Comparison of the predictive values of MRI-based vertebral bone quality scores for the determination of osteoporosis in different diseases.

PURPOSE: The study aimed to examine the consistency of vertebral bone quality (VBQ) scores for assessing osteoporosis across different etiologies and explore the predictive value of various VBQ scores for fragility vertebral fractures. METHODS: Patients with fragility fractures were matched by age and sex to patients with lumbar degeneration. VBQ scores were calculated in T1- and T2-weighted magnetic resonance imaging. Differential analysis of bone quality was performed based on etiology. RESULTS: A total of 96 inpatients were retrospectively enrolled. VBQT1 scores were only sensitive to osteoporotic bone in degenerative group (p < 0.01), failing to identify osteoporosis in fractured group (p > 0.05). For the degenerative group, the area under the curve (AUC) using the VBQT1 scores to differentiate osteoporosis was 0.72. After controlling the confounding variables, only VBQT2 scores were significantly higher in fractured group than degenerative group, with a greater AUC of 0.82 predicting fragility fractures. VBQT1 scores moderately correlated with femoral neck T-scores in degenerative group (r = -0.45, p < 0.01) but not in fractured group (r = -0.24, p > 0.05). VBQT2 scores were not associated with femoral neck T-scores (p > 0.05). CONCLUSION: This study is the first to evaluate the effectiveness of VBQs scores in assessing osteoporosis post-fracture. Only non-fractured patients' bone quality is fully susceptible to VBQT1 scores. While VBQT1 scores may not correlate with fragility fractures, VBQT2 scores present a viable alternative.

What are the differences in paraspinal muscle morphometry among degenerative spondylolisthesis patients, isthmic spondylolisthesis patients, and healthy individuals? A propensity score matching analysis.

PURPOSE: To compare the morphometry of paraspinal muscles in patients with degenerative spondylolisthesis (DS), isthmic spondylolisthesis (IS), and healthy individuals. METHODS: Thirty-seven pairs of DS patients were selected using propensity score matching with IS patients, while 37 healthy individuals matched for age, sex, and BMI were selected as controls. The relative cross-sectional area (rCSA), and relative functional cross-sectional area (rfCSA) of paraspinal muscles were measured, and the degree of fatty infiltration (FI) was calculated. Based on occupational differences, the patients were also divided into worker and farmer groups, and the same measurements were taken on them. RESULTS: At the L3/L4 level, the multifidus (MF) FI was greater in the DS and IS groups than in the control group, the erector spinae (ES) rfCSA was higher in the IS group than in the DS and control groups. At the L4/L5 level, MF rfCSA was smaller in the DS and IS groups than in the control group; ES rfCSA was higher in the IS group than in the DS and control groups. At the L5/S1 level, MF rfCSA was smaller in the DS and IS groups than in the control group; ES rfCSA was higher in the IS group than in the DS group. At the L3/L4, L4/L5 level, MF rfCSA were higher in the worker group than in the farmer group (p < 0.05). CONCLUSION: The morphological changes in paraspinal muscles in patients with DS were dominated by selective atrophy of the MF, while in patients with IS, the morphological changes in paraspinal muscle showed selective atrophy of the MF accompanied by compensatory hypertrophy of the ES. The surgeon should consider the morphological differences in paraspinal muscle between different types of lumbar spondylolisthesis when establishing the appropriate surgical program.

Osteoporosis and cement usage in total hip arthroplasty.

PURPOSE: Cement usage in total hip arthroplasty (THA) is increasingly common. However, osteoporosis-related fracture risk in cemented vs uncemented THA patients is poorly characterized. We aim to analyze the usage of metabolic bone care and osteoporosis fracture risk in cemented vs uncemented THA patients using FRAX and radiographic bone measurements. METHODS: Chart review on 250 THA patients was performed retrospectively. Demographics, FRAX scores, hip radiograph measurements, osteoporosis diagnosis, treatment and screening were compared between cemented and uncemented THA patients. Logistic regression model was used to analyze factors influencing cement usage. RESULTS: Cemented THA patients have significantly higher osteoporosis-related fracture risk as measured by FRAX major (20% vs 13%) and FRAX hip (8% vs 5%). There is no significant difference in osteoporosis treatment, vitamin D / calcium supplementation, or metabolic bone disease screening based on patients' cement status. Female sex and rheumatoid arthritis status significantly predict cement usage, but FRAX scores do not predict cement usage. Additionally, 50% (10/20) of patients with Dorr C classification were uncemented. CONCLUSION: Although some patients undergoing THA with high osteoporosis-related fracture risk were identified and cemented, some risk factors including poor proximal femur shape (by Dorr classification) and poor bone quality (as measured by FRAX score) were potentially overlooked. Cemented patients had an increased risk for fractures but did not receive appropriately increased osteoporosis screening or treatment. LEVEL OF EVIDENCE: III.

Bone loss after denosumab discontinuation is prevented by alendronate and zoledronic acid but not risedronate: a retrospective study.

A retrospective study of 121 patients who stopped denosumab (Dmab) then received no treatment (NT), risedronate (RIS), alendronate (ALN), or zoledronic acid (ZOL). Bone density (spine and hip) during and after Dmab discontinuation was measured. Treatment with ALN or ZOL, not NT and RIS, mitigated BMD loss after Dmab discontinuation. INTRODUCTION: Denosumab (Dmab) discontinuation is associated with bone loss and multiple vertebral fractures. The purpose was to compare bone mineral density (BMD) change in patients following Dmab discontinuation with no subsequent treatment (NT) and three bisphosphonate (BP) treatments: risedronate (RIS), alendronate (ALN), and zoledronic acid (ZOL). METHODS: In a review of 121 patients aged 71.2 ± 8.1 years, discontinuing Dmab (mean 5.4 doses), 33 received NT and 88 received BP (22 RIS; 34 ALN; 32 ZOL). BMD change after 1 year was compared between groups at the lumbar spine (LS), femoral neck (FN), and total hip (TH). Risk factors for bone loss after Dmab discontinuation were compared between groups and incidence of vertebral fractures was determined. RESULTS: Following Dmab discontinuation, LS mean change (g/cm2; 95% CI) was for NT: - 0.041 (- 0.062 to - 0.021); RIS: - 0.035 (- 0.052 to - 0.017); ALN: - 0.005 (- 0.020 to 0.009); and ZOL: - 0.009 (- 0.025 to 0.008). Differences in LS were found between NT and ALN (p =  0.015), and NT and ZOL (p=0.037), but not between NT and RIS. The only significant difference in TH was found between NT and ZOL (p 0.034) with no group differences in FN. BMD gains during Dmab treatment were associated with BMD loss after Dmab discontinuation. In a subset, discontinuation after Dmab treatment (> 5 doses) followed by ALN (n = 22) and ZOL (n = 11) showed no difference in BMD. Five of 7 vertebral fractures occurred after Dmab discontinuation in NT. CONCLUSION: Subsequent treatment with ALN or ZOL but not NT and RIS mitigates BMD loss after Dmab discontinuation.

Molecular characterization of a cation-dependent mannose-6-phosphate receptor gene in Crassostrea hongkongensis and its responsiveness in Vibrio alginolyticus infection.

The cation-dependent mannose-6-phosphate receptor (CD-M6PR) is a P-type lectin that plays a crucial role in lysosomal enzyme transport, bacterial resistance, and viral entry. In this study, we cloned and analyzed the ORF of the CD-M6PR gene from Crassostrea hongkongensis and named it ChCD-M6PR. We analyzed the nucleotide and amino acid sequence of ChCD-M6PR, its tissue expression pattern and immune response to Vibrio alginolyticus. Our results showed that the ORF of ChCD-M6PR was 801 bp long and encoded a protein of 266 amino acids with a signal peptide at the N-terminus, as well as Man-6-P_recep, ATG27 and transmembrane structural domains. Phylogenetic analysis indicated that Crassostrea hongkongensis shared the highest similarity with Crassostrea gigas in the terms of CD-M6PR. The ChCD-M6PR gene was found to be expressed in various tissues, with the highest expression observed in the hepatopancreas and the lowest in the hemocytes by the fluorescence quantitative PCR. Furthermore, the expression of ChCD-M6PR gene was significantly up-regulated for a short time in response to Vibrio alginolyticus infection in the gill and hemocytes, while it was down-regulated in the gonads. The expression patterns of ChCD-M6PR also varied in the other tissues. The 96 h cumulative mortality rate of Crassostrea hongkongensis infected with Vibrio alginolyticus after knockdown the ChCD-M6PR gene was significantly higher. Overall, our findings suggests that ChCD-M6PR plays a crucial role in the immune response of Crassostrea hongkongensis to Vibrio alginolyticus infection, and its tissue-specific expression patterns may be indicatitive of varied immune responses across tissues.

Association between metabolic healthy obesity and female infertility: the national health and nutrition examination survey, 2013-2020.

BACKGROUND: Obesity has been confirmed to be associated with infertility. However, the association between metabolically healthy obesity (MHO), a subset of obesity with no metabolic abnormalities, and female infertility has not yet been investigated. This study aimed to examine the association between MHO and the risk of female infertility among United States. METHODS: This study utilized a cross-sectional design and included 3542 women aged 20-45 years who were selected from the National Health and Nutrition Examination Survey (NHANES) 2013-2020 database. The association between MHO and the risk of infertility was evaluated using risk factor-adjusted logistic regression models. RESULTS: Higher BMI and WC were associated with increased infertility risk after adjusting for potential confounding factors (OR (95% CI): 1.04(1.02, 1.06), P = 0.001; OR (95% CI): 1.02 (1.01, 1.03), P < 0.001; respectively). After cross-classifying by metabolic health and obesity according to BMI and WC categories, individuals with MHO had a higher risk of infertility than those with MHN (OR (95% CI): 1.75(0.88, 3.50) for BMI criteria; OR (95% CI): 2.01(1.03, 3.95) for WC criteria). A positive linear relationship was observed between BMI/WC and infertility risk among metabolically healthy women (Pnon-linearity=0.306, 0.170; respectively). CONCLUSIONS: MHO was associated with an increased risk of infertility among reproductive-aged women in the US. Obesity itself, regardless of metabolic health status, was associated with a higher infertility risk. Our results support implementing lifestyle changes aimed at achieving and maintaining a healthy body weight in all individuals, even those who are metabolically healthy.

Changes of the posterior paraspinal and psoas muscle in patients with low back pain: a 3-year longitudinal study.

PURPOSE: This study aimed to investigate the changes of the posterior paraspinal muscles (PPM) and psoas muscle in patients with low back pain (LBP) over time. METHODS: Patients with LBP who had a repeat lumbar MRI with a minimum of 3-years apart at a tertiary referral center were analyzed. MRI-based quantitative assessments of the PPM and the psoas muscle were conducted for the baseline and follow-up MRI. The cross sectional area (CSA), the functional cross sectional area (fCSA) and the fat area (FAT) were calculated using a dedicated software program. The fatty infiltration (FI,%) of the regions of interest was calculated. Differences between the 1st and 2nd MRI were calculated for all assessed muscular parameters. RESULTS: A total of 353 patients (54.4%female) with a median age of 60.1 years and BMI of 25.8 kg/m2 at baseline were analyzed. The mean time between the 1st and 2nd MRI was 3.6 years. The fCSAPPM declined in both sexes significantly from the 1st to the 2nd MRI, whereas the FATPPM increased. In line with this result, the FIPPM increased in both males (29.9%) and females (19.4%). Females had a higher FIPPM and FIPsoas than males in both MRIs. In females, no significant changes were found for the psoas muscle. The CSAPsoas and fCSAPsoas in males were significantly smaller in the 2nd MRI. With increasing age, a significant trend in a decrease in ∆FIPPM was observed for both sexes. CONCLUSION: The study revealed significant quantitatively muscular changes in males and females, especially in the posterior paraspinal muscles in only three years' time.

Ideal entry point and trajectory for C2 pedicle screw placement in children: a 3D computed tomography study.

PURPOSE: To identify the ideal entry point for pediatric C2 pedicle screw and to obtain parameters of it for the indication of pediatric atlantoaxial fusion arthrodesis. METHODS: The pediatric cervical CT images were reconstructed into the 3D digital models and the C2 vertebrae were separated. The location of ideal entry point and screw placement related linear and angular parameters were assessed on the 3D digital models. RESULTS: A total of 214 pedicles from 107 C2 digital models were analyzed. The average entry point for C2 was 3.80 ± 2.78 mm medial to the lateral notch (LN) and 2.57 ± 1.70 mm superior to the LN. The average pedicle diameter (PD) was 6.02 ± 1.31 mm, and the average pedicle screw length (PSL) was 25.63 ± 3.46 mm. Statistical differences were found between different sex for PD and PSL (P < 0.05). As patient age increases, using the most lateral and inferior edge of the lateral mass as a reference marker, the entry point tends to move medial and cephalad, when using the LN as a reference marker, the entry point tends to move medial and slightly caudad. Univariate linear regression analysis suggested that these linear parameters were associated with age (P < 0.01). CONCLUSION: In this study, we found that the measurement results of C2 pedicle screw varied based on sex, laterality, and ages for children younger than 18 years. The entry point of the screws facilitating ideal trajectory tends to change in a linear way as a function of age. This information helps the surgeon to establish the specific anatomy related to C2 pedicle screw placement to facilitate fixation in the pediatric patients.

Proteomic Analysis Reveals the Vital Role of Synaptic Plasticity in the Pathogenesis of Temporal Lobe Epilepsy.

Temporal lobe epilepsy (TLE) is a chronic neurological disorder that is often resistant to antiepileptic drugs. The pathogenesis of TLE is extremely complicated and remains elusive. Understanding the molecular mechanisms underlying TLE is crucial for its diagnosis and treatment. In the present study, a lithium-pilocarpine-induced TLE model was employed to reveal the pathological changes of hippocampus in rats. Hippocampal samples were taken for proteomic analysis at 2 weeks after the onset of spontaneous seizure (a chronic stage of epileptogenesis). Isobaric tag for relative and absolute quantization (iTRAQ) coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS) technique was applied for proteomic analysis of hippocampus. A total of 4173 proteins were identified from the hippocampi of epileptic rats and its control, of which 27 differentially expressed proteins (DEPs) were obtained with a fold change > 1.5 and P < 0.05. Bioinformatics analysis indicated 27 DEPs were mainly enriched in "regulation of synaptic plasticity and structure" and "calmodulin-dependent protein kinase activity," which implicate synaptic remodeling may play a vital role in the pathogenesis of TLE. Consequently, the synaptic plasticity-related proteins and synaptic structure were investigated to verify it. It has been demonstrated that CaMKII-α, CaMKII-ß, and GFAP were significant upregulated coincidently with proteomic analysis in the hippocampus of TLE rats. Moreover, the increased dendritic spines and hippocampal sclerosis further proved that synaptic plasticity involves in the development of TLE. The present study may help to understand the molecular mechanisms underlying epileptogenesis and provide a basis for further studies on synaptic plasticity in TLE.

Elbow varus torque and ball velocity associations in high school and professional pitchers with increased sagittal-plane trunk tilt.

BACKGROUND: Increased sagittal-plane trunk tilt is thought to increase drive in the anterior direction toward home plate, transferring energy from the trunk to the distal upper extremity, ultimately generating greater ball velocity. Increased sagittal trunk tilt has also been implicated in the risk of upper-extremity joint loading in baseball pitchers by way of elbow varus torque (EVT), a metric previously associated with elbow injury in professional pitchers. The purposes of this study were (1) to compare sagittal trunk tilt positioning between high school and professional pitchers throughout the pitch and (2) to identify the potential associations between sagittal-plane trunk tilt, ball velocity, and EVT for both cohorts. METHODS: Professional and high school pitchers were instructed to throw fastballs while being evaluated with 3-dimensional motion capture (480 Hz). Sagittal trunk tilt motion throughout the pitching motion was compared between cohorts from maximum knee height to maximum shoulder internal rotation. To assess the effects of sagittal-plane trunk tilt on ball velocity and EVT, linear mixed-effect models were created. RESULTS: Professional pitchers (n = 100, 882 pitches) achieved greater sagittal trunk tilt than high school pitchers (n = 57, 519 pitches) during early portions of the pitching motion, including maximum positive sagittal trunk tilt (46.6° ± 8.3° vs. 43.6° ± 10.2°, P = .042). Professional pitchers also had greater sagittal trunk tilt excursion throughout the pitch motion (68.0° ± 11.4° vs. 62.5° ± 11.0°, P = .004). For every 10° increase in sagittal trunk tilt at ball release for professional pitchers, ball velocity increased by 0.36 m/s (B = 0.036 and ß = 0.194, P < .001) or 0.9% average ball velocity whereas EVT increased by 0.14% body weight × body height (B = 0.014 and ß = 0.159, P < .001) or 2.9% average normalized EVT. For every 10° increase in sagittal trunk tilt at ball release for high school pitchers, ball velocity increased by 0.34 m/s (B = 0.097 and ß = 0.025, P = .025) or 1.1% average ball velocity whereas EVT increased by 0.07% body weight × body height (B = 0.007 and ß = 0.086, P = .016) or 1.7% average normalized EVT. CONCLUSION: Increased positive sagittal-plane trunk tilt was significantly associated with greater ball velocity and increased EVT for both professional and high school pitchers. Peak EVT estimates were consistently more pronounced than ball velocity benefits for both populations, suggesting that no specific time point may provide a ball velocity benefit while concomitantly minimizing EVT. Both professional and high school pitchers should consider this trade-off, which may influence injury risk, when engaging in higher degrees of positive sagittal-plane trunk tilt.

Joint and segment sequencing and its relationship to ball velocity and throwing arm kinetics in professional pitchers.

BACKGROUND: Temporal variations during the pitch have demonstrated significant impacts on the kinetic chain, and as such, have implications in injury risk. PURPOSE: To determine the effect of varying chronological orders of maximum joint and segment velocities on ball velocity and upper extremity kinetics. METHODS: Professional baseball pitchers (n = 287) were assessed with 3D-motion capture (480 Hz) while pitching. Pitches were categorized into one of the following groups dependent on the first maximum joint or segment velocity achieved out of chronological order in an inferior to superior direction: knee extension (DscK), pelvis rotation (DscP), trunk rotation (DscT), shoulder rotation (DscS), forearm pronation (DscF), and Proper (for pitchers with the correct temporal sequence), and Total Population, for all pitchers. Ten normalized throwing arm kinetic variables were compared among groups. Regression analysis was conducted on the timing of maximum velocities with ball velocity. RESULTS: The majority of pitches were in the DscK group (64.5%). The DscK group had a significantly slower maximum lead knee extension velocity compared with the Proper group (253°/s vs. 316°/s, P = .017). The Proper group had a significantly faster ball velocity compared with the Total Population (39.0 ± 1.9 m/s vs. 38.3 ± 2.1 m/s, P = .013). The DscP group had a significantly slower maximum pelvis rotation velocity compared with the Proper group (596°/s vs. 698°/s, P < .001). The Proper group had no significant difference in kinetics relative to the population. For every 1 standard deviation delay in attaining maximum lead knee extension velocity, ball velocity increased by 0.38 m/s (B = 3.5, ß = 0.18, P < .001). For every 1 standard deviation delay in timing to achieve maximum pelvis rotation velocity, maximum pelvis rotation velocity and ball velocity increased by 22.5°/s (B = 1107.0, ß = 0.23, P < .001) and 0.48 m/s (B = 23.4, ß = 0.23, P < .001), respectively. CONCLUSION: Pitchers with a discordant sequence of knee extension and pelvis rotation velocity timing had significantly slower corresponding segment/joint velocities. Conversely, pitchers with a proper sequence had the fastest ball velocity with minimal differences in throwing arm kinetics. To maximize ball velocity, professional pitchers should consider achieving maximal velocities in an inferior to superior chronological sequence, with a particular focus on the knee and pelvis.

Kinetic and kinematic comparisons in high school pitchers with low and high pitch location consistency.

BACKGROUND: Although ball velocity has often been associated with increased kinetics at the upper extremity and risk of injury in youth and adolescent pitchers, it is unclear if the performance metric pitch location consistency has any positive or negative associations with pitching kinetics. METHODS: High school pitchers (n = 59) pitched 8-12 fastballs using 3D motion capture (480 Hz). Pitchers were divided into high-consistency (HiCon) and low-consistency (LoCon) groups based on the absolute center deviation of each pitcher's pitch to the center of the pitcher's mean pitch location. Ninety-five percent confidence ellipses with major and minor radii were constructed, and kinematics and kinetics were compared between groups. RESULTS: Compared with LoCon pitchers, HiCon pitchers had decreased lead hip flexion at elbow extension (40° ± 12° vs. 52° ± 13°, respectively, P = .008), and at foot contact, decreased back hip extension (-1° ± 10° vs. -10° ± 13°, respectively, P = .038) and increased back hip internal rotation (9° ± 15° vs. -2° ± 15°, respectively, P = .043). LoCon pitchers achieved maximum lead hip flexion earlier in the pitch (61.3% ± 23.2% vs. 75.8% ± 15.1%, respectively, P = .039). A multiregression model predicted 0.49 of variance in pitch location consistency using kinematic inputs. DISCUSSSION AND CONCLUSION: Pitchers who differ in pitch location consistency outcomes do not appear to demonstrate physiologically unsafe kinematics. High school pitchers who strive for improved pitch consistency can consider adjusting parameters of hip kinematics during early portions of the pitch.

Total Joint Arthroplasty and Osteoporosis: Looking Beyond the Joint to Bone Health.

BACKGROUND: Metabolic bone diseases in the total joint arthroplasty (TJA) population are undertested and undertreated, leading to increased risk of adverse outcomes such as periprosthetic fractures. This study aims to better characterize the current state of bone care in TJA patients using Fracture Risk Assessment Tool (FRAX) score risk stratifications. METHODS: In total, 505 consecutive TJA patients who meet the Endocrine Society guidelines for osteoporosis screening were included for review. They were divided into a high risk or low risk group depending on FRAX scores and were compared based on screening, diagnosis, and treatment of metabolic bone disease. Logistic regression models were used to analyze factors influencing screening and treatment. A population analysis involving 2,000 TJA patients, and a complication analysis involving 40 periprosthetic fracture patients were conducted. RESULTS: Among high risk patients undergoing TJA, 90% did not receive any pharmacological treatment for osteoporosis, 45% were not treated with vitamin D or calcium, and 88% did not receive bone density testing in the routine care period. Among patients with pre-existing osteoporosis undergoing TJA, 80% were not treated with any osteoporosis medications and 33% of these patients were not taking vitamin D or calcium. Female gender and past fracture history contributed to whether patients received screening and treatment. Patients with periprosthetic hip fractures have significantly higher FRAX scores compared to control THA patients. CONCLUSION: There are significant gaps in metabolic bone care of the geriatric TJA population regarding both screening and treatment. Metabolic bone care and risk identification with FRAX should be highly considered for TJA patients.

Fracture Risk Assessment Tool Scores and Radiographical Bone Measurements in Total Hip Arthroplasty Patients.

BACKGROUND: Osteoporosis is a major risk factor for periprosthetic fractures (PPFx) in total hip arthroplasty (THA) patients but is not routinely screened for in this population. Given the availability of hip x-rays and preoperative screenings, Fracture Risk Assessment Tool (FRAX) scores and radiographic bone measurements are potentially promising, novel risk stratification tools. This study aims to characterize FRAX scores and radiographic bone measurements in THA and PPFx patients. METHODS: A retrospective chart review for demographic variables and FRAX scores was performed on 250 THA and 40 PPFx patients. Radiographic bone measurements including cortical thicknesses (both antero-posterior [AP] and lateral), canal to calcar ratio, canal flare index, and Dorr classifications were obtained from preoperative x-rays. Correlation between FRAX scores and radiographic bone measurements was investigated with linear regressions. FRAX scores and radiographic bone measurements were compared between the THA and PPFx patients. Multivariate logistic regressions were used to identify factors predicting PPFx. RESULTS: FRAX scores were significantly correlated with both AP (P < .001) and lateral (P = .007) cortical thicknesses. Compared to THA patients, those with PPFx had significantly higher FRAX scores (P = .003) and lower AP cortical thickness (P = .005). Multivariate logistic regressions demonstrated that FRAX major osteoporotic fracture risk score and AP cortical thickness were independent predictors of PPFx (P = .001 and .024, respectively). CONCLUSION: Cortical thicknesses are good proxy measurements of osteoporosis-related fracture risk in THA patients. In addition, both major and AP cortical thickness indices are promising tools for identifying patients who are at a high risk of PPFx in the THA population.

Lactobacillus johnsonii activates porcine monocyte derived dendritic cells maturation to modulate Th cellular immune response.

Lactobacilli are abundant in the intestinal tract where they constantly regulate immune system via interacting with a great diversity of immune cells, such as dendritic cells (DCs). Notably, DCs are powerful antigen-presenting cells and they are capable of initiating primary immune responses. In this study, we studied the effects of Lactobacillus johnsonii (L. johnsonii) and Lactobacillus johnsonii cell-free supernatant (L. johnsonii-CFS) on the activation of porcine monocyte-derived dendritic cells (MoDCs) and their regulation of Th cellular immune responses in vitro. The MoDCs generated from porcine peripheral blood monocytes were stimulated by L. johnsonii and L. johnsonii-CFS, respectively. Pre-incubation with L. johnsonii increased expression of CD172a, CD80, major histocompatibility complex class II (MHCII) in MoDCs, and enhanced the ability of MoDCs to induce the proliferation of CD4+ T cell, while pre-incubation with L. johnsonii-CFS merely upregulated the expression of MHCII. Analysis of the cytokines showed that L. johnsonii stimulated up-regulation of Th1-type cytokines (IL-12p40, IFN-γ, TNF-α), pro-inflammatory cytokine IL-1ß, chemokine CCL20, and Treg-type / anti-inflammatory cytokines IL-10 in MoDCs. Notably, a high production of IL-10 was observed in the MoDCs treated with L. johnsonii-CFS, indicating L. johnsonii-CFS exerted anti-inflammatory effects. Furthermore, L. johnsonii induced up-regulation of TLR2 and TLR6, but L. johnsonii-CFS not. Moreover, MoDCs stimulated by L. johnsonii mainly promoted T cell differentiate into Th1/Th2/Treg cells and plays an important role in improving the balance between Th1/Th2/Treg-type cells, whereas MoDCs stimulated by L. johnsonii-CFS mainly directed T cell to Th2/Treg subset polarization. In conclusion, L. johnsonii and L. johnsonii-CFS exhibited the ability of modulating innate immunity by regulating immunological functions of MoDCs in vitro, suggesting their potential ability to use as microecological preparations and medicines.

Long non-coding RNA RP11-283G6.5 confines breast cancer development through modulating miR-188-3p/TMED3/Wnt/ß-catenin signalling.

The contributions of long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) to breast cancer are critical areas of investigation. In this study, we identified a novel lncRNA RP11-283G6.5 which was lowly expressed in breast cancer and whose low expression was correlated with poor overall survival and disease-free survival of breast cancer patients. Functional experiments revealed that ectopic expression of RP11-283G6.5 confined breast cancer cellular growth, migration, and invasion, and promoted cellular apoptosis. Conversely, RP11-283G6.5 silencing facilitated breast cancer cellular growth, migration, and invasion, and repressed cellular apoptosis. Moreover, RP11-283G6.5 was found to confine breast cancer tumour growth and metastasis in vivo. Mechanistically, RP11-283G6.5 competitively bound to ILF3, reduced the binding of ILF3to primary miR-188 (pri-miR-188), abolished the suppressive effect of ILF3 on pri-miR-188 processing, and therefore promoted pri-miR-188 processing, leading to the reduction of pri-miR-188 and the upregulation of mature miR-188-3p. The expression of RP11-283G6.5 was significantly positively correlated with that of miR-188-3p in breast cancer tissues. Through increasing miR-188-3p, RP11-283G6.5 decreased TMED3, a target of miR-188-3p. RP11-283G6.5 further suppressed Wnt/ß-catenin signalling via decreasing TMED3. Rescue assays revealed that inhibition of miR-188-3p, overexpression of TMED3 or blocking Wnt/ß-catenin signalling all attenuated the roles of RP11-283G6.5 in breast cancer. Collectively, these findings demonstrated that RP11-283G6.5 is a tumour suppressive lncRNA in breast cancer via modulating miR-188-3p/TMED3/Wnt/ß-catenin signalling. This study indicated that RP11-283G6.5 might be a promising prognostic biomarker and therapeutic target for breast cancer.

The association of stride length to ball velocity and elbow varus torque in professional pitchers.

Professional basebal pitchers (n =315) were divided into quartiles based on increasing stride length and random intercept linear mixed-effect models were used to correlate stride length with ball velocity, pelvis and trunk rotation at foot contact, and throwing arm kinetics. Average stride length among all pitchers was 78.3±5.3%body height (%BH). For every 10% increase in stride length, ball velocity increased by 0.9 m/s (B =0.089, ß =0.25, p <0.001) and trunk rotation initiation occurred 4.23 ms earlier (B =-0.42, ß =-0.14, p <0.001). When divided into quartiles pelvis rotation was less towards home plate in Q1 compared to Q3 and Q4 (70.0±10.7° vs. 60.9±8.9° and 58.6±9.1°, p <0.001). No significant differences in shoulder internal rotation torque (p =0.173) or elbow varus torque (p =0.072) were noted between quartiles. Professional baseball pitchers who reached stride lengths of 80%BH or greater achieved faster ball velocity without an increase in elbow varus torque. This may, be a byproduct of rotating the pelvis for a greater proportion of the pitching motion and thereby more effectively utilising the lower extremities in the kinetic chain. Encouraging players to achieve this threshold of stride length may enhance ball velocity outcomes.

CELF6 modulates triple-negative breast cancer progression by regulating the stability of FBP1 mRNA.

BACKGROUND: Triple-negative breast cancer (TNBC) remains a great challenge in clinical treatment due to a shortage of effective therapeutic targets and acquired chemoresistance. Here, we identified the role of an RNA-binding protein, CUG-BP Elav-like family member 6 (CELF6), in the TNBC development and paclitaxel (PTX) chemoresistance. METHODS: Stable CELF6-overexpressing cell lines were established in BT549 and MDA-MB-231 cells. Cell proliferation was determined using cell counting, two-dimensional colony formation, and MTT assay. Meanwhile, cell migration and cell invasion were detected by Transwell assay. Furthermore, the downstream target gene of CELF6 was identified and the direct interaction was further determined by luciferase reporter assay, immunoprecipitation, and RNA pull-down. Additionally, the PTX resistant cell line was established to determine the role of CELF6 in PTX resistance. RESULTS: CELF6 overexpression suppressed cell proliferation, cell migration, and cell invasion. Mechanistically, Fructose-Bisphosphatase 1 (FBP1) was identified as the target gene of CELF6 and stabilized by CELF6 via binding 3'UTR. CELF6 overexpression mediated inhibition in TNBC development was dependent on FBP1. Moreover, CELF6 overexpression increased the sensitivity to PTX treatment. CONCLUSION: CELF6 functions as a tumor suppressor by upregulating FBP 1 expression via stabilizing its mRNA, and thereby inhibits TNBC progression.

NEK5 promotes breast cancer cell proliferation through up-regulation of Cyclin A2.

NEK5, a contraction of NIMA Related Kinase 5, has been shown to regulate the centrosome integrity of cells though; it has been little described in cancer. Herein, to explore the clinicopathological meaning of NEK5 expression in breast cancer, immunohistochemistry was performed to detect the expression of NEK5 on tissue blocks, totaling 203 cases. Quantitative real-time PCR (qRT-PCR) was used to evaluate NEK5 mRNA expression with 30 cases of fresh tissues. To observe the function of NEK5 in the growth of breast cancer cells, both MTT and xenografted nude mice were performed. And Transwell assay was employed to observe the variation of migration and invasion. It was shown that up-regulated NEK5 was significantly associated with tumor progression and poor overall prognosis; and that silencing of NEK5 can significantly suppress the proliferation both in vivo and in vitro, inhibiting migration, and invasion. To get insight into the underlying mechanism by which NEK5 operates in proliferation of breast cancer cells, we showed that NEK5 can up-regulate Cyclin A2 and down-regulate Cyclin D1, Cyclin D3, and Cyclin E1 expression. Additionally, Cyclin A2 was also identified as a novel interacting protein for NEK5. Taking together, we firstly defined the oncogenic role of NEK5 in breast cancer that was related to proliferation, supporting that NEK5 might be used a new therapeutic target in breast cancer.

TMED3 promotes cell proliferation and motility in breast cancer and is negatively modulated by miR-188-3p.

BACKGROUND: The role of TMED3 involved in cancers has been seldom described, let alone in breast cancer. To explore the clinicopathological significance of TMED3 expression and the biological roles involved in breast cancer cells, we undertook the study. METHODS: Immunohistochemistry was performed to observe the pattern of TMED3 expression in breast cancer tissues, totaling 224 cases; followed by detailed statistical analysis between TMED3 expression versus clinicopathological information available. To explore the role of TMED3 involved in the malignant behaviors of breast cancer cells, wound-healing and Transwell assays were conducted to evaluate the variation of migration and invasion of MCF-7 and MDA-MB-231 cells whose TMED3 has been stably silenced using lenti-viral based short hairpin RNA (shRNA) vectors. MTT, clonogenic assay and xenograft nude mice model were undertaken to observe the variation of proliferation both in vitro and in vivo. RESULTS: It was shown that elevated TMED3 markedly correlated with ER, PR, Her-2 status, and lymph nodes metastases in addition to significant association with poor overall prognosis. In vitro, TMED3 was shown to promote proliferation, migration and invasion of breast cancer cells. Moreover, miR-188-3p was identified as a novel negative regulator of TMED3 in breast cancer, which can slow down the proliferation, migration and invasion of MCF-7 cells. Results from in vivo xenograft nude mice models showed that lenti-viral based miR-188-3p re-expression can markedly impair the tumor growth. CONCLUSIONS: Our data define and bolster the oncogenic role of TMED3 in breast cancer.