Leptin combined with withaferin A boost posthemorrhagic neurogenesis via activation of STAT3/SOCS3 pathway.

Neurogenesis as a potential strategy to improve the consequences of intracerebral hemorrhage (ICH). The current study investigates the effects of withaferin A (WFA) in combination with leptin (LEP) on ICH and neurogenesis mechanisms. LEP levels were dramatically reduced on days 7 and 14 following ICH insults in mice, but continuous WFA therapy significantly improved the potency of intrinsic LEP on day 14 after ICH.

EAAT3 impedes oligodendrocyte remyelination in chronic cerebral hypoperfusion-induced white matter injury.

Background: Chronic cerebral hypoperfusion-induced demyelination causes progressive white matter injury, although the pathogenic pathways are unknown.

Methods: The Single Cell Portal and PanglaoDB databases were used to analyze single-cell RNA sequencing experiments to determine the pattern of EAAT3 expression in CNS cells. Immunofluorescence (IF) was used to detect EAAT3 expression in oligodendrocytes and oligodendrocyte progenitor cells (OPCs).

[Retracted] Isoquercitrin inhibits the progression of liver cancer and via the MAPK signalling pathway.

Subsequently to the publication of the above article, a concerned reader drew to our attention that the data panel shown in Fig. 7A for the 400 μM isoquercitrin experiment had previously appeared in Fig. 4A in another article published in the journal [Tang B, Li Y, Yuan S, Tomlinson S and He S: Upregulation of the δ opioid receptor in liver cancer promotes liver cancer progression both in vitro and in vivo.

Leptin Promotes Angiogenesis via Pericyte STAT3 Pathway upon Intracerebral Hemorrhage.

Angiogenesis is a vital endogenous brain self-repair processes for neurological recovery after intracerebral hemorrhage (ICH). Increasing evidence suggests that leptin potentiates angiogenesis and plays a beneficial role in stroke. However, the proangiogenic effect of leptin on ICH has not been adequately explored.

Hemorrhage-Induced Sphingosine Kinase 1 Contributes to Ferroptosis-Mediated Secondary Brain Injury in Intracerebral Hemorrhage.

The pathogenic processes of brain injury after intracerebral hemorrhage (ICH) have not yet been fully elucidated. Increasing evidence suggests that ferroptosis activation aggravates injury after ICH, but the underlying mechanism remains unclear. Sphingosine kinase 1 (Sphk1) is a key enzyme in the regulation of sphingosine metabolism involved in the ferroptosis pathway, but its role in ICH needs clarification.

Dithiocarbazate-Copper Complexes for Bioimaging and Treatment of Pancreatic Cancer.

Anticancer agents that present nonapoptotic cell death pathways are required for treating apoptosis-resistant pancreatic cancer. Here, we synthesized three fluorescent dithiocarbazate-copper complexes, {[Cu(L)(Cl)] , [Cu(L)(NO)] , and [CuCu(L)(Br)] }, to assess their antipancreatic cancer activities. Complexes showed significantly greater cytotoxicity toward several pancreatic cancer cell lines with better IC than those of the HL ligand and cisplatin.

Novel Pt(ii) complexes with modified aroyl-hydrazone Schiff-base ligands: synthesis, cytotoxicity and action mechanism.

To develop new anti-tumour Pt(ii) agents, we designed and synthesized five Pt(ii) complexes. These Pt(ii) complexes were modified benzene rings of 2-hydroxybenzylidene with a hydrocarbyl or halogen group. The five Pt(ii) complexes possessed remarkable cytotoxicity against tumour cells in vitro.

Anticancer Function and ROS-Mediated Multi-Targeting Anticancer Mechanisms of Copper (II) 2-hydroxy-1-naphthaldehyde Complexes.

Multi-targeting of oncoproteins by a single molecule represents an effectual, rational, and an alternative approach to target therapy. We carried out a systematic study to reveal the mechanisms of action of newly synthesized Cu compounds of 2-naphthalenol and 1-(((2-pyridinylmethyl)imino)methyl)- (C1 and C2). The antiproliferative activity of the as-synthesized complexes in three human cancer cell lines indicates their potential as multi-targeted antitumor agents.

Anticancer and biological properties of a Zn-2,6-diacetylpyridine bis(thiosemicarbazone) complex.

Herein, to develop a multi-target anticancer metal agent and achieve a "1 + 1 > 2" pharmaceutical effect, we rationally designed and synthesized five complexes (C1-C5) by synergistically exploiting the properties of Zn(ii) and a series of modified 2,6-diacetylpyridine bis(thiosemicarbazone) ligands. By investigating the structure-activity relationships, we found that the binuclear Zn(ii) complex (C5) acts against human bladder cancer cells (T-24) with significant cytotoxicity. We subsequently determined the multiple anticancer mechanisms of C5 to T-24 cells, including inhibiting the activity of topoisomerase I (Topo I), blocking the cell cycle in the S phase, and inducing apoptosis and autophagy in T-24 cells.

Designing anticancer copper(II) complexes by optimizing 2-pyridine-thiosemicarbazone ligands.

To develop potential next-generation metal anticancer agents, we designed and synthesised five Cu(II) 2-pyridine-thiosemicarbazone complexes by modifying the hydrogen atom at the N-4 position of ligands, and then investigated their structure-activity relationships and anticancer mechanisms. Modification of the N-4 position with different groups caused significant differences in cellular uptake and produced superior antitumor activity. Cu complexes arrested the cell cycle at S phase, leading to down-regulation of levels of cyclin and cyclin-dependent kinases and up-regulation of expression of cyclin-dependent kinase inhibitors.

Mixed-ligand Cu(II) hydrazone complexes designed to enhance anticancer activity.

The ligand quantity, ligand type, and coordination geometry have important influences on the anticancer activity of metal-based complexes. On the basis of the structures of previously reported 1:1 Cu(II)/ligand complexes ([Cu(L1)Cl]·2HO 1a, [Cu(L2)Cl]·HO 2a, and [Cu(L2)NO]·HO 3a), we subsequently designed, developed, and characterized a series of corresponding 1:1:1 Cu(II)/ligand/co-ligand complexes ([Cu(L1)(Py)Cl]·HO 1b, [Cu(L2)(Py)Cl] 2b, and [Cu(L2)(Py)NO] 3b), where L1 = (E)-N'-(2-hydroxybenzylidene)acetohydrazide, L2 = (E)-N'-(2- hydroxybenzylidene)benzohydrazide, and Py = pyridine. All six Cu(II) complexes were assessed for their in vitro anticancer properties against a panel of human cancer cells, including cisplatin-resistant A549cisR cell lines.

Structure and biological properties of five Pt(II) complexes as potential anticancer agents.

We synthesized and validated five Schiff base Pt(II) complexes derived from 2-hydroxy-1-naphthaldehyde benzoyl hydrazone and its derivatives, which are modified at the benzohydrazide structures (L1-L5). The complexes were [Pt(L1)(DMSO)Cl] (C1), [Pt(L2)(DMSO)Cl] (C2), [Pt(L3)(DMSO)Cl] (C3), [Pt(L4)(DMSO)Cl] (C4), and [Pt(L5)(DMSO)Cl] (C5). Crystal structures showed that the Pt centers of all complexes were tetra-coordinated with other atoms.

Novel 2-pyridinecarboxaldehyde thiosemicarbazones Ga(III) complexes with a high antiproliferative activity by promoting apoptosis and inhibiting cell cycle.

Two types of 2-pyridinecarboxaldehyde thiosemicarbazones Ga(III) complexes, which are 2:1 and 1:1 ligand/Ga(III) complexes, were synthesized and determined by X-ray single crystal diffraction. The antiproliferative activity of these Ga(III) complexes have been examined to illuminate the structure-activity relationships essential to form Ga(III) complexes with remarkable anticancer activity. In addition, Ga(III) complexes where the metal/ligand ratio was 1:1 (C4) had observably higher antiproliferative activity than 1:2 (C3).

Synthesis of Dipyridyl Ketone Isonicotinoyl Hydrazone Copper(II) Complex: Structure, Anticancer Activity and Anticancer Mechanism.

In an effort to better understand the biological efficacy of the tridentate aroyl hydrazone Cu(II) complexes, the Cu(II) complex of di-2-pyridyl ketone isonicotinoyl hydrazone ligand (HL), {[Cu(L)(HO)]·HO·NO} (C1) was synthesized and characterized. Single crystal X-ray study reveals that complex C1 forms 1D zigzag chains in solid state. In water, the hydrolysis of the 1D zigzag chains was observed, and finally formation of monomeric species.

The Cu/ligand stoichiometry effect on the coordination behavior of aroyl hydrazone with copper(II): Structure, anticancer activity and anticancer mechanism.

In an effort to better understand the biological efficacy of the tridentate aroyl hydrazone Cu(II) complexes, three Cu(II) complexes of acetylpyridine benzoyl hydrazone (HL), [Cu(L)(NO3) (H2O)]·H2O (C1), [Cu(L)2] (C2) and [Cu(L)(HL)]·(NO3)(Sas) (C3) (Sas=salicylic acid) were synthesized and characterized. X-ray crystal structures and infrared (IR) spectra of the complexes reveal that the L(-) ligand of C1 and C2 are predominantly in the enolate resonance form, while one L(-) ligand in C3 is represented enolate resonance form and the other HL ligand exhibits keto resonance form. All Cu(II) complexes showed significantly more anticancer activity than the ligand alone.

Isoquercitrin inhibits the progression of liver cancer in vivo and in vitro via the MAPK signalling pathway.

Liver cancer is a malignant tumour with high morbidity and fatality rates that is common worldwide. At present, the clinical approaches to treating primary liver cancer include partial hepatectomy, systemic or local chemotherapy, radiotherapy, radiofrequency ablative surgery and liver transplantation. However, all of these approaches have shortcomings, including poor prognosis and numerous side-effects.

Safety, tolerability and pharmacokinetic study of recombinant human parathyroid hormone [rhPTH (1-84)] in Chinese healthy volunteers.

The current study was designed to determine the safety, tolerability and pharmacokinetic parameters of recombinant human parathyroid hormone [rhPTH (1-84)] used for the treatment of osteoporosis. In the single-dose format pharmacokinetic study, thirty-six healthy male volunteers received three dose levels of rhPTH (1-84) subcutaneously: 1, 2, and 4 microg/kg. The blood was timing drawn and the serum concentration of rhPTH (1-84) was determined by enzyme linked immunosorbent assay (ELISA).

Safety, pharmacokinetic and pharmacodynamic studies of batifiban injection following single- and multiple-dose administration to healthy Chinese subjects.

Batifiban, a synthetic cyclic peptide, is a potent platelet glycoprotein GPIIb/IIIa antagonist which may be useful in the treatment and prevention of acute coronary syndromes. The pharmacokinetics and pharmacodymanic (inhibition of platelet aggregation) effects, and tolerability of batifiban were investigated in healthy subjects following single bolus injection with doses of 55, 110, or 220 microg/kg, or multiple doses of an bolus followed intravenous infusion for 24 h (180 microg/kg plus 2.0 microg/min.

HPLC determination of 4-hydroxy-anethole trithione in plasma via enzymatic hydrolysis and its application to bioequivalence study.

A simple, selective and reproducible high-performance liquid chromatographic (HPLC) method via enzymatic hydrolysis of glucuronide conjugates of 4-hydroxy-anethole trithione (ATX) was established for simultaneous determination of ATX. Human plasma samples were hydrolyzed by beta-glucuronidase and followed by subsequent extraction with cyclohexane-isopropanol (95:5, v/v) using mifepristone as the internal standard. Chromatography was carried out on a reverse phase C(18) column (250 mm x 4.

[Effect of Smilax china on adjunctive arthritis mouse].

Objective: To study the therapeutic action of decoction of Smilax china L. on adjunctive arthritis(AA) mouse and its mechanism.

Methods: To observe the change of secondary inflammation, thymus and spleen weights, T cell subgroup, B cell, NK cell.