Screening and identification of key chromatin regulator biomarkers for ankylosing spondylitis and drug prediction: evidence from bioinformatics analysis.

BACKGROUND: Ankylosing spondylitis (AS) is one of the most common immune-mediated arthritic diseases worldwide. Despite considerable efforts to elucidate its pathogenesis, the molecular mechanisms underlying AS are still not fully understood. METHODS: To identify candidate genes involved in AS progression, the researchers downloaded the microarray dataset GSE25101 from the Gene Expression Omnibus (GEO) database. They identified differentially expressed genes (DEGs) and functionally enriched them for analysis. They also constructed a protein-protein interaction network (PPI) using STRING and performed cytoHubba modular analysis, immune cell and immune function analysis, functional analysis and drug prediction.The results showed that DEGs were mainly associated with histone modifications, chromatin organisation, transcriptional coregulator activity, transcriptional co-activator activity, histone acetyltransferase complexes and protein acetyltransferase complexes. RESULTS: The researchers analysed the differences in expression between the CONTROL and TREAT groups in terms of immunity to determine their effect on TNF-α secretion. By obtaining hub genes, they predicted two therapeutic agents, AY 11-7082 and myricetin. CONCLUSION: The DEGs, hub genes and predicted drugs identified in this study contribute to our understanding of the molecular mechanisms underlying the onset and progression of AS. They also provide candidate targets for the diagnosis and treatment of AS.

Effects of swimming on pain and inflammatory factors in rats with lumbar disc herniation.

The aim of the present study was to identify the effect of swimming on nerve root pain in rats with lumbar disc herniation (LDH). A total of 72 male Sprague Dawley rats (215±15 g) were randomly divided into three groups (n=24/group): The sham operation, model and exercise intervention groups, with the latter undergoing 4 weeks of swimming training. On days 0, 7, 14 and 28 following surgery, the changes in the post-limb mechanical claw threshold, the phospholipase A2 (PLA2), interleukin (IL)-6 and tumor necrosis factor (TNF)-α mRNA expression levels, the secretory PLA2 (sPLA2) expression, the IL-6 and TNF-α content, the nuclear factor (NF)-κBp65 protein expression level in the nucleus pulposus, and the apoptotic rate of the nucleus pulposus cells were detected. The results demonstrated that, in the model group, the threshold of hind paw withdrawal was decreased, and that the sPLA2 expression, IL-6 and TNF-α content, PLA2, IL-6 and TNF-α mRNA and NF-κBp65 protein expression levels in the nucleus pulposus were increased. The apoptotic rate of the nucleus pulposus cells was increased from day 7 following surgery, as compared with the sham operation group. In the exercise intervention group, the hind paw withdrawal threshold increased and the TNF-α and IL-6 content, sPLA2 expression and PLA2, IL-6 and TNF-α mRNA and NF-κBp65 protein expression levels were decreased from day 14 following surgery, and the apoptotic nucleus pulposus cells were decreased from day 7 following surgery, as compared with the model group. Collectively, the present data suggest that swimming can significantly reduce nerve root pain and inhibit inflammatory reaction in LDH, which can have positive effects on the treatment of LDH.

A Pd corolla-human serum albumin-indocyanine green nanocomposite for photothermal/photodynamic combination therapy of cancer.

In this work, a novel nanoplatform based on Pd corolla-human serum albumin-indocyanine green (PdCs-HSA-ICG) was developed for cancer photothermal/photodynamic combination therapy. Pd corollas (denoted as PdCs) with good near-infrared photothermal conversion efficiency (η≈ 37%) were first prepared and modified with human serum albumin (HSA) and indocyanine green (ICG) to get the PdCs-HSA-ICG nanocomposite. The prepared PdCs-HSA-ICG not only improves the colloid and thermal stability of ICG, but also shows a higher temperature increase than that of PdCs and free ICG as well as a comparable singlet oxygen (1O2) generation capability to that of free ICG. Upon single 808 nm laser irradiation, the photothermal (PTT)/photodynamic (PDT) combined therapeutic efficacy of PdCs-HSA-ICG at both cellular and animal levels was superior to PdCs-HSA (PTT) or free ICG (PTT and PDT), respectively. Thus, the designed PdCs-HSA-ICG nanocomposite holds great potential as a new class of photosensitive agent for cancer phototherapy.

The biodistribution, excretion and potential toxicity of different-sized Pd nanosheets in mice following oral and intraperitoneal administration.

Two-dimensional (2D) Pd-based nanomaterials with strong near-infrared absorption have recently shown great application prospects in cancer diagnosis and therapy. Most previous studies mainly focused on understanding the in vivo behaviors and treatment effects of these Pd-based nanomaterials after intravenous injection into mice. However, it remains unclear whether other administration routes will affect the in vivo biodistribution, excretion and potential toxicity of Pd-based nanomaterials. In this study, for the first time we systematically explored the in vivo behaviors of different-sized Pd nanosheets (NSs) (approximately 5 nm, 30 nm and 80 nm) following oral feeding and intraperitoneal injection. It was found that Pd NSs with oral administration had a rather low accumulation that decreased with time in all examined organs, and became almost undetectable in these organs at 24 h post-injection. In comparison, the intraperitoneally injected Pd NSs exhibited obvious time-dependent and size-dependent accumulations in the reticuloendothelial (RES) system including the liver and spleen within 24 h post-injection, and then the accumulation amounts decreased with the lapse of time. Moreover in tumor tissue, smaller-sized Pd NSs (5 nm) had a higher uptake than larger-sized Pd NSs (30 nm and 80 nm). Excretion studies uncovered that more than 70% ID of Pd NSs could be rapidly excreted from the body through urine and feces within two days after oral administration, whereas Pd NSs with intraperitoneal injection could be gradually cleared, mainly via urine within 8 days. Further histological examination of organ sections and blood biochemical analysis evidenced that these different-sized Pd NSs do not cause obvious toxicity in the treated mice at the tested period with the given dose. These results not only indicate that the biodistribution and excretion capabilities of Pd NSs are closely related to their administration routes, but also imply that the intraperitoneally injected Pd NSs have greater potential for in vivo biomedical studies compared to oral feeding, because of their relatively higher tissue absorption and gradual excretion from the body. This study will provide valuable information for the clinical translation of 2D Pd-based nanomaterials.

Platinum(IV) prodrug conjugated Pd@Au nanoplates for chemotherapy and photothermal therapy.

Owing to the excellent near infrared (NIR) light absorption and efficient passive targeting toward tumor tissue, two-dimensional (2D) core-shell PEGylated Pd@Au nanoplates have great potential in both photothermal therapy and drug delivery systems. In this work, we successfully conjugate Pd@Au nanoplates with a platinum(IV) prodrug c,c,t-[Pt(NH3)2Cl2(O2CCH2CH2CO2H)2] to obtain a nanocomposite (Pd@Au-PEG-Pt) for combined photothermal-chemotherapy. The prepared Pd@Au-PEG-Pt nanocomposite showed excellent stability in physiological solutions and efficient Pt(IV) prodrug loading. Once injected into biological tissue, the Pt(IV) prodrug was easily reduced by physiological reductants (e.g. ascorbic acid or glutathione) into its cytotoxic and hydrophilic Pt(II) form and released from the original nanocomposite, and the NIR laser irradiation could accelerate the release of Pt(II) species. More importantly, Pd@Au-PEG-Pt has high tumor accumulation (29%ID per g), which makes excellent therapeutic efficiency at relatively low power density possible. The in vivo results suggested that, compared with single therapy the combined thermo-chemotherapy treatment with Pd@Au-PEG-Pt resulted in complete destruction of the tumor tissue without recurrence, while chemotherapy using Pd@Au-PEG-Pt without irradiation or photothermal treatment using Pd@Au-PEG alone did not. Our work highlights the prospects of a feasible drug delivery strategy of the Pt prodrug by using 2D Pd@Au nanoplates as drug delivery carriers for multimode cancer treatment.

Simultaneous Enhancement of Intracellular Optical Imaging and Photothermal Therapeutic Response by Octaarginine-Modified Fluorescent Dye Doped Pd@Ag@SiO2(RITC) Multifunctional Nanoparticles.

In the work, a novel multifunctional silica-based nanoplatform (Pd@Ag@SiO2(RITC)-R8) for bioimaging and photothermal therapy (PTT) of cancer cells has been developed. The Pd@Ag nanosheets encapsulated inside silica can act as effective near-infrared (NIR) absorbers for cancer photothermal therapy. Fluorescent dye, rhodamine B isothiocyanate (RITC), was covalently doped into the silica network to provide the capacity for optical imaging. After amine modification, the Pd@Ag@SiO2(RITC)-NH2 can be further conjugated with octaarginine (R8, a cell penetrating peptide) for enhancing the uptake of nanoparticles by cells. Confocal fluorescent images and flow cytometry analysis revealed that R8-conjugated nanoparticles (Pd@Ag@SiO2(RITC)-R8) were taken up by cells more efficiently. Correspondingly, the optical imaging and photothermal therapeutic efficiency of Pd@Ag@SiO2(RITC)-R8 upon cancer cells were also raised due to their higher cellular uptake when compared with that of Pd@Ag@SiO2(RITC)-NH2. Our results indicate that these multifunctional Pd@Ag@SiO2(RITC)-R8 may have great potential for applications in imaging-guided cancer photothermal therapy.