Melanoma is the most lethal skin cancer characterized by its high metastatic potential. It is urgent to find novel therapy strategies to overcome this feature. Metformin has been confirmed to ...suppress invasion and migration of various types of cancer. However, additional mechanisms underlying the antimetastatic effect of metformin on melanoma require further investigation. Here, we performed microarray analysis and uncovered an altered mRNA and miRNA expression profile between melanoma and nevus. Luciferase reporter assay confirmed that miR-5100 targets SPINK5 to activate STAT3 phosphorylation. Migration and wound healing assays showed that the miR-5100/SPINK5/STAT3 axis promotes melanoma cell metastasis; the mechanism was proven by initiation of epithelial-mesenchymal transition. Co-immunoprecipitation (Co-IP) further confirmed an indirect interaction between SPINK5 and STAT3. Furthermore, metformin dramatically inhibited miR-5100/SPINK5/STAT3 pathway, and decreased B16-F10 cell metastasis to lung in C57 mouse module. Intriguingly, pretreatment of metformin before melanoma cell injection improved this effect further. These findings exposed the underlying mechanisms of action of metformin and update the use of this drug to prevent metastasis in melanoma.
Objective
To compare the clinical results of two surgical techniques, Wiltse approach and conventional transforaminal interbody fusion, for the treatment of unstable thoracolumbar fracture associated ...with traumatic intervertebral disc lesion (TIDL).
Methods
A total of 76 patients with unstable thoracolumbar fracture associated with TIDL treated by posterior pedicle screw fixation and transforaminal thoracolumbar interbody fusion from June 2010 and July 2016 were reviewed retrospectively. These patients including 48 male and 28 female patients were divided into Wiltse approach transforaminal thoracolumbar interbody fusion (W‐TLIF) group (n = 38) and conventional transforaminal thoracolumbar interbody fusion (C‐TLIF) group (n = 38). Patients were followed up for about 33 months. Clinical and radiological records, kyphotic angle, fractured vertebral body height, visual analogue score (VAS), Oswestry Disability Index (ODI), complications, neurological improvement and fusion rate were compared between two groups.
Results
All patients underwent posterior surgery successfully. Blood loss, operation time and hospital stay in the W‐TLIF group was 437.84 ± 143.98 ml, 118.64 ± 20.55 min and 12.32 ± 2.87 days, respectively. While those parameters in the C‐TLIF group was 862.70 ± 300.24 ml, 141.35 ± 31.72 min and 15.51 ± 2.08 days, respectively. Average operation time and hospital stay time were significantly shorter, and blood loss was significantly less in the W‐TLIF group than in the C‐TLIF group (P < 0.05). VAS and ODI in the W‐TLIF group were significantly less than those in the C‐TLIF group at 1 week after operation and final follow‐up. The kyphotic angle and vertebral body height were improved. There was 1–2 grade improvement in patients with neurological deficit. Thirty‐three patients in the W‐TLIF group and 32 patients in the C‐TLIF group had achieved fusion during follow‐up. No internal fixation failure was observed in two groups.
Conclusions
The both techniques of W‐TLIF and C‐TLIF were feasible and effective for unstable thoracolumbar fracture with TIDL. Compare to C‐TLIF, The technique of W‐TLIF was a relatively less invasive way to decompress the neural elements and an easy method to reconstruct the anterior column using the same posterior approach.
This modified technique of W‐TLIF is a feasible and effective technique for unstable thoracolumbar fracture with traumatic intervertebral disc lesion. The technique is a relatively less invasive way to decompress the neural elements and an easy method to reconstruct the anterior column using the same posterior approach.
This study aimed to evaluate the safety and feasibility of subaxial cervical pedicle screw (CPS) insertion by comparing the morphological parameters between developmental canal stenosis (DCS) and ...non-developmental canal stenosis (NDCS) patients.
A total of 120 Chinese patients who had undergone cervical spinal multiplanar CT imaging from September 2010 to December 2014 were included in this study. According to the Pavlov ratio (PR), participants were classified into a DCS group (PR < 0.82) and an NDCS group (PR ≥0.82). CT reconstruction images of the cervical pedicles from C3 to C7 were selected for further analysis, and detailed morphological parameters for subaxial CPS insertion including pedicle outer width (POW), tiny cervical pedicle (TCP), pedicle transverse angle (PTA), and range of safe angle (RSA) were measured and compared in these two groups.
A total of 600 images (1200 pedicles) from these 120 patients were measured. The POW in the DCS group was wider than that in the NDCS group at each level, while the number of TCPs in the DCS group was significantly less than that in the NDCS group at the C3, C4, and C5 vertebrae. There was no significant difference in PTA at any level between the two groups, however the RSA in the DCS group was greater than that in the NDCS group from C4 to C7.
Subaxial CPS for DCS patients may be safer and more feasible than that for NDCS patients. However, as the subaxial cervical pedicle is relatively small, CPS insertion is difficult and preoperative CT evaluation is recommended for both DCS and NDCS patients.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Metformin can enhance cancer cell chemosensitivity to anticancer drugs. IGF-1R is involved in cancer chemoresistance. The current study aimed to elucidate the role of metformin in osteosarcoma (OS) ...cell chemosensitivity modulation and identify its underlying mechanism in IGF-1R/miR-610/FEN1 signalling. IGF-1R, miR-610, and FEN1 were aberrantly expressed in OS and participated in apoptosis modulation; this effect was abated by metformin treatment. Luciferase reporter assays confirmed that FEN1 is a direct target of miR-610. Moreover, metformin treatment decreased IGF-1R and FEN1 but elevated miR-610 expression. Metformin sensitised OS cells to cytotoxic agents, while FEN1 overexpression partly compromised metformin's sensitising effects. Furthermore, metformin was observed to enhance adriamycin's effects in a murine xenograft model. Metformin enhanced OS cell sensitivity to cytotoxic agents via the IGF-1R/miR-610/FEN1 signalling axis, highlighting its potential as an adjuvant during chemotherapy.
An increasing body of research indicates that immunotherapy has demonstrated substantial effectiveness in the realm of metastatic colorectal cancer(mCRC), especially among patients with deficient ...mismatch repair (dMMR) or microsatellite instability-high (MSI-H) (dMMR/MSI-H mCRC). This study constitutes the inaugural bibliometric and visual analysis of immunotherapy related to mCRC during the last decade. Between 2013 and the conclusion of 2022, we screened 306 articles from Web of Science and subjected them to analysis using CiteSpace and VOSviewer. The United States stood out as the primary contributor in this area, representing 33.33% of the publications, with China following closely at 24.51%. The most prolific institution has the lowest average citation rate. Sorbonne University were the most highly cited institutions. Notably,
published the largest quantity of articles. Andre, Thierry, and Overman, Michael J. were prominent authors known for their prolific output and the high citation rates of their work. The focus areas in this field encompass "tumor microenvironment," "liver metastasis," "tumor-associated macrophages," "combination therapy" and "gut microbiota." Some keywords offer promise as potential biomarkers for evaluating the effectiveness of immunotherapeutic interventions.
Aeromonas hydrophila B11 strain was isolated from diseased Anguilla japonica, which had caused severe gill ulcers in farmed eel, causing huge economic losses. EnvZ‐OmpR is a model two‐component ...system in the bacteria and is widely used in the research of signal transduction and gene transcription regulation. In this study, the ompR of A. hydrophila B11 strain was first silenced by RNAi technology. The role of ompR in the pathogenicity of A. hydrophila B11 was investigated by analyzing both the bacterial comparative transcriptome and phenotype. The qRT‐PCR results showed that the expression of ompR in the ompR‐RNAi strain decreased by 97% compared with the wild‐type strain. The virulence test showed that after inhibition of the ompR expression, the LD50 of A. hydrophila B11 decreased by an order of magnitude, suggesting that ompR is involved in the regulation of bacterial virulence. Comparative transcriptome analysis showed that the expression of ompR can directly regulate the expression of several important virulence‐related genes, such as the bacterial type II secretion system; moreover, ompR expression also regulates the expression of multiple genes related to bacterial chemotaxis, motility, adhesion, and biofilm formation. Further studies on the phenotype of A. hydrophila B11 and ompR‐RNAi also confirmed that the downregulation of ompR expression can decrease bacterial chemotaxis, adhesion, and biofilm formation.
After the expression of ompR was inhibited, the virulence of Aeromonas hydrophila B11 decreased, which suggested that ompR is involved in the bacterial virulence regulation. Comparative transcriptome analysis revealed that the expression of ompR can directly regulate the expression of some important virulence‐related genes, especially the bacterial type II secretion system, as well as regulate the expression of multiple genes related to bacterial chemotaxis, motility, adhesion, and biofilm formation.
Varied environmental stress can affect cell growth and activity of the cellular catalyst. Traditional path of adaptive evolution generally takes a long time to achieve a tolerance phenotype, ...meanwhile, it is a challenge to dissect the underlying genetic mechanism. Here, using SCRaMbLE, a genome scale tool to generate random structural variations, a total of 222 evolved yeast strains with enhanced environmental tolerances were obtained in haploid or diploid yeasts containing six synthetic chromosomes. Whole genome sequencing of the evolved strains revealed that these strains generated different structural variants. Notably, by phenotypic-genotypic analysis of the SCRaMbLEd strains, we find that a deletion of gene YFR009W (GCN20) can improve salt tolerance of Saccharomyces cerevisiae, and a deletion of gene YER056C can improve 5-flucytosine tolerance of Saccharomyces cerevisiae. This study shows applications of SCRaMbLE to accelerate phenotypic evolution for varied environmental stress and to explore relationships between structural variations and evolved phenotypes.
To detect the expressions of IL-1 and IL-6 in the degenerative intervertebral discs of patients with discogenic low back pain (DLBP), record the modified Japanese Orthopedic Association (mJOA) scores ...and analyze the correlation between the expressions and the scores.
The study chose 30 cases of DLBP aged between 45-65 years old from the same race and district and 10 control cases of vertebral fractures scheduled for surgical treatment but with no history of low back pain within one year and no disc degeneration based on imaging data. The degree of DLBP was evaluated by mJOA scores. Immunohistochemistry and Western blotting were used to observe the expressions of IL-1 and IL-6 in the discs. The relationship between the IL-1, IL-6 expressions and the mJOA scores was revealed by Pearson linear correlation analysis.
Compared with the control group, the expressions of IL-1 and IL-6 in the discs of DLBP patients increased significantly as immunohistochemistry and Western blotting indicated. The highest mJOA score o
To investigate the effect of a porous calcium phosphate/bone matrix gelatin (BMG) composite cement (hereinafter referred to as the "porous composite cement") for repairing lumbar vertebral bone ...defect in a rabbit model.
BMG was extracted from adult New Zealand rabbits according to the Urist's method. Poly (lactic-co-glycolic) acid (PLGA) microsphere was prepared by W/O/W double emulsion method. The porous composite cement was developed by using calcium phosphate cement (CPC) composited with BMG and PLGA microsphere. The physicochemical characterizations of the porous composite cement were assessed by anti-washout property, porosity, and biomechanical experiment, also compared with the CPC. Thirty 2-month-old New Zealand rabbits were used to construct vertebral bone defect at L
in size of 4 mm×3 mm×3 mm. Then, the bone defect was repaired with porous composite cement (experimental group,
=15) or CPC (control group,
=15). At 4, 8, and 12 weeks after implantation, each bone specimen was assessed by X-ray films f
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