Search

Background: Patients with bipolar disorder (BD) present widespread and significant neurocognitive impairments during all stages of the disorder. Repetitive transcranial magnetic stimulation (rTMS) has been used to improve clinical outcomes in common psychiatric diseases, such as depression, anxiety disorders, schizophrenia, and BD. Whether rTMS can improve cognitive function in BD patients remains unclear. The present study explored the regulatory effects of rTMS on cognitive function in patients with BD.Methods: Fifty-two eligible subjects with BD were randomly assigned to receive active or sham rTMS via high-speed magnetic stimulator with a figure-of-eight coil for 10 consecutive days. In the active rTMS group, a total of 25,000 stimuli were applied over the left dorsolateral prefrontal cortex at 110% of the motor threshold. The sham group received corresponding sham stimulation. Clinical manifestations and cognitive functions were assessed using a modified 24-item Hamilton Depression Rating Scale (HDRS), the Young Mania Rating Scale (YMRS), and the MATRICS Consensus Cognitive Battery (MCCB).Results: Ten consecutive days of high-frequency active rTMS improved scores on the Wechsler Memory Scale-III Spatial Span, and the MCCB Category Fluency subtest, without intolerable adverse effects. No significant differences in HDRS or YMRS scores were found between groups.Limitations: No follow-up after the intervention. The effect of the drug on cognitive function in subjects was not excluded.Conclusions: Short-term rTMS can improve cognitive function in BD patients. [ABSTRACT FROM AUTHOR]

Although paraquat (PQ) is one of the most extensively used herbicides worldwide, it is hazardous to the environment and the public due to its extreme toxicity towards non-target organisms especially animals and humans. Therefore, developing a detection system for selectively and sensitively detecting PQ remains a great challenge. This report demonstrates the design of a novel highly fluorescent rhodamine-based probe fabricated by rationally inserting adamantane-modified rhodamine into a host cucurbit[7]uril (CB[7]) with a host-guest interaction induced spirocyclic ring-opening process. This host-guest binary complex (1 &CB[7]) had a stronger fluorescence intensity than rhodamine B, which was exploited for PQ detection. Notably, complex 1 &CB[7] displayed high sensitivity toward PQ, with an excellent nanomolar limit of detection of 10 nM. It was determined that this unique detection mechanism involved a process of self-assembly, disassembly, and reassembly, thereby providing a reversible fluorescence response to PQ. With such merits, we successfully quantified and mapped PQ in actual water samples, live cells, and various agricultural products. We anticipated that the constructed complex 1 &CB[7] could acts as a potential alternative for PQ tracking in various applications, highlighting a new paradigm for engineering host-guest probes with spirocyclic ring-opening process for analyte detection. [Display omitted] • A new fluorescent supramolecular probe is fabricated by adamantane-modified rhodamine B and cucurbit[7]uril. • The supramolecular complex can selectively, sensitively, and reversible detect herbicide paraquat through host-guest interaction. • A reversible detection system is realized with host-guest interaction induced spirocyclic ring-opening process. • The supramolecular probe is useful for visual detecting paraquat in actual samples including water and agricultural products. [ABSTRACT FROM AUTHOR]

• Spraying ABA improved the drought resistance ability of Bupleurum chinense. • Exogenous ABA inhibited the expression of saikosaponin synthesis pathway genes. • Cultivators need to pay attention to the change of ABA in medicinal plants. • Drought can affect molecular mechanisms important for medicinal plant quality. Abscisic acid (ABA) plays an important role in stress resistance and secondary metabolism of plants under drought stress. Bupleurum chinense DC. is a medicinal plant cultivated in arid areas in China. In this study, the effects of progressive drought stress (22 days) and exogenous ABA (5 mg L–1) treatment on plant physiological characteristics and saikosaponin secondary metabolism were investigated in 2-year-old B. chinense. The samples were collected on 6, 10, 14, 18 and 22 days after drought stress (DADS). In drought stressed B. chinense plants treated with ABA, root weight loss and malondialdehyde accumulation was reduced, while drought resistance increased, as indicated by the accumulation of soluble protein and soluble sugar content, and by the increased activities of superoxide dismutase and peroxidase. At the early stage of drought stress (first 6 days), saikosaponin increased more sharply in plants exposed to drought stress and its accumulation indicated increased sensitivity to this condition. At this time, saikosaponin content reached 31.83 mg g−1, which was 33.6 % higher than that in control plants. Using principal component analysis and fuzzy membership function calculation, comprehensive evaluation values of gene expression in the drought (D) and D + ABA treated groups at different drought exposure time were evaluated. Exogenous ABA inhibited the expression of saikosaponin biosynthesis-related genes from 6 to 14 DADS of drought stress. However, gene expression was up-regulated at later stages of drought stress (the 22 DADS), while genes involved in saikosaponin content were down-regulated in the D group compared with those in the D + ABA group. Indeed, saikosaponin content in both of these groups was significantly higher than that in the control group. Correlation analysis suggested that the expression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGR) gene was positively correlated with total saikosaponin (SSs) (p < 0.01), and saikosaponin a (SS-a) and saikosaponin d (SS-d) (p < 0.05) content, while that of farnesyl pyrophosphate synthase (FPS) gene was positively correlated with SSs (p < 0.05), and SS-a and SS-d (p < 0.01) content in the D group. These results indicated that HMGR and FPS play a key role in saikosaponin biosynthesis during drought stress. Moreover, the negative correlations between multiple genes and saikosaponin after ABA treatment [particularly that of cytochrome P450−7 with SS-d (p < 0.01) and glycosyl transferase-8 with SS-d (p < 0.05)], indicated that exogenous ABA reduced saikosaponin accumulation by inhibiting the expression of saikosaponin biosynthesis-related genes in B. chinense exposed to drought stress. This study provides new insight into the effect of ABA on secondary metabolism and it will be of great importance to cultivators and researchers aiming to understand how ABA application affects medicinal plant cultivation. [ABSTRACT FROM AUTHOR]

Drought stress affects vegetative and reproductive growth processes and synthesis of secondary metabolites in plants. We assessed relevant indicators of vegetative and reproductive growth in Bupleurum chinense DC. during drought stress. Samples were collected on days 4, 8, 12, 20, and 24 of a drought treatment according to drought stress severity in order to elucidate potential effects on synthesis of flavonoids in leaves and saikosaponins in roots of B. chinense. The results showed that B. chinense can adapt to drought stress mainly by increasing concentrations of osmoregulatory substances (soluble protein and proline) and increasing activity of protective enzymes (superoxide dismutase and catalase), as observed on days 12 and 20 of the treatment. Secondary metabolite concentrations in B. chinense roots and leaves showed significant differences—drought stress increased saikosaponin concentrations in roots by 9.85% and 6.41% during vegetative and reproductive growth, respectively, on day 20, and saikosaponin concentrations in roots were higher during vegetative growth than during reproductive growth. In leaves, large amounts of antioxidants were consumed owing to drought stress, which decreased leaf rutin concentrations by 38.79% and 30.11% during vegetative and reproductive growth, respectively, as observed on day 20; overall, leaf rutin concentrations were lower during vegetative growth than during reproductive growth. Changes in soil water content are known to affect synthesis of secondary metabolites in medicinal plants by altering gene transcription, and affected genes may synergistically respond to soil water changes and alter concentrations of flavonoid in leaves and of saikosaponin in roots. The gene F3H down-regulates flavonoid production in leaves. Squalene epoxidase and β-amyrin synthase genes may be key genes regulating saikosaponin accumulation, and changes in their expression corresponded to accumulation of saikosaponins. Our results provide insights in B. chinense adaptation to drought stress through physiological changes and regulation of secondary metabolite production in different plant tissues. The vegetative growth and reproductive growth Bupleurum chinense DC. adapts to the continuous drought stress process by changing the expression of secondary metabolites synthesis genes and metabolites concentrations in different tissues. Image 1 • Drought stress increased saikosaponin content but decreased rutin content. • The vegetative growth Bupleurum chinense accumulates more saikosaponin. • Plants adapt to adversity by regulating secondary metabolism in different parts. • Effective management can enhance the content of secondary metabolites. [ABSTRACT FROM AUTHOR]

• Uniaxial magnetic anisotropy of amorphous FeNiPGd can reach 116Oe. • Magnetic field can improve the surface and dynamic permeability of film. • The ferromagnetic-resonance frequency can achieve 500 MHz under 40 mT. Uniaxial magnetic anisotropy has been induced in multi-element soft magnetic amorphous FeNiPGd thin films, which were fabricated by electroplating with an external magnetic field applied parallel to the plane of the electrode. After the application of the magnetic field, surface morphology of the FeNiPGd layer is improved. The crystal grains are refined, and the number of pores generated on the surface is remarkably reduced. The introduction of external magnetic field can significantly improve the deposition rate and dynamic permeability. And the cutoff frequency can achieve 500 MHz when the applied magnetic field is 40 mT during the deposition process. Specifically, the in-plane anisotropy field of the film was calculated by the area integral method to be approximately 116Oe while the magnetic field is 10 mT, which is obviously higher than that of the binary FeNi material. [ABSTRACT FROM AUTHOR]

Repetitive transcranial magnetic stimulation (rTMS) has been introduced as a new and effective treatment option for major depression. This paper examined the effectiveness of rTMS on first episode depressed patients when combined with antidepressant drugs. A random sample of forty-three first-episode depressed patients received active or sham rTMS to the left dorsolateral prefrontal cortex, and concomitantly took paroxetine for 4 weeks, and paroxetine monotherapy for 4 weeks afterwards. Response was defined as a ≥50% decrease on the total Hamilton Depression Rating Scale (HDRS) from the baseline, and remission was defined as an HDRS total residual score <8. The dosage of paroxetine was the average dose per day in each week. Repeated-measures ANOVA revealed a significant improvement in the HDRS with active compared with sham rTMS from the end of the 1st week to the 4th week. At the end of the 4th week, response rate was 95.5% with active and 71.4% with sham rTMS, remission rate was 68.2% with active and 38.1% with sham rTMS, while these significant differences disappeared at the endpoint of the study. These findings indicate that rTMS at 10-Hz accelerated the onset of action and augmented the response to paroxetine for first-episode depressed patients. [ABSTRACT FROM AUTHOR]

Reactive oxygen species (ROS), reactive nitrogen species (RNS), and reactive sulfur species (RSS) serve as vital mediators essential for preserving intracellular redox homeostasis within the human body, thereby possessing significant implications across physiological and pathological domains. Nevertheless, deviations from normal levels of ROS, RNS, and RSS disturb redox homeostasis, leading to detrimental consequences that compromise bodily integrity. This disruption is closely linked to the onset of various human diseases, thereby posing a substantial threat to human health and survival. Small-molecule fluorescent probes exhibit considerable potential as analytical instruments for the monitoring of ROS, RNS, and RSS due to their exceptional sensitivity and selectivity, operational simplicity, non-invasiveness, localization capabilities, and ability to facilitate in situ optical signal generation for real-time dynamic analyte monitoring. Due to their distinctive transition from their spirocyclic form (non-fluorescent) to their ring-opened form (fluorescent), along with their exceptional light stability, broad wavelength range, high fluorescence quantum yield, and high extinction coefficient, rhodamine fluorophores have been extensively employed in the development of fluorescent probes. This review primarily concentrates on the investigation of fluorescent probes utilizing rhodamine dyes for ROS, RNS, and RSS detection from the perspective of different response groups since 2016. The scope of this review encompasses the design of probe structures, elucidation of response mechanisms, and exploration of biological applications. [Display omitted] • Recent advances in rhodamine fluorescent probes for ROS, RNS and RSS are reviewed. • The design strategy and detection mechanism of fluorescent probes are discussed. • The bio-applications of the probes in the study of ROS, RNS and RSS are summarized. • The challenges and prospects of probes for ROS, RNS and RSS species are presented. [ABSTRACT FROM AUTHOR]

QT interval prolongation, a potential risk for arrhythmias, may result from gene polymorphisms relevant to cardiomyocyte repolarization. Another noted cause of QT interval prolongation is the administration of chemical compounds such as anesthetics, which may affect a specific type of cardiac K + channel encoded by the human ether-a-go-go- related gene (hERG). hERG K + current was recorded using whole-cell patch clamp in human embryonic kidney (HEK293) cells expressing wild type (WT) or mutated hERG channels. Expression of hERG K + channel proteins was evaluated using western blot and confirmed by fluorescent staining and imaging. Computational modeling was adopted to identify the possible binding site(s) of propofol with hERG K + channels. Propofol had a significant inhibitory effect on WT hERG K + currents in a concentration-dependent manner, with a half-maximal inhibitory concentration (IC 50 ) of 60.9±6.4 μM. Mutations in drug-binding sites (Y652A or F656C) of the hERG channel were found to attenuate hERG current blockage by propofol. However, propofol did not inhibit the trafficking of hERG protein to the cell membrane. Meanwhile, for the three selective hERG K + channel mutant heterozygotes WT/Q738X-hERG, WT/A422T-hERG, and WT/H562P-hERG, the IC 50 of propofol was calculated as 14.2±2.8 μM, 3.3±1.2 μM, and 5.9±1.9 μM, respectively, which were much lower than that for the wild type. These findings indicate that propofol may potentially increase QT interval prolongation risk in patients via direct inhibition of the hERG K + channel, especially in those with other concurrent triggering factors such as hERG gene mutations. [ABSTRACT FROM AUTHOR]

[Display omitted] • A novel host–guest nanoprobe is fabricated by adamantane-modified rhodamine B and cucurbit[7]uril. • The constructed nanoprobe exhibits highly selective and sensitive to detect salicylic acid. • The fluorescence signal amplification strategy is engineered to detect salicylic acid with 330-fold fluorescent enhancement. • The detection mechanism attributes to the synergetic effect of host–guest and hydrogen bond interactions. • The nanoprobe is useful for visually detecting SA in callus and plants. Salicylic acid (SA), the crucial phytohormone, is biosynthesized by plants in response to fight against multifarious phytopathogens and is a central mediator for regulating plant physiology and pathology processes including biotic and abiotic stress. However, current research still lacks of effective and simple tactics to track SA for understanding the underlying mechanisms in plants. Herein, we constructed a supramolecular host–guest nanoprobe (RAD&CB[7]) based on cucurbit[7]uril (CB[7]) and adamantane (AD)-modified rhodamine derivative, the nanoprobe selectivity and sensitivity for SA were very satisfactory. The nanoprobe RAD&CB[7] has been employed to (1) improve the fluorescent signal for detecting SA about 330-fold at lower concentration of SA (20 μM) in vitro, which is very difficult to realize by previous SA fluorescent probes. The density functional theory (DFT) calculations demonstrated the signal amplification is significantly higher than other fluorescent probes reported in literature due to the synergetic effects of host–guest and hydrogen-bond interaction. (2) realize the detection of SA in living Nicotiana glutinosa L. callus, Arabidopsis thaliana, and tomato seedlings even at ultra-low concentrations of RAD&CB[7] (minimum 1 μM) and SA (minimum 5 μM), compared with previous probes (minimum 10 μM) for detecting SA (minimum 25 μM) in vivo, thus realized quantitatively detected SA in callus and Arabidopsis thaliana roots. (3) verify SA-induced stomatal closure in the leaves of Arabidopsis thaliana by host–guest fluorescent probe technology for the first time. The remarkable in vitro and in vivo performance make this fluorescence signal amplification strategy a powerful tool for studying SA-related physiology and pathology in biological processes and discovering novel immune activators for crop protection. [ABSTRACT FROM AUTHOR]

Two iridium(III) polypyridyl complexes [Ir(ppy) 2 (HPIP)](PF 6) (Ir-1), [Ir(ppy) 2 (BHPIP)](PF 6) (Ir-2) and their liposomes Ir-1-Lipo and Ir-2-Lipo were synthesized and characterized by elemental analysis, IR, 1H NMR and 13C NMR. The anticancer activity in vitro and in vivo was evaluated. The cytotoxic activity in vitro of the complexes and their liposomes Ir-1-Lipo and Ir-2-Lipo against cancer cells was investigated by MTT methods. Ir-1 and Ir-2 show no cytotoxic activity, while Ir-1-Lipo and Ir-2-Lipo exhibit high cytotoxic effect. The IC 50 values range from 5.2 ± 0.8 to 22.3 ± 1.8 μM. The apoptosis, reactive oxygen species, the change of mitochondrial membrane potential, intracellular Ca2+ levels and a release of cytochrome c were investigated. The effect of Ir-1-Lipo and Ir-2-Lipo on microtubules was also explored. In the C57BL/6 mice model, Ir-1 only displays a tumor inhibitory rate of 23.21%, while lr-1-Lipo exhibits satisfactory in vivo antitumor efficacy with tumor inhibitory rate of 72.55%. This study demonstrates that complexes encapsulated in liposomes induce apoptosis in B16 through ROS-mediated lysosomal-mitochondria dysfunction, inhibition of polymerization of microtubules and induce cell cycle arrest at S phase. Two iridium(III) complexes [Ir(ppy) 2 (HPIP)](PF 6) (Ir - 1) and [Ir(ppy) 2 (BHPIP)](PF 6) (Ir - 2) were synthesized and characterized. The complexes Ir-1 and Ir-2 were encapsulated in liposomes Ir-1-Lipo and Ir-2-Lipo. The anticancer activity of the complexes and liposomes was investigated by apoptosis, comet assay, ROS, mitochondrial membrane potential, release of cytochrome c , tubules and Western blot analysis and in vivo antitumor activity. Image 1 • Two iridium(III) complexes Ir-1 and Ir-2 and their liposomes Ir-1-Lipo and Ir-2-Lipo were synthesized and characterized. • The cytotoxicity in vitro or in vivo of the complexes and liposomes was investigated. • The apoptosis and cell cycle distribution were assayed by flow cytometry. • ROS and mitochondrial membrane potential were studied under fluorescence microscope. • The expression of Bcl-2 family proteins was assayed by western blot analysis. [ABSTRACT FROM AUTHOR]

This work mainly introduces the synthesis and characterization of three iridium(III) complexes [Ir(ppy) 2 (adppz)](PF 6) (Ir-1), [Ir(bzq) 2 (addpz)](PF 6) (Ir-2) and [Ir(piq) 2 (adppz)](PF 6) (Ir-3). The complexes are more cytotoxic than cisplatin against tumor cell lines such as SGC-7901, A549, HeLa, Eca-109, HepG2 and BEL-7402. The toxicity test results indicated that complexes Ir-1 , Ir-2 and Ir-3 can effectively inhibit the cell growth of SGC-7901 cells, and the measured IC 50 values are 1.8 ± 0.4, 1.6 ± 0.3 and 0.8 ± 0.1 μM, respectively. AO/EB staining and flow apoptosis confirmed that SGC-7901 cells were caused apoptosis after being treated with the complexes. Along with the increase of endogenous ROS and Ca2+ levels, mitochondrial membrane potential collapse and massive release of cytochrome c , it is fully demonstrated that these complexes induce apoptosis through ROS-mediated mitochondrial pathway. At the same time, the complex Ir-3 is outstanding in the inhibition of tumor growth in vivo. Combined with the above results, it provides a favorable foundation for the future development of more effective anti-tumor drugs. Three new iridium(III) complexes were synthesized and characterized. The cytotoxicity in vitro and in vivo was investigated. The complexes show high anticancer activity in vitro and in vivo. Image 1 • The iridium(III) complexes were synthesized and characterized. • The cytotoxicity in vitro was studied by MTT method. • The apoptosis, cell cycle arrest and intracellular ROS levels were assayed. • The effect of the complex on the tumor growth was evaluated. [ABSTRACT FROM AUTHOR]

Salicylic acid (SA) is a crucial molecule that is not only involved in plant immunity but also of wide interest in the ecological environment and human health. However, developing rapid, sensitive, and convenient tools for the selective detection of SA remains a significant challenge. In this study, we aimed to engineer a series of six- and five-membered benzothiazole-containing rhodamine fluorescent probes used a new synthesis method and compare probes' fluorescence performance. Probe 1 demonstrated an excellent sensing performance for SA, including fast response (< 1 min), high selectivity, sensitivity, photostability, low detection limit (1 nM), and reversibility. As a representative fluorescence pattern, probe 1 can visualize SA in plant tissues for possible plant biology study and detected excess SA in food including grapes, bananas, and cucumbers to warn of SA-sensitized individuals. This proof-of-concept study highlights the potential application of probe 1 as a molecular tool for monitoring SA in plants and food, and it will potentially be used to detect SA in other areas of sewage detection, food industry, and cosmetics residue detection with economical, reusable, and fast response performance. • The six- and five-membered rhodamine B fluorescent probes were prepared using a new synthetic method. • Probe 1 demonstrated an excellent sensing performance for detection of salicylic acid. • Probe 1 could visualize salicylic acid in plant tissues for possible plant biology study. • The test strips based on probe 1 have the potential for the rapid and reversible detection of salicylic acid in food samples. [ABSTRACT FROM AUTHOR]

Three iridium(III) complexes [Ir(ppy) 2 (CPIP)](PF 6) (Ir-1 , ppy = 2-phenylpyridine, CPIP = 2-(4-chlorophenyl)-1 H -imidazo[4,5-f][1,10]phenanthroline), [Ir(ppy) 2 (DCPIP)](PF 6) (Ir-2 , DCPIP = 2-(3,4-dichlorophenyl)-1 H -imidazo[4,5- f ][1,10]phenanthroline) and [Ir(ppy) 2 (TCPIP)](PF 6) (Ir-3 , TCPIP = 2,3,5-trichlorophenyl)-1H-imidazo[4,5-f][1,10]phenanthroline) were synthesized and characterized. The complexes Ir-1 , Ir-2 and Ir-3 were encapsulated in liposomes to form Ir-1-Lipo , Ir-2-Lipo and Ir-3-Lipo. Morphology, size distribution, and zeta potential of liposomes were examined by transmission electron microscopy (TEM) and Zetasizer. The cytotoxic activity in vitro of Ir-1 , Ir-2 and Ir-3 against cancer A549, HTC-116, HepG2, BEL-7402, Eca-109, B16, HeLa SGC-7901 and normal NIH3T3 cells was evaluated by 3-(4,5-dimethylthiazole-2-yl)-2,5-biphenyl tetrazolium bromide (MTT) method. Ir-2 and Ir-3 show no cytotoxic activity against the selected cancer cells, and Ir-1 displays moderate cytotoxic effect on the cell growth in A549 cells. However, Ir-1 , Ir-2 and Ir-3 were encapsulated in liposomes, the cytotoxic activity was greatly enhanced. In particular, Ir-1-Lipo and Ir-2-Lipo can effectively inhibit the cell growth in A549 cells with a low IC 50 value of 3.1 ± 0.3 and 1.2 ± 0.4 μM. The apoptosis was assayed by flow cytometry. Ir-1 , Ir-2 and Ir-3 reveal weak apoptotic effect, whereas Ir-1-Lipo , Ir-2-Lipo and Ir-3-Lipo induce an apoptotic percentage of 55.6%, 69.3% and 16.7% in A549 cells, respectively. Specially, in the assay of antitumor activity in vivo, the inhibiting percentage of tumor growth induced by Ir-2 is 27.65%, while inhibiting percentage of tumor growth caused by Ir-2-Lipo is 57.45%. Obviously, the liposomes can enhance anticancer activity in vitro and in vivo compared with the complexes. The results show that the iridium(III) complexes encapsulated liposomes induce apoptosis in A549 cells through ROS-mediated lysosome-mitochondria dysfunction pathway and target the microtubules. Iridium(III) complexes [Ir(ppy) 2 (CPIP)](PF 6) (Ir - 1 , ppy = 2-phenylpyridine, CPIP = 2-(4-chlorophenyl)-1 H -imidazo[4,5-f][1,10]phenanthroline), [Ir(ppy) 2 (DCPIP)](PF 6) (Ir - 2 , DCPIP = 2-(3,4-dichlorophenyl)-1 H -imidazo[4,5- f ][1,10]phenanthroline) and [Ir(ppy) 2 (TCPIP)](PF 6) (Ir - 3 , TCPIP = 2,3,5-trichlorophenyl)-1H-imidazo[4,5-f][1,10]phenanthroline) were synthesized and characterized. Ir-1 , Ir-2 and Ir-3 were encapsulated in liposomes Ir-1-Lipo , Ir-2-Lipo and Ir-3-Lipo. The anticancer activity of them was investigated in vitro and in vivo. Unlabelled Image • Complexes Ir-1, Ir-2, Ir-3 and their liposomes were synthesized and characterized. • The cytotoxicity in vitro was studied by 3-(4,5-dimethylthiazole-2-yl)-2,5-biphenyl tetrazolium bromide (MTT) method. • Colonies, apoptosis, reactive oxygen species (ROS), mitochondrial membrane potential were investigated. • The effect of liposomes Ir-1-Lipo, Ir-2-Lipo and Ir-3-Lipo on microtubules was explored. • The antitumor in vivo of Ir-2-Lipo was studied. [ABSTRACT FROM AUTHOR]

• FTY720 had a long-term neuroprotection in photothrombotic ischemic stroke. • Neuroprotection of FTY720 in PT was partly mediated by microglial polarization. • Angiogenesis was indirectly enhanced via microglial polarization mediated by FTY720. Microglial activation plays a crucial role in the pathology of ischemic stroke. Recently, we demonstrated that fingolimod (FTY720) exerted neuroprotective effects via immunomodulation in ischemic white matter damage induced by chronic cerebral hypoperfusion, which was accompanied by robust microglial activation. In this study, we assessed the pro-angiogenic potential of FTY720 in a murine model of acute cortical ischemic stroke. The photothrombotic (PT) method was used to induce cortical ischemic stroke in mice. We evaluated cortical damage, behavioral deficits, microglial polarization, and angiogenesis to identify the neuroprotective effects and possible molecular mechanisms of FTY720 in acute ischemic stroke. In vivo , a reduction in neuronal loss and improved motor function were observed in FTY720-treated mice after PT stroke. Immunofluorescence staining revealed that robust microglial activation and the associated neuroinflammatory response in the peri-infarct area were ameliorated by FTY720 via its ability to polarize microglia toward the M2 phenotype. Furthermore, both in vivo and in vitro, angiogenesis was enhanced in the microglial M2 phenotype state. Behaviorally, a significant improvement in the FTY720-treated group compared to the control group was evident from days 7 to 14. Our research indicated that FTY720 treatment promoted angiogenesis via microglial M2 polarization and exerted neuroprotection in PT ischemic stroke. [ABSTRACT FROM AUTHOR]