Mitochondrial ACSS1-K635 acetylation knock-in mice exhibit altered metabolism, cell senescence, and nonalcoholic fatty liver disease.

Acetyl-CoA synthetase short-chain family member 1 (ACSS1) uses acetate to generate mitochondrial acetyl-CoA and is regulated by deacetylation by sirtuin 3. We generated an ACSS1-acetylation (Ac) mimic mouse, where lysine-635 was mutated to glutamine (K635Q). Male Acss1K635Q/K635Q mice were smaller with higher metabolic rate and blood acetate and decreased liver/serum ATP and lactate levels. After a 48-hour fast, Acss1K635Q/K635Q mice presented hypothermia and liver aberrations, including enlargement, discoloration, lipid droplet accumulation, and microsteatosis, consistent with nonalcoholic fatty liver disease (NAFLD). RNA sequencing analysis suggested dysregulation of fatty acid metabolism, cellular senescence, and hepatic steatosis networks, consistent with NAFLD. Fasted Acss1K635Q/K635Q mouse livers showed increased fatty acid synthase (FASN) and stearoyl-CoA desaturase 1 (SCD1), both associated with NAFLD, and increased carbohydrate response element-binding protein binding to Fasn and Scd1 enhancer regions. Last, liver lipidomics showed elevated ceramide, lysophosphatidylethanolamine, and lysophosphatidylcholine, all associated with NAFLD. Thus, we propose that ACSS1-K635-Ac dysregulation leads to aberrant lipid metabolism, cellular senescence, and NAFLD.

Injectable self-assembled GDF5-containing dipeptide hydrogels for enhanced tendon repair.

Owing to the tissue characteristics of tendons with few blood vessels and cells, the regeneration and repair of injured tendons can present a considerable challenge, which considerably affects the motor function of limbs and leads to serious physical and mental pain, along with an economic burden on patients. Herein, we designed and fabricated a dipeptide hydrogel (DPH) using polypeptides P11-4 and P11-8. This hydrogel exhibited self-assembly characteristics and could be administered in vitro. To endow the hydrogel with differentiation and regeneration abilities, we added different concentrations of growth differentiation factor 5 (GDF5) to form GDF5@DPH. GDF5@DPH promoted the aggregation and differentiation of tendon stem/progenitor cells and promoted the regeneration and repair of tendon cells and collagen fibers in injured areas. In addition, GDF5@DPH inhibited inflammatory reactions in the injured area. Owing to its injectable properties, DPH can jointly inhibit adhesion and scar hyperplasia between tissues caused by endogenous inflammation and exogenous surgery and can provide a favorable internal environment for the regeneration and repair of the injured area. Overall, the GDF5@DPH system exhibits considerable promise as a novel approach to treating tendon injury.

Early result of percutaneous full-endoscopic transforaminal lumbar interbody fusion in the treatment of single-level lumbar degenerative diseases: a retrospective study.

OBJECTIVE: The study aimed to evaluate the short-term clinical efficacy of percutaneous full-endoscopic transforaminal lumbar interbody fusion (Endo-TLIF) for lumbar degenerative diseases (LDD). METHODS: From July 2020 to July 2021, 93 patients who underwent single-level lumbar fusion procedure were retrospective analysis. The patients were divided into Endo-TLIF group and transforaminal lumbar interbody fusion (TLIF) group. General demographic and perioperative data were recorded, the clinical outcomes were evaluated using visual analogue scale (VAS) and oswestry disability index (ODI). The disk height (DH) was compared between the two groups. RESULTS: All of the surgical procedures were successfully completed, and the patients were followed for a minimum of 2 years. Intraoperative blood loss, drainage volume, time to independent ambulation and hospital length of stay in the Endo-TLIF group were significantly decreased in comparison with the open TLIF group (p < 0.05). The VAS for back pain on postoperative 7 day and ODI on postoperative 1 month were lower in the Endo-TLIF group than in the open TLIF group (P < 0.05), but no significant difference at 1 year and 2 years postoperatively (P > 0.05). The VAS score of leg pain had no demographic statistically significant differences between the groups (P > 0.05). The DH were significantly heightened after surgery compared to the preoperative height (p < 0.05). CONCLUSION: Endo-TLIF is a minimally invasive, safety surgery which can achieve comparable short-term effects as open TLIF. It may be a promising option for the treatment of LDD.

Heterotopic mineralization (ossification or calcification) in aged musculoskeletal soft tissues: A new candidate marker for aging.

Aging can lead to various disorders in organisms and with the escalating impact of population aging, the incidence of age-related diseases is steadily increasing. As a major risk factor for chronic illnesses in humans, the prevention and postponement of aging have become focal points of research among numerous scientists. Aging biomarkers, which mirror molecular alterations at diverse levels in organs, tissues, and cells, can be used to monitor and evaluate biological changes associated with aging. Currently, aging biomarkers are primarily categorized into physiological traits, imaging characteristics, histological features, cellular-level alterations, and molecular-level changes that encompass the secretion of aging-related factors. However, in the context of the musculoskeletal soft tissue system, aging-related biological indicators primarily involve microscopic parameters at the cellular and molecular levels, resulting in inconvenience and uncertainty in the assessment of musculoskeletal soft tissue aging. To identify convenient and effective indicators, we conducted a comprehensive literature review to investigate the correlation between ectopic mineralization and age-related changes in the musculoskeletal soft tissue system. Here, we introduce the concept of ectopic mineralization as a macroscopic, reliable, and convenient biomarker for musculoskeletal soft tissue aging and present novel targets and strategies for the future management of age-related musculoskeletal soft tissue disorders.

Biomimetic Multimodal Receptors for Comprehensive Artificial Human Somatosensory System.

Electronic skin (e-skin) capable of acquiring environmental and physiological information has attracted interest for healthcare, robotics, and human-machine interaction. However, traditional 2D e-skin only allows for in-plane force sensing, which limits access to comprehensive stimulus feedback due to the lack of out-of-plane signal detection caused by its 3D structure. Here, a dimension-switchable bioinspired receptor is reported to achieve multimodal perception by exploiting film kirigami. It offers the detection of in-plane (pressure and bending) and out-of-plane (force and airflow) signals by dynamically inducing the opening and reclosing of sensing unit. The receptor's hygroscopic and thermoelectric properties enable the sensing of humidity and temperature. Meanwhile, the thermoelectric receptor can differentiate mechanical stimuli from temperature by the voltage. The development enables a wide range of sensory capabilities of traditional e-skin and expands the applications in real life.

Is unilateral-approach full-endoscopic lumbar fusion effective for single-level lumbar spondylolisthesis with bilateral symptoms? A preliminary report of 43 CT analysis.

PURPOSE: To investigate the clinical results and radiological parameters changes after unilateral-approach endoscopic lumbar interbody fusion (Endo-LIF) for lumbar spondylolisthesis with bilateral symptoms. METHODS: 43 single-level lumbar spondylolisthesis patients with bilateral lower limb symptoms were included from June 2020 to May 2022. All patients underwent unilateral-approach Endo-LIF and postoperative computed tomography. Radiological parameters including disk height (DH), degree of upper vertebral slip (DUVS), and foramen intervertebral parameters including bilateral foraminal height (FH), contralateral foraminal areas (FA) were evaluated. The clinical outcomes including low back pain and bilateral leg pain were evaluated using Visual Analog Scale (VAS) and the Oswestry Disability Index (ODI) before and after surgery. RESULTS: All cases were successfully completed surgery and followed for average 15.16 ± 5.2 months. DH (44% ± 11%) and DUVS were significantly improvement postoperatively compared with preoperatively (p < 0.05). Statistically significant increases in bilateral FH (25% ± 11% on the surgical side, 17% ± 8% on the contralateral side) and contralateral FA (26% ± 6%) were observed (p < 0.05). The VAS and the ODI scores were significantly decreased in comparison with the preoperative scores (p < 0.05). CONCLUSION: Unilateral-approach with contralateral indirect decompression in Endo-LIF can acquire satisfactory clinical outcomes. Therefore, unilateral-approach Endo-LIF may be a promising option for lumbar spondylolisthesis with bilateral symptoms.

Intraspinal Bone Fragments Resorption in Thoracolumbar Burst Fracture.

This case report describes a man in his 30s transported to a surgical ward with a 7-hour history of unintentional fall from over 20 m.

Ambient Pressure Drying of Freeze-Cast Ceramics from Aqueous Suspension.

Freeze-casting has been wildly exploited to construct porous ceramics but usually requires costly and demanding freeze-drying (high vacuum, size limit, and supercooled chamber), which can be avoided by the ambient pressure drying (APD) technique. However, applying APD to freeze-cast ceramic based on an aqueous suspension is still challenging due to inert surface chemistry. Herein, a modified APD strategy is developed to improve the drying process of freeze-cast ceramics by exploiting the simultaneous ice etching, ionic cross-linking, and solvent exchange under mild conditions (-10-0 °C, ambient pressure). This versatile strategy is applicable to various ceramic species, metal ions, and freezing techniques. The incorporated metal ions not only enhance liquid-phase sintering, producing ceramics with higher density and mechanical properties than freeze-cast counterparts, but also render customizable coloration and antibacterial property. The cost-/time-efficient APD is promising for mass production and even successive production of large-size freeze-cast ceramics that exceed the size of commercial freeze-dryers.

Which surgery is better for obese patients with lumbar degenerative diseases: open TLIF or Endo-LIF? A retrospective matched case-control study.

OBJECTIVE: This study aimed to evaluate short-term clinical efficacy of percutaneous endoscopic posterior lumbar interbody fusion (Endo-LIF) in the treatment of obese patients with lumbar degenerative diseases (LDD). METHODS: Patients who underwent single-level lumbar fusion surgery from July 2020 to July 2022 were retrospectively analyzed in this study. The main inclusion criterion was a body mass index (BMI) ≥30kg/m2. A matched case-control design was conducted to compare the short-term outcomes between the Endo-LIF and transforaminal lumbar interbody fusion (TLIF) in obese patients. Cases were defined as those who underwent Endo-LIF, and controls were matched from those patients with open TLIF according to corresponding matched criteria. Surgeon satisfaction was evaluated by questionnaires at the end of each surgery, patient satisfaction and their willingness to undergo the same surgery again were collected. RESULTS: Two groups of patients were successfully completed surgery. In comparison with the open TLIF group, the Endo-LIF group had significantly less blood loss, less time to postoperative ambulation, less postoperative complications and shorter hospitalization days, but longer operation time and x-ray exposure times. The satisfaction of surgeons and patients in Endo-LIF group significantly were superior to open TLIF group. CONCLUSION: Endo-LIF is a safe and effective surgery in the treatment of obese patients. Although this procedure needs longer operation time and x-ray exposure times, it still maybe a promising option for obese patients with LDD.

Body Mass Index and Physical Fitness among Chinese Adolescents Aged 15-18: A Cross-Sectional Study of Gender Differences.

OBJECTIVE: The aim of this study is to examine the relationship between varying levels of obesity and physical fitness test scores among Chinese adolescents, while also investigating gender differences in physical fitness and overall health. Data on height, weight, 50 m sprints, 1000/800 m runs, standing long jumps, sit and reach exercises, pull-ups/bent-leg sit-ups, and additional variables were collected from the DYH health database. Physical fitness indicators were evaluated based on the revised 2014 National Physical Fitness Standards for Students, and scores were assigned accordingly. An ordinal logistic regression (ologit) model was employed to analyze the relationship between body mass index (BMI) and physical fitness. RESULTS: (1) Normal-weight boys achieved significantly higher physical fitness test scores than boys in other weight categories. (2) Underweight and normal-weight girls obtained significantly higher physical fitness test scores compared to overweight and obese girls, with underweight girls scoring slightly higher than those with a normal weight. CONCLUSIONS: (1) There is a significant non-linear relationship between BMI levels and physical fitness test scores. (2) Gender differences were observed in physical fitness and overall health outcome. (3) The findings indicate an inverted U-shaped association between BMI and physical fitness among boys, while girls displayed an inverse relationship. This could be attributed to the cultural association between thinness and beauty among girls in China.

Superflexible Artificial Soft Wood.

Soft woods have attracted enormous interest due to their anisotropic cellular microstructure and unique flexibility. The conventional wood-like materials are usually subject to the conflict between the superflexibility and robustness. Inspired by the synergistic compositions of soft suberin and rigid lignin of cork wood which has good flexibility and mechanical robustness, an artificial soft wood is reported by freeze-casting the soft-in-rigid (rubber-in-resin) emulsions, where the carboxy nitrile rubber confers softness and rigid melamine resin provides stiffness. The subsequent thermal curing induces micro-scale phase inversion and leads to a continuous soft phase strengthened by interspersed rigid ingredients. The unique configuration ensures crack resistance, structural robustness and superb flexibility, including wide-angle bending, twisting, and stretching abilities in various directions, as well as excellent fatigue resistance and high strength, overwhelming the natural soft wood and most wood-inspired materials. This superflexible artificial soft wood represents a promising substrate for bending-insensitive stress sensors.

Postoperative awake prone position in geriatric patients with hip fractures: a protocol for a randomized controlled trial on the efficacy of postoperative prone position in reducing pulmonary complications and improving oxygenation.

INTRODUCTION: Postoperative pulmonary complications (PPCs) are prevalent in geriatric patients with hip fractures. Low oxygen level is one of the most important risk factors for PPCs. Prone position has been proven efficacy in improving oxygenation and delaying the progress of pulmonary diseases, especially in patients with acute respiratory distress syndrome induced by multiple etiologies. The application of awake prone position (APP) has also attracted widespread attention in recent years. A randomized controlled trial (RCT) will be carried out to measure the effect of postoperative APP in a population of geriatric patients undergoing hip fracture surgery. METHODS: This is an RCT. Patients older than 65 years old admitted through the emergency department and diagnosed with an intertrochanteric or femoral neck fracture will be eligible for enrollment and assigned randomly to the control group with routine postoperative management of orthopedics or APP group with an additional prone position for the first three consecutive postoperative days (PODs). Patients receiving conservative treatment will not be eligible for enrollment. We will record the difference in the patient's room-air-breathing arterial partial pressure of oxygen (PaO2) values between the 4th POD (POD 4) and emergency visits, the morbidity of PPCs and other postoperative complications, and length of stay. The incidence of PPCs, readmission rates, and mortality rates will be followed up for 90 PODs. DISCUSSION: We describe the protocol for a single-center RCT that will evaluate the efficacy of postoperative APP treatment in reducing pulmonary complications and improving oxygenation in geriatric patients with hip fractures. ETHICS AND DISSEMINATION: This protocol was approved by the independent ethics committee (IEC) for Clinical Research of Zhongda Hospital, Affiliated to Southeast University, and is registered on the Chinese Clinical Trial Registry. The findings of the trial will be disseminated through peer-reviewed journals. ETHICS APPROVAL NUMBER: 2021ZDSYLL203-P01 TRIAL REGISTRATION: ChiCTR ChiCTR2100049311 . Registered on 29 July 2021. TRIAL STATUS: Recruiting. Recruitment is expected to be completed in December 2024.

General Anesthesia Versus Regional Anesthesia in the Elderly Patients Undergoing Hip Fracture Surgeries: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

BACKGROUND: Surgery is the preferred treatment option for the elderly patients with hip fractures. However, the choice of general anesthesia (GA) or regional anesthesia (RA) remains controversial. The quality of evidence has further improved with the advent of several high-quality randomized clinical trials (RCTs) in the last two years. The purpose of this study was to compare the clinical outcomes of two anesthetic techniques in elderly patients undergoing hip fracture surgeries. METHODS: Eligible studies were identified from PubMed/MEDLINE, Web of Science, Scopus, EMBASE and reference lists from January 2000 to June 2022 in this current systematic review and meta-analysis. The outcomes included the surgery-related outcomes (duration of surgery, duration of anesthesia, intraoperative blood loss and number of transfusions) and postoperative outcomes (30-day mortality, postoperative delirium,cardiovascular events and other complications). RESULTS: A total of 10 RCTs were included, and a total of 3594 patients were analyzed. RA was associated with shorter duration of surgery, shorter length of hospital stays and less intraoperative blood loss compared to GA. There were no significant differences between the two groups in the number of blood transfusions, duration of anesthesia, 30-day mortality or postoperative delirium. CONCLUSIONS: Our pooled analysis identified no significant differences in terms of the safety between RA and GA, while RA reduces intraoperative blood loss, length of hospital stays and duration of surgery. These results suggest that RA appears to be preferable for the elderly patients with hip fractures.

What are Risk Factors of Postoperative Pneumonia in Geriatric Individuals after Hip Fracture Surgery: A Systematic Review and Meta-Analysis.

Postoperative pneumonia (POP) is a common postoperative complication. Negative consequences associated with POP included prolonged hospital length of stay, more frequent intensive care unit (ICU) stays, and a higher rate of sepsis, readmission, and mortality. This meta-analysis aimed to assess the incidence and risk factors associated with POP after hip fracture surgery in elderly patients. PubMed, Web of Science, and Cochrane Library were searched (up to March 31, 2022). All studies on the risk factors for POP after hip fracture surgery in elderly patients, published in English, were reviewed. The qualities of the included studies were assessed using the Newcastle-Ottawa Scale. Data were pooled, and a meta-analysis was performed. Ten studies, including 12,084 geriatric patients undergoing hip fracture surgery, were included. Of these 12,084 patients, POP occurred in 809 patients. The results indicated that age (mean difference [MD] = 4.95, 95% confidence interval [CI]: 3.22-6.69), male (odds ratio [OR] = 1.41, 95% CI: 1.02-1.93), the American Society of Anaesthesiologists classification ≥3 (OR = 3.48, 95% CI: 1.87-6.47), dependent functional status (OR = 5.23, 95% CI: 2.18-12.54, P = 0.0002), smoking (OR = 1.33, 95% CI: 1.07-1.65), chronic obstructive pulmonary disease (OR = 3.76, 95% CI: 2.07-6.81), diabetes mellitus (OR = 1.19, 95% CI: 1.01-1.40), coronary heart disease (OR = 1.74, 95% CI: 1.23-2.46), arrhythmia (OR = 1.47, 95% CI: 1.01-2.14), cerebrovascular disease (OR = 1.88, 95% CI: 1.56-2.27), dementia (OR = 2.36, 95% CI: 1.04-5.36), chronic renal failure (OR = 1.85, 95% CI: 1.29-2.67), hip arthroplasty (OR = 1.30, 95% CI: 1.08-1.56), delayed surgery (OR = 6.40, 95% CI: 3.00-13.68), preoperative creatinine (MD = 5.32, 95% CI: 0.55-10.08), and preoperative serum albumin (MD = -3.01, 95% CI: -4.21 - -1.80) were risk factors for POP. Related prophylactic measures should be provided in geriatric patients with the above-mentioned risk factors to prevent POP after hip fracture surgery.

Subcutaneous Lumbar Spine Index (SLSI) as a Risk Factor for Surgical Site Infection After Lumbar Fusion Surgery: A Retrospective Matched Case-Control Study.

STUDY DESIGN: A retrospective matched case-control study. OBJECTIVE: This study aims to investigate the value of Subcutaneous Lumbar Spine Index (SLSI) as a predictor of early surgical site infection (SSI) after lumbar intervertebral fusion surgery. METHODS: A retrospective case-control study was performed on patients who underwent transforaminal lumbar interbody fusion (TLIF) from January 1, 2014 to December 31, 2019 in a single institution. Cases were defined as those who developed early SSI according to the US Center for Disease Control and Prevention criteria, and controls were matched from those patients without early SSI using the following matched criteria: gender, age, time of surgery and diabetes. Subcutaneous fat thickness (SFT) and SLSI were measured on preoperative MRI mid-sagittal T2 weighted images. RESULTS: A total of 3615 patients who underwent TLIF were enrolled in this study. Thirty-three patients were included in early SSI, and sixty-six patients were selected as matched controls. Univariate analysis indicated that fusion levels (P = .007), operation time (P = .022), obesity (P = .013), SFT (P = .002) and SLSI (P = .001) were significantly associated with early SSI. Multiple logistic regression analysis revealed that multilevel fusion levels (P = .021), obesity (P = .035), a large SFT (P = .026) and a high SLSI (P = .012) were independent risk factors. Body mass index (BMI) and SLSI were moderately correlated (r2 = .55). ROC curve demonstrated that SLSI was more sensitive than SFT to predict the early SSI. CONCLUSION: SLSI is a novel radiological risk factor for early SSI development and is a better indicator than SFT to predict early SSI risk after lumbar intervertebral fusion.

MnSOD Lysine 68 acetylation leads to cisplatin and doxorubicin resistance due to aberrant mitochondrial metabolism.

Manganese superoxide dismutase (MnSOD) acetylation (Ac) has been shown to be a key post-translational modification important in the regulation of detoxification activity in various disease models. We have previously demonstrated that MnSOD lysine-68 (K68) acetylation (K68-Ac) leads to a change in function from a superoxide-scavenging homotetramer to a peroxidase-directed monomer. Here, we found that estrogen receptor positive (ER+) breast cancer cell lines (MCF7 and T47D), selected for continuous growth in cisplatin (CDDP) and doxorubicin (DXR), exhibited an increase in MnSOD-K68-Ac. In addition, MnSOD-K68-Ac, as modeled by the expression of a validated acetylation mimic mutant gene (MnSODK68Q ), also led to therapy resistance to CDDP and DXR, altered mitochondrial structure and morphology, and aberrant cellular metabolism. MnSODK68Q expression in mouse embryo fibroblasts (MEFs) induced an in vitro transformation permissive phenotype. Computerized molecular protein dynamics analysis of both MnSOD-K68-Ac and MnSOD-K68Q exhibited a significant change in charge distribution along the α1 and α2 helices, directly adjacent to the Mn2+ binding site, implying that this decrease in surface charge destabilizes tetrameric MnSOD, leading to an enrichment of the monomer. Finally, monomeric MnSOD, as modeled by amber codon substitution to generate MnSOD-K68-Ac or MnSOD-K68Q expression in mammalian cells, appeared to incorporate Fe to maximally induce its peroxidase activity. In summary, these findings may explain the mechanism behind the observed structural and functional change of MnSOD-K68-Ac.

Emerging Bioinspired Artificial Woods.

As an abundant natural resource, wood has gained great attention for thousands of years, spanning from the primitive construction materials to the modern high-added-value engineering materials. The unique delicate microstructures and the wonderful properties (e.g., low-density, high strength and stiffness, good toughness, and environmental sustainability) have made wood a natural source of inspiration that guides researchers to invent various wood-inspired materials. Herein, as an emerging material system, bioinspired artificial wood, with similar cellular structures and comparable mechanical properties, is discussed in the view of the design concept, fabrication strategy, properties, and possible applications. The present challenges and further research opportunities are also presented for artificial woods to thrive. To achieve the final eco-friendly artificial wood, more endeavors should be made in biomaterials and biodegradable or recyclable engineering of polymers to gain high mechanical properties and environmental sustainability simultaneously.

Ultrathin porous amine-based solid adsorbent incorporated zeolitic imidazolate framework-8 membrane for gas separation.

A novel gas separation approach is proposed in this work by combining an amine-based solid adsorbent with a zeolitic imidazolate framework-8 (ZIF-8) membrane. This was achieved by incorporating the amine-based solid adsorbent during the fabrication of the ZIF-8 membrane on a macroporous substrate. An amine-based solid adsorbent was prepared using porous ZIF-8-3-isocyanatopropyltrimethoxysilane (IPTMS) and N-[(3-trimethoxysilyl)propyl]diethylenetriamine (3N-APS) amine compounds. The as-prepared porous amine-based solid adsorbent (denoted as ZIF-8-IPTMS-3N-APS) possessed excellent adsorptive CO2/N2 and CO2/CH4 separation performances. As the adsorbent needs to be regenerated, this could indicate that the CO2 adsorption separation process cannot be continuously operated. In this work, an amine-based solid adsorbent was applied during the preparation of the ZIF-8 membranes owing to the following reasons: (i) gas separation by the membrane can be operated continuously; (ii) the amino group provides a heterogeneous nucleation site for ZIF-8 to grow; and (iii) the reparation of surface defects on the macroporous substrate can be performed prior to the growth of the ZIF-8 membrane. Herein, the ZIF-8 membrane was successfully fabricated, and it possessed excellent CO2/CH4, CO2/N2, and H2/CH4 separation performances. The 0.6 µm ultrathin ZIF-8 membrane demonstrated a high CO2 permeance of 4.75 × 10-6 mol m-2 s-1 Pa-1 at 35 °C and 0.1 MPa, and ideal CO2/N2 and CO2/CH4 selectivities of 4.67 and 6.02, respectively. Furthermore, at 35 °C and 0.1 MPa, the ideal H2/CH4 selectivity of the ZIF-8 membrane reached 31.2, and a significantly high H2 permeance of 2.45 × 10-5 mol m-2 s-1 Pa-1.

Sinomenine ameliorates intervertebral disc degeneration via inhibition of apoptosis and autophagy in vitro and in vivo.

BACKGROUND: Aberrant apoptosis in nucleus pulposus (NP) cells is the primary cause of intervertebral disc degeneration (IDD). In contrast, a large number of studies have confirmed that autophagy may protect NP cells from apoptosis. Sinomenine is an alkaloid monomer, which has been reported to stimulate cell autophagy. Therefore, the aim of the present study was to investigate the effects of sinomenine on IDD. METHODS: The effects of sinomenine on the proliferation and apoptosis of NP cells were evaluated with the CCK-8 assay and Annexin V/PI staining, respectively. RESULTS: The data obtained from the present study demonstrated that sinomenine could notably reverse TBHP-induced growth inhibition and apoptosis in rat NP cells. In addition, sinomenine significantly induced autophagy in rat NP cells, which was completely inhibited by 3-methyladenine (3MA). In addition, the protective effect of sinomenine against TBHP in rat NP cells was abolished following treatment with 3MA. Finally, an in vivo study further confirmed that sinomenine could ameliorate rat IDD. CONCLUSION: Taken together, the results of the present study indicated sinomenine could ameliorate rat IDD via induction of autophagy in vitro and in vivo. These findings suggest the therapeutic potential of sinomenine in the prevention of IDD.

Lysine 68 acetylation directs MnSOD as a tetrameric detoxification complex versus a monomeric tumor promoter.

Manganese superoxide dismutase (MnSOD) functions as a tumor suppressor; however, once tumorigenesis occurs, clinical data suggest MnSOD levels correlate with more aggressive human tumors, implying a potential dual function of MnSOD in the regulation of metabolism. Here we show, using in vitro transformation and xenograft growth assays that the MnSOD-K68 acetylation (Ac) mimic mutant (MnSODK68Q) functions as a tumor promoter. Interestingly, in various breast cancer and primary cell types the expression of MnSODK68Q is accompanied with a change of MnSOD's stoichiometry from a known homotetramer complex to a monomeric form. Biochemical experiments using the MnSOD-K68Q Ac-mimic, or physically K68-Ac (MnSOD-K68-Ac), suggest that these monomers function as a peroxidase, distinct from the established MnSOD superoxide dismutase activity. MnSODK68Q expressing cells exhibit resistance to tamoxifen (Tam) and cells selected for Tam resistance exhibited increased K68-Ac and monomeric MnSOD. These results suggest a MnSOD-K68-Ac metabolic pathway for Tam resistance, carcinogenesis and tumor progression.