Unveiling the antioxidant superiority of α-tocopherol: Implications for vitamin E nomenclature and classification.

Since the discovery of tocopherols a century ago, α-tocopherol has been distinguished for its unique biological functions. In this study, we aim to elucidate the unique characteristics of α-tocopherol from a chemical perspective. Utilizing density functional theory (DFT) calculations, we evaluated the thermodynamic and kinetic properties of tocopherols, tocotrienols and their oxidation products. Our findings highlight the superior thermodynamic and kinetic properties of α-tocopherol. Although tocopherol substrates generally exhibit similar reactivities, α-tocopherol is distinguished by a larger gap between the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) in intermediates, indicating a potential for greater energy release and favoring reaction progression. Moreover, α-tocopherol shows enhanced efficiency in quenching radical intermediates, especially when combined with vitamin C. All these dates provide valuable support for the naming of vitamin E.

Midbrain dopamine oxidation links ubiquitination of glutathione peroxidase 4 to ferroptosis of dopaminergic neurons.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the gradual loss of midbrain dopaminergic neurons in association with aggregation of α-synuclein. Oxidative damage has been widely implicated in this disease, though the mechanisms involved remain elusive. Here, we demonstrated that preferential accumulation of peroxidized phospholipids and loss of the antioxidant enzyme glutathione peroxidase 4 (GPX4) were responsible for vulnerability of midbrain dopaminergic neurons and progressive motor dysfunctions in a mouse model of PD. We also established a mechanism wherein iron-induced dopamine oxidation modified GPX4, thereby rendering it amenable to degradation via the ubiquitin-proteasome pathway. In conclusion, this study unraveled what we believe to be a novel pathway for dopaminergic neuron degeneration during PD pathogenesis, driven by dopamine-induced loss of antioxidant GPX4 activity.

Multiple sparganosis spinal infections mainly in the thoracic region: A case report.

BACKGROUND: Spinal infection with sparganosis is rarely seen, and multiple spinal infections with sparganosis in the thoracic spine have not been reported. CASE SUMMARY: In this case report, a 56-year old male patient suffered from back pain for 3 mo. Computed tomography examination of the thoracic spine showed bone destruction of the T4-5 vertebral body, as well as the right pedicle and lamina of T5. Magnetic resonance imaging showed high signals on T2W1 images and fat-suppressed images in the right vertebral body of T4-5 and the right pedicle and lamina of T5, a high signal in the vertebral canal, and similar high signals in the paravertebral and subcutaneous regions of the whole spine. Puncture biopsy showed sparganosis. Following definite diagnosis, the patient was treated with debridement of T4-5 infected lesions under a microscope, bone grafting and internal fixation. Postoperatively, the patient's back pain symptoms were significantly relieved; the incision healed after one-stage treatment, and albendazole antiparasitic treatment was administered. CONCLUSION: Puncture biopsy is the most reliable method to diagnose infection by sparganum. Removal of infected lesions under the microscope and albendazole for antiparasitic treatment are safe and effective.

(+)-Clausenamide protects against drug-induced liver injury by inhibiting hepatocyte ferroptosis.

Drug-induced liver injury is the major cause of acute liver failure. However, the underlying mechanisms seem to be multifaceted and remain poorly understood, resulting in few effective therapies. Here, we report a novel mechanism that contributes to acetaminophen-induced hepatotoxicity through the induction of ferroptosis, a distinctive form of programmed cell death. We subsequently identified therapies protective against acetaminophen-induced liver damage and found that (+)-clausenamide ((+)-CLA), an active alkaloid isolated from the leaves of Clausena lansium (Lour.) Skeels, inhibited acetaminophen-induced hepatocyte ferroptosis both in vivo and in vitro. Consistently, (+)-CLA significantly alleviated acetaminophen-induced or erastin-induced hepatic pathological damages, hepatic dysfunctions and excessive production of lipid peroxidation both in cultured hepatic cell lines and mouse liver. Furthermore, treatment with (+)-CLA reduced the mRNA level of prostaglandin endoperoxide synthase 2 while it increased the protein level of glutathione peroxidase 4 in hepatocytes and mouse liver, confirming that the inhibition of ferroptosis contributes to the protective effect of (+)-CLA on drug-induced liver damage. We further revealed that (+)-CLA specifically reacted with the Cys-151 residue of Keap1, which blocked Nrf2 ubiquitylation and resulted in an increased Nrf2 stability, thereby leading to the activation of the Keap1-Nrf2 pathway to prevent drug-induced hepatocyte ferroptosis. Our studies illustrate the innovative mechanisms of acetaminophen-induced liver damage and present a novel intervention strategy to treat drug overdose by using (+)-CLA.

Compensatory Mechanism of Maintaining the Sagittal Balance in Degenerative Lumbar Scoliosis Patients with Different Pelvic Incidence.

OBJECTIVE: To investigate the compensatory mechanism of maintaining the sagittal balance in degenerative lumbar scoliosis patients with different pelvic incidence (PI). METHODS: This was a retrospective imaging observation study. Patients in our department with degenerative lumbar scoliosis between 2017 and 2019 were reviewed. A total of 36 patients were eligible and included in the present study. The average age of those patients was 64.22 years, including 8 men and 28 women. The coronal and sagittal parameters were measured on full-length spine X-ray film, including globe kyphosis (GK), lumber lordosis (LL), thoracolumbar kyphosis (TLK), thoracic kyphosis (TK), sagittal vertical axis (SVA), sagittal shift angle, Cobb angle, coronal shift angle, and vertebra. The anterior pelvic plane angle (APPA) and pelvic parameters were also measured, including the pelvic tilt (PT), the PI, and the sacral slope (SS). PI-LL, LL-SS, and GK-SS were calculated. Traditional pelvic tilt was also calculated using the following formula: cPT = PI × 0.37-7. These patients were divided into two groups according to their PI values. The patients' PI value in Group 1 was smaller than 50°. The patients' PI value in Group 2 was equal to or larger than 50°. RESULTS: These patients' SS, PT, PI, LL, TLK, TK, and GK were 28.70° ± 11.36°, 23.28° ± 6.55°, 52.00° ± 11.03°, 31.66° ± 14.12°, 12.12° ± 14.9°, 17.81° ± 13.53°, and -13.17° ± 16.27°. The sagittal shift angle, the APPA, the Cobb angle, the coronal shift angle, vertebra, PI-LL, cPT, APPA-4, LL-SS, and GK-SS were 4.38° ± 5.75°, -12.55° ± 8.83°, 30.03° ± 12.59°, 2.40° ± 2.13°, 4.08 ± 0.93, 19.86° ± 10.97°, 12.35° ± 4.55°, -8.30° ± 9.07°, 3.30° ± 8.82°, and 15.53° ± 9.83°, respectively. There was no significant difference between PT and cPT + APPA-4 or between cPT and PT-APPA+4. There was significant difference between PT and cPT + APPA or between cPT and PT-APPA. This demonstrated that the APPA-4 is reliable as degree of the pelvic sagittal retroversion. There were significant differences in SS, PI, LL, TLK, GK, APPA, PT-APPA, PT-APPA+4, cPT, and APPA-4 between Group 1 and Group 2. There were no significant differences in PT, TK, sagittal shift angle, SVA, Cobb angle, coronal shift angle, vertebra number, PI-LL, cPT + APPA, cPT + APPA-4, LL-SS, and GK-SS between Group 1 and Group 2. The Pearson tests showed that PI-LL had significant correlations with TK, LL, sagittal shift angle, SVA, and LL-SS. There was no significant correlation between PI-LL and Cobb angle, GK, TLK, APPA, vertebra, Coronal Shift Angle, or GK-SS. CONCLUSION: The APPA-4 is reliable as degree of the pelvic sagittal retroversion. In degenerative lumbar scoliosis, patients with smaller PI tended to rely more on the pelvic retroversion to maintain the sagittal balance than patients with larger PI, or patients with smaller PI were likely to start up the pelvic retroversion compensatory mechanism earlier than the patients with larger PI.

Tianma Gouteng granules decreases the susceptibility of Parkinson's disease by inhibiting ALOX15-mediated lipid peroxidation.

ETHNOPHARMACOLOGICAL RELEVANCE: Tianma Gouteng granules (TG), a clinical prescription of traditional Chinese medicine, has been clinically applied to treat Parkinson's disease (PD) in combination with Madopar, as included in the Chinese Pharmacopoeia (2015). TG has the potential to decrease the susceptibility of PD pharmacologically, however the mechanisms need detailed demonstration. AIM OF THE STUDY: To evaluate the pharmacological activities, as well as the possible mechanism of TG in diverse models of PD. MATERIALS AND METHODS: 6-OHDA-treated rats, MPTP-treated mice, and α-synuclein A53T overexpressed mice, were utilized as PD animal models. Rotarod, locomotor activity, inclined plane and traction tests were used for behavioral assessment. Immunohistochemistry was used for tyrosine hydrolase determination. Western blot were conducted for detection of 4-HNE and 15-lipoxygenase-1 (ALOX15). The interactions of ALOX15 with the components in TG were predicted by molecular docking approach. RESULTS: Lipid peroxidation was involved in dopaminergic neuron damage in 6-OHDA-induced rat models. In MPTP-treated mice, the inhibition of lipid peroxidation improved behavioral and pathological symptoms of PD. The lipid peroxidation-related protein, ALOX15 was found to be the key factor in PD process in diverse PD models including 6-OHDA-treated rats, MPTP-treated mice, and α-synuclein A53T overexpressed mice. TG treatment significantly relieved behavioral and pathological symptoms of MPTP-induced PD mouse models with a potential mechanism of alleviating ALOX15-induced lipid peroxidation. Moreover, the results of molecular docking analysis show that compounds in TG might have interactions with ALOX15. CONCLUSIONS: TG effectively improved the behavioral and dopaminergic neuron damage in diverse PD models. The mechanism of this action may be related to the direct inhibition of ALOX15 and the relief of lipid peroxidation.

Identification of Serum Exosomal MicroRNA Expression Profiling in Menopausal Females with Osteoporosis by High-throughput Sequencing.

Estrogen deficiency, which mainly occurs in postmenopausal women, is a primary reason for osteoporosis in clinical diagnosis. However, the molecular regulation of osteoporosis in menopausal females is still not adequately explained in the literature, with the diagnosis and treatment for osteoporosis being limited. Herein, exosomal microRNAs (miRNAs) were used to evaluate their diagnosis and prediction effects in menopausal females with osteoporosis. In this study, 6 menopausal females without osteoporosis and 12 menopausal females with osteoporosis were enrolled. The serum exosomes were isolated, and the miRNA expression was detected by miRNA high-throughput sequencing. Exosomal miRNA effects were analyzed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. The miRNA-targeted genes were evaluated by Targetscan 7.2 and the protein-protein interactions (PPI) by STRING. Hub genes were analyzed by the CytoHubba app of Cytoscape. The results showed that 191 aberrant miRNAs were found in the group of menopausal females with osteoporosis, including 72 upregulated miRNAs and 121 downregulated miRNAs. Aberrant miRNAs were involved in many signaling pathways, such as the Wnt, MAPK, and Hippo pathways. Based on PPI network analysis, FBXL3, FBXL13, COPS2, UBE2D3, DCUN1D1, DCUN1D4, CUL3, FBXO22, ASB6, and COMMD2 were the 10 most notable genes in the PPI network. In conclusion, aberrant serum exosomal miRNAs were associated with an altered risk of osteoporosis in menopausal females and may act as potential biomarkers for the prediction of risk of osteoporosis in menopausal females.

Evaluation of the chemical composition of nephrolithiasis using dual-energy CT in Southern Chinese gout patients.

BACKGROUND: A study to evaluate the prevalence of uric acid (UA) nephrolithiasis with dual-energy CT (DECT) and explore the risk factors for kidney stones in primary gout patients. METHODS: Eighty-four consecutive gout patients underwent urinary tract ultrasonography or DECT to confirm the existence of kidney stones. Urine and blood samples were also taken for laboratory analysis. RESULTS: Forty-one subjects (48.8%) had nephrolithiasis diagnosed; 38 had a kidney stone. Thirty-two of the 38 patients underwent a DECT scan, and 27 patients had nephrolithiasis in DECT. Among them, 63.0% (17/27) and 14.8% (4/21) of the patients had pure UA and UA-based mixed stone, respectively, and 22.2% (6/27) had a non-UA stone. Those with nephrolithiasis suffered from more frequent acute attacks and had longer disease durations of gout. At least one urine biochemical abnormality was found in 81% of patients. Forty-four (55.0%) patients presented hypomagnesuria. Forty-three (51.8%) patients had low urine volume. Unduly acidic urine (UAU) was present in 36 patients (44.4%). Hyperuricosuria was only found in ten (12.2%) patients. In comparison to the non-lithiasic group, the lithiasic group was more likely to have a UAU. Binary logistic regression showed that female gender was a protective factor, while disease duration of gout and low urine pH were risk factors for nephrolithiasis. CONCLUSION: Our results indicated that nephrolithiasis, especially UA stones, were more common than previous reports in gout patients indicated, and that disease duration of gout, and low urine pH, were risk factors for nephrolithiasis.

[Efficacy of intramedullary and extramedullary decompression and lavage therapy under microscope for treatment of chronic cervical spinal cord injury].

OBJECTIVE: To analyze the clinical effect of spinal cord decompression and lavage therapy on chronic cervical spinal cord injury and explore the possible mechanism. METHODS: Fifty-seven patients with chronic cervical spinal cord injury treated in our hospital from January, 2008 to January, 2015 were enrolled, including 17 with multilevel cervical disc herniation, 25 with long segmental ossification of the posterior longitudinal ligament, 13 with hypertrophy or calcification of neck ligamentum flavum, and 2 with old cervical fractures. Open-door spinal canal laminoplasty via a posterior approach and decompression in simple extramedullary decompression was performed in 31 cases (group A), and open-door spinal cord incision decompression via a posterior approach, saline irrigation, and spinal canal laminoplasty in intramedullary decompression was performed in 26 cases (group B). The pre-operative cerebrospinal fluid in group B patients was collected to examine the inflammatory factors. All the patients were followed up and evaluated for pre- and postoperative JOA scores to calculate the improvement rate with regular examinations by X-ray, CT or MRI. RESULTS: Imaging examinations 2 weeks after the operation showed obvious relief of the primary lesion in both groups, and the improvement of high signals was better in group B than in group A. The mean improvement rate at 12 months after the operation was 52.33% in group A and 61.52% in group B (P<0.05), and the mean JOA score was significantly higher in group B than in group A (14.80∓1.51 vs 13.58∓0.56; P<0.05). Cerebrospinal fluid leakage occurred in 3 cases, epidural hematoma in 2 cases, internal fixation loosening in 1 case in group A; portal shaft fracture and internal fixation loosening occurred in 1 case in group B. Postoperative recovery time was shorter in group B and entered the platform phase in 3 months. The inflammatory factors IFN-γ, IL-17F, IL-6 and sCD40L were all significantly higher than the normal levels after spinal cord injury, and the increment of IL-6 was the most conspicuous (P<0.05). CONCLUSION: Intramedullary and extramedullary decompression can achieve better outcomes than extramedullary decompression in patients with chronic cervical cord injury. This may be related not only to relieving adhesions and secondary compression by cutting the dura under the microscope, but also to removal of local inflammatory factors.

[Efficacy of Shangbai ointment in alleviating pain in patients with acute ankle joint lateral collateral ligament injury: a randomized controlled trial].

OBJECTIVE: To investigate the effect of Shangbai ointment in relieving pain in patients with acute ankle joint lateral collateral ligament injury. METHODS: Fifty patients with unilateral ankle injury were randomized into Shangbai ointment treatment group and control group (n=25). The Visual Analog Scale (VAS) pain scores, ankle joint circumference, Kofoed score and self-rated lower limb function were recorded before and at 3, 7, and 14 days after the treatment. RESULTS: The baseline data were comparable between the two groups. The VAS pain score and swelling elimination in the treatment group were better than those in the control group at 3, 7, and 14 days after treatment; the Kofoed ankle score was higher in the treatment group than in the control group at 7 and 14 days after treatment. The patients in the treatment also reported better self-rated lower limb function than those in the control group at 7 and 14 days after the treatment. CONCLUSION: Shangbai ointment treatment can rapidly relieve pain in patients with acute ankle joint lateral collateral ligament injury and improve the functional scores of the joint.

[microRNA-181b promotes migration and invasion of osteosarcoma cells by targeting N-myc downstream regulated gene 2].

OBJECTIVE: To investigate the effects of miR-181b on the migration and invasion of osteosarcoma cells. METHODS: Three cultured osteosarcoma cell lines and MG-63 cells transfected with miR-181b inhibitor were examined for miR-181b expression using qRT-PCR analysis. The cell migration and invasion of the transfected cells were assessed with Transwell assay. The targets of miR-181b were predicted using a miRNA target prediction software and the results were verified with luciferase reporter assay. The target protein expression in osteosarcoma cells lines was determined by Western blotting, and the cell migration and invasion changes following inhibition of miR-181b or its target protein were assessed using Transwell assay. RESULTS: All the 3 osteosarcoma cells lines showed significantly up-regulated miR-181b expression. Inhibition of miR-181b expression obviously suppressed the migration and invasion of MG-63 cells. Based on luciferase reporter assay, N-myc downstream regulated gene 2 (NDRG2) was identified as the direct target gene of miR-181b, and inhibition of NDRG2 expression significantly reversed the effect of miR-181b on cell migration and invasion in MG-63 cells. CONCLUSION: miR-181b is over-expressed in osteosarcoma cells, and inhibition of miR-181b, which directly targets NDRG2, can suppress the migration and invasion of osteosarcoma cells.

Relationship between hWAPL polymorphisms and cervical cancer susceptibility.

PURPOSE: To analyze the correlation of the polymorphisms of human wing-apart like (hWAPL) gene (rs7083506 and rs11202058) with the susceptibility to cervical cancer. Besides, the relationship of haplotypes between the polymorphisms with cervical cancer susceptibility was analyzed. METHODS: Taqman probe genotyping method was adopted to detect the genotype distribution of hWAPL rs7083506 and rs11202058 polymorphisms in 117 cervical cancer patients and 128 healthy controls. Linkage disequilibrium and haplotypes were analyzed by Haploview software. χ(2) test was utilized to analyze the differences of genotype, allele and haplotype frequencies between the case and control groups. RESULTS: Correlation analysis of hWAPL rs7083506 and rs11202058 polymorphisms with cervical cancer susceptibility was based on the five genetic models. TT genotype of rs7083506 increased the susceptibility of cervical cancer in TT vs. CC model and TT vs. CT+TT model (OR=2.249, 95% CI=1.018-4.970; OR=2.287, 95% CI=1.069-4.896). For rs11202058, the A allele increased the cervical cancer susceptibility (A vs. G, OR=1.502, 95% CI=1.005-2.245). No significant correlation was observed between rs11202058 genotypes and cervical cancer susceptibility. We performed the haplotype analysis between the two polymorphisms, and found that T-A haplotype significantly correlated with cervical cancer, the susceptibility of cervical cancer increased to 1.78 times. CONCLUSIONS: Rs7083506 and rs11202058 polymorphisms of hWAPL and their haplotype T-A were associated with cervical cancer.

Efficacy of spinal pia mater incision and laminoplasty combined with internal fixation for old spinal cord injury / 中国医学科学杂志(英文版)

<p><b>OBJECTIVE</b>To evaluate the clinical efficacy of incising spinal pia mater to relieve pressure and unilateral open-door laminoplasty with internal screw fixation for treatment of the dated spinal cord injury.</p><p><b>METHODS</b>From March, 2009 to July, 2010, 16 cases with chronic cervical cord injury underwent spinal dura mater incision and unilateral open-door laminoplasty with internal screw fixation. Nerve functions of pre- and postoperation were evaluated by Frankel classification and the Japanese Orthopaedic Association (JOA) scale.The improvement rate of JOA score at the indicated time was recorded.</p><p><b>RESULTS</b>Postoperative Frankel classification rating of 16 patients improved obviously.JOA scores at the 1st month, 3rd month, 6th month, and 12th month after surgery were 7.9 ± 2.3, 8.5 ± 1.6, 8.9 ± 2.1, and 12.4 ± 2.5, respectively, and significantly increased compared with that prior to surgery (5.5 ± 0.6). At the end of follow-up period, JOA score was significantly higher than that of pre-treatment (P<0.05). The recovery was relatively rapid during the first 3 months following the surgery, then entered a platform period.</p><p><b>CONCLUSION</b>It is effective for patients with dated spinal cord injury to undergo spinal decompression and laminoplasty.</p>

[Application of titanium mesh in anterior cervical subtotal corpectomy with locking plate for cervical spondylotic myelopathy].

OBJECTIVE: To evaluate the clinical effect of titanium mesh in anterior cervical subtotal subcorpectomy with locking plate for treatment of cervical spondylotic myelopathy. METHODS: Thirty-eight patients with cervical spondylotic myelopathy were treated with anterior cervical subtotal corpectomy using titanium mesh and locking plate. The JOA score of the patients were assessed before and after the operation, and the pre- and postoperative lateral cervical radiographs were taken to observe the instability of the titanium mesh, dynamic plates and changes of the cervical curvature. RESULTS: The patients were followed up for 12-18 months. Radiographic cervical fusion was achieved in 12-16 months (36 cases) or 18 months (2 cases) postoperatively. The degree of Jordosis was improved and the height of the anterior spinal column and physical curvature were effectively maintained after the operation. The titanium mesh and locking plate showed no signs of loosening and the JOA scores was significantly improved after the operation (P<0.05). CONCLUSION: Titanium mesh in anterior cervical subtotal corpectomy with locking plate allows effective treatment of cervical spondylotic myelopathy, but the indications of this procedure must be carefully evaluated. The long-term effect of this approach still needs verification by further follow-up data.