Research progress of microRNA in spinal cord injury.

Spinal cord injury (SCI) is a serious central nervous system disease with high disability and mortality rates and complex pathophysiologic mechanisms. MicroRNA (miRNA), as a kind of non-coding RNA, plays an important role in SCI. miRNA is involved in the regulation of inflammatory response, oxidative stress, axonal regeneration, and apoptosis after SCI, and interacts with long non-coding RNA (lncRNA) and circular RNA (circRNA) to regulate the pathophysiological process of SCI. This paper summarizes the changes in miRNA expression after SCI, and reviews the targeting mechanism of miRNA in SCI and the current research status of miRNA-targeted drugs to provide new targets and new horizons for basic and clinical research on SCI.

Theranostic Fluorescent Probes.

The ability to gain spatiotemporal information, and in some cases achieve spatiotemporal control, in the context of drug delivery makes theranostic fluorescent probes an attractive and intensely investigated research topic. This interest is reflected in the steep rise in publications on the topic that have appeared over the past decade. Theranostic fluorescent probes, in their various incarnations, generally comprise a fluorophore linked to a masked drug, in which the drug is released as the result of certain stimuli, with both intrinsic and extrinsic stimuli being reported. This release is then signaled by the emergence of a fluorescent signal. Importantly, the use of appropriate fluorophores has enabled not only this emerging fluorescence as a spatiotemporal marker for drug delivery but also has provided modalities useful in photodynamic, photothermal, and sonodynamic therapeutic applications. In this review we highlight recent work on theranostic fluorescent probes with a particular focus on probes that are activated in tumor microenvironments. We also summarize efforts to develop probes for other applications, such as neurodegenerative diseases and antibacterials. This review celebrates the diversity of designs reported to date, from discrete small-molecule systems to nanomaterials. Our aim is to provide insights into the potential clinical impact of this still-emerging research direction.

Exosomes Secreted by Hypoxia-Pre-conditioned Adipose-Derived Mesenchymal Stem Cells Reduce Neuronal Apoptosis in Rats with Spinal Cord Injury.

Neuronal death is the main cause of nerve function impairment after spinal cord injury (SCI). Exosome-based therapy has become a novel strategy for tissue injury repair. We designed a method to treat SCI using exosomes secreted by adipose tissue-derived stromal cells (ADSCs) under hypoxic conditions. We established a neuronal oxygen-glucose deprivation and reperfusion (OGD/R) model in vitro to simulate the hypoxic environment after SCI. We observed that exosomes derived from hypoxia-conditioned ADSCs (Hypo-exo) significantly reduced neuronal apoptosis after OGD. By establishing a rat SCI model, we found that Hypo-exo can significantly reduce the formation of cavities in the injured area and improve the functional recovery of the hindlimbs of rats after injury. To explore the molecular mechanism, we conducted microRNA sequencing analysis of exosomes. Through real-time polymerase chain reaction, dual luciferase reporter assays and signaling pathway chip analysis, we determined that miR-499a-5p regulates the JNK3/c-jun-apoptotic signaling pathway by targeting JNK3. Further, we verified the expression of the key proteins in the JNK3/c-jun-apoptotic signaling pathway by immunofluorescence and Western blotting. These results support the hypothesis that Hypo-exo can reduce neuronal apoptosis after SCI and may provide new methods to treat SCI.

Tuning the organelle specificity and cytotoxicity of iridium(III) photosensitisers for enhanced phototheranostic applications.

Luminescent cyclometallated iridium(III) complexes with a polyhedral oligomeric silsesquioxane (POSS) unit were designed as efficient theranostic agents that displayed tuneable organelle-targeting properties, minimal dark cytotoxicity and substantial photocytotoxicity even under hypoxic conditions.

Luminescent Neutral Cyclometalated Iridium(III) Complexes Featuring a Cubic Polyhedral Oligomeric Silsesquioxane for Lipid Droplet Imaging and Photocytotoxic Applications.

New neutral iridium(III) complexes featuring a cubic polyhedral oligomeric silsesquioxane (POSS) unit, [Ir(N∧C)2(L1-POSS)] [HN∧C = 2-phenylpyridine (Hppy; 1), 2-phenylbenzothioazole (Hbt; 2), and 2-(1-naphthyl)benzothiazole (Hbsn; 3); L1-POSS = (E)-4-[(2-hydroxybenzylidene)amino]benzyl 3-heptakis(isobutyl)POSS-propyl carbamate], were designed and synthesized. Their POSS-free counterparts, [Ir(N∧C)2(L1)] [L1 = (E)-N-(4-hydroxymethylphenyl)-1-(2-hydroxyphenyl)methanimine; HN∧C = Hppy (1a), Hbt (2a), and Hbsn (3a)], and the poly(ethylene glycol) (PEG) derivatives [Ir(N∧C)2(L1-PEG)] [L1-PEG = (E)-4-[(2-hydroxybenzylidene)amino]benzyl 3-[2-[ω-methoxypoly(1-oxapropyl)]ethyl]carbamate; HN∧C = Hppy (1b), Hbt (2b), and Hbsn (3b)] were also prepared. The photophysical, photochemical, and biological properties of the POSS complexes were compared with those of their POSS-free and PEG-modified counterparts. Upon irradiation, all of these complexes displayed orange-to-red emission and long emission lifetimes under ambient conditions. The bsn complexes 3, 3a, and 3b exhibited the highest singlet oxygen (1O2) generation quantum yields (ΦΔ = 0.85-0.86) in aerated CH3CN. Laser-scanning confocal microscopy images revealed that complexes 1-3 and 1a-3a showed exclusive lipid-droplet staining upon cellular uptake, while the PEG derivatives 1b-3b displayed lysosomal localization. Complex 3 was utilized to study various lipid-droplet-related biological events including lipid-droplet accumulation under oleic acid stimulation, the movement of lipid droplets, and preadipocyte differentiation. Notably, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays indicated that the ppy complexes 1 and 1b and the bt complexes 2 and 2b were noncytotoxic both in the dark and upon irradiation at 450 nm for 5 min (IC50 > 200 µM), while the bsn complexes 3, 3a, and 3b showed low dark cytotoxicity (IC50 = 52.9 to >200 µM) and high photocytotoxicity (IC50 = 1.1-5.3 µM). The cellular uptake, internalization mechanisms, and cell death pathways of these complexes were also investigated. This work not only offers promising luminescent probes for lipid droplets through the structural modification of iridium(III) complexes but also paves the way to the construction of new reagents for theranostics.

Tenosynovial giant cell tumor involving the cervical spine: A case report.

BACKGROUND: Tenosynovial giant cell tumors (TGCTs) are a frequent benign proliferative disease originating from the synovial membrane. However, TGCTs rarely occur in the spine. The purpose of this paper is to report a case of TGCT occurring in the cervical spine. Although the disease is rare, it is essential to consider the possibility of TGCT in axial skeletal lesions. Awareness of spinal TGCTs is important because their characteristics are similar to common spinal tumor lesions. CASE SUMMARY: A 49-year-old man with a 2-year history of neck pain and weakness in both lower extremities was referred to our ward. Imaging revealed a mass extending from the left epidural space to the C4-5 paravertebral muscles with uneven enhancement. The tumor originated in the synovium of the C4-5 lesser joint and eroded mainly the C4-5 vertebral arch and spine. Puncture biopsy was suggestive of a giant cell-rich lesion. The patient had pulmonary tuberculosis, and we first administered anti-tuberculosis treatment. After the preoperative requirements of the anti-tuberculosis treatment were met, we used a posterior cervical approach to completely remove the mass after fixation with eight pedicle screws. The mass was identified as a TGCT by postoperative immunohistochemical analysis. Recurrence was not detected after 1 year of follow-up. CONCLUSION: Spinal TGCTs are often misdiagnosed. The radiological changes are not specific. The ideal treatment comprises complete excision with proper internal fixation, which can significantly reduce postoperative recurrence.

PTEN-silencing combined with ChABC-overexpression in adipose-derived stem cells promotes functional recovery of spinal cord injury in rats.

The efficiency of cell therapy after spinal cord injury (SCI) depend on the survival of transplanted cells. However, sterile microenvironment and glial scar hyperplasia extremely reduce their numbers. Our previous study found overexpression of ChABC gene is positively correlated to migration ability. Expression of PTEN gene is closely associated with proliferation. However, whether manipulation of PTEN and ChABC on adipose-derived mesenchymal stem cells (ADSCs) promote motor recovery is unknown. This study aimed to promote hindlimb function recovery in SCI rats by enhancing proliferation and migration ability of ADSCs, transiently silencing expression of PTEN following overexpression of ChABC (double-gene modified ADSCs, DG-ADSCs). After PTEN silencing, we observed strong proliferation and accelerated G1-S transition in DG-ADSCs using CCK8 assay and flow cytometry. In addition, we demonstrated that migration numbers of DG-ADSCs were higher than control group using Transwell assay. The protein and mRNA levels of MAP2 and ßⅢ-tubulin in DG-ADSCs were increased compared with ADSCs. These results were further confirmed in SCI rats. Increased survival cells and reduction of glial scars were quantitatively analyzed in DG-ADSCs groups, which is definitely correlated to function recovery. Recovery of motor function was observed in DG-ADSCs treatment rats using BBB score, which emphasized that improved viability of transplanted cells and reduction of glial scars were an effective strategy for enhancing recovery of neurological function after SCI.

Luminescent Molecular Octopuses with a Polyhedral Oligomeric Silsesquioxane (POSS) Core and Iridium(III) Polypyridine Arms: Synthesis, Aggregation Induced Emission, Cellular Uptake, and Bioimaging Studies.

A new class of luminescent molecular hybrids in which eight cyclometalated iridium(III) polypyridine complexes are grafted onto a polyhedral oligomeric silsesquioxane (POSS) unit [POSS-{Ir(N^C)2 (py-im)}8 ](PF6 )8 [py-im=pyridine imine; HN^C=N-phenylpyrazole (Hppz) (1 a), 2-phenylpyridine (Hppy) (2 a), 2-phenylquinoline (Hpq) (3 a)] were synthesized and characterized. On photoexcitation, the complexes showed intense and long-lived orange-red to red emission in fluid solutions at room temperature and in low-temperature glasses. The photophysical properties including aggregation-induced emission and biological properties of these complexes were studied and compared with those of their POSS-free counterparts [Ir(N^C)2 (py-im)](PF6 ) [HN^C=Hppz (1 b), Hppy (2 b), Hpq (3 b)]. The (photo)cytotoxicity of the complexes was examined by the MTT assay, and their cellular uptake and intracellular localization were investigated by inductively coupled plasma-mass spectrometry and laser-scanning confocal microscopy.

Low-dose tacrolimus combined with donor-derived mesenchymal stem cells after renal transplantation: a prospective, non-randomized study.

Calcineurin inhibitors, including tacrolimus, are largely responsible for advances in allotransplantation. However, the nephrotoxicity associated with these immunosuppressants impairs patients' long-term survival after renal allograft. Therefore, novel regimens that minimize or even eliminate calcineurin inhibitors could improve transplantation outcomes. In this pilot study, we investigated the use of low-dose tacrolimus in combination with mesenchymal stem cells (MSCs), which are immunosuppressive and prolong allograft survival in experimental organ transplant models. Donor-derived, bone marrow MSCs combined with a sparing dose of tacrolimus (0.04-0.05 mg/kg/day) were administered to 16 de novo living-related kidney transplant recipients; 16 other patients received a standard dose of tacrolimus (0.07-0.08 mg/kg/day). The safety of MSC infusion, acute rejection, graft function, graft survival, and patient survival were evaluated over ≥24 months following kidney transplantation. All patients survived and had stable renal function at the 24 month follow-up. The combination of low-dose tacrolimus and MSCs was as effective as standard dose tacrolimus in maintaining graft survival at least 2 years after transplantation. In addition, both groups had similar urea, urine protein, urinary RBC, urinary WBC, 24-h urine protein, and creatinine clearance rates from 7 days to 24 months after transplantation. Furthermore, no differences in the proportion of lymphocytes, CD19, CD3, CD34, CD38, and natural killer cells were detected between the control and experimental groups. None of the MSC recipients experienced immediate or long-term toxicity from the treatment. This preliminary data suggests that the addition of MSCs permits the use of lower dosages of nephrotoxic calcineurin inhibitors following renal transplantation.

Selective colorimetric and fluorescent quenching determination of uranyl ion via its complexation with curcumin.

Under pH4.0 HAc-NaAc buffer medium, curcumin alone possesses extraordinary weak fluorescence emission. Nevertheless, the introduction of Triton X-100 micelles can largely enhance the fluorescence intensity of curcumin. Uranyl ions can complex with micelles-capped curcumin, along with the slight red shift of curcumin fluorescence (about 1-7 nm), a clear decrement of absorbance (424 nm) and fluorescence (507 nm) intensities, and a distinct color change from bright yellow to orange. The fluorescence decrements (ΔF, 507 nm) are positively correlated to the amount of uranyl ions in the concentration range of 3.7×10(-6)-1.4×10(-5) mol L(-1). The detection limit of this fluorescence quenching methods is 3.7×10(-6) mol L(-1), which is nearly 9000 times lower than the maximum allowable level in drinking water proposed by World Health Organization. Good selectivity is achieved because of a majority of co-existing substances (such as Ce(4+), La(3+), and Th(4+)) do not affect the detection. The content of uranyl ions in tap water samples was determined by the proposed method with satisfactory results.