Do modic changes affect the fusion rate in spinal interbody fusion surgery? A systematic review and network meta-analysis.

OBJECTIVE: To compare the fusion rates of spinal interbody fusion in patients with modic changes (MCs). METHODS: This meta-analysis was registered at PROSPERO, and the project number was CRD42024538023. This network meta-analysis was conducted according to the PRISMA 2020 statement. The PubMed, Embase, Web of Science Core Collection, ClinicalTrials.gov and Cochrane Library databases were searched from inception to March 28, 2024 for potential studies. STATA 13.0 and Review Manager 5.3 were used to perform the meta-analysis. RESULTS: Seven studies with a total of 1162 patients or segments assigned to four groups according to MCs grade were identified. The fusion rate in the non-modic changes (NMCs) was significantly greater than that in the MCs at the 3-month (p = 0.0001) and 6-month (p = 0.002) follow-ups. No significant difference was detected in the fusion rate at 12-month (p = 0.34) and final follow-ups (p = 0.41). No significant difference was found in cervical fusion (p = 0.88) or transforaminal lumbar interbody fusion (TLIF) (p = 0.51). The fusion rate of NMCs was significantly greater than that of MCs in posterior lumbar interbody fusion (PLIF) (p < 0.00001). No significant differences were identified among the four groups in the overall comparison, cervical fusion or TLIF subgroups. The fusion rate in the NMCs was significantly greater than that in the MCs-2 and MCs-3 in the PLIF. CONCLUSION: MCs decreased the fusion rate at the 3- and 6-month follow-ups. MCs-2 and MCs-3 decrease the fusion rate in PLIF.

Efficacy and safety of Aprepitant-containing triple therapy for the prevention and treatment of chemotherapy-induced nausea and vomiting: A meta-analysis.

BACKGROUND: Most cancer patients suffer from the pain of chemotherapy-induced nausea and vomiting (CINV). This meta-analysis was performed to evaluate the efficacy and safety of a regimen consisting of aprepitant, dexamethasone, and 5-HT3 receptor antagonists in the prevention and treatment of CINV. METHODS: A systematic literature search was conducted across multiple databases, including PubMed, EMbase, Cochrane Library, MEDLINE, CENTRAL, HEED, CNKI, Wanfang, and VIP, to identify randomized controlled trials (RCTs) investigating the use of triple therapy (aprepitant, 5-HT3 receptor antagonist, and dexamethasone) to prevent and treat CINV. Meta-analysis was performed using RevMan 5.4 and Stata17 software, employing either a fixed-effect or random-effect model based on statistical heterogeneity. RESULTS: A meta-analysis of 23 randomized controlled trials (RCTs) involving 7956 patients was conducted. Efficacy: Results showed significantly improved complete responses (CRs) for CINV in the test group versus the control group in the overall, acute, and delayed phases. Furthermore, in the test group, substantial alleviation of nausea symptoms was observed in the delayed and overall phases but not in the acute phase. Safety: There was no statistically significant difference in the incidence of febrile neutropenia, diarrhea, anorexia, and headache between the 2 groups. The incidence of fatigue and hiccups in the test group was higher than that in the control group; however, the incidence of constipation was significantly lower. CONCLUSIONS: Aprepitant-containing triple therapy is highly effective in the prevention and treatment of CINV, with reliable medication safety.

Flavonoid Synthesis by Deinococcus sp. 43 Isolated from the Ginkgo Rhizosphere.

Flavonoids are crucial in physiological and pharmaceutical processes, especially the treatment of cancer and the prevention of cardiovascular and cerebrovascular diseases. Flavonoid-producing plants and fungi have been extensively reported, but bacteria have been much less investigated as a source of flavonoid production. Deinococcus sp. 43, a spherical flavonoid-producing bacteria from the Ginkgo rhizosphere, was reported in this study. First, the whole genome of Deinococcus sp. 43 was sequenced and a series of flavonoid anabolic genes were annotated. Simultaneously, High Performance Liquid Chromatography (HPLC) results showed that Deinococcus sp. 43 was capable of producing flavonoids, with a maximum quercetin output of 2.9 mg/L. Moreover, the relative expression of key genes involved in flavonoid synthesis was determined to test the completeness of the flavonoid anabolic pathway. The results of LC-MS analysis demonstrated that the flavonoids produced by Deinococcus sp. 43 were significantly different between intracellular and extracellular environments. The concentration of multiple glycosylated flavonoids was substantially higher in extracellular than intracellular environments, while the majority of flavonoids obtained in intracellular environments were hydroxylated multiple times. Lastly, the flavonoid biosynthetic pathway of Deinococcus sp. 43 was constructed based on the genomic analysis and the detected flavonoids. In conclusion, this study represents the first comprehensive characterization of the flavonoid-producing pathway of Deinococcus. The findings demonstrate that the strain has excellent potential as a genetically engineered strain for the industrial production of flavonoids.

Dynamic variation of Paris polyphylla root-associated microbiome assembly with planting years.

MAIN CONCLUSION: P. polyphylla selectively enriches beneficial microorganisms to help their growth. Paris polyphylla (P. polyphylla) is an important perennial plant for Chinese traditional medicine. Uncovering the interaction between P. polyphylla and the related microorganisms would help to utilize and cultivate P. polyphylla. However, studies focusing on P. polyphylla and related microbes are scarce, especially on the assembly mechanisms and dynamics of the P. polyphylla microbiome. High-throughput sequencing of the 16S rRNA genes was implemented to investigate the diversity, community assembly process and molecular ecological network of the bacterial communities in three root compartments (bulk soil, rhizosphere, and root endosphere) across three years. Our results demonstrated that the composition and assembly process of the microbial community in different compartments varied greatly and were strongly affected by planting years. Bacterial diversity was reduced from bulk soils to rhizosphere soils to root endosphere and varied over time. Microorganisms benefit to plants was selectively enriched in P. polyphylla roots as was its core microbiome, including Pseudomonas, Rhizobium, Steroidobacter, Sphingobium and Agrobacterium. The network's complexity and the proportion of stochasticity in the community assembly process increased. Besides, nitrogen metabolism, carbon metabolism, phosphonate and phosphinate metabolism genes in bulk soils increased over time. These findings suggest that P. polyphylla exerts a selective effect to enrich the beneficial microorganisms and proves the sequential increasing selection pressure with P. polyphylla growth. Our work adds to the understanding of the dynamic processes of plant-associated microbial community assembly, guides the selection and application timing of P. polyphylla-associated microbial inoculants and is vital for sustainable agriculture.

Protein phosphatase PPM1A inhibition attenuates osteoarthritis via regulating TGF-ß/Smad2 signaling in chondrocytes.

TGF-ß signaling is crucial for modulating osteoarthritis (OA), and protein phosphatase magnesium-dependent 1A (PPM1A) has been reported as a phosphatase of SMAD2 and regulates TGF-ß signaling, while the role of PPM1A in cartilage homeostasis and OA development remains largely unexplored. In this study, we found increased PPM1A expression in OA chondrocytes and confirmed the interaction between PPM1A and phospho-SMAD2 (p-SMAD2). Importantly, our data show that PPM1A KO substantially protected mice treated with destabilization of medial meniscus (DMM) surgery against cartilage degeneration and subchondral sclerosis. Additionally, PPM1A ablation reduced the cartilage catabolism and cell apoptosis after the DMM operation. Moreover, p-SMAD2 expression in chondrocytes from KO mice was higher than that in WT controls with DMM induction. However, intraarticular injection with SD-208, repressing TGF-ß/SMAD2 signaling, dramatically abolished protective phenotypes in PPM1A-KO mice. Finally, a specific pharmacologic PPM1A inhibitor, Sanguinarine chloride (SC) or BC-21, was able to ameliorate OA severity in C57BL/6J mice. In summary, our study identified PPM1A as a pivotal regulator of cartilage homeostasis and demonstrated that PPM1A inhibition attenuates OA progression via regulating TGF-ß/SMAD2 signaling in chondrocytes and provided PPM1A as a potential target for OA treatment.

Mid-term outcomes of microfragmented adipose tissue plus arthroscopic surgery for knee osteoarthritis: A randomized, active-control, multicenter clinical trial.

BACKGROUND: Osteoarthritis (OA) is the most prevalent form of degenerative whole-joint disease. Before the final option of knee replacement, arthroscopic surgery was the most widely used joint-preserving surgical treatment. Emerging regenerative therapies, such as those involving platelet-rich plasma, mesenchymal stem cells, and microfragmented adipose tissue (MFAT), have been pushed to the forefront of treatment to prevent the progression of OA. Currently, MFAT has been successfully applied to treat different types of orthopedic diseases. AIM: To assess the efficacy and safety of MFAT with arthroscopic surgery in patients with knee OA (KOA). METHODS: A randomized, multicenter study was conducted between June 2017 and November 2022 in 10 hospitals in Zhejiang, China. Overall, 302 patients diagnosed with KOA (Kellgren-Lawrence grades 2-3) were randomized to the MFAT group (n = 151, were administered MFAT following arthroscopic surgery), or the control group (n = 151, were administered hyaluronic acid following arthroscopic surgery). The study outcomes were changes in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, the visual analog scale (VAS) score, the Lequesne index score, the Whole-Organ Magnetic Resonance Imaging Score (WORMS), and safety over a 24-mo period from baseline. RESULTS: The changes in the WOMAC score (including the three subscale scores), VAS pain score, and Lequesne index score at the 24-mo mark were significantly different in the MFAT and control groups, as well as when comparing values at the posttreatment visit and those at baseline (P < 0.001). The MFAT group consistently demonstrated significant decreases in the WOMAC pain scores and VAS scores at all follow-ups compared to the control group (P < 0.05). Furthermore, the WOMAC stiffness score, WOMAC function score, and Lequesne index score differed significantly between the groups at 12 and 24 mo (P < 0.05). However, no significant between-group differences were observed in the WORMS at 24 mo (P = 0.367). No serious adverse events occurred in both groups. CONCLUSION: The MFAT injection combined with arthroscopic surgery treatment group showed better mid-term clinical outcomes compared to the control group, suggesting its efficacy as a therapeutic approach for patients with KOA.

Analysis of Prognostic Factors in Osteoporotic Patients Who Were Treated with Percutaneous Vertebroplasty for Refracture After Vertebral Augmentation.

OBJECTIVE: To retrospectively analyze prognostic factors in osteoporotic patients who treated with percutaneous vertebroplasty for refracture after vertebral augmentation. METHODS: A retrospective analysis was performed of 61 patients with refractures after vertebral augmentation who received percutaneous vertebroplasty treatment again from January 2019 to December 2021. Based on the presence of back pain at the last follow-up, 17 patients were placed in the pain group, and 44 patients were placed in the pain-free group. The following covariates were reviewed: age; bone mineral density; bone cement dosage; bone cement leakage; body mass index; and rate of anterior vertebral height (AVH) loss in the target before surgery, 1 week after surgery, and at last follow-up. Patients were assessed using visual analogue scale score and Oswestry Disability Index. RESULTS: Binary logistic regression analysis revealed that the rate of AVH loss after surgery was associated with postoperative back pain. According to the receiver operating characteristic curve analysis, the area under the curve of AVH loss rate at 1 week after surgery was 0.6845, and the cutoff value was 0.18; the area under the curve of AVH loss rate at the last follow-up was 0.7306, and the cutoff value was 0.2815. Kaplan-Meier survival analysis showed that patients with lower AVH loss rates had lower incidence of postoperative back pain and better prognosis. CONCLUSIONS: Occurrence of postoperative back pain was strongly associated with AVH loss after surgery. Patients with a lower rate of AVH loss had a lower incidence of postoperative back pain and a better prognosis.

Identification of Gene as Predictive Biomarkers for the Occurrence and Recurrence of Osteosarcoma.

PURPOSE: Osteosarcoma is the most common malignant bone cancer affecting adolescents and young adults. This study aimed to screen potential diagnostic and therapeutic markers for osteosarcoma. METHODS: Differential expression analysis between osteosarcoma and control was performed in GSE99671, the differentially expressed genes (DEGs) were subjected to co-expression analysis. Enrichment analysis was employed to identify the biological functions and KEGG signaling pathways of module genes. In addition, a differential analysis was also performed between recurrent and non-recurrent osteosarcoma samples in GSE39055, and enrichment analysis was performed for DEGs. Further, Kaplan-Meier curve analysis was performed on the module genes, and receiver operating characteristic (ROC) curve was drawn. Comparison of the module with the highest correlation to osteosarcoma identified key genes. Cox regression model was utilized to identify the predictive ability of key genes for the prognosis of osteosarcoma. RESULTS: A total of 13 co-expression modules were identified from 4871 DEGs of GSE99671, module 1 had the highest positive correlation with osteosarcoma. Module genes were mainly enriched in autophagy and macrophage migration functions. A total of 1126 DEGs were obtained from GSE39055, significantly involved in neutrophil mediated immunity. Screening of genes with area under the ROC curve (AUC) values greater than 0.73 in both GSE99671 and GSE39055 identified 5 key genes when compared with genes from module 1. The nomogram results showed that ATF5, CHCHD8, ENOPH1, and LOC286367 might predict 5-year or 8-year survival time of osteosarcoma patients. The Cox model results confirmed that the signals of ATF5, CHCHD8, and LOC286367 were robust, and it may be used in the diagnosis, treatment, and prognosis of osteosarcoma. CONCLUSION: We found that ATF5, CHCHD8, and LOC286367 can effectively identify osteosarcoma tumorigenesis and even recurrence status. This is helpful for early diagnosis and treatment, improving the clinical treatment of patients with osteosarcoma.

Cefazolin sodium pentahydrate combined with vacuum sealing drainage in the treatment of open fracture complicated with soft tissue injury.

OBJECTIVE: To investigate the clinical efficacy of cefazolin sodium pentahydrate combined with vacuum sealing drainage (VSD) in the treatment of open fracture complicated with soft tissue injury. METHODS: Sixty-three patients with open fracture complicated with soft tissue injury were divided into observation (n = 33) and control (n = 30) groups. After surgical reduction, fixation, and repair of the fractures, the control group was treated with VSD for 10 days, and the observation group was treated with cefazolin sodium pentahydrate based on VSD for 10 days. The infection control time was recorded. After treatment, the pain of patients was evaluated. Before and after treatment, the serum levels of C-reactive protein (CRP), interleukin (IL)-6, IL-8, tumor necrosis factor α (TNF-α), cortisol, epinephrine, norepinephrine, and glucose were detected. After 6 months of treatment, the total effective rate of the treatment was evaluated. RESULTS: The infection control time and Visual Analogue Scale score after treatment in the observation group were significantly lower than in the control group, respectively (P < 0.05). After the treatment, the serum levels of CRP, IL-6, IL-8, TNF-α, cortisol, epinephrine, norepinephrine, and glucose in each group were significantly lower than before the treatment (P < 0.05), and each index in observation was significantly lower than in the control group (P < 0.05). CONCLUSIONS: In the treatment of open fractures complicated with soft tissue injury, cefazolin sodium pentahydrate combined with VSD can effectively reduce inflammation and stress, thus improving the treatment efficacy.

Chondroprotective and antiarthritic effects of Daphnetin used in vitro and in vivo osteoarthritis models.

AIMS: Daphnetin (DAP) is a traditional Chinese drug usually used to treat cardiovascular diseases. Studies have confirmed the anti-inflammatory, antioxidant, anti-bacterial and insecticidal, anti-tumor and neuro-protective effects of DAP. However, its anti-arthritic potential remains unexplored. The aim of this study is to investigate the in vitro and in vivo chondroprotective effects of DAP. MAIN METHODS: The effect of DAP on primary rabbit chondrocytes was examined using recombinant human IL-1ß for 24 h. For the in vivo studies, rabbits were randomly divided into groups: a normal control group and osteoarthritis (OA) groups. The OA groups received three different doses of DAP for 4 or 8 weeks. The anti-arthritic effect of DAP was assessed using histopathological examinations, qRT-PCR, western blotting and immunohistochemical analysis. KEY FINDINGS: Both in vitro and in vivo results indicate that DAP exerts a protective effect against IL-1ß in chondrocytes. In vitro, DAP inhibits the expression of IL-6, IL-12, MMP-3, MMP-9 and MMP-13, induced by IL-1ß in rabbit chondrocytes, and stimulates the production of IL-10. The inhibitory effect of DAP on the MMPs is partially regulated by the inhibition of the PI3K/AKT, MAPK and NF-κB signaling pathways. The effect of DAP on OA may be attributed to the suppression of inflammatory factor secretion, chondrocyte apoptosis observed by the decrease in pro-apoptotic Caspase-3 and BAX, and the activation of anti-apoptotic BCL-2. SIGNIFICANCE: DAP has a broad range of prospects in the treatment of OA, which provides a novel therapeutic strategy for OA.

The therapeutic effects of edaravone on collagen-induced arthritis in rats.

Current research suggests that synovial phagocytic cells remove excessive amounts of free oxygen radicals (reactive oxygen species [ROS]), thereby preventing damage to synovial tissues. Moreover, ROS may affect the expression of growth arrest and DNA damage inducible α (GADD45A), thus further promoting the activation of synovial fibroblasts. Male adult rats were assessed for progression of collagen-induced arthritis (CIA) using a macroscopic arthritis scoring system of the hind paws and by measuring the changes in the rat's body weight, and activity level before and after diagnosis of CIA. Rats were intraperitoneally injected twice daily with edaravone at doses of 3, 6, and 9 mL/kg. Samples were taken at 2, 4, and 6 weeks, respectively. Edaravone was found to significantly reduce macroscopic arthritis and microscopic pathology scores in CIA rats. The concentration of endothelial nitric oxide synthase-6, glutathione, and heme oxygenase-1 in the serum of rats decreased, as was the production of ROS around the synovium and inflammatory factors. Moreover, ROS-1 increased the expression of the nuclear factor-κB (NF-κB) p65 protein by altering the expression level of GADD45A, causing aggravation of tissue damage. Edaravone also significantly improved the physiological condition of CIA rats, including appetite, weight changes, and loss of fur, as well as limb mobility. We believe that edaravone acts to reduce the expression of NF-ĸB p65 by clearing ROS, which causes reduced expression of GADD45A, and subsequently reduces the level of apoptosis and inflammatory response proteins, thereby reducing the symptoms of CIA. We, therefore, propose that edaravone is an effective option for clinical treatment of rheumatic arthritis.

Roux-en-Y gastric bypass surgery restores insulin-mediated glucose partitioning and mitochondrial dynamics in primary myotubes from severely obese humans.

BACKGROUND/OBJECTIVES: Impaired insulin-mediated glucose partitioning is an intrinsic metabolic defect in skeletal muscle from severely obese humans (BMI ≥ 40 kg/m2). Roux-en-Y gastric bypass (RYGB) surgery has been shown to improve glucose metabolism in severely obese humans. The purpose of the study was to determine the effects of RYGB surgery on glucose partitioning, mitochondrial network morphology, and the markers of mitochondrial dynamics skeletal muscle from severely obese humans. SUBJECT/METHODS: Human skeletal muscle cells were isolated from muscle biopsies obtained from RYGB patients (BMI = 48.0 ± 2.1, n = 7) prior to, 1 month and 7 months following surgery and lean control subjects (BMI = 22.4 ± 1.1, n = 7). Complete glucose oxidation, non-oxidized glycolysis rates, mitochondrial respiratory capacity, mitochondrial network morphology, and the regulatory proteins of mitochondrial dynamics were determined in differentiated human myotubes. RESULTS: Myotubes derived from severely obese humans exhibited enhanced glucose oxidation (13.5%; 95% CI [7.6, 19.4], P = 0.043) and reduced non-oxidized glycolysis (-1.3%; 95% CI [-11.1, 8.6]) in response to insulin stimulation at 7 months after RYGB when compared with the presurgery state (-0.6%; 95% CI [-5.2, 4.0] and 19.5%; 95% CI [4.0, 35.0], P = 0.006), and were not different from the lean controls (16.7%; 95% CI [11.8, 21.5] and 1.9%; 95% CI [-1.6, 5.4], respectively). Further, the number of fragmented mitochondria and Drp1(Ser616) phosphorylation were trended to reduce/reduced (0.0104, 95% CI [0.0085, 0.0126], P = 0.091 and 0.0085, 95% CI [0.0068, 0.0102], P = 0.05) in myotubes derived from severely obese humans at 7 months after RYGB surgery in comparison with the presurgery state. Finally, Drp1(Ser616) phosphorylation was negatively correlated with insulin-stimulated glucose oxidation (r = -0.49, P = 0.037). CONCLUSION/INTERPRETATION: These data indicate that an intrinsic metabolic defect of glucose partitioning in skeletal muscle from severely obese humans is restored by RYGB surgery. The restoration of glucose partitioning may be regulated through reduced mitochondrial fission protein Drp1 phosphorylation.

Cefazolin sodium pentahydrate combined with vacuum sealing drainage in the treatment of open fracture complicated with soft tissue injury

SUMMARY OBJECTIVE To investigate the clinical efficacy of cefazolin sodium pentahydrate combined with vacuum sealing drainage (VSD) in the treatment of open fracture complicated with soft tissue injury. METHODS Sixty-three patients with open fracture complicated with soft tissue injury were divided into observation (n = 33) and control (n = 30) groups. After surgical reduction, fixation, and repair of the fractures, the control group was treated with VSD for 10 days, and the observation group was treated with cefazolin sodium pentahydrate based on VSD for 10 days. The infection control time was recorded. After treatment, the pain of patients was evaluated. Before and after treatment, the serum levels of C-reactive protein (CRP), interleukin (IL)-6, IL-8, tumor necrosis factor α (TNF-α), cortisol, epinephrine, norepinephrine, and glucose were detected. After 6 months of treatment, the total effective rate of the treatment was evaluated. RESULTS The infection control time and Visual Analogue Scale score after treatment in the observation group were significantly lower than in the control group, respectively (P < 0.05). After the treatment, the serum levels of CRP, IL-6, IL-8, TNF-α, cortisol, epinephrine, norepinephrine, and glucose in each group were significantly lower than before the treatment (P < 0.05), and each index in observation was significantly lower than in the control group (P < 0.05). CONCLUSIONS In the treatment of open fractures complicated with soft tissue injury, cefazolin sodium pentahydrate combined with VSD can effectively reduce inflammation and stress, thus improving the treatment efficacy.

RESUMO OBJETIVO Investigar a eficácia clínica do cefazolin penta-hidrato de sódio combinado com drenagem por vedação a vácuo (VSD) no tratamento da fratura exposta complicada com lesão nos tecidos moles. MÉTODOS Sessenta e três doentes com fratura exposta complicada com lesões nos tecidos moles foram divididos em grupos de observação (n=33) e controle (n=30). Após redução cirúrgica, fixação e reparação da fratura, o grupo de controle foi tratado com VSD durante dez dias e o grupo de observação foi tratado com cefazolina penta-hidrato de sódio com base no VSD durante dez dias. O tempo de controle de infecção foi gravado. Após o tratamento, a dor dos doentes foi avaliada. Antes e após o tratamento, foram detectados os níveis séricos de proteína C-reativa (CRP), interleucina (IL)-6, IL -8, fator de necrose tumoral alfa (TNF-α), cortisol, epinefrina, norepinefrina e glicose. Após seis meses de tratamento, a taxa efetiva total de tratamento foi avaliada. RESULTADOS O tempo de controle da infecção e a pontuação da Escala Visual Analógica após o tratamento no grupo de observação foram significativamente inferiores ao do grupo de controle, respectivamente (P<0,05). Após o tratamento, os níveis séricos de CRP, IL-6, IL-8, TNF-α, cortisol, epinefrina, norepinefrina e glicose em cada grupo foram significativamente menores do que antes do tratamento, respectivamente (P<0,05), e cada índice de observação foi significativamente inferior ao do grupo de controle (P<0,05). CONCLUSÃO No tratamento da fratura exposta complicada com lesões nos tecidos moles, o cefazolin penta-hidrato de sódio combinado com VSD pode efetivamente reduzir a inflamação e o estresse, melhorando assim a eficácia do tratamento.

Preparation of a NiAl-Oxide@Polypyrrole Composite for High-Performance Supercapacitors.

A core-shell NiAlO@polypyrrole composite (NiAlO@PPy) with a 3D "sand rose"-like morphology was prepared via a facile in situ oxidative polymerization of pyrrole monomer, where the role of PPy coating thickness was investigated for high-performance supercapacitors. Microstructure analyses indicated that the PPy was successfully coated onto the NiAlO surface to form a core-shell structure. The NiAlO@PPy exhibited a better electrochemical performance than pure NiAlO, and the moderate thickness of the PPy shell layer was beneficial for expediting the electron transfer in the redox reaction. It was found that the NiAlO@PPy5 prepared at 5.0 mL L-1 addition amount of pyrrole monomer demonstrated the best electrochemical performance with a high specific capacitance of 883.2 F g-1 at a current density of 1 A g-1 and excellent capacitance retention of 91.82 % of its initial capacitance after 1000 cycles at 3 A g-1 . The outstanding electrochemical performance of NiAlO@PPy5 were due to the synergistic effect of NiAlO and PPy, where the uniform network-like PPy shell with the optimal thickness made electrolyte ions more easily accessible for faradic reactions. This work provided a simple approach for designing organic-inorganic core-shell materials as high-performance electrode materials for electrochemical supercapacitors.

Flavonoid Biosynthesis Is Likely More Susceptible to Elevation and Tree Age Than Other Branch Pathways Involved in Phenylpropanoid Biosynthesis in Ginkgo Leaves.

Ginkgo leaves are always resources for flavonoids pharmaceutical industry. However, the effect of the elevation and tree age changes on flavonoid biosynthesis have not been detailly explored in Ginkgo leaves. In addition, whether these environmental pressures have similar effects on the biosynthesis of other non-flavonoids polyphenolics in phenylpropanoid biosynthesis is not known at present. In this research, de novo transcriptome sequencing of Ginkgo leaves was performed coupled with ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry analyses to obtain a comprehensive understanding of the influence of elevation and tree age on phenylpropanoid biosynthesis. A total of 557,659,530 clean reads were assembled into 188,155 unigenes, of which 135,102 (71.80%) were successfully annotated in seven public databases. The putative DFRs, LARs, and ANRs were significantly up-regulated with the increase of elevation in young Ginkgo tree leaves. The relative concentration of flavonoid derivatives with high parent ion intensity was likely to imply that the elevation increase promoted the biosynthesis of flavonoids. Complex gene variations involved in flavonoid biosynthesis were observed with the tree age increase. However, flavonoid derivatives analysis predicted that the rise of tree age was more likely to be detrimental to the flavonoids manufacture. Otherwise, multiple genes implicated in the synthesis of hydroxycinnamates, lignin, and lignan exhibited fluctuations with the elevation increase. Significantly up-regulated CADs and down-regulated PRDs potentially led to the accumulation of p-Coumaryl alcohol, one of the lignin monomers, and might inhibit further lignification. Overall, the putative DFRs seemed to show more considerable variability toward these stress, and appeared to be the main regulatory point in the flavonoid biosynthesis. Light enhancement caused by elevation increase may be the main reason for flavonoids accumulation. Flavonoid biosynthesis exhibited a greater degree of perturbation than that of hydroxycinnamates, lignins and lignans, potentially suggesting that flavonoid biosynthesis might be more susceptible than other branch pathways involved in phenylpropanoid biosynthesis. This research effectively expanded the functional genomic library and provide new insights into phenylpropanoid biosynthesis in Ginkgo.

Plasma lactate as a marker of metabolic health: Implications of elevated lactate for impairment of aerobic metabolism in the metabolic syndrome.

BACKGROUND: Fasting lactate is elevated in metabolic diseases and could possibly be predictive of the risk of developing the metabolic syndrome. METHODS: Plasma samples were analyzed for fasting lactate to compare lean subjects, nondiabetic subjects with severe obesity, and metabolically impaired subjects. Subjects with severe obesity were studied 1 week before and 1 week to 9 months after gastric bypass surgery. Subjects with components of the metabolic syndrome were studied before and after 6 months of an exercise intervention. RESULTS: Metabolically impaired subjects had higher fasting lactate concentrations (P < .0001) and respond to a glucose or insulin challenge with higher lactates than non-obese subjects (P < .004). Lactate was significantly reduced a week after gastric bypass surgery (P < .05) and further reduced 1 to 9 months after surgery (0.95 ± 0.04 mM in non-obese, 1.26 ± 0.12 mM in subjects with severe obesity, and 0.68 ± 0.03 mM 1-3 months after gastric bypass). Six months of chronic exercise resulted in a 16% reduction (P = .028) in fasting lactate. CONCLUSION: Fasting plasma lactate was elevated in obese subjects with the metabolic syndrome compared with healthy lean individuals. Lactate was reduced by exercise and bariatric surgery, interventions that improve metabolic health and risk for subsequent disease. The results of this study and those previously published by our research group suggest that elevated lactate may be caused by an impairment in aerobic metabolism and may offer a metric assessing the severity of the metabolic syndrome.

GABARAP promotes bone marrow mesenchymal stem cells-based the osteoarthritis cartilage regeneration through the inhibition of PI3K/AKT/mTOR signaling pathway.

Osteoarthritis (OA) is a degenerative disease of the cartilage prevalent in the middle-aged and elderly demographic. Direct transplantation of bone marrow mesenchymal stem cells (BMSCs) or stem cell-derived chondrocytes into the damaged cartilage is a promising therapeutic strategy for OA, but is limited by the poor survival and in situ stability of the chondrocytes. Autophagy is a unique catabolic pathway conserved across eukaryotes that maintains cellular homeostasis, recycles damaged proteins and organelles, and promotes survival. The aim of this study was to determine the role of the proautophagic γ-aminobutyric acid receptor-associated protein (GABARAP) on the therapeutic effects of BMSCs-derived chondrocytes in a rat model of OA, and elucidate the underlying mechanisms. Anterior cruciate ligament transection (ACLT) was performed in Sprague-Dawley rats to simulate OA, and the animals were injected weekly with recombinant human His6-GABARAP protein, BMSCs-derived differentiated chondrocytes (DCs) or their combination directly into the knee cartilage. The regenerative effects of GABARAP and/or DCs were determined in term of International Cartilage Repair Society scores and cartilage thickness. The combination treatment of DCs and GABARAP significantly increased the levels of the ECM proteins Col II and SOX9, indicating formation of hyaline-like cartilage, and decreased chondrocyte apoptosis and inflammation. DCs + GABARAP treatment also upregulated the mediators of the autophagy pathway and suppressed the PI3K/AKT/mTOR pathway, indicating a mechanistic basis of its therapeutic action.

Risk factors for colorectal neoplasia in patients with underlying inflammatory bowel disease: a multicenter study.

BACKGROUND: This study sought to evaluate the risk factors for the development of colitis-associated neoplasia (CAN) in Chinese patients with inflammatory bowel disease (IBD). METHODS: IBD patients who developed CAN between 1999 and 2016 were identified from eight medical centers. In addition to initial pathology evaluation, a CAN diagnosis was confirmed by two expert pathologists. Patients with CAN (n = 29) were compared with non-CAN controls (n = 87). Matching was performed for gender and IBD type with a ratio of three controls to one subject. RESULTS: Of the 29 patients with CAN, 8 (27.6%) had colorectal cancer (CRC), 20 (69.0%) had a final diagnosis of low-grade dysplasia and 1 (3.4%) had high-grade dysplasia. Multivariate analysis revealed that an older age at the time of IBD diagnosis and a longer IBD duration were independent risk factors for the development of CAN, with odds ratios of 1.09 [95% confidence interval (CI): 1.04-1.14, P < 0.001] and 1.14 (95% CI: 1.03-1.27, P = 0.013), respectively. Comparison between IBD patients with CRC and those with dysplasia indicated that the former were older at the time of IBD diagnosis (P = 0.012) and had longer IBD durations (P = 0.019). CONCLUSIONS: Older age at the time of IBD diagnosis and longer IBD duration were found to be associated with the development of CAN in IBD patients.

Seabuckthorn berry polysaccharide extracts protect against acetaminophen induced hepatotoxicity in mice via activating the Nrf-2/HO-1-SOD-2 signaling pathway.

BACKGROUND: Oxidative stress is concomitant with acetaminophen (APAP)-induced hepatotoxicity, which has been highlighted as therapeutic targets for such diseases. The berries of Seabuckthorn (Hippophae rhamnoides L.) have been traditionally used in Tibetan medicine for thousands of years. The effect of Seabuckthorn berry polysaccharide on drug- induced liver injury (DILI) has not yet been elucidated. PURPOSE: This study aims to investigate the protective effects and mechanisms of Seabuckthorn polysaccharide (SP) against APAP-induced hepatotoxicity. STUDY DESIGN: Sixty C57BL/6 mice were randomly divided into six groups (n = 10 per group), namely the control group (Ctrl), APAP-induced-liver injury group (APAP), NAC pretreated group (NAC), 100 mg/kg SP pretreated group (APAP/SP100), 200 mg/kg SP pretreated group (APAP/SP200) and 200 mg/kg SP pretreated group without APAP challenge (SP200). SP was given orally to mice for 30 consecutive days prior to APAP exposure (300 mg/kg). NAC (150 mg/kg) was administrated 1 h before APAP challenge. METHODS: ALT and AST were detected 16 h after APAP treatment; Hepatic expression of GSH, SOD, NO, iNOS and GSH-Px were examined. The expression of p-JNK, Bcl-2/Bax, p62, Keap-1 and SOD-2 was detected by Western blotting. The expression of Nrf-2 and its target genes HO-1, GCLC and NQO-1 were analyzed by RT-PCR and Western blotting. RESULTS: Pretreatment with SP led to decreased levels of ALT and AST in APAP mice, without affecting APAP metabolism. This was accompanied by diminished liver injuries, increased levels of GSH and GSH-Px, reduced NO and iNOS expression. SP increased the activity of SOD as well as SOD-2 expression in APAP mice. SP suppressed APAP-induced JNK phosphorylation and increased the ratio of Bcl-2/Bax. Furthermore, SP decreased the expression of Keap-1 and increased the nuclear expression of Nrf-2. The expression of Nrf-2 target gene HO-1 was increased by SP pretreatment in APAP mice. CONCLUSION: SP alleviates APAP-induced hepatotoxicity. The protective effects of SP are associated with the activation of the Nrf-2/HO-1-SOD-2 signaling pathway.

Seabuckthorn berry polysaccharide protects against carbon tetrachloride-induced hepatotoxicity in mice via anti-oxidative and anti-inflammatory activities.

The berries of Seabuckthorn (Hippophae rhamnoides L.) are traditional medicinal foods that have been used by Tibetans and Mongolians for thousands of years. The polysaccharides are the main components of Seabuckthorn berries, possessing immune stimulating, anti-cancer and anti-fatigue activities. The present study focused on evaluating the protective effects and mechanisms of Seabuckthorn berry polysaccharide (SP) against carbon tetrachloride (CCl4)-induced hepatotoxicity. Mice were orally administrated with 50, 100 and 200 mg kg-1 of SP once daily for 14 consecutive days prior to CCl4 challenge. Pretreatment with SP significantly decreased alanine transaminase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBIL) levels, while increasing the levels of prealbumin (PALB) in the CCl4-challenged mice, which were accompanied by diminished liver injuries, increased superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities, increased GSH levels, and reduced malondialdehyde (MDA) content. The pretreatment with SP also markedly reduced the CCl4-induced expression of tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1ß), inducible nitric oxide synthase (iNOS) and nitric oxide (NO). Furthermore, the pretreatment with SP decreased hepatic Toll-like receptor 4 (TLR4) expression and inhibited the phosphorylation of p38 MAPK, extracellular signal-regulated kinase (p-ERK), c-Jun N-terminal kinase (p-JNK) and nuclear factor-kappa B (NF-κB) in the CCl4-challenged mice. These results suggest that the pretreatment with SP protected against CCl4-induced liver damage via its anti-oxidative and anti-inflammatory activities. SP might be suitable for functional foods and natural drugs in preventing CCl4-induced hepatotoxicity.