Longitudinal Change of Serum Inter-α-Trypsin Inhibitor Heavy Chain H4 and its Relation with Inflammation, Disease Recurrence, and Mortality in Acute Ischemic Stroke Patients.

Inter-α-trypsin inhibitor heavy chain H4 (ITIH4) modulates atherosclerosis, lipid, and inflammation, which is involved in the development of acute ischemic stroke. Hence, this study aimed to investigate the longitudinal change and prognostic role of ITIH4 in acute ischemic stroke. In 267 patients with acute ischemic stroke, serum ITIH4 after admission (baseline), the 1st day after admission (D1), D3, D7, and D30, and inflammatory cytokines at baseline were detected by enzyme-linked immunosorbent assay (ELISA). Additionally, serum ITIH4 of 30 controls after enrollment was detected by ELISA. ITIH4 was reduced in acute ischemic stroke patients than controls [median (interquartile range, IQR): 131.0 (95.5-194.3) vs. 418.6 (241.5-506.8) ng/mL] (P < 0.001). Among acute ischemic stroke patients, ITIH4 was negatively associated with tumor necrosis factor-alpha (r = -0.211, P = 0.001), interleukin (IL)-1ß (r = -0.164, P = 0.007), IL-6 (r = -0.121, P = 0.049), and IL-17A (r = -0.188, P = 0.002). ITIH4 presented a decreased trend from admission to D3, then increased from D3 to D30 (P < 0.001). The 1-year, 2-year, and 3-year cumulative recurrence rate was 7.5%, 18.0%, and 19.1%, respectively; meanwhile, 1-year, 2-year, and 3-year cumulative death rate was 2.2%, 7.1%, and 7.1%, accordingly. The further analysis presented that ITIH4 at baseline (P = 0.002), D1 (P = 0.049), D3 (P = 0.003), D7 (P < 0.001), and D30 (P < 0.001) was decreased in recurrent patients than non-recurrent patients; besides, ITIH4 at D3 (P = 0.017), D7 (P = 0.004), and D30 (P = 0.002), but not at baseline (P = 0.151) or D1 (P = 0.013), was decreased in deaths than survivors. Serum ITIH4 declines at first and then elevates with time, and its reduction is correlated with higher inflammation, increased risk of recurrence and mortality in acute ischemic stroke patients.

Clinical value of serum JKAP in acute ischemic stroke patients.

BACKGROUND: Jun N-terminal kinase pathway-associated phosphatase (JKAP) regulates neuronal function, T helper (Th) 1/2/17 cell differentiation, and inflammatory process, but its clinical role in acute ischemic stroke (AIS) patients remains unclear. Hence, this study intended to evaluate JKAP level and its relationship with disease severity, Th1, 2, 17 secreted cytokines, adhesion molecules, and prognosis of AIS patients. METHODS: Serum JKAP of 122 AIS patients and 50 controls was detected by ELISA. For AIS patients only, Th1, 2, 17 secreted cytokines IFN-γ, IL-4, IL-17; TNF-α, ICAM-1, and VCAM-1 were also detected by ELISA. RESULTS: JKAP was decreased in AIS patients compared with controls (46.350 (interquartile range (IQR): 34.250-59.875) pg/ml vs. 84.500 (IQR: 63.175-113.275) pg/ml, p < 0.001), which could distinguish AIS patients from controls (area under curve (AUC): 0.810, 95% confidence interval (CI): 0.732-0.888). In AIS patients, JKAP negatively linked with the National Institutes of Health Stroke Scale (NIHSS) score (rs  = -0.342, p < 0.001); besides, it was positively related to IL-4 (rs  = 0.213, p = 0.018) and negatively associated with IL-17 (rs  = -0.270, p = 0.003) but not related to IFN-γ (rs  = -0.146, p = 0.109). Furthermore, elevated JKAP associated with declined TNF-α (rs  = -0.219, p = 0.015) and ICAM-1 (rs  = -0.235, p = 0.009) but not related to VCAM-1 (rs  = -0.156, p = 0.085). Besides, declined JKAP was linked with 2-year recurrence (p = 0.027) and 3-year recurrence (p = 0.010) in AIS patients; while JKAP was not related to 1-year recurrence or death risk (both p > 0.050). CONCLUSION: JKAP may sever as a candidate prognostic biomarker in AIS patients, indicating its potency for AIS management.

Serum Exosomal microRNA-27-3p Aggravates Cerebral Injury and Inflammation in Patients with Acute Cerebral Infarction by Targeting PPARγ.

Acute cerebral infarction (ACI) possesses high mortality. Exosomes present in serum have potential application value in ACI diagnosis. This study investigated the mechanism of serum exosomes in ACI. Serum exosomes isolated from ACI patients and normal people were identified and then injected into the established middle cerebral artery occlusion (MCAO) rat model to evaluate cerebral injury and inflammation. Exosomal microRNA (miR)-27-3p expression was detected and interfered to analyze rat cerebral inflammation. The binding relationship between miR-27-3p and PPARγ was predicted and verified. The lipopolysaccharide (LPS)-treated microglia model was established and intervened with miR-27-3p to detect PPARγ, Iba-1, and inflammation-related factor expressions. After overexpressing PPARγ, rat cerebral inflammation was evaluated. The clinical significance of serum exosomal miR-27-3p in ACI was evaluated. Serum exosomes from ACI patients caused exacerbated MCAO rat cerebral injury and poor behavior recovery, as well as promoted cerebral inflammation. Serum exosomal miR-27-3p deepened rat brain inflammation. miR-27-3p targeted PPARγ to promote microglia activation and inflammation-related factor expressions in MCAO rats, and overexpressing PPARγ attenuated MCAO rat cerebral inflammation. Serum exosomal miR-27-3p promised to be a biomarker for ACI. We proved that serum exosomes from ACI patients aggravated ACI patient cerebral inflammation via the miR-27-3p/PPARγ axis.

Auxiliary ligand-induced structural diversities of octacyanometalate-based heterobimetallic coordination polymers towards diverse magnetic properties.

Three octacyanometalate-based bimetallic coordination polymers (CPs), {[µ4-MV(CN)8][Co(DMF)4]2(ClO4)}n (M = W CP-1, Mo CP-2) and {[µ4-WIV(CN)8]Co2(azpy)4}n CP-3, were synthesized in the absence (for CPs 1 and 2) or presence (for CP-3) of auxiliary ligand 4,4'-azopyridine (azpy), respectively. CPs 1 and 2 exhibit the same three-dimensional (3D) polymeric cation frameworks with [ClO4]- as the counterions, while CP-3 displays a porous 3D framework in an unusual 2-nodal (4,6)-connected 4,6T155 topology with point symbol as {42·64}{46·64·7·84}2. Notably is that octacyanometalate [WV(CN)8]3- has been reduced into [WIV(CN)8]4- during the synthetic process of CP-3. The magnetic investigations indicate that CP-1 exhibits the typical ferromagnetic property due to the ferromagnetic coupling between W(v) and Co(ii) spin centers, while CP-3 displays the weak ferromagnetic interaction at low temperature, which is consistent with the valence change of W center in CP-3.

Potent toxic macrocyclic trichothecenes from the marine-derived fungus Myrothecium verrucaria Hmp-F73.

Activity-guided fractionation of a methanol extract from the culture broth of Myrothecium verrucaria Hmp-F73, a fungus associated with the sponge Hymeniacidon perleve, afforded six macrocyclic trichothecenes, verrucarin J (1), 8-hydroxyverrucarin J (2), verrucarin A (3), 8-acetoxyroridin H (4), isororidin E (5), and roridin E (6), along with trichoverrin B (7). All seven metabolites displayed potent toxicity to the brine shrimp (Artemia salina). In addition, compounds 2, 3, and 6 showed weak phytotoxic activities against lettuce seeds. A preliminary structure-activity relationship of the metabolites is also discussed.

{2-[6-(1H-Benzimidazol-2-yl-κN)-2-pyridyl-κN]benzimidazolato-κN}(dicyanamido-κN)(methanol-κO)copper(II).

In the title compound, [Cu(C(19)H(12)N(5))(C(2)N(3))(CH(3)OH)], the Cu(II) atom is coordinated by three N atoms from an anionic 2,6-bis-(1H-benzimidazol-2-yl)pyridine (bbp) ligand, an O atom from a methanol mol-ecule and one N atom from a dicyanamide anion. The crystal structure is stabilized by O-H⋯N and N-H⋯N hydrogen bonds, forming a three-dimensional network.