Natural Product Quercetin-3-methyl ether Promotes Colorectal Cancer Cell Apoptosis by Downregulating Intracellular Polyamine Signaling.

Dysregulation of cellular metabolism is a key marker of cancer, and it is suggested that metabolism should be considered as a targeted weakness of colorectal cancer. Increased polyamine metabolism is a common metabolic change in tumors. Thus, targeting polyamine metabolism for anticancer therapy, particularly polyamine blockade therapy, has gradually become a hot topic. Quercetin-3-methyl ether is a natural compound existed in various plants with diverse biological activities like antioxidant and antiaging. Here, we reported that Quercetin-3-methyl ether inhibits colorectal cancer cell viability, and promotes apoptosis in a dose-dependent and time-dependent manner. Intriguingly, the polyamine levels, including spermidine and spermine, in colorectal cancer cells were reduced upon treatment of Quercetin-3-methyl ether. This is likely resulted from the downregulation of SMOX, a key enzyme in polyamine metabolism that catalyzes the oxidation of spermine to spermidine. These findings suggest Quercetin-3-methyl ether decreases cellular polyamine level by suppressing SMOX expression, thereby inducing colorectal cancer cell apoptosis. Our results also reveal a correlation between the anti-tumor activity of Quercetin-3-methyl ether and the polyamine metabolism modulation, which may provide new insights into a better understanding of the pharmacological activity of Quercetin-3-methyl ether and how it reprograms cellular polyamine metabolism.

One-pot co-crystallized hexanal-loaded ZIF-8/quaternized chitosan film for temperature-responsive ethylene inhibition and climacteric fruit preservation.

Controlling ethylene production and microbial infection are key factors to prolong the shelf life of climacteric fruit. Herein, a nanocomposite film, hexanal-loaded ZIF-8/CS (HZCF) with "nano-barrier" structure, was developed by a one-pot co-crystallized of ZIF-8 in situ growth on quaternized chitosan (CS) and encapsulation of hexanal into ZIF-8 via microporous adsorption. The resultant film realized the temperature responsive release of hexanal via the steric hindrance and hierarchical pore structure as "nano-barrier", which can inhibit ethylene production in climacteric fruit on demand. Based on this, the maximum ethylene inhibition rate of HZCF was up to 52.6 %. Meanwhile, the film exhibits excellent antibacterial, mechanical, UV resistance and water retention properties, by virtue of the functional synergy between ZIF-8 and CS. Contributed to the multifunctional features, HZCF prolonged the shelf life of banana and mango for at least 16 days, which is 8 days longer than that of control fruit. More strikingly, HZCF is washable and biodegradable, which is expected to replace non-degradable plastic film. Thus, this study provides a convenient novel approach to simplify the encapsulation of active molecule on metal-organic frameworks (MOFs), develops a packaging material for high-efficient freshness preservation, and helps to alleviate the survival crisis caused by food waste.

Gait function assessed using 3D gait analysis in patients with cervical spinal myelopathy before and after surgical decompression: a systematic review and meta-analysis.

BACKGROUND: Degenerative cervical myelopathy (DCM) is the most common cause of cervical spinal cord dysfunction in adults and the result of chronic degenerative changes of the cervical spine. The compression of the spinal cord can lead to ischemia, inflammation, and neuronal apoptosis with a consequent impairment of the neurological function. Gait impairment is one of the most frequent signs of DCM. PURPOSE: To investigate the changes in spatio-temporal gait parameters assessed using 3D gait analysis in patients affected by DCM compared with healthy controls and the effect of surgical decompression on these parameters. STUDY DESIGN/SETTING: Systematic review and meta-analysis. PATIENT SAMPLE: The meta-analysis included 267 patients with DCM and 276 healthy controls. OUTCOME MEASURES: Spatio-temporal parameters of gait were assessed. The primary outcome was gait speed; the secondary outcomes were cadence, stride length, step width, stride time, single-limb support time, and double-limb support time. METHODS: Studies reporting spatial and/or temporal gait parameters measured using 3D gait analysis in patients with DCM were included. Data sources were Embase, Medline, and the Core Collection of Web of Science. Meta-analyses were performed to investigate the influence of surgical decompression in patients measured before and after surgery as well as to compare gait parameters of patients with DCM with controls. RESULTS: Thirteen studies reporting on 267 patients with DCM and 276 healthy controls met the inclusion criteria. Seven studies compared patients with DCM with healthy controls, three studies compared gait in patients with DCM before and after surgical decompression, and three studies performed both comparisons. Compared with healthy controls, patients with DCM had slower gait speed (Standardized Mean Difference (SMD), -1.49; 95% confidence interval (CI) [-1.86; -1.13]; p<.001), lower cadence (SMD, -0.78; 95%CI [-1.00; -0.56]; p<.001), shorter stride length (SMD, -1.27; 95%CI [-1.53, -1.01]; p<.001), greater step width (SMD, 0.98; 95%CI [0.42, 1.54]; p=.003), longer stride time (SMD, 0.77; 95%CI [0.37, 1.16]; p=.009), single-limb support phase (SMD, -0.68; 95%CI [-1.06; -0.29]; p=.011), and double-limb support phase (SMD 0.84; 95%CI [0.35, 1.32]; p=.012). After surgical decompression, patients with DCM showed an improvement in gait speed (SMD, 0.57 (95%CI [0.29; 0.85]; p=.003) and no significant differences in other spatio-temporal parameters. CONCLUSIONS: Patients with DCM have clearly different spatio-temporal gait parameters than healthy controls. Gait speed is the only spatio-temporal gait parameter that improves significantly after surgical decompression suggesting that gait speed may be an important clinical outcome parameter in patients with DCM.

Is Age a Risk Factor for Early Postoperative Cage Subsidence After Transforaminal Lumbar Interbody Fusion? A Retrospective Study in 170 Patients.

STUDY DESIGN: Retrospective observational study. OBJECTIVES: We aim to evaluate whether age is a risk factor for cage subsidence, and whether other patient characteristics, preoperative radiological or imaging parameters are associated with cage subsidence and the need for revision surgery in patients undergoing transforaminal lumbar interbody fusion (TLIF). METHODS: Patient demographics and surgery-related information were extracted. Cage subsidence was evaluated using upright standing sagittal plane X-rays and defined as more than 2 mm migration of the cage into the adjacent vertebral body. Patients who received revision surgery within 1 year for any reason were recorded. Radiographic parameters were measured. Univariable logistic regression models were used to evaluate the risk factors for cage subsidence and need for revision surgery. RESULTS: At 3-month and 1-year follow-up, cage subsidence was observed in 28 patients (16.5%) and 58 patients (34.1%), respectively. Twenty-seven patients received revision surgery within the first year after TLIF. Age (odds ratio (OR): 1.07 per year) and male sex (OR: 2.76) had a significantly increased odds ratio for cage subsidence 3 months after TLIF. Male sex (OR: 2.55) but not age was a significant risk factor for cage subsidence 1 year after TLIF. Of all assessed risk factors, only BMI (OR: 1.11 per kg/m2) had a significantly increased risk for the need of revision surgery. CONCLUSIONS: Age was associated with cage subsidence 3 months but not 1 year after TLIF suggesting that age is only a risk factor for early cage subsidence and not in a longer follow-up.

Radiographic study of peak velocity of pelvic incidence in adolescent idiopathic scoliosis.

BACKGROUND: Pelvic incidence (PI), a parameter related to the ideal spinopelvic alignment, is a morphological parameter that is usually considered fixed, but the PI's growth during adolescence has been reported. We investigated the peak PI velocity during adolescence and describe the relationship between increasing PI and changes in the morphology of the pelvis and sacrum. METHODS: We measured standing height (SH) and radiological anatomical parameters including pelvic height (PH), pelvic width (PW), sacral width (SW), femoral head-sacrum (FH-S), sacrum-coccyx (S-C) length, and S-C distance at each follow-up of 76 adolescent idiopathic scoliosis (AIS) patients. ΔParameter was the difference between the next measurement and the previous one. Growth velocity was ΔParameter divided by time interval. All ΔParameters were compared between different Risser stages using repeated-measures analysis of variance (ANOVA). The Pearson coefficients of correlation were calculated to assess the relationships between PI and ΔParameters. RESULTS: PI reached peak growth with a 1.6°/year growth in females and 1.8°/year in males at Risser stage 1. PI tended to grow rapidly with Risser 0 and closed triradiate cartilage (female: 1.3°/year and male: 1.4°/year) and to slow down at Risser 2 (female: 1.2°/year and male: 1.3°/year). ΔPI strongly correlated with ΔFH-S (R>0.508, P<0.05) and also correlated with ΔSH, ΔPH, ΔPW, ΔSW, and ΔS-C length (R>0.192, P<0.05) but not correlated with ΔS-C distance and ΔS-C ratio. CONCLUSIONS: In patients with AIS, the peak PI velocity is at Risser 1, and it is still increasing at Risser 5. Our result suggested that the growth of the PI may be associated with SH and changing pelvic morphology during skeletal growth of adolescence.

Assessing Fatty Infiltration of Paraspinal Muscles in Patients With Lumbar Spinal Stenosis: Goutallier Classification and Quantitative MRI Measurements.

Objective: Fatty infiltration of paraspinal muscle is associated with spinal disorders. It can be assessed qualitatively (i.e., Goutallier classification) and quantitatively using image processing software. The aims of this study were to compare paraspinal muscle fatty infiltration as assessed using the Goutallier classification vs. quantitative magnetic resonance images (MRI) measurements and to investigate the association between anthropometric parameters and paraspinal muscle morphology and fatty infiltration in patients with symptomatic lumbar spinal stenosis (LSS). Methods: Patients affected by symptomatic LSS scheduled for surgery with available MRI of the lumbar spine were included in this retrospective cross-sectional study. Fatty infiltration at each lumbar level was rated qualitatively according to the Goutallier classification and quantified based on the cross-sectional area (CSA) of the paraspinal muscle, of its lean fraction (LeanCSA), and the ratio between LeanCSA and CSA and the CSA relative to the CSA of vertebral body (RCSA). Considering the muscle as a single unit, overall fatty infiltration according to Goutallier, overall CSA, LeanCSA, LeanCSA/CSA, and RCSA were computed as averages (aGoutallier, aCSA, aLeanCSA, aLeanCSA/aCSA, and aRCSA). Associations among parameters were assessed using Spearman's respective Pearson's correlation coefficients. Results: Eighteen patients, with a mean age of 71.3 years, were included. aGoutallier correlated strongly with aLeanCSA and aLeanCSA/aCSA (R = -0.673 and R = -0.754, both P < 0.001). There was a very strong correlation between values of the left and right sides for CSA (R = 0.956, P < 0.001), LeanCSA (R = 0.900, P < 0.001), and LeanCSA/CSA (R = 0.827, P < 0.001) at all levels. Among all anthropometric measurements, paraspinal muscle CSA correlated the most with height (left: R = 0.737, P < 0.001; right: R = 0.700, P < 0.001), while there was a moderate correlation between vertebral body CSA and paraspinal muscle CSA (left: R = 0.448, P < 0.001; right: R = 0.454, P < 0.001). Paraspinal muscle CSA correlated moderately with body mass index (BMI; left: R = 0.423, P < 0.001; right: R = 0.436, P < 0.001), and there was no significant correlation between aLeanCSA or aLeanCSA/CSA and BMI. Conclusions: The Goutallier classification is a reliable yet efficient tool for assessing fatty infiltration of paraspinal muscles in patients with symptomatic LSS. We suggest taking body height as a reference for normalization in future studies assessing paraspinal muscle atrophy and fatty infiltration.

Cervical vertebral maturation (CVM) stage as a supplementary indicator for the assessment of peak height velocity (PHV) in adolescent idiopathic scoliosis (AIS).

BACKGROUND: Radiographic methods in evaluating the skeletal maturity include Risser sign and Tanner-Whitehouse score. They are either inappropriate or too complex for a busy clinic setting. The cervical vertebral maturation (CVM) stage is commonly used in orthodontics but has been less acknowledged in studies of spinal growth. The purpose of this study was to evaluate whether the CVM stage could be used as an alternative to Risser sign in determining peak height velocity (PHV). METHODS: This was a two-stage study. Inclusion criteria for stage I study were adolescent female idiopathic scoliosis (AIS) patients, aged between 9-16 years old, who had undergone full spine imaging with clear visibility of the cervical spine. Patients in the stage II study had follow-up through CVM stage 2-4. The correlation between CVM and Risser was analyzed. The spinal growth parameters were measured at each follow-up, and the growth velocity of parameters (PaGVs) was calculated. The PaGVs at CVM stage 2-4 were further compared. RESULTS: A total of 170 AIS patients were included for stage I study (mean age 12.7 years). The CVM stages were found to correlate strongly with the Risser sign (r=0.85, P<0.01). For those patients with Risser stage 0 with closed TC, 71% were CVM stage 3. Fifty-one patients were included for stage II study. The stature growth velocity averaged 5.4 cm/year in CVM stage 2 patients and 6.3 cm/year in CVM stage 3 patients, which was significantly greater growth than that in CVM stage 4 patients (3.3 cm/year, both P<0.01); similarly, the growth velocity of arm span, trunk height, and spinal lengths were also significantly higher in CVM stage 3 patients compared to CVM stage 2 and 4 patients. CONCLUSIONS: The CVM stage could provide an alternative option for the assessment of skeletal maturity of subjects with idiopathic scoliosis. CVM stage 3 may be a new sign of PHV.

Elastin-Based Thermoresponsive Shape-Memory Hydrogels.

A shape-memory hydrogel is a programmable hydrogel material that can store specific shapes and execute functions in response to stimuli. In this report, we developed shape-memory hydrogels by creating double-network polymeric structures using a physically cross-linking elastin-like polypeptide (ELP) and a chemically cross-linking polyacrylamide (PAM). We synthesized the hydrogel matrix by polymerizing the acrylamide mixed in an ELP solution. We exploited the lower critical solution temperature transition of the ELP to enable the hydrogel to hold a new desired shape at an elevated temperature of 55 °C. The original shape of the hydrogel can then be recovered by lowering the temperature to 20 °C. The shape-memory hydrogels we developed exhibit ultrafast functionality and high repeatability. Taking advantage of the temperature-induced shape-memory capability, we also demonstrate practical functions such as gripping an object and connecting two tubes. Our materials with effective temperature-driven shape-memory functionality will be useful for developing novel materials for biomedical applications in the future.

Sequential correction technique to avoid postoperative global coronal decompensation in rigid adult spinal deformity: a technical note and preliminary results.

PURPOSE: This study aims to evaluate this new sequential correction technique for preventing postoperative coronal imbalance. METHODS: Adult Spinal deformity (ASD) patients were stratifies into two types: primary thoracolumbar/lumbar (TL/L) curve with compensatory lumbosacral (LS) curve (Type I) and primary LS curve with compensatory TL/L curve (Type II): for Type I patients: correction of major TL/L curve and one- or two-level segmental rod installed at the convexity of the TL/L curve, L4-S1 TLIF to correct fractional curve and a short rod installed on the contralateral side and installation of long rods; for Type II patients: horizontalize L4 and L5, short rod installation at the convexity of the LS curve, distraction of curve with regional rod and installation of long rods. ASD patients were enrolled with inclusion criteria: with pre-op TL/L Cobb angle more than 30°, with pelvic fixation and with UIV over T10. Radiographic parameters were analyzed. RESULTS: Twenty-one patients were recruited (14 patients Type I and 7 Type II patients). Both Cobb angle and coronal offset were significantly improved after surgery. In Type I patients, Cobb angle was improved from 50.48° to 26.91° and coronal offset from 2.94 to 0.95 cm; in Type II patients, Cobb angle was improved from 61.42° to 28.48° and coronal offset from 2.82 to 1.38 cm. In the 10 patients with baseline coronal imbalance, 9 were corrected to coronal balance after surgery. CONCLUSION: The sequential correction technique allows decomposing the complex correction surgery into several steps, and each step focuses only on one task. It can also reduce the difficulty of rod installation due to the separated maneuvers and multi-rod system. LEVEL OF EVIDENCE: IV These slides can be retrieved under Electronic Supplementary Material.

Could pelvic parameters determine optimal postoperative thoracic kyphosis in Lenke type 1 AIS patients?

BACKGROUND: A proper restoration of sagittal alignment is essential in AIS patients, but few studies provided a formula to predict an optimal surgical thoracic kyphosis (TK) gain in adolescent idiopathic scoliosis (AIS) patients. A formula was recently proposed (LL = (PI+TK)/2 + 10) to predict the optimal lumbar lordosis (LL) in adult spinal deformity patients, which has not been validated in adolescents. The aim of this study is to establish a formula with TK and pelvic parameters in normal adolescents and predict an optimal TK with this formula pre- and post-operatively in Lenke 1 AIS patients. METHODS: A total of 60 asymptomatic adolescents were used to validate the proposed formula. The subject was considered to match with the formula, if the difference between the virtual TK and the theoretical TK was less than 10°. Then regression analysis was performed to establish a new formula to predict TK in adolescents. The predictive efficiency of the new formula was also validated in 40 Lenke 1 AIS patients. RESULTS: Of the 60 asymptomatic adolescents, only 26 (43.33%) asymptomatic adolescents matched with the adjusted formula: TK = 2 × (LL-10)-PI. The paired t test revealed a significantly different theoretical TK (tTK) compared to the virtual TK (41.23 ± 18.29° vs. 24.80 ± 8.75°, P < 0.001). Multiple linear regression showed that TK had a relationship with LL, SS and age (R2 = 0.331): TK = - 0.785 × LL-0.843 × SS + 0.858 × age + 3.754. There were 27 (67.50%), 32 (80.00%) and 35 (87.50%) Lenke 1 AIS patients matched this formula preoperatively, postoperatively and at the last follow-up. CONCLUSION: Our results revealed that the predictive formula for sagittal alignment for adults was not applicable in adolescents. This study established a new predictive formula for TK based on asymptomatic adolescents. In Lenke 1 AIS patients, post-op TK in 87.5% of patients matched the predictive value, indicating that the new formula can be considered as a reference when making a surgery strategy.

High level of homeobox A9 and PBX homeobox 3 expression in gastric cancer correlates with poor prognosis.

The homeobox protein homeobox (HOXA9) is a transcriptional factor that regulates patterning during embryogenesis and controls cell differentiation. HOXA9 dysfunction has been implicated in certain cancers. However, the role of HOXA9 in gastric cancer is poorly understood. The present study investigated HOXA9 and its cofactor PBX homeobox 3 (PBX3) expression in patients with gastric cancer. Paired tissue samples from 24 patients and paraffin embedded tissues of gastric cancer patients (104 males and 24 females) were included. HOXA9 and PBX3 expression levels were determined by reverse transcription quantitative polymerase chain reaction in fresh tissues, and by immunohistochemical staining in paraffin embedded tissues. The association between HOXA9/PBX3 expression and clinicopathological features was established. The results demonstrated that HOXA9 and PBX3 mRNA levels were significantly upregulated (P=0.032 for HOXA9 and P=0.031 for PBX3) in gastric cancer tissue. Immunohistochemical staining revealed that HOXA9 expression was associated with differentiation, lymph node metastasis and tumor-node-metastasis (TNM) stage, and PBX3 expression was associated with lymph node metastasis and TNM stage. Correlation analysis revealed a high coincidental expression of HOXA9 and PBX3 levels in gastric cancer (r=0.391; P<0.001). Survival analysis showed that high expression of HOXA9 or PBX3 was associated with poor survival of gastric cancer, and multivariate analysis using Cox's regression model showed that PBX3 expression was an independent prognostic factor in gastric cancer. There was elevated expression of HOXA9 and PBX3 in gastric cancer patients, and high-level expression of those proteins was associated with poor prognosis of gastric cancer. The present study underlines the significance of HOXA9/PBX3 in the development of gastric cancer.