Limited value of platelet-related markers in diagnosing periprosthetic joint infection.

OBJECTIVE: To evaluate the diagnostic values of serum platelet count (PC), mean platelet volume ratio (MPV), platelet count to mean platelet volume ratio (PVR), platelet to lymphocyte ratio (PLR), platelet to neutrophil ratio (PNR), PC/Albumin-globulin ratio (PC/AGR), and PC/C-reactive protein (PC/ CRP) in the diagnosis of periprosthetic joint infection (PJI). METHODS: The medical records were retrospectively analyzed of the 158 patients who had undergone hip or knee revisions from January 2018 to May 2022. Of them, 79 cases were diagnosed with PJI and 79 with aseptic loosening (AL). PJI was defined using the Musculoskeletal Infection Society criteria. The plasma levels of CRP, the erythrocyte sedimentation rate (ESR), PC, MPV, PVR, PLR, PNR, PC/AGR, and PC/CRP in the 2 groups were recorded and analyzed. In addition, tests were performed according to different joint types. The receiver operating characteristic curve was used to calculate the sensitivity and specificity of each indicator. The diagnostic value for each indicator was calculated according to the area under the curve (AUC). RESULTS: The PC, PVR, PLR and PC/AGR levels in the PJI group were significantly higher than those in the AL group, while PC/CRP levels were significantly lower (P < 0.001). The AUC for PC/CRP, and PC/AGR was 0.804 and 0.802, respectively, which were slightly lower than that of CRP (0.826) and ESR (0.846). ROC analysis for PC/CRP, and PC/AGR revealed a cut-off value of 37.80 and 160.63, respectively, which provided a sensitivity of 73.42% and 84.81% and a specificity of 75.95% and 65.82% for PJI. The area under the curve of PLR and PC was 0.738 and 0.702. The area under the curve values for PVR, PNR, and MPV were 0.672, 0.553, and 0.544, respectively. CONCLUSIONS: The results of this study suggest that PC, PLR, PC/CRP, and PC/AGR values do not offer significant advantages over ESR or CRP values when employed for the diagnosis of PJI. PVR, PNR, and MPV were not reliable in the diagnosis of PJI.

Sulforaphane activates anti-inflammatory microglia, modulating stress resilience associated with BDNF transcription.

Sulforaphane (SFN) is an organic isothiocyanate and an NF-E2-related factor-2 (Nrf2) inducer that exerts prophylactic effects on depression-like behavior in mice. However, the underlying mechanisms remain poorly understood. Brain-derived neurotrophic factor (BDNF), a neurotrophin, is widely accepted for its antidepressant effects and role in stress resilience. Here, we show that SFN confers stress resilience via BDNF upregulation and changes in abnormal dendritic spine morphology in stressed mice, which is accompanied by rectifying the irregular levels of inflammatory cytokines. Mechanistic studies demonstrated that SFN activated Nrf2 to promote BDNF transcription by binding to the exon I promoter, which is associated with increased Nrf2, and decreased methyl-CpG binding protein-2 (MeCP2), a transcriptional suppressor of BDNF, in BV2 microglial cells. Furthermore, SFN inhibited the pro-inflammatory phenotype and activated the anti-inflammatory phenotype of microglia, which was associated with increased Nrf2 and decreased MeCP2 expression in microglia of stressed mice. Hence, our findings support that Nrf2 induces BDNF transcription via upregulation of Nrf2 and downregulation of MeCP2 in microglia, which is associated with changes in the morphology of damaged dendritic spines in stressed mice. Meanwhile, the data presented here provide evidence for the application of SFN as a candidate for the prevention and intervention of depression.

Identification of key genes involved in axon regeneration and Wallerian degeneration by weighted gene co-expression network analysis.

Peripheral nerve injury repair requires a certain degree of cooperation between axon regeneration and Wallerian degeneration. Therefore, investigating how axon regeneration and degeneration work together to repair peripheral nerve injury may uncover the molecular mechanisms and signal cascades underlying peripheral nerve repair and provide potential strategies for improving the low axon regeneration capacity of the central nervous system. In this study, we applied weighted gene co-expression network analysis to identify differentially expressed genes in proximal and distal sciatic nerve segments from rats with sciatic nerve injury. We identified 31 and 15 co-expression modules from the proximal and distal sciatic nerve segments, respectively. Functional enrichment analysis revealed that the differentially expressed genes in proximal modules promoted regeneration, while the differentially expressed genes in distal modules promoted neurodegeneration. Next, we constructed hub gene networks for selected modules and identified a key hub gene, Kif22, which was up-regulated in both nerve segments. In vitro experiments confirmed that Kif22 knockdown inhibited proliferation and migration of Schwann cells by modulating the activity of the extracellular signal-regulated kinase signaling pathway. Collectively, our findings provide a comparative framework of gene modules that are co-expressed in injured proximal and distal sciatic nerve segments, and identify Kif22 as a potential therapeutic target for promoting peripheral nerve injury repair via Schwann cell proliferation and migration. All animal experiments were approved by the Institutional Animal Ethics Committee of Nantong University, China (approval No. S20210322-008) on March 22, 2021.

Transcriptome analysis of molecular mechanisms underlying facial nerve injury repair in rats.

Although the transcriptional alterations inside the facial nucleus after facial nerve injury have been well studied, the gene expression changes in the facial nerve trunk after injury are still unknown. In this study, we established an adult rat model of facial nerve crush injury by compressing the right lateral extracranial nerve trunk. Transcriptome sequencing, differential gene expression analysis, and cluster analysis of the injured facial nerve trunk were performed, and 39 intersecting genes with significant variance in expression were identified. Gene Ontology annotation and Kyoto Encyclopedia of Genes and Genomes pathway analyses of the 39 intersecting genes revealed that these genes are mostly involved in leukocyte cell-cell adhesion and phagocytosis and have essential roles in regulating nerve repair. Quantitative real-time polymerase chain reaction assays were used to validate the expression of pivotal genes. Finally, nine pivotal genes that contribute to facial nerve recovery were identified, including Arhgap30, Akr1b8, C5ar1, Csf2ra, Dock2, Hcls1, Inpp5d, Sla, and Spi1. Primary Schwann cells were isolated from the sciatic nerve of neonatal rats. After knocking down Akr1b8 in Schwann cells with an Akr1b8-specific small interfering RNA plasmid, expression levels of monocyte chemoattractant protein-1 and interleukin-6 were decreased, while cell proliferation and migration were not obviously altered. These findings suggest that Akr1b8 likely regulates the interaction between Schwann cells and macrophages through regulation of cytokine expression to promote facial nerve regeneration. This study is the first to reveal a transcriptome change in the facial nerve trunk after facial nerve injury, thereby revealing the potential mechanism underlying repair of facial nerve injury. This study was approved by the Animal Ethics Committee of Nantong University, China in 2018 (approval No. S20180923-007).

Synthesis, structural characterization and antitumor activity of six rare earth metal complexes with 8-hydroxyquinoline derivatives.

The rare earth metal Gd(III), Yb(III), Lu(III), Eu(III), Tb(III) and Ho(III) complexes 1-6 with 2-((2-(pyridin-2-yl)hydrazono)methyl)quinolin-8-ol (H-L) as ligands were synthesized. The in vitro cytotoxicity assay indicated that the cytotoxicity of 1 was equivalent to cisplatin and higher than that of H-L and other complexes towards T24 tumor cells. The mechanism study indicated that 1 caused significant up-regulation of the proteins p27, p21 and p53 in T24 cells and cell cycle arrest in G2 phase. In addition, 1 induced effective T24 cells apoptosis via mitochondrial dysfunction pathway, which was indicated by changes in mitochondrial membrane potential (Δψ), reactive oxygen species (ROS), intracellular Ca2+ and the mitochondria-related proteins (including cytochrome C (Cyt C), B-cell lymphoma-2 (Bcl-2), Bcl-2-associated x (Bax) and apoptotic protease activating factor-1 (Apaf-1)). Moreover, 1 could activate caspase-3/8/9 in T24 cells. Therefore, complex 1 is a promising and potent anticancer drug candidate.

Adiponectin, exercise and eye diseases.

Adiponectin, one kind of adipokines, has been shown to be neuroprotective in different neurodegenerative diseases. Adiponectin exerts its role through combination with its receptors and activates downstream molecular pathways. In the retinas, the expression of adiponectin can be detected and adiponectin receptors (AdipoRs) locate in different retinal cells. Adiponectin is mainly produced by adipose tissue, enters the circulation and passes through blood-brain barrier (BBB) without injury. It can also be produced locally in the brains as well as in the retinas. Therefore, it is possible that adiponectin from blood as well as that produced locally in the retinas take part in defense of different eye diseases. Here we have summarized the published data about the protective effects of adiponectin in eye diseases. Because exercise can increase the production of adiponectin systemically in the whole body and locally in the brain although no evidence has shown that exercise can increase the production of adiponectin in the eyes until now, we hypothesize that exercise will have a potential protective effect for the eyes via increasing the levels of adiponectin which needs further investigation.

Synthesis and in vitro antitumor activity evaluation of copper(II) complexes with 5-pyridin-2-yl-[1,3]dioxolo[4,5-g]isoquinoline derivatives.

Seven Cu(II) complexes with 5-pyridin-2-yl-[1,3]dioxolo[4,5-g]isoquinoline derivatives as ligands: [Cu2(L1)2Cl4] (1), [Cu(L2)Cl2] (2), [Cu(L1)(NO3)2] (3), [Cu(L2)(NO3)2] (4), [Cu(L3)Cl2] (5), [Cu(L3)Br2] (6) and [Cu(L3)(NO3)2] (7){L1=9-nitro-5-pyridin-2-yl-[1,3]dioxolo[4,5-g]isoquinoline, L2=4-nitro-5-pyridin-2-yl-[1,3]dioxolo[4,5-g]isoquinoline, L3=9-bromo-5-pyridin-2-yl-[1,3]dioxolo[4,5-g]isoquinoline}, were synthesized and characterized. Their in vitro anticancer activities against T-24, MGC-80-3, HeLa, Hep-G2, A549 and SK-OV-3 were evaluated. Compared with their corresponding ligands, most of these complexes exhibited enhanced anticancer activities in contrast to their corresponding ligands and copper salt. Among them, complexes 1 and 3 displayed selective cytotoxicity to HeLa cells comparing with normal liver cell HL-7702, with IC50 values of 5.03 ±â€¯1.20 µM and 10.05 ±â€¯0.52 µM, respectively. Complexes 1 and 3 inhibited telomerase activity by interacting with c-myc promoter elements, and therefore exerted their antitumor activity. Furthermore, complexes 1 and 3 could trigger cell apoptosis via disruption of mitochondrial pathway through notably increased reactive oxygen species (ROS) levels, loss of mitochondrial membrane potential (Δψm), increase of the cytochrome c and apaf-1, decrease of bcl-2, and activation of caspases 3/9. Complexes 1 and 3 exhibited enhanced cytotoxicity, presenting synergetic effect after the ligands coordinated to copper(II) center.

Alteration of Androgen Receptor Protein Stability by Triptolide in LNCaP Cells.

Background and Objective: Although triptolide was effective for prostate cancer (PCa), the mechanism is still unclear. Androgen receptor (AR) plays a large role in the development and progression of PCa, even after castration. The present study aimed at investigating the effects of triptolide on AR protein stability and the possible mechanism. Materials and Methods: By blocking protein synthesis with cycloheximide (CHX), the effect of triptolide on AR protein stability was investigated with western blot assay. The potential role of calpains in triptolide reduced AR protein stability was investigated with calpain inhibitor and Ca2+ chelator. Results: Triptolide down-regulated AR protein level when protein synthesis was blocked by CHX, demonstrating the decrease of AR protein stability. The AR protein level was restored when the cells were co-treated with triptolide and calpain inhibitor or Ca2+ chelator, indicating the important role of calpains. Conclusions: The results indicate that triptolide can activate calpain via promoting intracellular Ca2+ accumulation, and thus decrease the stability of AR protein, subsequently resulting in the breakdown of the AR protein in LNCaP cells. This work provides an experimental basis and evidence to elucidate the anti-PCa mechanisms of triptolide.

Syntheses, Crystal Structures, and Antitumor Activities of Copper(II) and Nickel(II) Complexes with 2-((2-(Pyridin-2-yl)hydrazono)methyl)quinolin-8-ol.

Two transition metal complexes with 2-((2-(pyridin-2-yl)hydrazono)methyl)quinolin-8-ol (L), [Cu(L)Cl2]2 (1) and [Ni(L)Cl2]·CH2Cl2 (2), were synthesized and fully characterized. Complex 1 exhibited high in vitro antitumor activity against SK-OV-3, MGC80-3 and HeLa cells with IC50 values of 3.69 ± 0.16, 2.60 ± 0.17, and 3.62 ± 0.12 µM, respectively. In addition, complex 1 caused cell arrest in the S phase, which led to the down-regulation of Cdc25 A, Cyclin B, Cyclin A, and CDK2, and the up-regulation of p27, p21, and p53 proteins in MGC80-3 cells. Complex 1 induced MGC80-3 cell apoptosis via a mitochondrial dysfunction pathway, as shown by the significantly decreased level of bcl-2 protein and the loss of Δψ, as well as increased levels of reactive oxygen species (ROS), intracellular Ca2+, cytochrome C, apaf-1, caspase-3, and caspase-9 proteins in MGC80-3 cells.

Synthesis, crystal structure, cytotoxicity and action mechanism of a Rh(iii) complex with 8-hydroxy-2-methylquinoline as a ligand.

A rhodium(iii) complex, [Rh(MQ)(DMSO)2Cl2] (1), with 8-hydroxy-2-methylquinoline as the ligand was synthesized and characterized. Complex 1 exhibited cytotoxicity against BEL-7404, Hep-G2, NCI-H460, T-24, and A549 cell lines with IC50 values in the micromolar range (6.52-17.86 µM). Various experiments on the Hep-G2 cells showed that complex 1 caused cell cycle arrest at the S phase, downregulation of cdc25 A, cyclin A, cyclin B and CDK2, and upregulation of p21, p27 and p53. Furthermore, cytotoxicity mechanism studies suggested that complex 1-induced apoptosis was achieved via disruption of the mitochondrial function, which led to a significant loss of the mitochondrial membrane potential, an increase in the cellular levels of reactive oxygen species, cytochrome c, and apaf-1, and a fluctuation of the intracellular Ca2+ concentration. Taken altogether, complex 1 can trigger cancer cell death by inducing apoptosis through a mitochondrial dysfunction pathway.

Synthesis and antitumor mechanism of a new iron(iii) complex with 5,7-dichloro-2-methyl-8-quinolinol as ligands.

A new iron(iii) complex with 5,7-dichloro-2-methyl-8-quinolinol (HClMQ) as ligands, i.e., [Fe(ClMQ)2Cl] (1), was synthesized and evaluated for its anticancer activity. Compared to the HClMQ ligand, complex 1 showed a higher cytotoxicity towards a series of tumor cell lines, including Hep-G2, BEL-7404, NCI-H460, A549, and T-24, with IC50 values in the range of 5.04-14.35 µM. Notably, the Hep-G2 cell line was the most sensitive to complex 1. Mechanistic studies indicated that complex 1 is a telomerase inhibitor targeting c-myc G-quadruplex DNA and can trigger cell apoptosis via inducing cell cycle arrest and DNA damage.

[Movement characteristics of Cyanobacteria under stress of water-lifting aeration].

In order to study the impact of algae control mixing technology on the distribution characteristics and movement of Cyanobacteria, the floating and subsiding velocity of Cyanobacteria in Taihu Lake was measured under different conditions such as different illuminance, temperature and pressure. The Cyanobacteria showed strong propensity of floating under the illuminance from 1500 1x to 6000 1x. The Cyanobacteria particle with floating velocity of more than 0.8 cm.min-1 accounted for 58% under the illuminance of 1 500 1x. The floating velocity slowed down when the illuminance was lower than 1 500 1x or higher than 6 000 1x. In the temperature range of 8 to 25 Celsius degree, the Cyanobacteria floated and the floating velocity increased with temperature. The Cyanobacteria floated under the pressure of 0- 0. 1 MPa and the floating velocity slowed down as the pressure increased. Most Cyanobacteria were suspended in the water when the pressure reached 0. 2-0. 3 MPa and only a small part of the Cyanobacteria floated or settled. When the pressure reached 0. 4-0. 6 MPa, the Cyanobacteria notably settled and the subsiding velocity increased with the increase of pressure. The Cyanobacteria particles with subsiding velocity of more than 1.0 cm.min-1 accounted for 52.5% when the pressure was 0. 6 MPa. Gas vesicles bursted when the gas vesicles of the Cyanobacteria could not bear the external pressure. The buoyancy of the Cyanobacteria diminished until the floating force became smaller than its weight, causing the particles of the Cyanobacteria to settle. Under normal atmospheric pressure, the particle diameter was positively correlated to the floating velocity, while negatively correlated to the density. Under high pressure, the particle diameter was positively correlated to the subsiding velocity and the density.