Calculated plasma volume status in hemodialysis patients.

BACKGROUND: Plasma volume (PV) calculated from hematocrit and body weight has applications in cardiovascular disease. The current study investigated the validity of the calculated PV for predicting volume overload and its prognostic utility in patients undergoing hemodialysis (HD). PATIENTS AND METHODS: Fifty-four HD patients were prospectively enrolled, and their actual PV (aPV) and relative PV status (PVS) were calculated. Bioelectrical impedance analysis (BIA) with assessment of and total body water (TBW), intracellular water (ICW), extracellular water (ECW), and overhydration (OH) and routine blood examinations were performed before dialysis. A second cohort of 164 HD patients was retrospectively enrolled to evaluate the relationship between the calculated PVS and the outcome, with an endpoint of all-cause mortality. RESULTS: aPV was significantly associated with TBW, ICW, ECW, OH, and ECW/TBW (all p < 0.001), and most strongly with ECW (r = 0.83). aPV predicted the extent of volume overload with an AUC of 0.770 (p < 0.001), but PVS did not (AUC = 0.617, p = 0.091). Median follow-up time was 53 months, during the course of which 60 (36.58%) patients died. Values for PVS (12.94 ± 10.87% vs. 7.45 ± 5.90%, p = 0.024) and time-averaged PVS (12.83 ± 11.20 vs. 6.78 ± 6.22%, p < 0.001) were significantly increased in patients who died relative to those who survived. A value of time-averaged PVS >8.72% was significantly associated with an increased incidence of all-cause mortality (HR = 2.48, p = 0.0023). CONCLUSIONS: aPV was most strongly associated with ECW measured using BIA. HD patients with higher time-averaged PVS had a higher rate of all-cause mortality.

Asporin regulated by miR-26b-5p mediates chondrocyte senescence and exacerbates osteoarthritis progression via TGF-ß1/Smad2 pathway.

OBJECTIVES: This study aimed to investigate the role and mechanism of asporin in modulating chondrocyte senescence in OA pathology. METHODS: Asporin and senescence-related hallmark expression were examined in human and experimental OA mouse cartilage samples. Twelve-week-old male C57 mice were administered with recombinant protein (rm-asporin)- or asporin-siRNA-expressing lentiviruses via intra-articular injection once a week after destabilization of the medial meniscus (DMM) surgery to induce OA. Cartilage damage was measured using the Osteoarthritis Research Society International score. Senescence-associated ß-galactosidase (SA-ß-Gal) staining, γH2AX, p21 and p16INK4a were analysed by immunofluorescence staining and western blot to assess the specific role of asporin in chondrocyte senescence. The TGF-ß1-Smad2 signalling pathway and miR-26b-5p were further evaluated to explore the mechanism of asporin in OA. RESULTS: Asporin was upregulated in articular chondrocytes of OA patients and DMM mice and accompanied by accumulation of senescent cells. Asporin overexpression exaggerated OA progression, whereas silencing asporin restored chondrocyte homeostasis and deferred chondrocyte senescence, leading to markedly attenuated DMM-induced OA. Cellular and molecular analyses showed that asporin can be inhibited by miR-26b-5p, which was significantly downregulated in OA cartilage, leading to exacerbation of experimental OA partially through inhibition of TGF-ß1-Smad2 signalling in chondrocytes. CONCLUSIONS: Our findings indicate that asporin plays an essential role in chondrocyte senescence and OA pathogenesis. Upregulated by miR-26b-5p, asporin inhibits the TGF-ß1-Smad2 pathway to accelerate chondrocyte senescence and exacerbate cartilage degeneration. Targeting the miR-26b-5p-asporin-Smad2 axis may serve as a practical therapeutic strategy to delay chondrocyte senescence and OA development.

Recurrent arthritis caused by Candida parapsilosis: a case report and literature review.

BACKGROUND: Candida arthritis is extremely rare and also represents a major challenge of diagnosis and treatment. Here we reported a rare case of recurrent arthritis caused by Candida parapsilosis. CASE PRESENTATION: A 56-year-old Chinese male suffered from recurrent pain and swelling in his right knee after several times of "small needle-knife" acupuncture and corticosteroid injection of the joint. Candida parapsilosis was cultured in his synovial fluid and identified by sequencing of its Internal Transcribed Spacer (ITS) gene. Here we present the radiological characteristics, arthroscopic pictures, and synovium pathology of this patient. Also, blood test and chemical analysis of his synovial fluid were listed as well as the ITS sequence of this Candida species identified. The patient underwent thorough arthroscopic debridement and then set on fluconazole 400 mg daily for 12 months. His symptoms resolved and no relapse was observed on the last follow-up. Additionally, a brief but comprehensive review of C. parapsilosis arthritis episodes from past to now were studied. CONCLUSION: With the detailed clinical information reported in this case and our literature review, we hope they would add to our knowledge of C. parapsilosis arthritis - its clinical settings, laboratory features, radiological characteristics, arthroscopic findings and experience of management.

Blocking PI3K/AKT signaling inhibits bone sclerosis in subchondral bone and attenuates post-traumatic osteoarthritis.

PI3K/AKT signaling is essential in regulating pathophysiology of osteoarthritis (OA). However, its potential modulatory role in early OA progression has not been investigated yet. Here, a mouse destabilization OA model in the tibia was used to investigate roles of PI3K/AKT signaling in the early subchondral bone changes and OA pathological process. We revealed a significant increase in PI3K/AKT signaling activation which was associated with aberrant bone formation in tibial subchondral bone following destabilizing the medial meniscus (DMM), which was effectively prevented by treatment with PI3K/AKT signaling inhibitor LY294002. PI3K/AKT signaling inhibition attenuated articular cartilage degeneration. Serum and bone biochemical analyses revealed increased levels of MMP-13, which was found expressed mainly by osteoblastic cells in subchondral bone. However, this MMP-13 induction was attenuated by LY294002 treatment. Furthermore, PI3K/AKT signaling was found to enhance preosteoblast proliferation, differentiation, and expression of MMP-13 by activating NF-κB pathway. In conclusion, inhibition of PI3K/AKT/NF-κB axis was able to prevent aberrant bone formation and attenuate cartilage degeneration in OA mice.

Myostatin serum concentrations are correlated with the severity of knee osteoarthritis.

OBJECTIVE: Myostatin, a member of the transforming growth factor-ß family, contributes to joint deterioration in mice. Thus, we aimed to assess the correlation of myostatin concentrations with the presence and severity of knee osteoarthritis (OA). MATERIAL AND METHODS: We determined serum and synovial fluid (SF) myostatin concentrations in a population of 184 patients with knee OA and 109 healthy controls. RESULTS: The knee OA group presented with higher serum myostatin concentrations than the controls. Knee OA patients with KL grade 4 showed higher serum and SF myostatin concentrations compared with those with KL grade 2 and 3. Knee OA patients with KL grade 3 had higher serum and SF myostatin concentrations compared with those with KL grade 2. Serum and SF myostatin concentrations were significantly correlated with KL grading. CONCLUSION: Serum and SF myostatin concentrations were correlated with the presence and severity of knee OA.

c-Jun N-terminal kinase - c-Jun pathway transactivates Bim to promote osteoarthritis.

Osteoarthritis (OA) is a chronic degenerative joint disorder. Previous studies have shown abnormally increased apoptosis of chondrocytes in patients and animal models of OA. TNF-α and nitric oxide have been reported to induce chondrocyte ageing; however, the mechanism of chondrocyte apoptosis induced by IL-1ß has remained unclear. The aim of this study is to identify the role of the c-Jun N-terminal kinase (JNK) - c-Jun pathway in regulating induction of Bim, and its implication in chondrocyte apoptosis. This study showed that Bim is upregulated in chondrocytes obtained from the articular cartilage of OA patients and in cultured mouse chondrocytes treated with IL-1ß. Upregulation of Bim was found to be critical for chondrocyte apoptosis induced by IL-1ß, as revealed by the genetic knockdown of Bim, wherein apoptosis was greatly reduced in the chondrocytes. Moreover, activation of the JNK-c-Jun pathway was observed under IL-1ß treatment, as indicated by the increased expression levels of c-Jun protein. Suppression of the JNK-c-Jun pathway, using chemical inhibitors and RNA interference, inhibited the Bim upregulation induced by IL-1ß. These findings suggest that the JNK-c-Jun pathway is involved in the upregulation of Bim during OA and that the JNK-c-Jun-Bim pathway is vital for chondrocyte apoptosis.

Coupled topological rainbow trapping of elastic waves in two-dimensional phononic crystals.

Rainbow trapping, observed in elastic waves, has attracted considerable scientific interest owing to its potential applications in energy harvesting, buffering, and wavelength-division multiplexing devices. However, previous approaches have often necessitated complex geometric modifications to the scatterer, such as altering dimensions or shifting along diagonals to corners, limiting practical utility. Here, we realize the coupled topological edge states (CTESs) of elastic waves in a two-dimensional (2D) solid phononic crystal (PC) with inversion center changes. Changing the inversion center along the x or y directions by a specific distance can induce the topological phase transition. The topological edge states (TESs) arise at the interface by combining PCs with different topologies positioned adjacent to each other. Furthermore, it is demonstrated that TES exhibits topological robustness against defects. By introducing a gradient into the PC structure by altering the geometrical parameters of scatterers along the interface, the topological rainbow trapping of elastic waves is achieved. Finally, the CTES are generated by the interaction between TESs of different interfaces, which can lead to coupled topological rainbow trapping in phononic heterostructures with different displacement parameters along the multiple interface gradient. Our results pave the way for manipulating the symmetric and antisymmetric topological modes of elastic waves in topologically coupled waveguides, which offers potential applications in selective filtering and multiband waveguiding.

Identification of osteoblastic autophagy-related genes for predicting diagnostic markers in osteoarthritis.

The development of osteoarthritis (OA) involves subchondral bone lesions, but the role of osteoblastic autophagy-related genes (ARGs) in osteoarthritis is unclear. Through integrated analysis of single-cell dataset, Bulk RNA dataset, and 367 ARGs extracted from GeneCards, 40 ARGs were found. By employing multiple machine learning algorithms and PPI networks, three key genes (DDIT3, JUN, and VEGFA) were identified. Then the RF model constructed from these genes indicated great potential as a diagnostic tool. Furthermore, the model's effectiveness in predicting OA has been confirmed through external validation datasets. Moreover, the expression of ARGs was examined in osteoblasts subject to excessive mechanical stress, human and mouse tissues. Finally, the role of ARGs in OA was confirmed through co-culturing explants and osteoblasts. Thus, osteoblastic ARGs could be crucial in OA development, providing potential diagnostic and treatment strategies.

TCF12 regulates the TGF-ß/Smad2/3 signaling pathway to accelerate the progression of osteoarthritis by targeting CXCR4.

Objective: Osteoarthritis (OA), which involves total joint damage and dysfunction, is a leading cause of disability worldwide. However, its exact pathogenesis remains unclear. Here, we identified TCF12 as an important regulator of the progression of OA. Methods: qRT-PCR, immunoblotting and immunohistochemistry (IHC) were used to detect the expression level of TCF12. The interaction of TCF12 with its downstream factor CXCR4 was assessed by Western blotting, immunofluorescence, qRT-PCR and luciferase assays. A mouse model was generated to examine the functions and mechanism of TCF12 in vivo. Result: TCF12 expression was upregulated in chondrocytes stimulated with IL-1ß and osteoarthritic chondrocytes. TCF12 upregulates the expression of CXCR4 and leads to dysfunction of the TGF-ß signaling pathway. Furthermore, knockdown of TCF12 alleviated cartilage damage in a mouse model generated by destabilization of the medial meniscus (DMM). Conclusion: TCF12 aggravates the progression of OA by targeting CXCR4 and then activating the TGF-ß signaling pathway, suggesting that TCF12 may be a new target for the treatment of OA. The translational potential of this article: Transcription Factor 12(TCF12), is known to regulate cell development and differentiation, It has been widely studied in various organs and diseases, but its role in OA remains unclear. Here, we identified Transcription Factor 12(TCF12) as an important regulator mediating chondrocyte senescence and cartilage extracellular matrix degradation indicating its role in OA. We found that TCF12 expression was upregulated both locally and systemically as OA advanced in patients with OA, and in mice after DMM surgery to induce OA. TCF12 expression caused striking progressive articular cartilage damage, synovial hyperplasia in OA mice, and remarkably, it was relieved by intra-articular administration of mutant mouse TCF12 lentiviral vector (shTCF12). Furthermore, TCF12 upregulated the expression of CXCR4, leading to exacerbation of experimental OA partially through activation of TGF-ß signaling in chondrocytes. TCF12 expression was upregulated in chondrocytes treated with IL-1ß and osteoarthritic chondrocytes. Our findings established an essential role of TCF12 in chondrocyte senescence and cartilage extracellular matrix degradation during OA, and identified intra-articular injection of TCF12 as a potential therapeutic strategy for OA prevention and treatment.

Assessment of pathogenicity and functional characterization of APPL1 gene mutations in diabetic patients.

BACKGROUND: Adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 1 (APPL1) plays a crucial role in regulating insulin signaling and glucose metabolism. Mutations in the APPL1 gene have been associated with the development of maturity-onset diabetes of the young type 14 (MODY14). Currently, only two mutations [c.1655T>A (p.Leu552*) and c.281G>A p.(Asp94Asn)] have been identified in association with this disease. Given the limited understanding of MODY14, it is imperative to identify additional cases and carry out comprehensive research on MODY14 and APPL1 mutations. AIM: To assess the pathogenicity of APPL1 gene mutations in diabetic patients and to characterize the functional role of the APPL1 domain. METHODS: Patients exhibiting clinical signs and a medical history suggestive of MODY were screened for the study. Whole exome sequencing was performed on the patients as well as their family members. The pathogenicity of the identified APPL1 variants was predicted on the basis of bioinformatics analysis. In addition, the pathogenicity of the novel APPL1 variant was preliminarily evaluated through in vitro functional experiments. Finally, the impact of these variants on APPL1 protein expression and the insulin pathway were assessed, and the potential mechanism underlying the interaction between the APPL1 protein and the insulin receptor was further explored. RESULTS: A total of five novel mutations were identified, including four missense mutations (Asp632Tyr, Arg633His, Arg532Gln, and Ile642Met) and one intronic mutation (1153-16A>T). Pathogenicity prediction analysis revealed that the Arg532Gln was pathogenic across all predictions. The Asp632Tyr and Arg633His variants also had pathogenicity based on MutationTaster. In addition, multiple alignment of amino acid sequences showed that the Arg532Gln, Asp632Tyr, and Arg633His variants were conserved across different species. Moreover, in in vitro functional experiments, both the c.1894G>T (at Asp632Tyr) and c.1595G>A (at Arg532Gln) mutations were found to downregulate the expression of APPL1 on both protein and mRNA levels, indicating their pathogenic nature. Therefore, based on the patient's clinical and family history, combined with the results from bioinformatics analysis and functional experiment, the c.1894G>T (at Asp632Tyr) and c.1595G>A (at Arg532Gln) mutations were classified as pathogenic mutations. Importantly, all these mutations were located within the phosphotyrosine-binding domain of APPL1, which plays a critical role in the insulin sensitization effect. CONCLUSION: This study provided new insights into the pathogenicity of APPL1 gene mutations in diabetes and revealed a potential target for the diagnosis and treatment of the disease.

NRBP1 modulates uric acid transporter ABCG2 expression by activating the Wnt/ß-catenin pathway in HK-2 cells.

BACKGROUND: Nuclear receptor binding protein 1 (NRBP1) and ATP-binding cassette subfamily G member 2 (ABCG2) was the gout risk gene and high-capacity urate exporter respectively. However, the relationship between NRBP1 and ABCG2 and the underlying molecular mechanism contributing to these associations are unknown. METHODS: Firstly, the efficiency of the overexpression and knockdown of NRBP1 was confirmed by western blot. Next, the effect of NRBP1 overexpression and knockdown on the expression of ABCG2, organic anion transporter 1 (OAT1), glucose transporter 9 (GLUT9) and urate transporter 1 (URAT1) was detected by qRT-PCR and western blot. At the same time, the cellular location of ABCG2 and its expression after NRBP1 overexpression and knockdown was tested by immunofluorescence (IF) staining. Then, the mechanism of NRBP1 modulates ABCG2 expression was evaluated by western blot with or without the ß-catenin inhibitor (21H7). RESULTS: The lentivirus system was used to generate stable NRBP1 overexpression, while the plasmids carrying a NRBP1 siRNA was generated to knockdown NRBP1 expression in HK-2 cells. Meanwhile, the overexpression of NRBP1 significantly decreased the mRNAs and proteins expression of GLUT9 and URAT1, while the knockdown of NRBP1 increased the mRNAs and proteins expression of ABCG2 significantly. In addition, the NRBP1 modulates the expression of ABCG2 was by ctivating the Wnt/ß-catenin pathway in HK-2 cells according to the IF and western blot results. CONCLUSION: Taken together, our study demonstrated that NRBP1 inhibition played an essential role in attenuating hyperuricemia and gout by upregulation of ABCG2 via Wnt/ß-catenin signaling pathway in HK-2 cells.

Association of beta-2-microglobulin with cardiovascular and all-cause mortality in the general and non-CKD population.

ß-2 microglobulin, a light chain in the major histocompatibility complex Class 1 molecule, is associated with mortality in dialysis or uremic patients. Current evidence on the relationship between beta-2-microglobulin (B2M) and mortality in the general and non-chronic kidney disease (CKD) population are limited and controversial. Data from the nutrition and health examination survey database and the nutrition and health examination survey linked mortality file were used. In total, 10,388 adults who had complete data for B2M were included. Weighted multivariable Cox proportional hazards regression models and regression splines were employed to evaluate the relationship between B2M with mortality. Moreover, subgroup and sensitivity analyses were performed. During a median follow up of 17.9 years (interquartile range 15.2-18.7), 2780 people died, 902 (32%) from cardiovascular disease. Restricted cubic splines showed that B2M is J-shaped nonlinear positively associated with all-cause mortality and cardiovascular disease mortality in the non-CKD and general population. Based on the multivariable adjustment model, the adjusted hazard ratios comparing the highest versus lowest quartile of the distribution of B2M were 2.50 (95% confidence interval: 1.90, 3.28) for all-cause mortality in the general population, 2.58 (95% confidence interval: 1.52, 4.37) for cardiovascular disease mortality in the general population, 2.58 (1.91, 3.49) for all-cause mortality in the non-CKD population and 2.62 (1.52, 4.53) for cardiovascular disease mortality in the non-CKD population. The positive associations between B2M and outcomes remained broadly significant across subgroups and sensitivity analyses. Higher B2M levels were associated with cardiovascular and all-cause mortality in the general and non-CKD population.

Gene/protein expression level, immunolocalization and binding characteristics of fatty acid binding protein from Clonorchis sinensis (CsFABP).

Clonorchis sinensis fatty acid-binding protein (CsFABP) belongs to a multigene family of lipid-binding proteins and is considered to be a promising vaccine candidate for human clonorchiasis. In this study, binding characteristics of CsFABP have been examined for the first time. The recombinant CsFABP (rCsFABP) was found to bind 11-(dansylamino) undecanoic acid (DAUDA), causing a blue shift in the fluorescence emission from 543 to 531 nm with an excitation wavelength of 345 nm and a substantial increase in fluorescence intensity. Fluorimetric titration of rCsFABP with DAUDA exhibited an apparent dissociation constant (K (d)) of 1.58 ± 0.14 µM. In the competitive experiment, the rCsFABP efficiently bound saturated C(10)-C(18) fatty acids and unsaturated fatty acids (oleic acid and linoleic acid), and the latter presented the higher affinity. Furthermore, quantitative RT-PCR and western blotting analysis revealed that CsFABP mRNA and protein were differentially expressed throughout the developmental cycle stages of the parasite, which occur in the definitive host (metacercariae, adult worms, and eggs). In addition, immunolocalization assay showed that CsFABP was localized on the vitelline gland, tegument, intestine, seminal vesicle, eggs in uterus, ovary, and testicle of C. sinensis adult worm, as well as on the vitelline gland of metacercaria. Intriguingly, the surface tissue of the bile duct where C. sinensis resided in the infected Sprague-Dawley rat was also strongly labeled, implying that CsFABP may possibly mediate direct interactions with host cells as a component of excretory/secretory products.

[Investigation on life quality of patients with chronic lymphatic filariasis in Yuhang district of Hangzhou].

Data were collected from chronic lymphatic filariasis patients and the public in Yuhang District of Hangzhou. Health status was assessed by using EuroQol (EQ)-5D. A total of 600 questionnaires were sent and 550 (91.7%) returned (276 chronic lymphatic filariasis patients and 274 members of the public). The EQ-SD index score for patients with chronic lymphatic filariasis (0.770 +/- 0.128) were lower than the general public (0.872 +/- 0.073). In contrast to the public (6.6%, 5.8%, 12.0%, 20.4%, and 10.6%), patients reported more problems with their mobility (43.8%), self-care (22.5%), daily activities (44.9%), anxiety/depression (47.8%), and pain/discomfort (29.0%) (P < 0.01). Strength of association were 6.67, 3.86, 3.74, 2.73, and 2.34, respectively. These results indicated that chronic lymphatic filariasis shows an impact on patients' health-related quality of life. It particularly causes great problems in the dimensions of mobility, self-care, and daily activities.

Characteristics of length of stay and cardiovascular pharmacotherapy advice among chronic obstructive pulmonary disease patients.

Chronic obstructive pulmonary disease (COPD) increases the global disease burden due to its diverse adverse health effects on the respiratory and cardiovascular systems. This study aimed to elucidate the potential indicators of length of stay (LOS) and pharmacotherapy advice among COPD patients. Thereafter, hospitalized COPD patients with clinical records and respiratory and cardiovascular pharmacotherapy advice were retrospectively collected from a tertiary hospital between April 2017 and September 2020, and the determinants of LOS and cardiovascular pharmacotherapy advice were explored using regression analyses. Overall, 475 patients with COPD were recruited and stratified according to exacerbation and presence of Cor pulmonale (CP). The extended LOS, increased B-type natriuretic peptides (BNP), and a higher percentage of cardiovascular pharmacotherapy advice were observed in COPD with CP regardless of exacerbation, although the percentage of respiratory prescriptions was comparable. The presence of CP indicated a longer LOS (B = 1.850, p < 0.001) for COPD regardless of exacerbation. Meanwhile, elevated BNP levels indicated cardiovascular pharmacotherapy advise for both COPD in exacerbation (OR = 1.003, p = 0.012) and absence of exacerbation (OR = 1.006, p = 0.015). Moreover, advice for trimetazidine use for COPD in exacerbation (OR = 1.005, p = 0.002) has been suggested. Therefore, CP appears to be an important comorbidity resulting in extended LOS for COPD, which is likely to be advised with cardiovascular pharmacotherapy, which might be guided through BNP monitoring.

BMP5 silencing inhibits chondrocyte senescence and apoptosis as well as osteoarthritis progression in mice.

In this study, we using the in vivo destabilization of the medial meniscus (DMM) mouse model to investigate the role of bone morphogenetic protein 5 (BMP5) in osteoarthritis (OA) progression mediated via chondrocyte senescence and apoptosis. BMP5 expression was significantly higher in knee articular cartilage tissues of OA patients and DMM model mice than the corresponding controls. The Osteoarthritis Research Society International scores based on histological staining of knee articular cartilage sections were lower in DMM mice where BMP5 was knocked down in chondrocytes than the corresponding controls 4 weeks after DMM surgery. DMM mice with BMP5-deficient chondrocytes showed reduced levels of matrix-degrading enzymes such as MMP13 and ADAMTS5 as well as reduced cartilage destruction. BMP5 knockdown also decreased chondrocyte apoptosis and senescence by suppressing the activation of p38 and ERK MAP kinases. These findings demonstrate that BMP5 silencing inhibits chondrocyte senescence and apoptosis as well as OA progression by downregulating activity in the p38/ERK signaling pathway.

Diffusion tensor magnetic resonance imaging of white matter integrity in patients with HIV-associated neurocognitive disorders.

BACKGROUND: This study investigated the efficacy and neurotoxicity of highly active antiretroviral therapy (HAART) by evaluating white matter (WM) injury using diffusion tensor magnetic resonance imaging (DTI) in patients with human immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND). METHODS: Forty-six patients with HAND underwent DTI before and every six months during HAART treatment. DTI data, including fractional anisotropy (FA) and mean diffusivity (MD) values of structural WM before and after HAART, were compared. The relationship between DTI values and plasma viral loads was tested. MD was more sensitive than FA for evaluating WM injury in HAND-positive patients. RESULTS: Following 12 months of HAART, increased MD values (compared to 6 months of HAART) were observed in the right temporal lobe, right parietal lobe, right occipital lobe, right anterior limb of the internal capsule, right lenticular nucleus, the right cerebral peduncle, left caudate nucleus, left dorsal thalamus, and left posterior limb of the internal capsule. MD values in the left genu of the internal capsule (r=0.350, P=0.017) and left corona radiata (r=0.338, P=0.021) were positively correlated with plasma viral loads. CONCLUSIONS: DTI may be useful for assessing the efficacy and neurotoxicity of HAART in HAND-positive patients. Starting HAART may halt WM injury; however, prolonged HAART could worsen WM injury, highlighting the importance of optimal HAART duration.

Influence of the pore size and porosity of selective laser melted Ti6Al4V ELI porous scaffold on cell proliferation, osteogenesis and bone ingrowth.

This paper systematically investigates the biomedical performance of selective laser melted (SLM) porous Ti6Al4V ELI scaffolds for bone implantation through in vitro and in vivo experiments. Scaffolds with pore sizes of 500 µm, 600 µm and 700 µm and porosities of 60% and 70% were manufactured in order to explore the optimum pore size and porosity. Rat bone marrow mesenchymal stem cells (rBMMSCs) were used in the in vitro experiments. Cell Counting Kit-8, live/dead staining and scanning electron microscope were used to assess the cytotoxicity of the porous scaffolds. DNA content quantification was performed to investigate cell proliferation on the porous scaffolds. The osteogenic differentiation of cells was measured by alkaline phosphatase (ALP) activity and osteogenic gene expressions, including bone morphogenetic protein-2 (BMP-2), collagen type 1α1 (COL-1), osteocalcin (OCN), osteopontin (OPN) and runt-related transcription factor-2 (RUNX-2). The Sprague-Dawley (SD) rat models with distal femoral condyles defect were used in the in vivo experiments. Micro-CT analysis and histological analysis were performed after implantation surgery to reveal the bone ingrowth into the porous scaffolds. All in vitro data were analyzed by one-way ANOVA followed by Tukey post hoc tests, in vivo data were analyzed using Kruskall-Wallis ANOVA and Conover-Inman post-hoc test. Based on the in vitro and in vivo experiments, it is found that the porous scaffolds manufactured by SLM did not induce a cytotoxic effect. Among all the porous scaffolds, the scaffold with a pore size of 500 µm and porosity of 60% showed the best cell proliferation and osteogenic differentiation (in vitro experiments) and bone ingrowth (in vivo experiments).

MiR-146b accelerates osteoarthritis progression by targeting alpha-2-macroglobulin.

Osteoarthritis (OA) is an aging-related chronic degenerative disease characterized by the degradation of chondrocyte extracellular matrix (ECM). Previous studies have suggested that microRNAs (miRNAs) are associated with OA, but the role of miR-146b in OA remains unclear. The aim of this study was to determine the role of miR-146b in OA progression. The effect of miR-146b on ECM degradation were studied in mouse chondrocytes transfected with miRNA and treated with IL-1ß. Cell viability and the expression levels of proteolytic enzymes in the transfected cells were assessed by real-time RT-PCR, ELISA and Western blots. We found downregulation of miR-146b expression in chondrocytes dramatically inhibited IL-1ß-induced caspase activation and proteolytic enzyme expression via influencing its targeted Alpha-2-macroglobulin (A2M). Luciferase reporter assays confirmed that A2M mRNA was negatively regulated by miR-146b in chondrocytes. Intra-articular injection of antago-miR-146b against miR-146b effectively protected mice from the progression of DMM-induced osteoarthritis by inhibiting cartilage proteoglycan degradation. Our study indicates that miR-146b plays a critical role in the progression of injury-induced osteoarthritis by directly targeting A2M expression to elevate the proteolytic enzyme production and stimulate chondrocytes apoptosis, and miR-146b as well as A2M could be therapeutic targets.

Hesperidin inhibits synovial cell inflammation and macrophage polarization through suppression of the PI3K/AKT pathway in complete Freund's adjuvant-induced arthritis in mice.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovitis. Synovitis can cause joint injury by releasing inflammatory factors and metalloproteinases (MMPs). Therefore, it is necessary to find drugs that can control synovitis in the process of RA. Herein, we investigate the anti-inflammatory effect of Hesperidin (HSN) on fibroblast-like synovial (FLS) cells induced by lipopolysaccharide (LPS) and the protective action of M1 polarization level of synovial macrophages on antigen-induced arthritis (AIA) in order to elucidate the reduction of inflammatory cytokines and MMPs and the inhibition of macrophage activation. The functional effect of HSN on LPS-induced mRNA and protein expressions of inflammatory cytokines and MMPs in FLS cells as well as on LPS-induced macrophage M1 and M2 polarization markers was determined by quantitative real-time PCR (qPCR) or Western blot analyses, respectively. AIA in 2-month-old mice was generated using intraperitoneal injection with HSN (20 mg/kg/day) or LY294002 (20 mg/kg/day). The results show HSN significantly inhibited the LPS-induced gene expression of the inflammatory mediators. Furthermore, treatment with HSN relieved the antigen-induced arthritis and reduced the protein levels of MMP3, MMP9, and MMP13 in FLS and inhibited the polarization of macrophages to M1. Based on the results of our analyses, we concluded that HSN has significant anti-inflammatory activities and reduces the potential of MMPs in rheumatoid arthritis and the degree of polarization of macrophages to M1. Through the study of signaling pathways, we established that the inhibition of the PI3K/AKT signaling pathway by HSN may show therapeutic effects in the progression of rheumatoid arthritis.