Publications by authors named "Ximing Xu"

211 Publications

Ulinastatin Ameliorates IL-1-Induced Cell Dysfunction in Human Nucleus Pulposus Cells via Nrf2/NF-B Pathway.

Oxid Med Cell Longev 2021 21;2021:5558687. Epub 2021 Apr 21.

Department of Orthopedic Surgery, Changzheng Hospital, Navy Medical University (Second Military Medical University), No. 415 Fengyang Road, Shanghai 200003, China.

Low back pain (LBP) has been a wide public health concern worldwide. Among the pathogenic factors, intervertebral disc degeneration (IDD) has been one of the primary contributors to LBP. IDD correlates closely with inflammatory response and oxidative stress, involving a variety of inflammation-related cytokines, such as interleukin 1 beta (IL-1), which could result in local inflammatory environment. Ulinastatin (UTI) is a kind of acidic protein extracted from human urine, which inhibits the release of tumor necrosis factor alpha (TNF-) and other inflammatory factors to protect organs from inflammatory damage. However, whether this protective effect of UTI on human nucleus pulposus (NP) exists, and how UTI affects the biological behaviors of human NP cells during IDD remain elusive. In this current study, we revealed that UTI could improve the viability of NP cells and promote the proliferation of NP cells. Additionally, UTI could protect human NP cells via ameliorating IL-1-induced apoptosis, inflammatory response, oxidative stress, and extracellular matrix (ECM) degradation. Molecular mechanism analysis suggested that the protective effect from UTI on IL-1-treated NP cells were through activating nuclear factor- (erythroid-derived 2-) like 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway and the suppression of NF-B signaling pathway. Therefore, UTI may be a promising therapeutic medicine to ameliorate IDD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2021/5558687DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084647PMC
May 2021

Gamabufotalin Inhibits Osteoclastgenesis and Counteracts Estrogen-Deficient Bone Loss in Mice by Suppressing RANKL-Induced NF-κB and ERK/MAPK Pathways.

Front Pharmacol 2021 23;12:629968. Epub 2021 Apr 23.

Department of Spine Surgery, Changzheng Hospital, Naval Medical University, Shanghai, China.

Osteolytic bone disease is a condition of imbalanced bone homeostasis, characterized mainly by excessive bone-resorptive activity, which could predispose these populations, such as the old and postmenopausal women, to developing high risk of skeletal fragility and fracture. The nature of bone homeostasis is the coordination between the osteoblasts (OBs) and osteoclasts (OCs). Abnormal activation of osteoclasts (OCs) could compromise the bone homeostasis, constantly followed by a clutch of osteolytic diseases, including postmenopausal osteoporosis, osteoarthritis, and rheumatoid arthritis. Thus, it is imperatively urgent to explore effective medical interventions for patients. The traditional Chinese medicine (TCM) gamabufotalin (CS-6) is a newly identified natural product from Chansu and has been utilized for oncologic therapies owing to its good clinical efficacy with less adverse events. Previous study suggested that CS-6 could be a novel anti-osteoporotic agent. Nevertheless, whether CS-6 suppresses RANK-(receptor activator of nuclear factor-κ B ligand)/TRAF6 (TNF receptor-associated factor 6)-mediated downstream signaling activation in OCs, as well as the effects of CS-6 on OC differentiation , remains elusive. Therefore, in this present study, we aimed to explore the biological effects of CS-6 on osteoclastogenesis and RANKL-induced activation of related signaling pathways, and further to examine the potential therapeutic application in estrogen-deficient bone loss in the mice model. The results of experiment showed that CS-6 can inhibit RANKL-induced OC formation and the ability of bone resorption in a dose-dependent manner at both the early and late stages of osteoclastogenesis. The gene expression of OC-related key genes such as tartrate-resistant acid phosphatase (TRAP), CTSK, DC-STAMP, MMP9, and β3 integrin was evidently reduced. In addition, CS-6 could mitigate the systemic estrogen-dependent bone loss and pro-inframammary cytokines in mice . The molecular mechanism analysis suggested that CS-6 can suppress RANKL/TRAF6-induced early activation of NF-κB and ERK/MAPK signaling pathways, which consequently suppressed the transcription activity of c-Fos and NFATc1. Taken together, this present study provided ample evidence that CS-6 has the promise to become a therapeutic candidate in treating osteolytic conditions mediated by elevated OC formation and bone resorption.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphar.2021.629968DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8104077PMC
April 2021

Neuropeptide Y prevents nucleus pulposus cells from cell apoptosis and IL‑1β‑induced extracellular matrix degradation.

Cell Cycle 2021 May 8;20(10):960-977. Epub 2021 May 8.

Department of Orthopedic Surgery, Spine Center, Changzheng Hospital, Naval Medical University, Shanghai, China.

Intervertebral disc degeneration (IDD) is characterized by excessive inflammatory reaction, and neuropeptide Y (NPY) was reported to have anti-inflammatory effect. However, the effect of NPY on NP cells has not been investigated up to date. This study aimed to clarify the role of NPY on the process of IDD. Fourteen fresh human lumbar intervertebral discs were harvested, and degeneration-related proteins were examined. Pfirrmann grading system was used to evaluate IDD. Rat nucleus pulposus (NP) cells were used to investigate the effect of NPY on the proliferation, apoptosis, and extracellular matrix (ECM) in NP cell induced by IL-1βin vitro. The expression levels of NPY and its receptors (type 1 receptor, Y1R, and type 2 receptor, Y2R) were detected via immunohistochemical analysis, western blot, and quantitative real-time polymerase chain reaction (qRT-PCR). Cell viability and proliferation were explored using cell counting kit-8 assay, western blot, and immunofluorescence analysis. Cell apoptosis was investigated by Hoechst staining, JC-1 Staining, annexin V-FITC/PI double staining, and western blot. The secretion of NPY from NP cells was determined via enzyme-linked immunosorbent assay (ELISA). The expression of anabolic and catabolic gene was analyzed by qRT-PCR, western blot, immunofluorescence analysis, and ELISA. The expression of Y2R was significantly increased in both human degenerative intervertebral discs and IL-1β-induced NP cells. Although no positive results for NPY indicated by western blot both in vivo and in vitro, ELISA results demonstrated that the secretion of NPY from NP cells was increased by low-concentration IL-1β, but was decreased when the concentration of IL-1β was 30 ng/ml and above. In addition, NPY could promote NP cells proliferation and protect NP cells against IL‑1β‑induced apoptosis via suppressing mitochondrial-mediated apoptosis pathway. What's more, NPY can suppress the expression of catabolic gene and ameliorate IL-1β- induced matrix degeneration in NP cells. In conclusion, NPY could promote NP cell proliferation and alleviate IL‑1β‑induced cell apoptosis via mitochondrial pathway. In addition, NPY can suppress the expression of ECM‑catabolic proteinases and ameliorate IL-1β- induced ECM degeneration in vitro.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/15384101.2021.1911914DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8172154PMC
May 2021

Enhancement of oral bioavailability and anti-hyperuricemic activity of aloe emodin via novel Soluplus®-glycyrrhizic acid mixed micelle system.

Drug Deliv Transl Res 2021 Apr 15. Epub 2021 Apr 15.

Department of Pharmaceutics, School of Pharmacy, Centre for Nano Drug/Gene Delivery and Tissue Engineering, Jiangsu University, Zhenjiang, 212013, People's Republic of China.

The objective of this study was to fabricate a novel drug delivery system using Soluplus® (polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer) and glycyrrhizic acid to improve solubility, bioavailability, and anti-hyperuricemic activity of aloe emodin (AE). The AE-loaded mixed micelles (AE-M) were prepared by thin-film hydration method. The optimal AE-M contained small-sized (30.13 ± 1.34 nm) particles with high encapsulation efficiency (m/m, %) of 90.3 ± 1.08%. The release rate of AE increased in the micellar formulation than that of free AE in the four media (DDW, pH 7.0; phosphate buffer solution, pH 7.4; phosphate buffer solution, pH 6.8; and hydrochloric acid aqueous solution, pH 1.2). In comparison to free AE, the pharmacokinetic study of AE-M showed that its relative oral bioavailability increased by 3.09 times, indicating that mixed micelles may promote gastrointestinal absorption. More importantly, AE-M effectively reduced uric acid level by inhibiting xanthine oxidase (XOD) activity in model rats. The degree of ankle swelling, serum levels of interleukin (IL)-1, and IL-6-related inflammatory factors levels all decreased in the gouty arthritis model established via monosodium urate (MSU) crystals. Taken together, the AE-M demonstrated the potential to improve the bioavailability, anti-hyperuricemic activity, and anti-inflammation of AE.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s13346-021-00969-8DOI Listing
April 2021

Comparison of Surgical Results of the Bridge Crane Technique Versus Laminectomy for the Treatment of Thoracic Myelopathy Caused by Ossification of the Ligamentum Flavum.

Global Spine J 2021 Mar 9:2192568221996689. Epub 2021 Mar 9.

Department of Spine Surgery, Changzheng Hospital, Naval Medical University, Shanghai, People's Republic of China.

Study Design: A retrospective study.

Objectives: This study aimed to evaluate the safety and effectiveness of the bridge crane technique versus laminectomy for the treatment of thoracic myelopathy caused by ossification of the ligamentum flavum (OLF).

Methods: Totally 41 patients who underwent surgical decompression due to thoracic OLF from May 2017 to June 2018 in our institution were enrolled in this study and were divided into group BG (bridge crane technique, n = 19) and group L (laminoectomy, n = 22). Demographic data was collected from medical records and the modified Japanese Orthopaedic Association (JOA) scoring system was used to evaluate the neurological outcomes during the follow-up. Surgery-related complications were analyzed.

Results: The mean duration of follow-up was comparable between group BG (19.4 ± 1.5 months) and group L (19.6 ± 1.4 months). No statistical differences were observed between two groups in terms of gender, age, duration of symptoms, preoperative occupying rate, involved levels, operation time, intraoperative blood loss, and complications. The JOA score significantly increased at the final follow-up in both groups. However, patients in group BG had higher JOA score and recovery rate ( < 0.05). Four patients in group L experienced complications, including 3 cerebrospinal fluid (CSF) leakage and one postoperative hematoma. Only one patient in group BG had CSF leakage.

Conclusion: The results of this study suggested that bridge crane technique may be relatively safe and effective for patients with symptomatic thoracic OLF with more satisfactory clinical improvement. However, high-quality studies are still required to validate the results of this study.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/2192568221996689DOI Listing
March 2021

The Gantry Crane Technique: A Novel Technique for Treating Severe Thoracic Spinal Stenosis and Myelopathy Caused by Ossification of the Ligamentum Flavum and Preliminary Clinical Results.

Global Spine J 2021 Mar 5:2192568221996693. Epub 2021 Mar 5.

Department of Spine Surgery, 56652Changzheng Hospital, Naval Medical University, Shanghai, People's Republic of China.

Study Design: Retrospective single-arm study.

Objective: To propose a novel technique named the gantry crane technique for treating severe thoracic spinal stenosis and myelopathy caused by thoracic ossification of the ligamentum flavum (TOLF) and investigate its clinical results.

Methods: From June 2017 to January 2019, 18 patients presenting with severe spinal stenosis and myelopathy caused by TOLF were included in our study. All patients were treated with gantry crane technique, pre-operative JOA score, as well as 3 days-, 3 months-, 6 months-, 12 months-, 24 months after operation, and Hirabayashi recovery rate were reported. Pre- and post-operative image were utilized for the assessment of post-operative effect. Peri-operative complications were recorded to assess the safety of the gantry crane technique.

Results: The JOA score increased from 10.56 ± 3.76 preoperatively to 12.94 ± 3.33, 13.56 ± 3.48, 13.94 ± 3.32, 14.17 ± 3.70 and 14.06 ± 3.54 in 3 days, 3 months, 6 months, 12 months and 24 months after surgery, respectively. The post-operative JOA scores were improved with statistical significance at the level of < 0.05. The recovery rate was (39.09 ± 33.85) %, (51.35 ± 42.60) %, (55.79 ± 36.10) %, (64.98 ± 29.24) % and (60.98 ± 35.96) % for 3 days, 3 months, 6 months, 12 months and 24 months after surgery, respectively. There were 2 cases of SSI (surgical site infection), 1 case of NI (neurovascular injury) and 1 case of cerebrospinal fluid (CSF) leakage.

Conclusions: This study highlights a safe and effective technique, the gantry crane technique, for treating severe thoracic spinal stenosis and myelopathy caused by TOLF.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/2192568221996693DOI Listing
March 2021

Biochemical Characterization of Arylamine acetyltransferases From .

Front Microbiol 2020 18;11:595083. Epub 2021 Jan 18.

Marine Drug Screening and Evaluation Platform (QNLM), School of Medicine and Pharmacy, Ocean University of China, Qingdao, China.

is a zoonotic bacterium that is capable of causing highly lethal diseases in humans; this pathogen is responsible for 95% of all seafood-related deaths in the United States. Arylamine -acetyltransferases (NAT, E.C. 2.3.1.5) is a major family of xenobiotic-metabolizing enzymes that can biotransform aromatic amine chemicals. In this research, to evaluate the effect of NAT on acetyl group transformation in arylamine antibiotics, we first used sequence alignment to study the structure of NAT [(VIBVN)NAT]. The gene encodes a protein of 260 amino acids, which has an approximate molecular mass of 30 kDa. Then we purified recombinant (VIBVN)NAT and determined the enzyme activity by PNPA and DTNB methods. The DTNB method indicates that this prokaryotic NAT has a particular substrate specificity towards aromatic substrates. However, (VIBVN)NAT lost most of its activity after treatment with high concentrations of urea and HO. In addition, we also explored the stability of the enzyme at different temperatures and pH values. In analyzing the influence of metal ions, the enzyme activity was significantly inhibited by Zn and Cu. The kinetic parameters and were determined using hydralazine, isoniazid, -amino salicylic acid, and -chloro--methylaniline as substrates, and the , and size distribution of (VIBVN)NAT were observed. In particular, a molecular docking study on the structure of (VIBVN)NAT was conducted to understand its biochemical traits. These results showed that (VIBVN)NAT could acetylate various aromatic amine substrates and contribute to arylamine antibiotic resistance in .
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fmicb.2020.595083DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7847940PMC
January 2021

Mixed micelles for enhanced oral bioavailability and hypolipidemic effect of liquiritin: preparation, and evaluation.

Drug Dev Ind Pharm 2021 Feb 5;47(2):308-318. Epub 2021 Feb 5.

Department of Pharmaceutics, School of Pharmacy, Center for Nano Drug/Gene Delivery and Tissue Engineering, Jiangsu University, Zhenjiang, People's Republic of China.

Objectives: Liquiritin, as one of the main flavonoids in Glycyrrhiza, exhibits extensive pharmacological effects, such as the anti-oxidant, anti-inflammatory, anti-tumor and so on. Herein, the aqueous solubility and oral bioavailability of liquiritin was purposely enhanced the preparation of the mixed micelles.

Methods: The liquiritin-loaded micelles (LLM) were fabricated thin-film dispersion method. The optimal LLM formulation was evaluated through physical properties including particle size (PS), encapsulation efficiency (EE) and drug loading (DL). accumulate release as well as pharmacokinetics were also evaluated. Moreover, the hypolipidemic activity of LLM was observed in the hyperlipidemia mice model.

Results: The LLM exhibited a homogenous spherical shape with small mean PS, good stability and high encapsulation efficiency. The accumulate release rates of the LLM were obviously higher than free liquiritin. The oral bioavailability of the formulation was heightened by 3.98 times in comparison with the free liquiritin. More importantly, LLM increased the hypolipidemic and effect of alleviating lipid metabolism disorder in hepatocytes of liquiritin in hyperlipidemia mice model.

Conclusions: Collectively, the improved solubility of liquiritin in water coupled with its enhanced oral bioavailability and concomitant hypolipidemic activity could be attributed to the incorporation of the drug into the mixed micelles.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/03639045.2021.1879839DOI Listing
February 2021

Improved Oral Bioavailability and Hypolipidemic Effect of Syringic Acid via a Self-microemulsifying Drug Delivery System.

AAPS PharmSciTech 2021 Jan 13;22(1):45. Epub 2021 Jan 13.

Key Lab for Drug Delivery & Tissue Regeneration, Jiangsu Provincial Research Center for Medicinal Function Development of New Food Resources, School of Pharmacy, Jiangsu University, Zhenjiang, 212013, People's Republic of China.

This study aimed to develop a self-microemulsifying drug delivery system (SMEDDS) to enhance the solubility, oral bioavailability, and hypolipidemic effects of syringic acid (SA), a bioactive and poorly-soluble polyphenol. Based on the response surface methodology-central composite design (RSM-CCD), an optimum formulation of SA-SMEDDS, consisting of ethyl oleate (oil, 12.30%), Cremophor-EL (surfactant, 66.25%), 1,2-propanediol (cosurfactant, 21.44%), and drug loading (50 mg/g), was obtained. The droplets of SA-SMEDDS were nanosized (16.38 ± 0.12 nm), spherically shaped, and homogeneously distributed (PDI = 0.058 ± 0.013) nanoparticles with high encapsulation efficiency (98.04 ± 1.39%) and stability. In vitro release study demonstrated a prolonged and controlled release of SA from SMEDDS. In vitro cell studies signified that SA-SMEDDS droplets substantially promoted cellular internalization. In comparison with the SA suspension, SA-SMEDDS showed significant prolonged T, t, and MRT after oral administration. Also, SA-SMEDDS exhibited a delayed in vivo elimination, increased bioavailability (2.1-fold), and enhanced liver accumulation. Furthermore, SA-SMEDDS demonstrated significant improvement in alleviating serum lipid profiles and hepatic steatosis in high-fat diet-induced hyperlipidemia in mice. Collectively, SMEDDS demonstrated potential as a nanosystem for the oral delivery of SA with enhanced bioavailability and hypolipidemic effects.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1208/s12249-020-01901-yDOI Listing
January 2021

The association between immune-related adverse events and the prognosis of solid cancer patients treated with immunotherapy: a systematic review and meta-analysis.

Ther Adv Med Oncol 2020 18;12:1758835920980546. Epub 2020 Dec 18.

Department of Oncology, RenMin Hospital of Wuhan University, Jiefang Road #238 Wuchang District, Wuhan, 430000, China.

Background: Immune-related adverse events (irAEs) are common during immune checkpoint inhibitor (ICI) treatment and reported to be associated with good survival. This study evaluated the association between onset timing of irAEs and survival of cancer patients treated with ICIs.

Methods: Databases including PubMed, Embase, and the Cochrane library were systematically searched to retrieve clinical studies assessing the relationship between irAEs and survival in cancer patients with ICIs. The overall response rate for treatment response and hazard ratio (HR) for overall survival (OS) and progression-free survival (PFS) were calculated using RevMan 5.3. Subgroup analysis in terms of cancer type, ICIs type, region, specific irAEs, accordingly.

Results: A total of 34 studies were included. The HRs for OS and PFS in cancer patients with without irAEs were 0.57 [95% confidence interval (CI): 0.44, 0.74;  < 0.0001], and 0.50 (95% CI: 0.37, 0.67;  < 0.00001), respectively. The odds ratio for overall response in cancer patients with irAEs was 4.72 (95% CI: 3.48, 6.40;  < 0.00001) compared with those without irAEs. Subgroup analyses suggested that the prognostic role of irAEs was associated with cancer types and region, but not irAEs types. The landmark analysis of OS revealed that there is a non-proportional (early) effect of irAEs on OS in ICI-treated cancer patients (landmark >12 weeks, HR = 1.08; 95% CI: 0.89, 1.30;  = 0.46).

Conclusion: Our findings suggest that the occurrence of irAEs could be a prognostic factor for cancer patients who were treated with ICIs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1758835920980546DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7758867PMC
December 2020

A t-SNE Based Classification Approach to Compositional Microbiome Data.

Front Genet 2020 14;11:620143. Epub 2020 Dec 14.

School of Statistics and Data Science, Nankai University, Tianjin, China.

As a data-driven dimensionality reduction and visualization tool, t-distributed stochastic neighborhood embedding (t-SNE) has been successfully applied to a variety of fields. In recent years, it has also received increasing attention for classification and regression analysis. This study presented a t-SNE based classification approach for compositional microbiome data, which enabled us to build classifiers and classify new samples in the reduced dimensional space produced by t-SNE. The Aitchison distance was employed to modify the conditional probabilities in t-SNE to account for the compositionality of microbiome data. To classify a new sample, its low-dimensional features were obtained as the weighted mean vector of its nearest neighbors in the training set. Using the low-dimensional features as input, three commonly used machine learning algorithms, logistic regression (LR), support vector machine (SVM), and decision tree (DT) were considered for classification tasks in this study. The proposed approach was applied to two disease-associated microbiome datasets, achieving better classification performance compared with the classifiers built in the original high-dimensional space. The analytic results also showed that t-SNE with Aitchison distance led to improvement of classification accuracy in both datasets. In conclusion, we have developed a t-SNE based classification approach that is suitable for compositional microbiome data and may also serve as a baseline for more complex classification models.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fgene.2020.620143DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7767995PMC
December 2020

Exosome-mediated delivery of antisense oligonucleotides targeting α-synuclein ameliorates the pathology in a mouse model of Parkinson's disease.

Neurobiol Dis 2021 01 6;148:105218. Epub 2020 Dec 6.

Department of Neurology, Renmin Hospital of Wuhan University, Wuhan 430060, China. Electronic address:

Parkinson's disease (PD) is the second most common neurodegenerative disease. Pathologically, PD is characterized by the formation of Lewy bodies (LBs) in the brain, which mainly comprises phosphorylated and aggregated α-synuclein (α-syn). The aberrant aggregation of α-syn is believed to play a key role in the pathogenesis of PD. While α-syn expression can be reduced by antisense oligonucleotides (ASOs), the challenge to deliver ASOs safely and effectively into the neurons remains unresolved. Here, we developed a safe and highly effective ASO delivery method by using exosomes. We first identified the ASO sequence that selectively reduced α-syn expression: ASO4. Exosome-mediated delivery of ASO4 (exo-ASO4) showed high cellular uptake and low toxicity in primary neuronal cultures. Exo-ASO4 also significantly attenuated α-syn aggregation induced by pre-formed α-syn fibrils in vitro. Exo-ASO4 intracerebroventricular injection into the brains of α-syn A53T mice, a transgenic model of PD, significantly decreased the expression of α-syn and attenuated its aggregation. Furthermore, exo-ASO4 ameliorated the degeneration of dopaminergic neurons in these mice. Finally, the α-syn A53T mice showed significantly improved locomotor functions after exo-ASO4 injection. Overall, this study demonstrates that exosome-mediated ASO4 delivery may be an effective treatment option for PD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.nbd.2020.105218DOI Listing
January 2021

Immune-related microRNA signature for predicting prognosis and the immune microenvironment in hepatocellular carcinoma.

Life Sci 2021 Jan 19;265:118799. Epub 2020 Nov 19.

Cancer Center, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan 430060, China. Electronic address:

Aims: As vital regulators of post-transcription gene expression, microRNAs are involved in the initiation and progression of hepatocellular carcinoma (HCC), including antitumor immune responses. We aimed to identify an immune-related microRNA signature and explore the influence of this signature on the prognosis and immunity of HCC.

Materials And Methods: Differentially expressed immune-related microRNAs were identified between high- and low-immunity groups in the TCGA-HCC dataset. Then, Cox regression models were used to construct an immune-related microRNA signature. We assessed the prognostic value and clinical relevance of this signature. Furthermore, we analyzed the effect of the immune-related microRNA signature on immune cells and immune checkpoints.

Key Findings: We screened 41 differentially expressed immune-related microRNAs, of which 7 microRNAs were used to construct the immune signature. Survival analysis showed that high-risk patients had a shorter survival. The immune-related microRNA signature was an independent prognostic marker and was associated with the clinical stage. To understand the functional mechanism of the seven-microRNA signature, we predicted target genes of microRNAs. Enrichment analysis indicated that these target genes participated in immune responses. Moreover, we found that the microRNA signature was related to tumor-infiltrating immune cells. In high-risk patients, there was a higher expression of inhibitory immune checkpoints. On the contrary, the expression of stimulatory immune checkpoints was lower in high-risk patients.

Significance: We successfully identified an immune-related microRNA signature that was strongly correlated with the prognosis and immune microenvironment of HCC. The immune-related microRNAs signature might have important implications for improving the clinical outcomes of HCC patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.lfs.2020.118799DOI Listing
January 2021

3D printable Sodium alginate-Matrigel (SA-MA) hydrogel facilitated ectomesenchymal stem cells (EMSCs) neuron differentiation.

J Biomater Appl 2021 01 15;35(6):709-719. Epub 2020 Oct 15.

School of Pharmacy, Jiangsu University, Zhenjiang, China.

Ectomesenchymal stem cells (EMSCs) are typical adult stem cells obtained from the cranial neural crest. They have the potential to differentiate into various cell types, such as osseous cells, neurons and glial cells. Three-dimensional (3 D) printing is a novel method to construct biological structures by rapid prototyping. Previously, our group reported on the stemness and multi-lineage differentiation potential of EMSCs on gels. However, the exploration of EMSCs in 3 D printing and then evaluation of the growth and neuronal differentiation of EMSCs on extruded 3 D printable hybrid hydrogels has not been reported. Therefore, the current study explored the novel hybrid Sodium alginate-Matrigel (SA-MA) hydrogel extruded 3 D printing to design an scaffold to promote the differentiation and growth of EMSCs. In addition, the physical properties of the hydrogel were characterized and its drug-releasing property determined. Notably, the results showed that the construct exhibited a sustain-released effect of growth factor BDNF in accordance with the Higuchi equation. Moreover, the cell survival rate on the 3 D printed scaffold was 88.22 ± 1.13% with higher neuronal differentiation efficiency compared with 2 D culture. Thus, SA-MA's ability to enhanced EMSCs neuronal differentiation offers a new biomaterial for neurons regeneration in the treatment of spinal cord injury.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0885328220961261DOI Listing
January 2021

Identify potent SARS-CoV-2 main protease inhibitors via accelerated free energy perturbation-based virtual screening of existing drugs.

Proc Natl Acad Sci U S A 2020 11 13;117(44):27381-27387. Epub 2020 Oct 13.

Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences, Sun Yat-Sen University, 510006 Guangzhou, People's Republic of China;

The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global crisis. There is no therapeutic treatment specific for COVID-19. It is highly desirable to identify potential antiviral agents against SARS-CoV-2 from existing drugs available for other diseases and thus repurpose them for treatment of COVID-19. In general, a drug repurposing effort for treatment of a new disease, such as COVID-19, usually starts from a virtual screening of existing drugs, followed by experimental validation, but the actual hit rate is generally rather low with traditional computational methods. Here we report a virtual screening approach with accelerated free energy perturbation-based absolute binding free energy (FEP-ABFE) predictions and its use in identifying drugs targeting SARS-CoV-2 main protease (M). The accurate FEP-ABFE predictions were based on the use of a restraint energy distribution (RED) function, making the practical FEP-ABFE-based virtual screening of the existing drug library possible. As a result, out of 25 drugs predicted, 15 were confirmed as potent inhibitors of SARS-CoV-2 M The most potent one is dipyridamole (inhibitory constant K = 0.04 µM) which has shown promising therapeutic effects in subsequently conducted clinical studies for treatment of patients with COVID-19. Additionally, hydroxychloroquine (K = 0.36 µM) and chloroquine (K = 0.56 µM) were also found to potently inhibit SARS-CoV-2 M We anticipate that the FEP-ABFE prediction-based virtual screening approach will be useful in many other drug repurposing or discovery efforts.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1073/pnas.2010470117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7959488PMC
November 2020

Effect of biochar on rice starch properties and starch-related gene expression and enzyme activities.

Sci Rep 2020 10 9;10(1):16917. Epub 2020 Oct 9.

Shenyang Agricultural University, Shenyang, China.

We determined the effects of biochar on starch properties and the activities of enzymes and expression levels of genes related to starch in two Japonica rice cultivars. The two rice varieties were subjected to five biochar treatments (0, control; and 5, 10, 20, and 40 t/hm). In both rice varieties, the content of apparent amylose and resistant starch were lower in biochar treatments than in the control. The proportion of fa chains was higher and that of fb3 chain was lower in the biochar treatments than in the control. Starch viscosity and cooking taste quality were improved by the biochar treatments. In both rice varieties, the activity of granule-bound starch synthase was significantly decreased by biochar treatments, and the activities of soluble starch synthase, starch branching enzyme, and starch debranching enzyme were significantly increased. The transcript levels of genes encoding starch synthases and starch branching enzymes were significantly increased by biochar treatments. We conclude that biochar at a dose of 5-10 t/hm can regulate the activity of starch-related enzymes, and this affects the type, content, and fine structure of starch. Therefore, the addition of biochar to soil can improve the viscosity and taste quality of rice starch.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-020-73888-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7547735PMC
October 2020

Enhanced oral bioavailability of self-assembling curcumin-vitamin E prodrug-nanoparticles by co-nanoprecipitation with vitamin E TPGS.

Drug Dev Ind Pharm 2020 Nov;46(11):1800-1808

Department of Pharmaceutics, School of Pharmacy, Center for Nano Drug/Gene Delivery and Tissue Engineering, Jiangsu University, Zhenjiang, PR China.

Curcumin (CUR), a nontoxic natural compound with potent antitumor activity, was limited in clinical application due to its insolubility and exceedingly low bioavailability. In this study, a novel prodrug-nanoparticle (CSSV/TPGS-NPs) self-assembled by co-nanoprecipitation of CUR-s-s-vitamin E conjugate and d-alpha-tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS) was prepared in attempt to solve aforementioned obstacles. CSSV/TPGS-NPs showed smaller sizes and better stability compared with that of CUR-s-s-vitamin E conjugate prodrug-nanoparticles (CSSV-NPs). Significantly, the absorption constant and effective permeability of CSSV/TPGS-NPs in different intestinal tracts increased 1.31-2.78 times and 1.81-6.95 times than that of CUR suspension, respectively. Pharmacokinetic study in Sprague-Dawley (SD) rats demonstrated that orally administered CSSV/TPGS-NPs displayed a prolonged plasma circulation with 8.06-fold increase in relative bioavailability compared to that of the CUR suspension. Altogether, conjugation of hydrophobic native CUR with vitamin E to form CSSV/TPGS-NPs is a promising technology for sustained and controlled drug delivery of CUR with improved oral bioavailability .
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/03639045.2020.1821049DOI Listing
November 2020

Enhanced oral bioavailability of Bisdemethoxycurcumin-loaded self-microemulsifying drug delivery system: Formulation design, in vitro and in vivo evaluation.

Int J Pharm 2020 Nov 18;590:119887. Epub 2020 Sep 18.

Department of Pharmaceutics, School of Pharmacy, Center for Nano Drug/Gene Delivery and Tissue Engineering, Jiangsu University, Zhenjiang 212013, China. Electronic address:

In this study, we sought to overcome the poor solubility and bioavailability of bismethoxycurcumin (BDMC) by fabricating a BDMC-loaded self micro-emulsifying system (BDMC-SMEDDS). Solubility and compatibility tests, pseudo-ternary phase diagrams (PTPDs) as well as d-optimal concept was applied to design the formulation. The assessment of the prepared BDMC-SMEDDS in-vitro mainly included droplet size (DS) and entrapment efficiency (EE) determination, morphology, drug release and stability testing. Besides, the in vivo behavior was also evaluated after oral administration of BDMC-SMEDDS to rats. The optimal formulation was found to compose of Kolliphor EL (K-EL, emulsifier, 645.3 mg), PEG 400 (co-emulsifier, 147.2 mg), ethyl oleate (EO, oil, 207.5 mg) and BDMC (50 mg). The BDMC-SMEDDS with satisfactory stability had a mean size of 21.25 ± 3.23 nm and EE of 98.31 ± 0.32%. Roughly 70% of BDMC was released from BDMC-SMEDDS within 84 h compared with <20% from the free BDMC. More importantly, the in-vivo behavior of BDMC-SMEDDS showed that the AUC and plasma concentration of BDMC increased substantially as compared to the free BDMC. Altogether, BDMC-SMEDDS has the potential to enhance the solubility and bioavailability of BDMC and could be applied in the clinics.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijpharm.2020.119887DOI Listing
November 2020

Sulfated polymannuroguluronate TGC161 ameliorates leukopenia by inhibiting CD4 T cell apoptosis.

Carbohydr Polym 2020 Nov 6;247:116728. Epub 2020 Jul 6.

Key Laboratory of Marine Drugs of Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao, 266003, China; Center for Innovation Marine Drug Screening & Evaluation, Pilot National Laboratory for Marine Science and Technology (Qingdao), Qingdao, 266237, China; Marine Biomedical Research Institute of Qingdao, Qingdao, 266071, China. Electronic address:

Polysaccharides have aroused considerable interest due to their diverse biological activities and low toxicity. In this study, we evaluated the effect of marine polysaccharide sulfated polymannuroguluronate (TGC161) on the leukopenia induced by chemotherapy. It is found that TGC161 ameliorates the leukopenia. Besides, TGC161 would promote CD4 T cell differentiation and maturation in the thymus, but does not have a significant effect on precursor cells in bone marrow. Furthermore, TGC161 inhibits CD4 T cell apoptosis in vitro. Collectively, our findings offer a natural and harmless polysaccharide to ameliorate leukopenia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.carbpol.2020.116728DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7336955PMC
November 2020

Extraction and structural analysis of polysaccharide with low molecular weight and its lipid-lowering effect on nonalcoholic fatty liver disease.

Food Sci Nutr 2020 Jul 18;8(7):3212-3224. Epub 2020 May 18.

Key Lab for Drug Delivery and Tissue Regeneration Jiangsu Provincial Research Center for Medicinal Function Development of New Food Resources School of Pharmacy Jiangsu University Zhenjiang China.

Nonalcoholic fatty liver disease (NAFLD) is one of the prevalent and typical chronic liver diseases. In this study, we extracted a novel polysaccharide (ASP) with low molecular weight (MW) of 3.2 kDa through optimized "one-step" purification process. The major monosaccharide components of ASP were mannose, rhamnose, glucuronic acid, galactose, arabinose, and xylose with weight ratio of 0.23:0.17:14.41:0.39:1.68:0.87, respectively. Herein, "small" ASP could serve as an effective therapeutic option for NAFLD both in free fatty acid-induced L02 models and in high-fat diet-induced mice models. Results revealed that low MW ASP dose-dependently decreased TG, TC in vitro and TG, TC, ALT, HDL-C, and LDL-C in vivo. Oil Red O-positive area and Nile red fluorescence intensity decreased in ASP treatment groups both in vitro and in vivo which suggested ASP could reduce lipid accumulation and fatty regeneration. Hematoxylin-eosin staining results shown a decrease in hepatocytes ballooning indicating that ASP could ameliorate liver lipid degeneration. Briefly, a novel polysaccharide with low MW was successfully obtained which can prospectively act as NAFLD therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/fsn3.1581DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7382173PMC
July 2020

Effects of Genetic Background and Environmental Conditions on Amylopectin Chain-Length Distribution in a Recombinant Inbred Line of an Inter-subspecies Rice Cross.

J Agric Food Chem 2020 Jul 1;68(28):7444-7452. Epub 2020 Jul 1.

Rice Research Institute of Shenyang Agricultural University, Shenyang, Liaoning 110866, People's Republic of China.

Amylopectin is an essential starch property, and the chain-length distribution of amylopectin (APCLD) is closely associated with the eating and cooking quality of rice. In this study, a series of recombinant inbred lines derived from an / cross were planted in four areas with distinct ecological conditions (LN, SC, JS, and GD), and the relationship among APCLD, environmental factors, and genetic background was analyzed. The results showed that APCLD was strongly influenced by environmental factors, which dynamically changed from heading to the mature stage. The solar radiation, luminous flux, and light hours were positively correlated with Fa but negatively correlated with Fb and Fb. The temperature was negatively correlated with Fa and Fb but positively correlated with Fb and Fb. The temperature was the primary factor affecting APCLD, followed by humidity and light. There was no significant correlation between the pedigree percentage and APCLD. Furthermore, we detected six quantitative trait loci related to Fa, Fb, Fb, and Fb chains, several of which shared a similar region to previously reported loci, including (). The truncated allele increased Fa, Fb, and Fb but decreased Fb in LN, whereas Fa was decreased but Fb and Fb were increased in JS. Elucidating the effects of climate factors and genetic background on APCLD could provide a theoretical basis and technical guidance for high-quality rice breeding.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.jafc.0c02713DOI Listing
July 2020

The prolonged disruption of a single-course amoxicillin on mice gut microbiota and resistome, and recovery by inulin, Bifidobacterium longum and fecal microbiota transplantation.

Environ Pollut 2020 Oct 23;265(Pt A):114651. Epub 2020 Apr 23.

School of Medicine, Nankai University, Tianjin, 300071, China. Electronic address:

The usages of antibiotics in treating the pathogenic infections could alter the gut microbiome and associated resistome, causing long term adverse impact on human health. In this study, mice were treated with human-simulated regimen 25.0 mg kg of amoxicillin for seven days, and their gut microbiota and resistome were characterized using the 16S rRNA amplicons sequencing and the high-throughput qPCR, respectively. Meanwhile, the flora restorations after individual applications of inulin, Bifidobacterium longum (B. longum), and fecal microbiota transplantation (FMT) were analyzed for up to 35 days. The results revealed the prolonged negative impact of single course AMX exposure on mice gut microbiota and resistome. To be specific, pathobionts of Klebsiella and Escherichia-Shigella were significantly enriched, while prebiotics of Bifidobacterium and Lactobacillus were dramatically depleted. Furthermore, β-lactam resistance genes and efflux resistance genes were obviously enriched after amoxicillin exposure. Compared to B. longum, FMT and inulin were demonstrated to preferably restore the gut microbiota via reconstituting microbial community and stimulating specific prebiotic respectively. Such variation of microbiome caused their distinct alleviations on resistome alteration. Inulin earned the greatest elimination on AMX induced ARG abundance and diversity enrichment. FMT and B. longum caused remove of particular ARGs such as ndm-1, blaPER. Network analysis revealed that most of the ARGs were prone to be harbored by Firmicutes and Proteobacteria. In general, gut resistome shift was partly associated with the changing bacterial community structures and transposase and integron. Taken together, these results demonstrated the profound disruption of gut microbiota and resistome after single-course amoxicillin treatment and different restoration by inulin, B. longum and FMT.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.envpol.2020.114651DOI Listing
October 2020

Expression of Nogo-A in dorsal root ganglion in rats with cauda equina injury.

Biochem Biophys Res Commun 2020 06 28;527(1):131-137. Epub 2020 Apr 28.

Department of Orthopedic Surgery, Spine Center, Changzheng Hospital, Second Military Medical University, No.415 Fengyang Road, Shanghai, 200003, People's Republic of China. Electronic address:

Objective: To investigate the expression of Nogo-A in dorsal root ganglion (DRG) in rats with cauda equina injury and the therapeutic effects of blocking Nogo-A and its receptor.

Methods And Materials: Fifty-eight male Sprague-Dawley rats were divided randomly into either the sham operation group (n = 24) or the cauda equina compression (CEC) control group (n = 34). Behavioral, histological, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) analyses were conducted to assess the establishment of the model. The dynamic expression change of Nogo-A was evaluated using real time-qPCR. Immunofluorescence was used to evaluate the expression of Nogo-A in the DRG and cauda equina. Furthermore, 20 male Sprague-Dawley rats were equally divided into 4 groups, including the sham group, the CEC group, the NEP1-40 (the NgR antagonist peptide) treatment group, and the JTE-013 (the S1PR2 antagonist) treatment group. Behavioral assessments and western blotting were used to evaluate the therapeutic effect of cauda equina injury via blocking Nogo-A and its receptor.

Results: Tactile allodynia and heat hyperalgesia in the CEC model developed as soon as 1 day after surgery and recovered to normal at 7 days, which was followed by the downregulation of Nogo-A in DRG neurons. However, the locomotor function impairment in the CEC model showed a different prognosis from the sensory function, which was consistent with the expression change of Nogo-A in the spinal cord. Immunofluorescence results also demonstrated that Nogo A-positive/NF200-negative neurons and axons increased in the DRG and cauda equina 7 days after surgery. Surprisingly, Schwann cells, which myelinate axons in the PNS, also expressed considerable amounts of Nogo-A. Then, after blocking the Nogo-A/NgR signaling pathway by NEP1-40, significant improvement of mechanical allodynia was identified in the first 2 days after the surgery. Western blotting suggested the NEP1-40 treatment group had lower expression of cleaved caspase-3 than the CEC and JTE-013 treatment group.

Conclusion: Neuronal Nogo-A in the DRG may be involved in regeneration and play a protective role in the CEC model. Whereas Nogo-A, released from the injured axons or expressed by Schwann cells, may act as an inhibiting factor in the process of CEC repairment. Thus, blocking the Nogo-A/NgR signaling pathway can alleviate mechanical allodynia by apoptosis inhibition.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbrc.2020.04.094DOI Listing
June 2020

Dosimetric Comparison of Three Radiotherapy Techniques in Irradiation of Left-Sided Breast Cancer Patients after Radical Mastectomy.

Biomed Res Int 2020 26;2020:7131590. Epub 2020 Mar 26.

Department of Radiation Oncology, Wuhan University, Renmin Hospital, Wuhan, 430060 Hubei Province, China.

Results: The VMAT plans showed superior to PTV dose conformity index (CI), homogeneity index (HI), protection of the ipsilateral lung, monitor units (MUs), and maximum dose (D) to the contralateral breast compared with TSP and 9FIMRT plans. The TSP provided better protection for D of the heart and left ventricle ( < 0.05). A dose for left anterior descending artery from the three techniques had no significant difference. Compared with the 9FIMRT plans, the V (%) and V (%) for the ipsilateral lung were significantly reduced with TSP and VMAT ( < 0.05). The V (%) and V (%) for the ipsilateral lung turned out to be similar between VMAT and TSP techniques.

Conclusions: Our study indicates that VMAT should be a better choice of radiotherapy for left-sided breast cancer patients after radical mastectomy. If VMAT is unavailable, 9FIMRT can achieve better CI and HI values and be more MU-efficient compared with TSP; however, TSP can effectively reduce the low dose volume of the ipsilateral lungs and heart.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2020/7131590DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7085359PMC
December 2020

Reliability and validity of multi-shot DWI in diagnosis of cervical spondylotic myelopathy: a study based on 3-T MRI.

Eur Spine J 2020 06 4;29(6):1219-1226. Epub 2020 Apr 4.

Department of Orthopedic Surgery, Spine Center, Changzheng Hospital, Second Military Medical University, No. 415, Fengyang Road, Shanghai, 200003, People's Republic of China.

Objective: To investigate whether multi-shot diffusion-weighted imaging (ms-DWI) could be applied in diagnosis and quantitative evaluation of cervical spondylotic myelopathy (CSM).

Methods: Thirty-three normal volunteers and 78 patients with CSM were included in this study. The apparent diffusion coefficient (ADC) values were measured at C2-C7 levels on sagittal section ADC map. The intraclass correlation coefficient (ICC) and Bland and Altman plot and Spearman coefficient were used to quantify the reproducibility of test and retest and inter-rater reliability. Pearson correlations were calculated to compare lADC and rADC versus mJOA and NDI scores. Receiver operating characteristic curve and the area under the curve (AUC) were applied to evaluate the diagnostic reliability.

Results: There was no statistically significant difference between ADC values obtained from normal volunteers at C2-C7 levels (P < 0.05). The ICC and spearman coefficient of lADC and rADC indicated excellent test-retest and inter-rater reliability. The mean lADC and rADC were significantly higher from patients than that from volunteers (all P < 0.01). The lADC had moderate to good correlations with mJOA and NDI (all P < 0.0001). Moreover, rADC had good to excellent correlations with mJOA and NDI (all P < 0.0001). Comparing AUCs, rADC was significantly superior in diagnosis which participants were CSM than lADC (P = 0.0118).

Conclusion: The ms-DWI could be applied in diagnosis and quantitive assessment of CSM according to lADC and rADC. A new parameter, rADC, could be served as a diagnostic indice for CSM, which may quantitively reflect the severity of CSM. These slides can be retrieved under Electronic Supplementary Material.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00586-020-06381-zDOI Listing
June 2020

The association between antibiotics use and outcome of cancer patients treated with immune checkpoint inhibitors: A systematic review and meta-analysis.

Crit Rev Oncol Hematol 2020 May 19;149:102909. Epub 2020 Feb 19.

Department of Oncology, Renmin Hospital of Wuhan University, Jiefang Road #238 Wuchang District, Wuhan 430000, China. Electronic address:

Objective: This meta-analysis was to evaluate the impact of antibiotics use on survival of cancer patients with immune checkpoint inhibitors (ICIs).

Methods: Electronic databases including Pubmed, Emabse, and the Cochrane library were searched. The primary endpoints were overall survival (OS) and progression-free survival (PFS).

Results: A total of 20 retrospective studies were included. The median OS (7.9 months versus 17.65 months) and PFS (2.4 months versus 4.4 months) of the antibiotics use group were shorter compared to control group. Meta-analysis also showed that the risks of death (HR = 1.90, 95 % CI: 1.55-2.34; P < 0.01) and disease progression (HR=1.53, 95 % CI: 1.30-1.79; P < 0.01) in antibiotics positive group were significantly higher than that of the negative group. The prognostic role of antibiotics use was still significant regardless of cancer types and timing of antibiotics (P < 0.01 for all).

Conclusion: Use of antibiotics may be associated with worse outcomes in cancer patients treated with ICIs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.critrevonc.2020.102909DOI Listing
May 2020

Glycyrrhizae Radix et Rhizoma Processed by Sulfur Fumigation Damaged the Chemical Profile Accompanied by Immunosuppression and Liver Injury.

Biomed Res Int 2020 6;2020:5439853. Epub 2020 Feb 6.

School of Pharmacy, Jiangsu University, 301 Xuefu Road, Zhenjiang 212013, Jiangsu Province, China.

Glycyrrhizae Radix et Rhizoma (GRER) has been used as a medicinal plant and dietary supplements for its beneficial effect in immunomodulatory effects. Sulfur fumigation (SF) processing was widely used in the storage and maintenance of Chinese medicine because of its convenience and cheapness. However, the disadvantage of SF has been reported, but the systematic study of SF on GRER was deficient. In this paper, the active ingredients, sulfur-fumigated products, immunomodulatory effect, and liver injury of SF-GRER were studied. After SF, the liquiritin decreased from 4.49 ± 0.03 mg/g to 3.94 ± 0.08 mg/g ( < 0.01). Compared with the NSF-GRER group, the SF-GRER group showed a decreased immunoregulation in the thymus index, spleen index, and serum IL-6 and SOD levels ( < 0.05). After 2 weeks of continuous intragastric administration of SF-GRER in healthy mice, the level of serum aspartate aminotransferase (AST) significantly increased ( < 0.05) and the area of liver lesion significantly increased compared with the NSF-GRER ( < 0.05) group. The sulfonated products (/, 631.13) corresponding to liquiritin apioside (/, 551.17) and isoliquiritin apioside (/, 551.17) were screened out in SF-GRER by using UPLC-Orbitrap-MS. The sulfonated products provided in this paper were discovered for the first time and could be powerfully applied for the identification of SF-GRER. SF destroyed the chemical composition of GRER, inhibited immunoregulation, and induced liver injury. The feasibility of this processing method needs to be reconsidered.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2020/5439853DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7026913PMC
November 2020

From transglutaminases (TGs) to arylamine N-acetyltransferases (NATs): Insight into the role of a spatially conserved aromatic amino acid position in the active site of these two families of enzymes.

Biochem Biophys Res Commun 2020 04 20;525(2):308-312. Epub 2020 Feb 20.

Université de Paris, BFA, UMR 8251, CNRS, 75013, Paris, France. Electronic address:

Transglutaminases (TG) and arylamine N-acetyltransferases (NAT) are important family of enzymes. Although they catalyze different reactions and have distinct structures, these two families of enzymes share a spatially conserved catalytic triad (Cys, His, Asp residues). In active TGs, a conserved Trp residue located close to the triad cysteine is crucial for catalysis through stabilization of transition states. Here, we show that in addition to sharing a similar catalytic triad with TGs, functional NAT enzymes also possess in their active site an aromatic residue (Phe, Tyr or Trp) occupying a structural position similar to the Trp residue of active TGs. More importantly, as observed in active TGs, our data indicates that in functional NAT enzymes this conserved aromatic residue is also involved in stabilization of transition states. These results thus indicate that in addition to the three triad residues, these two families of enzymes also share a spatially conserved aromatic amino acid position important for catalysis. Identification of residues involved in the stabilization of transition states is important to develop potent inhibitors. Interestingly, NAT enzymes have been shown as potential targets of clinical interest.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbrc.2020.02.082DOI Listing
April 2020

A modified procedure of single-level transforaminal lumbar interbody fusion reduces immediate post-operative symptoms: a prospective case-controlled study based on two hundred and four cases.

Int Orthop 2020 05 21;44(5):935-945. Epub 2020 Feb 21.

Department of Orthopedic Surgery, Spine Center, Changzheng Hospital, Second Military Medical University, No. 415 Fengyang Road, Shanghai, 200003, People's Republic of China.

Study Design: This is a prospective case-controlled study.

Purpose: The purpose of this study is to investigate the effect of a modified transforaminal lumbar interbody fusion (TLIF) on the immediate post-operative symptoms in patients with lumbar disc herniation (LDH) accompanied with stenosis.

Methods: A total of 204 LDH patients with single-level TLIF were enrolled. According to the sequence of the placement of rods and cage, patients were divided into group R (rod-prior-to-cage) and group C (cage-prior-to-rod). Neurological function was evaluated by the Japanese Orthopedic Association (JOA) score. Radiological assessment includes height of intervertebral space (HIS), foraminal height (FH), foraminal area (FA), and segmental lordosis (SL). Change of original symptoms (pain/numb) and new-onset symptoms (pain/numb) after surgery were also recorded.

Results: Patients in group R had less change of HIS at L3/4, L4/5, and L5/S1 levels compared with pre-operation (all p > 0.05), whereas group C had larger change (all p < 0.05). No statistical difference was found in FH between the two groups before and after surgery at L3/4, L4/5, and L5/S1, respectively (all p > 0.05). In terms of FA, patients in group R had better improvement after surgery than those in group C at L3/4 and L4/5 (both p < 0.05). Patients in both groups acquired good improvement of neurological function. However, there were fewer patients in group R who experienced post-operative leg pain or numb compared with those in group C (p < 0.05).

Conclusion: The modified open TLIF can significantly reduce the incidence of immediate post-operative symptoms for patients with single-level lumbar disc herniation via installation of rods prior to insertion of cage and the "neural standard" should serve as the goal of decompression for spine surgeons to restore disc/foraminal height and to minimize nerve distraction.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00264-020-04508-xDOI Listing
May 2020

Perinatal Antibiotic Exposure Affects the Transmission between Maternal and Neonatal Microbiota and Is Associated with Early-Onset Sepsis.

mSphere 2020 02 19;5(1). Epub 2020 Feb 19.

Department of Neonatology, Jinan University-affiliated Shenzhen Baoan Women's and Children's Hospital, Shenzhen, China

Intrapartum antibiotic prophylaxis reduces the risk of infection to a mother and neonate, but antibiotic-mediated maternal and neonatal microbiota dysbiosis increases other health risks to newborn infants. We studied the impact of perinatal antibiotic prophylaxis on the microbiota in mothers and newborns with full-term or preterm delivery. Ninety-eight pregnant women and their neonates were divided into the following four groups: full term without antibiotic exposure (FT), full term with antibiotic exposure (FTA), preterm without antibiotic exposure (PT), and preterm with antibiotic exposure (PTA). Bacterial composition was analyzed by sequencing the 16S rRNA gene from maternal vaginal swabs (V) and neonatal meconium (F). The results showed that in maternal vaginal and neonatal meconium microbiota, FT and PT groups had a higher load of spp. than did the FTA and PTA groups. In addition, whether in the mother or newborn, the dissimilarity in microbiota between FT and PT was the lowest compared to that between other groups. Compared to the FT and PT groups, the dissimilarity in microbial structures between the vagina and meconium decreased in the FTA and PTA groups. The health outcome of infants reveals an association between early-onset sepsis and antibiotic-mediated microbiota dysbiosis. In conclusion, perinatal antibiotic exposure is related to the establishment of gut microbiota and health risks in newborns. Promoting the rational usage of antibiotics with pregnant women will improve neonatal health. Perinatal antibiotic prophylaxis is an effective method for preventing group B (GBS) infection in newborns. Antibiotic exposure unbalances women's vaginal microbiota, which is associated with the establishment of the newborn gut microbiota. However, the influence of perinatal antibiotic exposure on neonatal gut microbiota colonization and health outcomes remains unclear. In this study, we found that perinatal antibiotic exposure induced microbiota dysbiosis in a woman's vagina and the neonatal gut, and we highlight a significant decrease in the abundance of spp. The influence of antibiotic use on the microbiota was greater than that from gestational age. Additionally, full-term newborns without antibiotic exposure had no evidence of early-onset sepsis, whereas in full-term or preterm newborns with antibiotic exposure before birth, at least one infant was diagnosed with early-onset sepsis. These results suggest an association between perinatal antibiotic exposure and microbial dysbiosis in maternal vaginal and neonatal gut environments, which may be related to the occurrence of early-onset sepsis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1128/mSphere.00984-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7031618PMC
February 2020