Novel perfluorocarbon-based oxygenation therapy alleviates Post-SAH hypoxic brain injury by inhibiting HIF-1α.

In comparison to other stroke types, subarachnoid hemorrhage (SAH) is characterized by an early age of onset and often results in poor prognosis. The inadequate blood flow at the site of the lesion leads to localized oxygen deprivation, increased level of hypoxia-inducible factor-1α (HIF-1α), and triggers inflammatory responses and oxidative stress, ultimately causing hypoxic brain damage. Despite the potential benefits of oxygen (O2) administration, there is currently a lack of efficient focal site O2 delivery following SAH. Conventional clinical O2 supply methods, such as transnasal oxygenation and hyperbaric oxygen therapy, do not show the ideal therapeutic effect in severe SAH patients. The perfluorocarbon oxygen carrier (PFOC) demonstrates efficacy in transporting O2 and responding to elevated levels of CO2 at the lesion site. Through cellular experiments, we determined that PFOC oxygenation serves as an effective therapeutic approach in inhibiting hypoxia. Furthermore, our animal experiments showed that PFOC oxygenation outperforms O2 breathing, leading to microglia phenotypic switching and the suppression of inflammatory response via the inhibition of HIF-1α. Therefore, as a new type of O2 therapy after SAH, PFOC oxygenation can effectively reduce hypoxic brain injury and improve neurological function.

Dual Delivery of NGF and bFGF Coacervater Ameliorates Diabetic Peripheral Neuropathy via Inhibiting Schwann Cells Apoptosis.

Diabetic neuropathy is a kind of insidious complications that impairs neural and vascular function and ultimately leads to somatic and visceral denervation. Basic fibroblast growth factor (bFGF) and nerve growth factor (NGF) are important neurotrophic factors for stimulating angiogenesis and improving peripheral nerve function. Administrating a single factor has good therapeutic effect on diabetic peripheral neuropathy (DPN). However, the short half-life and rapid diffusion of growth factors under physiological conditions limits its clinical applications. Here, we used a biodegradable coacervate, composed of heparin and polycation, to dominate the combined release of bFGF and NGF in a steady fashion. We found this combined growth factors (GFs) coacervate, administered as a single injection, improved motor and sensory functions, restored morphometric structure and decreased apoptosis of Schwann cells in a rat model of prolonged DPN. Similarly the GFs coacervate, as compared with free bFGF and NGF combination, markedly reduced the apoptosis level of a rat Schwann cell line, RSC 96 cells in vitro. We also demonstrated that neuroprotective effects of the GFs coacervate in both rat DPN model and hyperglycemia-induced RSC 96 cell model is likely due to suppression of endocytoplasmic reticulum stress (ERS).

Synthesis and in vitro cytotoxicity of cis-[Pt(NH(3))(NH(2)OH)Cl(2)].

A novel mixed NH(3)/NH(2)OH platinum(II) complex cis-[Pt(NH(3))(NH(2)OH)Cl(2)] was synthesized and characterized by elemental analysis, FAB-MS, FT-IR and (1)H NMR spectroscopy. This complex was determined to have a good water-solubility and satisfactory stability. The pertinent complex was evaluated for its in vitro cytotoxicity against 3AO, HCT-116, LNcap, A549/ATCC and SGC-7901 human carcinoma cell lines. It shows appreciable cytotoxic activity that is comparable with cisplatin and is much more active than carboplatin.

Synthesis, characterization and cytotoxicity of dihalogeno-platinum(II) complexes with L-histidine ligand.

Diiodo-, dibromo- and dichloro-platinum(II) complexes containing L-histidine ligand were prepared. Their spectra and X-ray crystal structure of the dibromo-platinum(II) complex were described. Only the dichloro-platinum(II) complex showed comparable cytotoxic activity with carboplatin against A549/ATCC, HT-29, and LNcap cell lines. Nevertheless the complexes with COOH-substituted ligands histidine may be good starting materials to synthesize targeting platinum complexes since they could be easily linked to suitable carrier molecules via esterification.

Bis(acetyl-acetonato-κO,O')-aqua-(diacetyl-methanido-κC)iridium(III).

In the crystal structure of the title compound, [Ir(C(5)H(7)O(2))(3)(H(2)O)], the Ir(III) atom is six-coordinated and situated in a slightly distorted octa-hedral environment. The complex contains both Ir-O and Ir-C bonds and was isolated from a reaction mixture of IrCl(3)(H(2)O)(x), pentane-2,5-dione and NaHCO(3). O-H⋯O hydrogen bonding between the water molecules and the carbonyl O atoms of adjacent molecules leads to a layered motif extending parallel to (010).

Synthesis and cytotoxicity of platinum(II) complexes of a physiologically active carrier histamine.

A series of novel platinum(II) complexes involving a physiologically active carrier histamine as the carrier, cis-[Pt(histamine)X2] (X2=2Cl-, oxalate, malonate, 1,1-cyclobutanedicarboxylate (CBDCA), 3-hydroxy-1,1-cyclobutanedicarboxylate (HO-CBDCA)), have been synthesized and characterized by elemental analysis and spectroscopic data along with X-ray crystal structure for a representative complex cis-[Pt(histamine)Cl2]. The cytotoxicity of the complexes has also been assessed in the human cancer cell lines A549/ATCC, HT-29, and LNcap. One complex, cis-[Pt(histamine)Cl2], is more active than carboplatin against both the sensitive and resistant cells.

Synthesis and anticancer activity of lipophilic platinum(II) complexes of 3,5-diisopropylsalicylate.

Novel lipophilic platinum(II) complexes (LSPt-1-3), containing 3,5-diisopropylsalicylate (DIPS) as a leaving group and 2NH(3) or 1R,2R-diaminocyclohexane or (4R,5R)-4,5-bis(aminomethyl)-2-isopropyl-1,3-dioxolane as the carrier, have been synthesized, characterized and evaluated in vitro and in vivo. The octanol/water distribution coefficient of the complexes has also been measured. The results showed that the complexes achieved a typical square planar and the octanol/water distribution coefficient logP was 4.27, 4.37 and 4.31. The complexes were tested by SRB method to be more cytotoxic than Carboplatin, Oxaliplatin and Eptaplatin against 3AO, A549, NCI-H460 and SGC-7901 human cancer cell lines. Among complexes, LSPt-2 was much more effective than Carboplatin and Oxaliplatin in treating the NCI-H460 non-small-cell lung tumor-bearing mice. Its optimal activity was 38.8% (T/C) at a dose of 30 mg/kg following i.p. administration. LD(50) for the complex was found to be 230.9 mg/kg. LSPt-2 exhibited great anticancer activity, good lipophilic ability and low toxicity and therefore, it is a promising candidate for effective and stable pharmaceutical liposomal platinum anticancer drug.

Synthesis, characterization and cytotoxicity of diam(m)-ineplatinum(II) complexes containing beta-phenylisosuccinate ligand.

Four diam(m)ineplatinum(II) complexes containing beta-phenylisosuccinate as the leaving groups were prepared, characterized, and evaluated for their cytotoxicity against A549/ATCC human lung cancer cell line and SGC-7901 human gastric cancer cell line. One of the complexes, (trans-1R,2R-diaminocyclohexane)-beta-phenylisosuccinatoplatinum(II) 4, was much more active than cisplatin and carboplatin.

Synthesis and in vitro cytotoxicity of novel lipophilic (diamine)platinum(II) complexes of salicylate derivatives.

Novel lipophilic (diamine)platinum(II) complexes of salicylate derivatives as the leaving groups were synthesized and characterized by elemental analysis, FAB(+)-MS, FT-IR, and (1)H NMR spectroscopy. Most of the resulting platinum complexes had high solubility in organic solvents such as ethanol, acetone, and ether, and had right partition coefficient suited to be encapsulated in liposomes. The pertinent complexes were evaluated for their in vitro cytotoxicity against A549 human lung carcinoma and SGC-7901 human gastric carcinoma cell lines. They showed better cytotoxic activity than carboplatin and oxaliplatin.

Langmuir aggregation of Nile blue and safranine T on sodium dodecylbenzenesulfonate surface and its application to quantitative determination of anionic detergent.

We studied the interaction of sodium dodecylbenzenesulfonate (SDBS) with Nile Blue (NB) and Safranine T (ST) by a spectral correction technique. The aggregations of NB and ST on an SDBS surface obeyed Langmuir isothermal adsorption. The adsorption ratios of NB and ST to SDBS were both 0.5, and the adsorption constants of the aggregates were 1.80 x 10(5) and 9.49 x 10(4). The aggregations were applied to the quantitative determination of anion detergent in samples; the recovery of SDBS was between 90.3 and 106% together with an RSD of 3.78%.