P-coumaric Acid: Advances in Pharmacological Research Based on Oxidative Stress.

P-coumaric acid is an important phenolic compound that is mainly found in fruits, vegetables, grains, and fungi and is also abundant in Chinese herbal medicines. In this review, the pharmacological research progress of p-coumaric acid in recent years was reviewed, with emphasis on its role and mechanism in oxidative stress-related diseases, such as inflammation, cardiovascular diseases, diabetes, and nervous system diseases. Studies have shown that p-coumaric acid has a positive effect on the prevention and treatment of these diseases by inhibiting oxidative stress. In addition, p-coumaric acid also has anti-tumor, antibacterial, anti-aging skin and other pharmacological effects. This review will provide reference and inspiration for further research on the pharmacological effects of p-coumaric acid.

Bone marrow mesenchymal stem cells-derived exosomes mediated delivery of tetramethylpyrazine attenuate cerebral ischemic injury.

OBJECTIVES: Tetramethylpyrazine (TEP) can protect the brain from ischemic damage, but it has defects such as short half-life, fast absorption, wide distribution, and rapid elimination, which limits its application. Exosomes (Exos) have the property of loading drugs and transporting signal substances. Here, we elucidated the effect of TEP-loaded bone marrow mesenchymal stem cell (BMSC)-derived Exos (Exo-TEP) on cerebral ischemic injury. MATERIALS AND METHODS: The Exos were extracted by ultracentrifugation and TEP was loaded into the Exos by electroporation. Oxygen-glucose deprivation (OGD) induced-primary cortical neurons and middle cerebral artery occlusion (MCAO)-induced mouse models were used to determine the effect of Exo-TEP on cerebral ischemic injury in vitro and in vivo. RESULTS: Exo-TEP exhibited a stable and sustained release pattern compared to free TEP. Exo-TEP treatment was more significant in improving OGD-mediated decrease in cell activity, as well as a elevation in apoptosis and ROS production in cortical neurons. In comparison with Exo and free TEP treatment, Exo-TEP treatment significantly improved pathological changes, shrunk cerebral infarction volume, as well reduced neurological deficit scores and neuronal apoptosis, and oxidative stress. CONCLUSIONS: Exo-TEP was superior to free TEP in improving cerebral ischemic injury by reducing neuronal apoptosis and oxidative stress.

Corrosion-tailoring, osteogenic, anti-inflammatory, and antibacterial aspirin-loaded organometallic hydrogel composite coating on biodegradable Zn for orthopedic applications.

Zn and its alloys are receiving increasing interest for biodegradable orthopedic implant applications owing to their moderate corrosion rate and the potential functionality of Zn2+. However, their non-uniform corrosion behavior and insufficient osteogenic, anti-inflammatory, and antibacterial properties do not meet the comprehensive requirements of orthopedic implants in clinical use. Herein, an aspirin (an acetylsalicylic acid, ASA, 10, 50, 100, and 500 mg/L)-loaded carboxymethyl chitosan (CMC)/gelatin (Gel)-Zn2+ organometallic hydrogel composite coating (CMC/Gel&Zn2+/ASA) was fabricated on a Zn surface via an alternating dip-coating method, aiming to obtain a material with these comprehensive properties improved. The organometallic hydrogel composite coatings, ca. 12-16 µm in thickness, showed compact, homogeneous, and micro-bulge structured surface morphology. The coatings protected well the Zn substrate from pitting/localized corrosion and contained the release of the bioactive components, Zn2+ and ASA, in a sustained and stable manner in long-term in vitro immersions in Hank's solution. The coated Zn showed greater ability to promote proliferation and osteogenic differentiation for MC3T3-E1 osteoblasts, and better anti-inflammatory capacity when compared with uncoated Zn. Additionally, this coating displayed excellent antibacterial activity against both Escherichia coli (>99 % antibacterial rate) and Staphylococcus aureus (>98 % antibacterial rate). Such appealing properties can be attributed to the compositional nature of the coating, namely the sustained release of Zn2+ and ASA, as well as the surface physiochemical properties because of its unique microstructure. This organometallic hydrogel composite coating can be considered a promising option for the surface modification of biodegradable Zn-based orthopedic implants among others.

Design, synthesis, antiviral activities of ferulic acid derivatives.

A series of novel ferulic acid derivatives were designed and synthesized, and the twenty-one compounds were evaluated for their antiviral activities against Respiratory syncytial virus (RSV), herpes simplex virus type 1 (HSV-1), and enterovirus type 71 (EV71). These derivatives with the core structure of diphenyl acrylic acids had cis-trans isomers, which were confirmed by 1H NMR, HPLC, and UV-vis spectra for the first time. The A5 had a selective effect against RSV but no work on herpes simplex virus type 1 and enterovirus type 71, which showed a therapeutic index (TI) of 32 and was significantly better than ferulic acid. The A5 had no scavenging effect on free radicals, but the A2 as the degradation of A5 showed an obvious scavenging effect on DPPH· and ABTS+·. In addition, the A5 had no toxicity to endothelial cells and even showed a proliferative effect. Therefore, the A5 is worth further optimizing its structure as a lead compound and investigating the mechanism of inhibiting Respiratory syncytial virus.

Preparation and application of chitosan-based medical electrospun nanofibers.

Chitosan is a kind of polysaccharide cationic polymer, which has excellent biocompatibility, biodegradability and biological activity. In recent years, chitosan has been widely used as medical materials because of its non-toxicity, non-immunogenicity and rich sources. This paper reviews chitosan chemistry, the basic principles and influence of electrospinning technology, the blending of chitosan with polyethylene oxide, polyvinyl alcohol, polycaprolactone, polylactic acid, protein, polysaccharide and other polymer materials, the blending of chitosan with oxides, metals, carbon-based and other inorganic substances for electrospinning, the application of chitosan electrospinning nanofibers in medical field and its mechanism in clinical application. In order to provide reference for the in-depth study of electrospinning technology in the field of medical and health.

The isolation, structural features and biological activities of polysaccharide from Ligusticum chuanxiong: A review.

Ligusticum chuanxiong, the dried rhizome of Ligusticum chuanxiong Hort, has been widely applied in traditional Chinese medicine for treating plague, and it has appeared frequently in the prescriptions against COVID-19 lately. Ligusticum chuanxiong polysaccharide (LCPs) is one of the effective substances, which has various activities, such as, anti-oxidation, promoting immunity, anti-tumor, and anti-bacteria. The purified fractions of LCPs are considered to be pectic polysaccharides, which are mainly composed of GalA, Gal, Ara and Rha, and are generally linked by α-1,4-d-GalpA, α-1,2-l-Rhap, α-1,5-l-Araf, ß-1,3-d-Galp and ß-1,4-d-Galp, etc. The pectic polysaccharide shows an anti-infective inflammatory activity, which is related to antiviral infection of Ligusticum chuanxiong. In this article, the isolation, purification, structural features, and biological activities of LCPs in recent years are reviewed, and the potential of LCPs against viral infection as well as questions that need future research are discussed.

The treatment of cardiovascular diseases: a review of ferulic acid and its derivatives.

Ferulic acid, a hydroxyl derivative extracted from plants, is abundant in free state in seeds and leaves, or covalently linked with cell wall polysaccharides, lignin and different polymers. It has various pharmacological activities, including antioxidant and anti-inflammatory effects, regulates immunity, protects the cardiovascular system, and contributes to the prevention of tumors and diabetes. The protective effect on cardiovascular system is the most valuable one in view of clinical application. Here, we are reviewing the research progress concerning the pharmacological effects of ferulic acid and its derivatives on cardiovascular diseases in the past five years, mainly focusing on mechanisms of action and clinical application. This should provide guidance for clinical applications of ferulic acid and its derivatives in the treatment of cardiovascular diseases.

[Keyhole Approach Endoscopic Surgery versus Stereotactic Aspiration plus Urokinase in Treating Basal Ganglia Hypertensive Intracerebral Hemorrhage].

Objective To compare the short-and long-term effect of two minimal invasive surgical therapies including keyhole approach endoscopic surgery(KAES)and stereotactic aspiration plus urokinase(SAU)in treating basal ganglia hypertensive intracerebral hemorrhage(hICH). Methods The clinical data of 117 hICH patients(63 received KAES and 54 received SAU)were retrospectively analyzed.The operation time,blood loss during surgery,and drainage time were compared between two groups.The residual hematoma volume,hematoma clearance rate(HCR),Glasgow coma scale(GCS)score,and National Institute of Health Stroke Scale(NIHSS)score were recorded at baseline and in the ultra-early stage,early stage,and sub-early stage after surgery.The 30-day mortality and serious adverse events were assessed and the 6-month modified Rankin scale(mRS)score was rated.Results Baseline data showed no significant difference between these two groups.Compared with the SAU group,the KAES group had significantly longer operation time,more intraoperative blood loss,and shorter drainage time(all P<0.001).In the ultra-early stage after surgery,HCR was significantly higher in the KAES group(P<0.001),whereas in the early and sub-early stage,HCR showed no significant differences(all P>0.05).In the ultra-early and early stage,the GCS and NIHSS scores showed no significant differences between two groups(all P>0.05),whereas in the sub-early stage,the NIHSS score was better in the SAU group(P=0.034).The 30-day mortality and incidences of serious adverse events showed no significant difference(all P>0.05).The good recovery(mRS≤3)at 6-months follow-up showed no significant difference between the two groups(P=0.413).Conclusions Both KAES and SAU are safe and effective in treating basal ganglia hICH.In the ultra-early stage after surgery,KAES achieves better residual hematoma volume and HCR,and patients undergoing SAU quickly catch up.The short-and long-term effectiveness of SAU is comparable or even superior to KAES.

Composition, isolation, purification and biological activities of Sargassum fusiforme polysaccharides: A review.

Sargassum fusiforme polysaccharides, acidic water-soluble polysaccharides extract from Sargassum fusiforme, are mainly composed of alginic acid, fucoidan and laminaran. Alginic acid is carboxyl-containing polysaccharide formed by joining ß-D-mannuronic acid and α-L-guluronic acid through ß-(1→4)/α-(1→4) glycosidic bond. Fucoidan, a natural water-soluble sulfated heteropolysaccharide with fucose and sulfuric acid groups as the core structure, is mainly linked by L-fucose through α-(1→3) glycosidic bond and has the strongest biological activity. Laminaran is mainly composed of ß-D-glucose through ß-(1→3) glycosidic bond linkage. Sargassum fusiforme polysaccharides have a variety of pharmacological activities, including antioxidant, anti-tumor, promoting immunity, anti-aging, prompting bone growth, lowering blood glucose, anti-coagulation, anti-virus, anti-bacteria, anti-fatigue, promoting growth and development, and skin protection. These activities are closely related to the functions of fucoidan in Sargassum fusiforme polysaccharides, which fucoidan is able to strengthen immune system and antioxidation in human body. In this review, the composition, the isolation and purification, and the biological activities of Sargassum fusiforme polysaccharides are discussed and can bereference for further study.

In situ incorporation of heparin/bivalirudin into a phytic acid coating on biodegradable magnesium with improved anticorrosion and biocompatible properties.

Heparin (Hep) or bivalirudin (BVLD) were immobilized in an organic phytic acid (PA) coating on Mg by an in situ chemical route. Such a drug-loaded PA coating was designed to enhance both corrosion control and biocompatibility. It was found that both Hep- and BVLD-loaded PA coatings exhibited a dual role in effectively controlling corrosion as well as providing a biofunctional effect. Experiments involving electrochemical corrosion and in vitro degradation by immersion revealed that PA&Hep- and PA&BVLD-coated Mg had the same effect or even slower corrosion/degradation in phosphate buffered saline compared to PA-coated Mg, and it degraded significantly slower than untreated Mg. Moreover, Hep- or BVLD-loaded PA coatings showed relatively good hemocompatibility, with a prolonged clotting time, inhibited platelets adhesion as well as reduced hemolysis compared to untreated Mg. In addition, both PA&Hep and PA&BVLD coatings promoted endothelial cells growth and restrained the proliferation of smooth muscle cells. In vivo assays indicated that PA&Hep-coated Mg exhibited a significant difference in mass loss compared to untreated Mg, as well as better histocompatibility than other samples. These results demonstrate that our coating strategy shows a great potential in surface modification of biodegradable Mg. Finally, the mechanism for the incorporation of the drugs into the PA coating is discussed from both theoretical and practical perspectives.

Prevention against diffuse spinal cord astrocytoma: can the Notch pathway be a novel treatment target?

This study was designed to investigate whether the Notch pathway is involved in the development of diffuse spinal cord astrocytomas. BALB/c nude mice received injections of CD133(+) and CD133(-) cell suspensions prepared using human recurrent diffuse spinal cord astrocytoma tissue through administration into the right parietal lobe. After 7-11 weeks, magnetic resonance imaging was performed weekly. Xenografts were observed on the surfaces of the brains of mice receiving the CD133(+) cell suspension, and Notch-immunopositive expression was observed in the xenografts. By contrast, no xenografts appeared in the identical position on the surfaces of the brains of mice receiving the CD133(-) cell suspension, and Notch-immunopositive expression was hardly detected either. Hematoxylin-eosin staining and immunohistochemical staining revealed xenografts on the convex surfaces of the brains of mice that underwent CD133(+) astrocytoma transplantation. Some sporadic astroglioma cells showed pseudopodium-like structures, which extended into the cerebral white matter. However, it should be emphasized that the subcortex xenograft with Notch-immunopositive expression was found in the fourth mouse received injection of CD133(-) astrocytoma cells. However, these findings suggest that the Notch pathway plays an important role in the formation of astrocytomas, and can be considered a novel treatment target for diffuse spinal cord astrocytoma.

Analysis of prognostic factors of endovascular therapy in 59 patients with acute anterior circulation stroke: a retrospective cohort study ­ observational.

INTRODUCTION: Endovascular therapy (ET) is increasingly used for stroke patients out of the time window, based on the multimodal treatment (MMT) it can be used alone or in combination. The purpose of this study was to assess the outcome of intra-arterial thrombolysis (IAT) and MMT for acute anterior circulation ischemic stroke (ACIS), and reveal prognostic factors of ET in the authors' stroke center. METHODS: A retrospective analysis of the data of 59 patients with ACIS who received ET from 2010 to 2014 in the stroke center was performed. A univariate analysis was conducted to reveal the differences between IAT and MMT, and the distinctions between favorable and unfavorable outcomes, logistic regression analysis was performed to determine the predictors of outcomes. RESULTS: Thirty-four patients who accepted MMT had a higher baseline National Institutes of Health Stroke Scale score on admission (18.3 ± 4.2) compared with 25 patients who were treated with IAT (12.6 ± 4.3). The MMT group had a higher patent flow (23/34) (thrombolysis in myocardial infarction grade 2-3) compared with the IAT group (10/25). Moreover, the MMT group had a longer time for emergency department (ED) (5.8 ± 1.4) than the IAT group (5.2 ± 0.8). In multivariate analysis, age, time to ED, and NIHSS score at discharge are predictors for poor outcome, whereas perfect recanalization was associated with favorable outcome. CONCLUSION: MMT might be suitable for patients with a severe admission NIHSS and a higher patency rate than IAT. Vessel recanalization was the only predictor for favorable outcome.

A dual-task design of corrosion-controlling and osteo-compatible hexamethylenediaminetetrakis- (methylene phosphonic acid) (HDTMPA) coating on magnesium for biodegradable bone implants application.

Magnesium as well as its alloys appears increasingly as a revolutionary bio-metal for biodegradable implants application but the biggest challenges exist in its too fast bio-corrosion/degradation. Both corrosion-controllable and bio-compatible Mg-based bio-metal is highly desirable in clinic. In present work, hexamethylenediaminetetrakis (methylenephosphonic acid) [HDTMPA, (H2 O3 P-CH2 )2 -N-(CH2 )6 -N-(CH2 -PO3 H2 )2 ], as a natural and bioactive organic substance, was covalently immobilized and chelating-deposited onto Mg surface by means of chemical conversion process and dip-coating method, to fullfill dual-task performance of corrosion-protective and osteo-compatible functionalities. The chemical grafting of HDTMPA molecules, by participation of functional groups on pretreated Mg surface, ensured a firmly anchored base layer, and then sub-sequential chelating reactions of HDTMPA molecules guaranteed a homogenous and dense HDTMPA coating deposition on Mg substrate. Electrochemical corrosion and immersion degradation results reveal that the HDTMPA coated Mg provides a significantly better controlled bio-corrosion/degradation behavior in phosphate buffer saline solution as compared with untreated Mg from perspective of clinic requirement. Moreover, the HDTMPA coated Mg exhibits osteo-compatible in that it induces not only bioactivity of bone-like apatite precipitation but also promotes osteoblast cells adhesion and proliferation. Our well-controlled biodegradable and biocompatible HDTMPA modified Mg might bode well for next generation bone implant application.

Ultra-early versus delayed coil treatment for ruptured poor-grade aneurysm.

INTRODUCTION: The timing of definitive aneurysm treatment (coiling or clipping) in poor-grade (Hunt-Hess IV or V) subarachnoid haemorrhage (SAH) patients has been a controversial topic. The purpose of this retrospective study was to analyse whether ultra-early coiling of ruptured intracranial aneurysms improves the clinical outcomes of poor-grade SAH patients. METHODS: The records of patients with aneurysmal SAH who were treated with endovascular coiling were retrieved. The patients were classified into two groups: group A (patients coiled within 24 h of SAH) and group B (patients coiled ≥ 24 h after SAH). For each group, the patient demographics, Fisher grade, aneurysm characteristics and clinical outcomes were recorded. Outcomes were measured at 6 months using the modified Rankin Scale (mRS). RESULTS: Thirty-one patients were coiled within 24 h of SAH (group A), and fourteen patients were coiled ≥24 h after SAH (group B). Groups A and B had similar clinical and angiographic characteristics. The clinical outcomes showed that a total of 58.1% of the patients (18 of 31) in group A were independent (mRS 0-2) compared with 21.4% of the patients (3 of 14) in group B (P = .028). Univariate analysis demonstrated that ultra-early coiling (P = .028) proved to be an independent predictor of better clinical outcomes (mRS 0-2). CONCLUSIONS: Ultra-early (<24 h after SAH) coiling of ruptured aneurysms was associated with improved clinical outcomes compared to coiling at ≥24 h in poor-grade SAH patients. Larger, prospective studies are required to adequately assess the outcome differences between these two groups.

Corrosion-controlling and osteo-compatible Mg ion-integrated phytic acid (Mg-PA) coating on magnesium substrate for biodegradable implants application.

Biodegradable, a new revolutionary concept, is shaping the future design of biomedical implants that need to serve only as a temporary scaffold. Magnesium appears to be the most promising biodegradable metal, but challenges remain in its corrosion-controlling and uncertain biocompatibility. In this work, we employ chemical conversion and alternating dip-coating methods to anchor and deposit an Mg ion-integrated phytic acid (Mg-PA) coating on Mg, which is supposed to function both corrosion-controlling and osteo-compatible. It was ascertained that PA molecules were covalently immobilized on a chemically converted Mg(OH)2 base layer, and more PA molecules were deposited subsequently via chelating reactions with the help of additive Mg ions. The covalent immobilization and the Mg ion-supported chelating deposition contribute to a dense and homogeneous protective Mg-PA coating, which guarantees an improved corrosion resistance as well as a reduced degradation rate. Moreover, the Mg-PA coating performed osteo-compatible to promote not only bioactivity of bonelike apatite precipitation, but also induced osteoblast cells adhesion and proliferation. This is ascribed to its nature of PA molecule and the biocompatible Mg ion, both of which mimic partly the compositional structure of bone. Our magnesium ion-integrated PA-coated Mg might bode well for the future of biodegradable bone implant application.

[Discussion of anti-inflammatory mechanism of cyclooxygenase (COX-2) inhibitor in improving cardiovascular safety].

The new generation cyclooxygenase (COX-2) inhibitor could reduce the gastrointestinal side effect of NSAID drugs, but eventually increase the cardiovascular risk, because its selective inhibition of COX-2 induces the imbalance between PGI2 and TXA2 and the reduction of vasodilatory NO. Under pathological conditions, active oxygen species (O2-*2, etc) were used to induce endo- thelial dysfunction, activate NF-κB to induce expressions of pro-inflammatory cytokines IL-1ß and TNF-α, increase ET-1, TXA2 with vasoconstrictor effect, reduce PGI2 and NO with vasodilatory effect, generate further oxidative damage together with NO, and reduce the bioavailability of NO. NO-NSAIDs and NO-Coxibs drugs raised the level of NO by introducing NO-donor (ONO2). NSAIDs drugs enhanced the anti-inflammatory activity of COX-2 and reduced gastrointestinal side effects by inhibiting selectively COX-2. If antioxidant structures with active ingredients of traditional Chinese medicines were introduced to improve the antioxidant activity of NSAIDs, they could scavenge the active oxygen species to protect the normal function of vascular endothelia and enhance the bioavailability of NO, which is conducive to enhance the cardiovascular safety of cyclooxygenase (COX-2) inhibitor.

Design, synthesis and biological evaluation of novel 4-hydroxybenzene acrylic acid derivatives.

A series of 4-hydroxybenzene acrylic acid derivatives were designed and synthesized based on the ferulic acid of natural active ingredients. The tested compound 5a, 5f and 6a have significant anti-inflammatory activity with suppression rates of 45.29%, 44.75% and 24.11%, respectively, compared with that of indomethacin, and their cardiac toxicity was not observed. The structure-function relationship shows that the p-hydroxyl group on the α-position benzene ring, particularly if acetylated, contributes to the considerable anti-inflammatory activity; that the carboxyl group on the double bond, if esterified, also contributes to the anti-inflammatory activity; that the p-methylsulfonyl group on the other benzene ring, whose introduction is due to the COX-2 selectivity, also contributes to anti-inflammatory activity surprisingly.