EZH2/hSULF1 axis mediates receptor tyrosine kinase signaling to shape cartilage tumor progression.

Chondrosarcomas are primary cancers of cartilaginous tissue and capable of alteration to highly aggressive, metastatic, and treatment-refractory states, leading to a poor prognosis with a five-year survival rate at 11 months for dedifferentiated subtype. At present, the surgical resection of chondrosarcoma is the only effective treatment, and no other treatment options including targeted therapies, conventional chemotherapies, or immunotherapies are available for these patients. Here, we identify a signal pathway way involving EZH2/SULF1/cMET axis that contributes to malignancy of chondrosarcoma and provides a potential therapeutic option for the disease. A non-biased chromatin immunoprecipitation sequence, cDNA microarray analysis, and validation of chondrosarcoma cell lines identified sulfatase 1 (SULF1) as the top EZH2-targeted gene to regulate chondrosarcoma progression. Overexpressed EZH2 resulted in downregulation of SULF1 in chondrosarcoma cell lines, which in turn activated cMET pathway. Pharmaceutical inhibition of cMET or genetically silenced cMET pathway significantly retards the chondrosarcoma growth and extends mice survival. The regulation of EZH2/SULF1/cMET axis were further validated in patient samples with chondrosarcoma. The results not only established a signal pathway promoting malignancy of chondrosarcoma but also provided a therapeutic potential for further development of effective target therapy to treat chondrosarcoma.

Allergenicity reduction of the bio-elicited peanut sprout powder (BPSP) and toxicological acceptance of BPSP-supplemented diets assessed with ICR mice.

The allergenic and toxicological acceptances of the bio-elicited peanut sprout powder (BPSP) have not been assessed. BPSP was generated from peanut kernels germinated at 26-28 °C for 72 h (designated as 72 h-NGS). The 72 h-NGS were subsequently sliced, incubated, dried, defatted and pulverized to generate bio-elicited peanut sprout powder (BPSP). Protein solubility of BPSP increased 2.6-fold compared to 72 h-NGS. SDS-PAGE analysis revealed BPSP production triggered extensive degradation of the high-molecular weight peanut allergic proteins, mainly Ara h 1 and Ara h 3. Western blotting detected with peanut allergic patients' IgE indicated decreased in vitro reactivity. Food safety assessment of BPSP was performed with ICR mice fed with basal (control) and three doses of formulated BPSP-supplemented diets containing 0.11 g (normal), 2.5 g (high) and 25 g (super high) BPSP /kg BW. Animals appeared healthy with steady body weight gain in all groups during the entire 35-day dietary intervention. Hematological and serum biochemical analyses revealed no significant difference among groups. Histopathological examination on the tissue sections of primary organs further supported safety with no pathologies. The in vitro allergic reduction and toxicological safety in the BPSP-supplemented dietary intervention in the ICR mice study, support moving forward with BPSP-involved product development. Supplementary Information: The online version contains supplementary material available at 10.1007/s13197-022-05537-7.

Central Pontine Myelinolysis in a Normonatremic Patient with Depression.

A 76-year-old male presented with a recurrent depressive episode, an unsteady gait and cognitive impairment. Extensive blood tests, including hemogram, biochemical tests, folic acid, vitamin B12, and thyroid hormone, showed normal results. With the exception of the unsteady gait, neurological examination was negative. Brian magnetic resonance imaging (MRI) showed the typical feature of central pontine myelinolysis (CPM); however, there was no history of alcoholism, liver transplantation, malnutrition or rapid correction of hyponatremia. The patient had taken venlafaxine to treat major depressive disorder for more than 20 years. After discontinuation of venlafaxine, the unsteady gait gradually resolved, and subsequent MRI revealed reduction of the lesions over 6 months. We discuss herein the possible correlation between chronic use of venlafaxine and CPM.

Comparison of the corticosteroid injection and hyaluronate in the treatment of chronic subacromial bursitis: A randomized controlled trial.

OBJECTIVE: To analyse the effectiveness of corticosteroid (CS) and hyaluronic acid (HA) subacromial - subdeltoid (SASD) injection compared with normal saline (NS) in patients with chronic subacromial bursitis (CSB). DESIGN: A prospective three-arm double-blinded randomised controlled trial. SETTING: Rehabilitation department of two teaching hospitals. SUBJECTS: Patients with CSB (N = 186) divided into CS (N = 68), HA (N = 60), and NS (N = 58) groups. INTERVENTIONS: Three SASD injections under ultrasound guidance: group A, 20 mg of triamcinolone; group B, 2.5 mL of HA; and group C, 2.5 mL of NS. OUTCOME MEASURES: The primary outcome measures were the pain visual analogue scale (VAS) score at eight weeks. The secondary outcomes were scores on the Shoulder Pain and Disability Index (SPADI) and Shoulder Disability Questionnaire. RESULTS: At eight weeks, the pain VAS scores during activity were 2.56 ± 2.29, 3.65 ± 2.50, and 4.71 ± 2.83 in the CS, HA, and NS groups, respectively (CS vs NS, P < 0.001; HA vs NS, P = 0.013; CS vs HA, P = 0.010). SPADI scores were 40.83 ± 21.75, 36.92 ± 22.78, and 33.35 ± 23.38 in the CS, HA, and NS groups, respectively (CS vs NS, P < 0.001; HA vs NS, P = 0.197; CS vs HA, P = 0.004). CONCLUSION: Ultrasound-guided corticosteroid injection into the subacromial - subdeltoid bursa was proven to be effective and superior to hyaluronic acid and normal saline injection for treating CSB. Hyaluronic acid injection was only marginally more effective than normal saline injection.Trial Registration: ClinicalTrials.gov: NCT02702206.

Add-on repetitive transcranial magnetic stimulation in patients with opioid use disorder undergoing methadone maintenance therapy.

Background: Repetitive transcranial magnetic stimulation (rTMS) shows potential therapeutic effects for individuals with addiction, but few studies have examined individuals with opioid use disorder (OUD).Objectives: We conducted an add-on double-blinded, sham-controlled rTMS feasibility pilot trial to examine OUD participants undergoing methadone maintenance therapy (MMT). The current report focused on the effects of rTMS on (1) craving and heroin use behavior and (2) depression, impulsivity, and attention.Methods: Active or sham rTMS treatment was applied to the left dorsolateral prefrontal cortex (DLPFC) over a total of 11 sessions in 4 weeks (15-Hz frequency, 4 seconds per train, intertrain interval of 26 seconds, 40 trains per session) in OUD participants (ClinicalTrials.gov registration number: NCT03229642). Craving, heroin use severity, urine morphine tests, the Hamilton Depression Rating Scale (HDRS), the Barratt Impulsiveness Scale-11 (BIS-11), and the Continuous Performance Tests (CPTs) were measured.Results: Twenty-two OUD participants were enrolled, of which eleven (8 males) were undergoing active rTMS and nine (8 males) were in the sham rTMS group. After 12 weeks of follow-up, the active rTMS group did not show significantly greater improvements than the sham group with respect to craving, heroin use, or urine morphine test results. However, HDRS scores, BIS-11 attentional subscales, and CPTs commission T-scores (C-TS) were significantly lower in the active rTMS group (P = .003, 0.04, and 0.02, respectively) than in the sham group.Conclusion: Add-on rTMS did not appear to improve heroin use behavior but may have benefitted depressive symptoms, impulse control and attention in OUD participants undergoing MMT.

Geometrical analysis for assessing torsional alignment of humerus.

BACKGROUND: Compared to other types of surgeries, minimally invasive surgeries (MISs) of humeral shaft fractures are associated with less radial nerve injury, less soft tissue injury and higher union rate. However, malrotation often occurs in MISs when closed reduction methods are used. This study aims to define specific palpable landmarks to help surgeons determine the correct torsional angle and reduce the incidence of malrotation. METHODS: Twenty-eight normal humeral computed tomography scans were retrieved from our image database. One line was drawn through the vertices of the intertubercular sulcus of the humeral head in the coronal view, and another line was drawn through the longest axis between the medial and lateral condyles in the coronal view. The angle between these two lines was measured at least 3 times for each scan. RESULTS: The profile of the intertubercular sulcus tangent line of the humeral head and the axis of the distal humerus was identified as the most accurate method for assessing the precision of torsion during MIS for humeral shaft fractures. The transepicondylar axis line is more internally rotated than the intertubercular sulcus tangent line. The mean angle was measured to be 41.1 degrees. CONCLUSIONS: The axis of the distal humeral condyles is internally rotated by approximately 41.1 degrees compared with the intertubercular sulcus tangent line of the humeral head. Minimally invasive surgeries can be performed by using these palpable landmarks. The torsional deformities can be reduced with the proper angle adjustment without the need for fluoroscopy. It can also be used to treat unstable comminuted humeral fractures. LEVEL OF EVIDENCE: Retrospective Study, Diagnostic study, Level III.

The social cognitive ability in Han Chinese euthymic patients with bipolar I and bipolar II disorder.

BACKGROUND/PURPOSE: Although social cognitive deficits were found in euthymic patients of bipolar disorder (BD), the characteristics of social cognition in Han Chinese euthymic BD patients remain obscure. This study aimed to examine social cognition in Han Chinese euthymic BD patients relative to healthy controls (HC). Moreover, we explore the differences in social cognition between euthymic BD I and BD II patients. METHODS: 43 Han Chinese BD patients (BD-I:25, BD-II:18) and 28 HC were recruited. All patients were euthymic (Young Mania Rating Scale (YMRS) ≤ 7 and Hamilton Depression Rating Scale (HDRS) ≤ 7). Social cognitive ability was measured using Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT), including 4 branches: perceiving emotions, facilitating emotions, understanding emotions, and managing emotions. Continuous performance Test (CPT) and Wisconsin Card Sorting Test (WCST) were used to examine attention and executive function. RESULTS: Significant difference in understanding emotions branch of MSCEIT was found between BD patients and HCs (Mann-Whitney U test, p = 0.005). Besides, BD patients had significantly worse performance in WCST and CPT. However, the differences in WCST, CPT, MSCEIT total scores and its subscales were not significant between BD I and BD II patients. CONCLUSION: Euthymic Han Chinese BD patients exhibit significant social cognitive deficits in understanding emotion and cognitive dysfunction in attention and executive function. Furthermore, Han Chinese BD I patients showed similar social cognitive and general cognitive ability as compared with BD II patients. Social cognitive rehabilitation on both euthymic BD I and II patients should be considered.

FOXA1 transcriptionally up-regulates cyclin B1 expression to enhance chondrosarcoma progression.

Chondrosarcoma is a malignant and common bone tumor that is highly resistant to radiation and chemotherapy. At this moment, amputation surgery is the only option which unfortunately has serious impact to daily lives of the patients. Thus, there is an urgent need to understand causative molecular mechanisms underlying the disease for more accurate prognosis and more effective targeted treatment. In the current study, we identify the transcription factor FOXA1 through cDNA microarray screening comparing normal versus chondrosarcoma cells and investigate the mechanisms underlying its function in chondrosarcoma development. We show that FOXA1 enhances expression of the cyclin B1 gene, which in turn drives cell cycle progression through G2-M transition thus promotes cell cycle progression of chondrosarcoma cells.

YY1 and HDAC9c transcriptionally regulate p38-mediated mesenchymal stem cell differentiation into osteoblasts.

Mesenchymal stem cells (MSCs) have a high self-renewal potential and can differentiate into various types of cells, including adipocytes, osteoblasts, and chondrocytes. Previously, we reported that the enhancer of zeste homolog 2 (EZH2), the catalytic component of the Polycomb-repressive complex 2, and HDAC9c mediate the osteogenesis and adipogenesis of MSCs. In the current study, we identify the role of p38 in osteogenic differentiation from a MAPK antibody array screen and investigate the mechanisms underlying its transcriptional regulation. Our data show that YY1, a ubiquitously expressed transcription factor, and HDAC9c coordinate p38 transcriptional activity to promote its expression to facilitate the osteogenic potential of MSCs. Our results show that p38 mediates osteogenic differentiation, and this has significant implications in bone-related diseases, bone tissue engineering, and regenerative medicine.

Comparison Between Corticosteroid and Lidocaine Injection in the Treatment of Tennis Elbow: A Randomized, Double-Blinded, Controlled Trial.

OBJECTIVE: The aim of the study was to compare the effects of corticosteroid injection with lidocaine injection in treating tennis elbow. DESIGN: It is a prospective, double-blinded, randomized controlled trial. Patients with tennis elbow for more than 1 mo were recruited from a hospital-based rehabilitation outpatient clinic. A total of 70 patients were recruited, and 61 patients completed the study. Patients received an injection of either 10 mg (1 ml) of triamcinolone (corticosteroid group, n = 30) or 1 ml of 1% lidocaine (lidocaine group, n = 31). All of the outcome measures were evaluated before the intervention and at 2 wks and 2 mos after treatment. RESULTS: No significant group differences were observed between the corticosteroid and lidocaine groups regarding Patient-Rated Tennis Elbow Evaluation, Disability of the Arm, Shoulder, and Hand, visual analog scale for pain, and grip strength at baseline and at 2 wks and 2 mos after treatment (P > 0.05). However, within-group comparison showed significant improvement after injection with regard to Patient-Rated Tennis Elbow Evaluation, Disability of the Arm, Shoulder, and Hand, visual analog scale for pain, and grip strength in both groups (P > 0.05). CONCLUSIONS: No differences in the short-term outcomes were found between lidocaine and corticosteroid injection in a small sample of people with tennis elbow with mean duration of 3.8 mos.

Enhancer of Zeste Homolog 2 and Histone Deacetylase 9c Regulate Age-Dependent Mesenchymal Stem Cell Differentiation into Osteoblasts and Adipocytes.

Mesenchymal stem cells (MSCs) are multipotent precursors that can undergo multilineage differentiation, including osteogenesis and adipogenesis, which are two mutually exclusive events. Previously, we demonstrated that enhancer of zeste homolog 2 (EZH2), the catalytic component of the Polycomb-repressive complex 2, mediates epigenetic silencing of histone deacetylase 9c (HDAC9c) in adipocytes but not in osteoblasts and that HDAC9c accelerates osteogenesis while attenuating adipogenesis of MSCs through inactivation of peroxisome proliferator-activated receptor gamma 2 activity. Importantly, disrupting the balance between adipogenesis and osteogenesis can lead to age-associated bone loss (osteoporosis) and obesity. Here, we investigated the relationship between age, and osteogenic and adipogenic differentiation potential of MSCs by comparing EZH2 and HDAC9c expression in osteoblasts and adipocytes of both human and mice origins to determine whether the EZH2-HDAC9c axis regulates age-associated osteoporosis and obesity. Our findings indicated that a decline in HDAC9c expression over time was accompanied by increased EZH2 expression and suggested that a therapeutic intervention for age-associated osteoporosis and obesity may be feasible by targeting the EZH2-HDAC9c axis. Stem Cells 2016;34:2183-2193.

Development of 3D carbon nanotube interdigitated finger electrodes on polymer substrate for flexible capacitive sensor application.

This study reports a novel approach to the implementation of 3D carbon nanotube (CNT) interdigitated finger electrodes on flexible polymer, and the detection of strain, bending curvature, tactile force and proximity distance are demonstrated. The merits of the presented CNT-based flexible sensor are as follows: (1) the silicon substrate is patterned to enable the formation of 3D vertically aligned CNTs on the substrate surface; (2) polymer molding on the silicon substrate with 3D CNTs is further employed to transfer the 3D CNTs to the flexible polymer substrate; (3) the CNT-polymer composite (~70 µm in height) is employed to form interdigitated finger electrodes to increase the sensing area and initial capacitance; (4) other structures such as electrical routings, resistors and mechanical supporters are also available using the CNT-polymer composite. The preliminary fabrication results demonstrate a flexible capacitive sensor with 50 µm high CNT interdigitated electrodes on a poly-dimethylsiloxane substrate. The tests show that the typical capacitance change is several dozens of fF and the gauge factor is in the range of 3.44-4.88 for strain and bending curvature measurement; the sensitivity of the tactile sensor is 1.11% N(-1); a proximity distance near 2 mm away from the sensor can be detected.

Tubular waveguide evanescent field absorption biosensor based on particle plasmon resonance for multiplex label-free detection.

A novel tubular waveguide particle plasmon resonance (TW-PPR) sensor is demonstrated for label-free biochemical detection. The sensor itself is a microchamber of a defined sample volume, a mechanical support for sensor coating, a waveguide to provide evanescent wave interrogation, and it can be easily extended to a multi-channel format. The sensor resolution is estimated to be 2.6×10(-6) RIU in measuring solutions of various refractive indices. The sensing system can perform multiple measurements simultaneously and its limit of detection for anti-DNP antibody and streptavidin is 1.2×10(-10) g/ml (0.55 pM) and 2.3×10(-10) g/ml (3.5 pM), respectively. Accurate determination of these analytes with known concentration spiked in artificial urine were examined and the bias is less than ±7%, supporting the utility of the device for analyte screening in more complex media. The TW-PPR sensor can be inexpensively fabricated and has a special niche for monitoring biomolecular interactions in real-time, hence it is ideally suitable for disposable uses, especially promising for convenient high-throughput biochemical sensing applications.

Multiple resonance fiber-optic sensor with time division multiplexing for multianalyte detection.

A proof-of-concept multiwindow fiber-optic sensor utilizing multiple particle plasmon resonance (PPR) of silver nanoparticles and gold nanorods separately on two unclad portions of the fiber for multianalyte detection is demonstrated. The detection is based on intensity interrogation of multiple wavelengths by a single detector. Time division multiplexing is employed to modulate the illumination of dual-wavelength LEDs to induce PPRs for simultaneous real-time and label-free monitoring of two types of biomolecular interactions. Preliminary results reveal that a refractive index resolution of 9 ×10(-6) RIU is achieved. Moreover, the measured intensities of two windows independently respond to their respective binding events. The potential of the sensor architecture with multiple sensing windows for cascaded, higher throughput, and multianalyte biochemical detection can be expected.

Efficiency of DNA transfection of rat heart myoblast cells H9c2(2-1) by either polyethyleneimine or electroporation.

Expression of exogenous DNA in vitro is significantly affected by the particular transfection method utilized. In this study, we evaluated the efficiency of two transfection methods, chemically mediated polyethyleneimine (PEI) treatment and physically mediated electroporation, on a rat heart myoblast cell line, H9c2(2-1). After PEI transfection of pPgk-1/EGFP into H9c2(2-1) cells, EGFP expression could be easily detected by fluorospectrometer after 48 h (210 ± 12 RFU) and continued to increase after 72 h (243 ± 14 RFU). However, when H9c2(2-1) cells were transfected by electroporation (200 V, 500 µF, and one pulse), low level EGFP expression was observed after 48 h (49 ± 4 RFU) or 72 h (21 ± 14 RFU). In contrast, the easily transfectable control CHO-K1 cell line displayed a stronger EGFP expression than the H9c2(2-1) cells either by PEI or electroporation transfection. When transfection efficiencies were assayed by flow cytometry after 72 h, 13.6 ± 2.2% of PEI and 10.1 ± 1.5% of electroporation (250 V, 500 µF, and two pulses) transfected cells of H9c2(2-1) expressed EGFP, and PEI-transfected cells appeared to be less damaged (viability 93.6%) as compared to electroporation-transfected cells (39.5%). However, both PEI and electroporation (580 V, 50 Ω, and 50 µF) were effective for transfection of CHO-K1 with a higher efficiency, cell viability, and EGFP expression than H9c2(2-1). Our results indicate that the transfection efficiency of different methods varies among cell lines and that PEI is more efficient than electropolation for transfection of H9c2(2-1) whereas both PEI and electroporation are suitable for CHO-K1 transfection.