specific inhibitor reduced the effects of irisin on PEPCK and G6Pase expression in hepatocytes. CONCLUSIONS: Our results suggest that irisin has an essential role in glucose utilization and lipid metabolism, and irisin is a promising pharmacological target for the treatment of diabetes and its complications.

Identification of genes and pathways associated with osteoarthritis by bioinformatics analyses.

OBJECTIVE: This study aimed to explore the molecular mechanism of osteoarthritis (OA) development and discover underlying genes associated with OA. DATA AND METHODS: Gene expression profile GSE48556 including 106 peripheral blood mononuclear cells (PBMCs) of osteoarthritis patients and 33 PBMCs of healthy controls was downloaded from the Gene Expression Omnibus database. The limma package was used to identify the differentially expressed genes (DEGs) by paired t-test. The functional enrichment analyses of DEGs was performed, followed by the construction of protein-protein interaction (PPI) network. RESULTS: Total 432 DEGs including 178 up-regulated DEGs and 254 down-regulated DEGs were identified. Pathways of cytokine-cytokine receptor interaction and T cell receptor signaling pathway were significantly up-regulated in OA. Biological processes of negative regulation of transcription from RNA polymerase II promoter and negative regulation of transcription, DNA-dependent were significantly down-regulated in OA. The platelet-derived growth factor receptor, beta polypeptide (PDGFRB), interferon, gamma (IFNG), early growth response 1 (EGR1), Fas ligand (TNF superfamily, member 6) (FASLG), H3 histone, family 3B (H3.3B) (H3F3B) and so on had higher connectivity degree in the PPI networks. CONCLUSIONS: DEGs of OA were mainly enriched in the pathways associated with cytokine-cytokine receptor interaction and T cell receptor signaling pathway. The DEGs such as PDGFRB, IFNG, EGR1, FASLG and H3F3B may be the potential targets for OA diagnosis and treatment.

Surface characterizations of laser modified biomedical grade NiTi shape memory alloys.

Laser processing of shape memory alloys (SMAs) promises to enable the multifunctional capabilities needed for medical device applications. Prior to clinical implementation, the surface characterisation of laser processed SMA is essential in order to understand any adverse biological interaction that may occur. The current study systematically investigated two Ni-49.8 at.% Ti SMA laser processed surface finishes, including as-processed and polished, while comparing them to a chemically etched parent material. Spectrographic characterisation of the surface included; X-ray photoelectron spectroscopy (XPS), auger electron spectroscopy (AES), and Raman spectroscopy. Corrosion performance and Ni ion release were also assessed using potentiodynamic cyclic polarization testing and inductively coupled plasma optical emission spectroscopy (ICP-OES), respectively. Results showed that surface defects, including increased roughness, crystallinity and presence of volatile oxide species, overshadowed any possible performance improvements from an increased Ti/Ni ratio or inclusion dissolution imparted by laser processing. However, post-laser process mechanical polishing was shown to remove these defects and restore the performance, making it comparable to chemically etched NiTi material.

Use a simple lower limb outrigger frame in intramedullary nailing fixation of a floating knee.

Closed intramedullary nailing is a classical therapeutic approach for floating knee injuries. An appropriate positioning is critical for a successful surgery. However, there is a lack of an ideal auxiliary device to facilitate the implantation of intramedullary nail. The authors developed a simple lower limb outrigger frame (SLLOF), which is made of nylon, to facilitate the nail implementation process. The SLLOF could be radiolucent and autoclavable. A total of 31 patients with floating knee injury underwent the closed intramedullary nailing assisted by SLLOF. The average operative duration was 91.0 min, and all tibial and femur fractures reached bony union. The SLLOF could assist well insertion of intramedullary nail for the treatment of floating knee injuries, with the advantages of simple operation, less manpower, easy imaging access but less radiation exposure, and more cost-effectiveness.

Overexpression of potassium channel ether à go-go in human osteosarcoma.

Human ether à go-go (hEAG) potassium channels are primarily expressed in brain but also frequently overexpressed in solid tumors, which could indicate their potential value for cancer diagnosis and therapy. hEAG1, one member of the hEAG subfamily, has been shown to play a role in neoplastic process. Here we report the expression of hEAG1 in human osteosarcoma detected by a new polyclonal antibody. The full-length hEAG1 cDNA was cloned from human osteosarcoma cell line MG63 by RT-PCR and expressed in Escherichia coli as His tagged protein. The 6His-hEAG1F protein was purified by nickel agarose and used as the antigen to immunize rabbits following standard protocols. The obtained antiserum could detect hEAG1 exogenously expressed in HEK 293 cells. Furthermore, the polyclonal antibody was used to evaluate hEAG1 expression in 42 human osteosarcoma specimens and 19 osteochondromas specimens by immunohistochemistry. hEAG1 was expressed in 71.4% (30/42) osteosarcoma, and 15.8% (3/19) osteochondromas. Moreover, statistical analysis revealed that hEAG1 expression was not dependent on age, sex, site, histology, grade and type in the osteosarcoma specimens. Our data provide evidence that hEAG1 is overexpressed in human osteosarcoma and the hEAG1 polyclonal antibody offers a good tool for further characterization of the oncogenic function of hEAG1 in osteosarcoma.

Interpretation errors in CT angiography of the head and neck and the benefit of double reading.

BACKGROUND AND PURPOSE: CTA provides high-resolution imaging of the head and neck vasculature but also of the soft tissues and bones. This results in a large volume of information to be interpreted. This study examines interpretation errors with head and neck CTAs and assesses whether double reading reduces miss rates. MATERIALS AND METHODS: Consecutive CTAs of the neck and intracranial circulation were retrospectively identified and reviewed for vascular and nonvascular findings by a consensus of 2 neuroradiologists. The results were compared with the official report. Significant discrepancies were considered those that would have influenced follow-up or management. RESULTS: We reviewed 503 studies; 144 were originally reported by a staff neuroradiologist alone, 209 by staff and diagnostic radiology resident, and 150 by staff and neuroradiology fellow. Twenty-six significant discrepancies were discovered in 20 studies, corresponding to 4.0% of studies with at least 1 miss, and an overall miss rate per study of 5.2%. There was at least 1 miss in 6.3% of studies interpreted by a staff neuroradiologist alone, 3.3% by staff and resident, and 2.7% by staff and fellow. The miss rate differences were not statistically significant. The most common misses were small aneurysms (50% of misses). CONCLUSIONS: CTA neck and head datasets are now large, and there is a potential for missed findings. Significant discrepancies can occur with a low but not insignificant rate. Arterial pathology accounted for most discrepancies. This study emphasizes the need for careful systematic scrutiny for both vascular and nonvascular pathology regardless of indication. Double reading reduces error rates.

Study of development in an experimental animal model of a pediatric physeal slide-traction plate.

BACKGROUND: To develop a physeal slide-traction plate for children can provide rigid internal fixation of a bone fracture without inhibiting epiphyseal growth. METHODS: The slide-traction plates and standard plates were designed to configure to the femoral condyle. Twelve of thirty goats were used as normal controls and the rest were implanted with plates (right femurs were fixed with standard plates, and left femurs were fixed with slide-traction plates). All goats underwent X-ray examination at 1 month, 3 months and 6 months after surgery, and femoral length were measured. Histological staining and electron microscopy were performed to evaluate the development of the epiphyseal plate at 3 and 6 months after surgery. RESULTS: Compared to the standard plate, the slide-traction plate group exhibited more normal physeal growth, histologic features, safranin O staining, and electron microscopy structural features. There were significant differences in length in the femurs of goats fixed with slide-traction plates and standard plates at 1 month, 3 months, and 6 months after surgery, respectively. There was no difference between femurs of the normal control group and the femurs fixed with the slide-traction plates. Thicker epiphyseal plates were found in the left vs. the right femurs of the group fixed with plates at 3 and 6 months after surgery. In the group fixed with plates, Safranin O staining showed that the epiphyseal plates of the left femurs had more fuscous staining than the right femurs at 3 and 6 months after surgery. Electron microscopy also showed that cells in the epiphyseal plates of the left femurs were healthier in appearance than cells from the right femurs in the group fixed with plates. CONCLUSION: The physeal slide-traction plate can slide with the growth of the physis and is suitable for fixation of fractures in this region.

Tribological behavior of nanocrystalline nickel.

During the last decade, an intensive investigative effort around the globe has been devoted to the understanding of scale effects on materials properties. In spite of their importance, nanoscale effects on tribological properties have attracted little attention. Such effects are of utmost importance to small scale devices such as nano and micro electromechanical systems that contain nanostructured dynamic components that would be difficult to replace or repair. The significant increase in strength arising from the grain size reduction in the nano domain is expected to impact on mechanical processes at asperity contacts that are dominating wear behavior. In the present work, nanocrystalline Ni produced by electroplating was used as a model system to study scale effects on tribological behavior. It was found that compared to bulk (microcrystalline), nanocrystalline Ni can cause a significant reduction in both, the coefficient of friction and wear rate. A consistent relationship was found between grain size, hardness and tribological behavior. It is suggested that the improved tribological behavior of the nanocrystalline Ni is due to the refinement of mechanical processes inhibiting plastic deformation by extensive dislocation motion leading to fracture events.