An electrophysiological analysis of the protective effects of felbamate, lamotrigine, and lidocaine on the functional recovery from in vitro ischemia in rat neocortical slices

In this study a polyphenolic extract from Cleome arabica leaves (CALE) was investigated for its antioxidant activity in vitro using DPPH•, metal chelating and reducing power methods and for its protective effects against AraC-induced hematological toxicity in vivo using Balb C mice. Results indicated that CALE exhibited a strong and dose-dependent scavenging activity against the DPPH• free radical (IC50 = 4.88 μg/ml) and a high reducing power activity (EC50 = 4.85 μg/ml). Furthermore, it showed a good chelating effects against ferrous ions (IC50 = 377.75 μg/ml). The analysis of blood showed that subcutaneous injection of AraC (50 mg/kg) to mice during three consecutive days caused a significant myelosupression (P < 0.05). The combination of CALE and AraC protected blood cells from a veritable toxicity. Where, the number of the red cells, the amount of hemoglobin and the percentage of the hematocrite were significantly high. On the other hand, AraC cause an elevation of body temperature (39 °C) in mice. However, the temperature of the group treated with CALE and AraC remained normal and did not exceed 37.5 °C. The observed biological effects of CALE, in vitro as well as in vivo, could be due to the high polyphenol and flavonoid contents. In addition, the antioxidant activity of CALE suggested to be responsible for its hematoprotective effect.

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Faculty Opinions recommendation of Multiple domains in the C-terminus of NMDA receptor GluN2B subunit contribute to neuronal death following in vitro ischemia.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.725947846.793564304 ◽

2019 ◽

Author(s):

Giles Hardingham

Keyword(s):

Nmda Receptor ◽

Neuronal Death ◽

In Vitro Ischemia ◽

C Terminus ◽

Multiple Domains

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Healing effects of curcumin nanoparticles in deep tissue injury mouse model.

Current Drug Delivery ◽

10.2174/1567201818666201214125237 ◽

2020 ◽

Vol 18 ◽

Author(s):

Zirui Zhang ◽

Shangcong Han ◽

Panpan Liu ◽

Xu Yang ◽

Jing Han ◽

...

Keyword(s):

Wound Healing ◽

Mrna Expression ◽

Tissue Injury ◽

Inflammatory Cells ◽

Pcr Analysis ◽

Protective Effects ◽

Deep Tissue ◽

Deep Tissue Injury

Background: Chronic inflammation and lack of angiogenesis are the important pathological mechanisms in deep tissue injury (DTI). Curcumin is a well-known anti-inflammatory and antioxidant agent. However, curcumin is unstable under acidic and alkaline conditions, and can be rapidly metabolized and excreted in the bile, which shortens its bioactivity and efficacy. Objective: This study aimed to prepare curcumin-loaded poly (lactic-co-glycolic acid) nanoparticles (CPNPs) and to elucidate the protective effects and underlying mechanisms of wound healing in DTI models. Methods: CPNPs were evaluated for particle size, biocompatibility, in vitro drug release and their effect on in vivo wound healing. Results : The results of in vivo wound closure analysis revealed that CPNP treatments significantly improved wound contraction rates (p<0.01) at a faster rate than other three treatment groups. H&E staining revealed that CPNP treatments resulted in complete epithelialization and thick granulation tissue formation, whereas control groups resulted in a lack of compact epithelialization and persistence of inflammatory cells within the wound sites. Quantitative real-time PCR analysis showed that treatment with CPNPs suppressed IL-6 and TNF-α mRNA expression, and up-regulated TGF-β, VEGF-A and IL-10 mRNA expression. Western blot analysis showed up-regulated protein expression of TGF-β, VEGF-A and phosphorylatedSTAT3. Conclusion: Our results showed that CPNPs enhanced wound healing in DTI models, through modulation of the JAK2/STAT3 signalling pathway and subsequent upregulation of pro-healing factors.

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Newly Developed Recombinant Antithrombin Protects the Endothelial Glycocalyx in an Endotoxin-Induced Rat Model of Sepsis

International Journal of Molecular Sciences ◽

10.3390/ijms22010176 ◽

2020 ◽

Vol 22 (1) ◽

pp. 176

Author(s):

Toshiaki Iba ◽

Jerrold H. Levy ◽

Koichiro Aihara ◽

Katsuhiko Kadota ◽

Hiroshi Tanaka ◽

...

Keyword(s):

Dose Group ◽

Low Dose ◽

Leukocyte Adhesion ◽

Endothelial Glycocalyx ◽

High Dose Group ◽

Control Group ◽

High Dose ◽

Protective Effects ◽

Circulating Levels

(1) Background: The endothelial glycocalyx is a primary target during the early phase of sepsis. We previously reported a newly developed recombinant non-fucosylated antithrombin has protective effects in vitro. We further evaluated the effects of this recombinant antithrombin on the glycocalyx damage in an animal model of sepsis. (2) Methods: Following endotoxin injection, in Wistar rats, circulating levels of hyaluronan, syndecan-1 and other biomarkers were evaluated in low-dose or high-dose recombinant antithrombin-treated animals and a control group (n = 7 per group). Leukocyte adhesion and blood flow were evaluated with intravital microscopy. The glycocalyx was also examined using side-stream dark-field imaging. (3) Results: The activation of coagulation was inhibited by recombinant antithrombin, leukocyte adhesion was significantly decreased, and flow was better maintained in the high-dose group (both p < 0.05). Circulating levels of syndecan-1 (p < 0.01, high-dose group) and hyaluronan (p < 0.05, low-dose group; p < 0.01, high-dose group) were significantly reduced by recombinant antithrombin treatment. Increases in lactate and decreases in albumin levels were significantly attenuated in the high-dose group (p < 0.05, respectively). The glycocalyx thickness was reduced over time in control animals, but the derangement was attenuated and microvascular perfusion was better maintained in the high-dose group recombinant antithrombin group (p < 0.05). (4) Conclusions: Recombinant antithrombin maintained vascular integrity and the microcirculation by preserving the glycocalyx in this sepsis model, effects that were more prominent with high-dose therapy.

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Long Noncoding RNA SPRY4-IT1 Modulates Ketamine-Induced Neurotoxicity in Human Embryonic Stem Cell-Derived Neurons through EZH2

Developmental Neuroscience ◽

10.1159/000513535 ◽

2021 ◽

pp. 1-9

Author(s):

Jingyuan Huang ◽

Yan Xu ◽

Fang Wang ◽

Haili Wang ◽

Lu Li ◽

...

Keyword(s):

Long Noncoding Rna ◽

Noncoding Rna ◽

Embryonic Stem ◽

Protective Effects ◽

Tyrosine Kinase Signaling ◽

Ezh2 Expression ◽

Induced Neurons ◽

Neurite Degeneration ◽

Dose Dependent

Objective: This study aimed to investigate whether long noncoding RNA sprouty receptor tyrosine kinase signaling antagonist 4-intronic transcript 1 (SPRY4-IT1) is involved in the regulation of ketamine-induced neurotoxicity. Methods: Human embryonic stem cells (hESCs) were induced into neurons in vitro and treated with ketamine. Apoptosis and neurite degeneration assays were used to determine ketamine-induced neurotoxicity and qRT-PCR to determine SPRY4-IT1 expression. SPRY4-IT1 was downregulated in hESC-induced neurons to examine its regulation on ketamine-induced neurotoxicity. The correlation between enhancer of zeste homolog 2 (EZH2) and SPRY4-IT1 was also examined. EZH2 was upregulated in SPRY4-IT1-downregualted hESC-induced neurons to further examine its participation in SPRY4-IT1-mediated ketamine neurotoxicity. Results: Ketamine-induced dose-dependent apoptosis, neurite degeneration, and SPRY4-IT1 upregulation in hESC-induced neurons. Lentivirus-mediated SPRY4-IT1 downregulation protected ketamine neurotoxicity. EZH2 expression was positively correlated with SPRY4-IT1 in hESC-induced neurons. EZH2 overexpression markedly reversed the protective effects of SPRY4-IT1 knockdown on ketamine neurotoxicity. Conclusions: SPRY4-IT1 is involved in anesthesia-induced neurotoxicity, possibly through the regulation on EZH2 gene.

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Grafts Derived from an α-Synuclein Triplication Patient Mediate Functional Recovery but Develop Disease-Associated Pathology in the 6-OHDA Model of Parkinson’s Disease

Journal of Parkinson s Disease ◽

10.3233/jpd-202366 ◽

2020 ◽

pp. 1-14

Author(s):

Shelby Shrigley ◽

Fredrik Nilsson ◽

Bengt Mattsson ◽

Alessandro Fiorenzano ◽

Janitha Mudannayake ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Cell Lines ◽

Functional Recovery ◽

Embryonic Stem ◽

Hesc Line ◽

Alternative Source ◽

And Function

Background: Human induced pluripotent stem cells (hiPSCs) have been proposed as an alternative source for cell replacement therapy for Parkinson’s disease (PD) and they provide the option of using the patient’s own cells. A few studies have investigated transplantation of patient-derived dopaminergic (DA) neurons in preclinical models; however, little is known about the long-term integrity and function of grafts derived from patients with PD. Objective: To assess the viability and function of DA neuron grafts derived from a patient hiPSC line with an α-synuclein gene triplication (AST18), using a clinical grade human embryonic stem cell (hESC) line (RC17) as a reference control. Methods: Cells were differentiated into ventral mesencephalic (VM)-patterned DA progenitors using an established GMP protocol. The progenitors were then either terminally differentiated to mature DA neurons in vitro or transplanted into 6-hydroxydopamine (6-OHDA) lesioned rats and their survival, maturation, function, and propensity to develop α-synuclein related pathology, were assessed in vivo. Results: Both cell lines generated functional neurons with DA properties in vitro. AST18-derived VM progenitor cells survived transplantation and matured into neuron-rich grafts similar to the RC17 cells. After 24 weeks, both cell lines produced DA-rich grafts that mediated full functional recovery; however, pathological changes were only observed in grafts derived from the α-synuclein triplication patient line. Conclusion: This data shows proof-of-principle for survival and functional recovery with familial PD patient-derived cells in the 6-OHDA model of PD. However, signs of slowly developing pathology warrants further investigation before use of autologous grafts in patients.

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Probiotic and Functional Properties of Limosilactobacillus reuteri INIA P572

Nutrients ◽

10.3390/nu13061860 ◽

2021 ◽

Vol 13 (6) ◽

pp. 1860

Author(s):

Patricia Diez-Echave ◽

Izaskun Martín-Cabrejas ◽

José Garrido-Mesa ◽

Susana Langa ◽

Teresa Vezza ◽

...

Keyword(s):

In Vitro Assays ◽

Immunomodulatory Activity ◽

Probiotic Properties ◽

Protective Effects ◽

Mice Model ◽

In Vivo Models ◽

Food Borne ◽

Gastrointestinal Conditions

Limosilactobacillus reuteri INIA P572 is a strain able to produce the antimicrobial compound reuterin in dairy products, exhibiting a protective effect against some food-borne pathogens. In this study, we investigated some probiotic properties of this strain such as resistance to gastrointestinal passage or to colonic conditions, reuterin production in a colonic environment, and immunomodulatory activity, using different in vitro and in vivo models. The results showed a high resistance of this strain to gastrointestinal conditions, as well as capacity to grow and produce reuterin in a human colonic model. Although the in vitro assays using the RAW 264.7 macrophage cell line did not demonstrate direct immunomodulatory properties, the in vivo assays using a Dextran Sulphate Sodium (DSS)-induced colitic mice model showed clear immunomodulatory and protective effects of this strain.

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