General physiology and biophysics最新文献

Sevoflurane is considered an effective neuroprotector in cerebral ischemia/reperfusion injury (CIRI). Sevoflurane preconditioning in CIRI, however, remains unknown precisely by its molecular mechanism. The middle cerebral artery occlusion reperfusion (MCAO/R) rat model was established, and neurological function was evaluated by Zea-Longa score. Cerebral water content was determined to assess cerebral edema. Brain pathological condition was observed by hematoxylin and eosin staining, the intact changes of rat neurons were observed by Nissl staining, and neuronal apoptosis was measured by TUNEL staining. In addition, miR-192-5p and DICER1 levels were detected by RT-qPCR or Western blot, and the targeting relationship between miR-192-5p and DICER1 was verified by bioinformatics analysis and luciferase reporting experiment. miR-192-5p was up-regulated and DICER1 was down-regulated in MCAO/R rats. Sevoflurane preconditioning could decrease miR-192-5p and promote DICER1 expression. Sevoflurane preconditioning could alleviate brain tissue injury and neuronal apoptosis in MCAO/R rats. DICER1 expression was negatively regulated by targeting miR-192-5p. Elevating miR-192-5p or suppressing DICER1 rescued the protective effect of sevoflurane preconditioning on MCAO/R rats. Sevoflurane alleviates brain injury in MCAO/R rats via miR-192-5p/DICER1 axis.

Anisodine hydrobromide injection has shown promising therapeutic effects in treating patients with cerebral infarction, improving recovery of neurological function during the post-cerebral infarction period. However, the effects of anisodine hydrobromide on brain recovery and neuroplasticity are unclear. This study explores the therapeutic effects and underlying mechanisms of anisodine hydrobromide in mice experiencing the chronic phase of an ischemia stroke. The electrocautery method established a distal middle cerebral artery occlusion (MCAO) model in healthy male C57BL/6 mice. Neurological deficits were evaluated using Golgi and immunofluorescence staining to measure the effects of anisodine hydrobromide on neural proliferation, migration and remodeling. DAPT (dipeptidic γ-secretase-specific inhibitor) was employed to explore the involvement of the Notch signaling pathway post-anisodine hydrobromide treatment. Compared to the control and MCAO groups, mice treated with anisodine hydrobromide showed improved post-stroke neurological function, increased neurite intersections, and dendritic spine density in the peri-infarct cortex. Anisodine hydrobromide also promoted neural cell regeneration which is dendritic and axonal structures and synaptic vesicle protein restructuring. Gap43, NGF, Notch1, and Hes1 protein level increased significantly in the ANI group provided inhibitor DAPT was absent. Anisodine hydrobromide can promote neurological function, neurotrophic factors, and neuroplasticity. Notch signaling pathways also impact the effects of anisodine hydrobromide on neural plasticity in ischemia stroke.

Hypoxanthine-tricyclano is a synthetic adenosine analogue, in which adenine and ribose have been replaced by hypoxanthine and a morpholino-derived tricyclic moiety, respectively. We investigated whether hypoxanthine-tricyclano could influence atrial inotropy and/or chronotropy, two important functions regulated by the A1 receptor, the main adenosine receptor type of the supraventricular myocardium. Paced left atria and spontaneously beating right atria, isolated from male, 30-35 weeks old, Wistar rats, were used. The ino- and chronotropic effects of adenosine and hypoxanthine-tricyclano (separately and together) were assessed in the absence and presence of 8-cyclopentyl-1,3-dipropylxanthine (CPX), a selective, orthosteric, reversible A1 adenosine receptor antagonist. We found that adenosine exerted a strong negative inotropic effect (similar in left and right atria). However, hypoxanthine-tricyclano elicited a moderate positive inotropic effect (also similar in all atria). In right atria, adenosine evoked a robust negative chronotropic effect, whereas hypoxanthine-tricyclano produced a slight positive chronotropy. CPX blunted the effects of both adenosine and hypoxanthine-tricyclano, although this antagonism was strong (and significant) for adenosine, while smaller (and non-significant) for hypoxanthine-tricyclano. Both effects of hypoxanthine-tricyclano were easily surmountable with adenosine. Thus, hypoxanthine-tricyclano may act as a week, orthosteric, reversible, inverse and low-affinity agonist of the A1 receptor, although alternative mechanisms of action cannot be excluded.

The present study aimed to explore the expression and molecular mechanisms of lncRNA SIX3OS1 in post-stroke cognitive impairment (PSCI). Middle cerebral artery occlusion (MCAO) and oxygen-glucose deprivation/reoxygenation (OGD/R) were applied to establish an in vitro and in vivo model of PSCI. RT-qPCR was conducted to examine the mRNA levels of SIX3OS1, miR-511-3p, and RBP4. Morris water maze test was used to evaluate spatial learning and memory ability. Cell viability and apoptosis were examined by CCK-8 and flow cytometry. The secretion level of inflammatory factors was analyzed by ELISA. DLR and RIP assay were performed to validate the target relationship. In MCAO rats and OGD/R-induced cells, SIX3OS1 and RBP4 levels were significantly elevated, while miR-511-3p was reduced. miR-511-3p targets SIX3OS1 and RBP4. Compared with the sham, the spatial learning and memory ability of MCAO rats were decreased, but the silencing of SIX3OS1 could restore them, but this restoration was partially impaired by lowing of miR-511-3p. Silencing of SIX3OS1 enhanced OGD/R-induced SH-SY5Y cell viability and inhibited apoptosis and inflammatory factor secretion, but they were both attenuated by the lowing of miR-511-3p. Silencing of SIX3OS1 can protect PSCI via targeting miR-511-3p to promote cell viability and inhibit apoptosis and inflammation.

Complexity characterizes behaviour of all physiological systems whose components interact in multiple ways usually quantified by entropy techniques. However, complexity analysis regarding electrodermal activity (EDA)-related sympathetic cholinergic nervous system is rare. Thus, we aimed to study EDA dynamics complexity changes from aspect of various embedding dimensions (m) and timescales (τ) (sample entropy (SampEn) with m ∈ <2,7>, and multiscale entropy (MSE) in τ ∈ <1,20>) in association with traditionally used EDA indices (skin conductance level (SCL) and non-specific skin conductance responses (NS.SCRs)) to mental stress (mental arithmetic test - MAT) in healthy participants at critical adolescent age. The cohort (total group) consisted of 60 adolescents (17.5 ± 0.5 yrs) divided into three groups: Group-1: early (13.1 ± 0.3 yrs), Group-2: middle (16.6 ± 0.2 yrs) and Group-3: late (22.9 ± 0.1 yrs) adolescence. SampEn (m > 2) and MSE (for all τ) were significantly higher during MAT than baseline in total group and Group-2 (p < 0.05). Index MSE for all τ was significantly higher during MAT than baseline in total group, and Group-2; for τ ∈ <2,13> in Group-1 (p < 0.05). Additionally, while SCL was significantly higher during MAT than baseline in all groups, NS.SCRs was lower during stress only in Group-3 (p < 0.05). In conclusion, this study revealed distinct EDA complexity characteristics in individual examined groups indicating importance of complexity evaluation in stress-related sympathetic regulatory mechanisms within individual adolescent age ranges.

The increasing incidence of neurodegenerative and other diseases is considered to involve an excessive production of reactive oxygen species (ROS). Water supplies are often characterized by excessive organic waste that is decomposed by bacteria, using dissolved oxygen, leading to oxygen depletion. The potassium content of these waters may also affect negatively the mitochondrial metabolism and cellular ROS formation. This work focused on characterizing mitochondrial autofluorescence changes, with flavoprotein origin, and fluorescence ROS signals measured using the 2',7'-dichlorodihydrofluorescein diacetate indicator H2DCFDA. All signals were evoked by hypoxia or by the depolarizing agent KCl (20 mM), at the hippocampal mossy fiber synapses of CA3 area. It was observed that both hypoxia and KCl-induced depolarization elicited a small rise in the autofluorescence and ROS changes. The hypoxia-induced signals were maintained upon normal reoxygenation, but of those evoked by KCl, the autofluorescence signals recovered during washout, while the ROS changes were irreversible.

This study aimed to explore the expression and mechanism of transforming growth factor β1 (TGF-β1) in oxygen glucose deprivation reperfusion (OGD/R)-induced ischemia/reperfusion (I/R) injury. An OGD/R model was established in cardiomyocytes H9c2, resulting in upregulation of Beclin-1 and LC3II/LC3I expression. Upon overexpression of TGF-β1, the viability of OGD/R-induced H9c2 cells was enhanced, while apoptosis was suppressed by downregulating Bax and upregulating Bcl-2. Additionally, TGF-β1 overexpression promoted autophagy in OGD/R-induced H9c2 cells by further upregulating the levels of Beclin-1 and LC3II/LC3I. Importantly, treatments with 3-methyladenine (3-MA), an autophagy inhibitor, and U0126, an extracellular signal-related kinases 1 and 2 (ERK1/2) inhibitor, significantly inhibited cell viability, increased intracellular reactive oxygen species levels, promoted cell apoptosis (by upregulating Bax and downregulating Bcl-2), and inhibited cell autophagy (by downregulating Beclin-1 and LC3II/LC3I) in OGD/R-induced H9c2 cells with TGF-β1 overexpression. Additionally, OGD/R induction significantly increased the levels of p-ERK, p-P38, and p-JNK, which were further enhanced by TGF-β1 overexpression. U0126 treatments significantly downregulated the p-ERK compared to OGD/R-induced H9c2 cells with TGF-β1 overexpression. Our study suggests that TGF-β1 could inhibit the growth of cardiomyocytes H9c2 by regulating autophagy and ERK pathways, providing a new theoretical basis for the treatment and prevention of OGD/R in clinical practice.

The present study aimed to provide experimental evidence that CDELNs (coffee-derived exosome-like nanoparticles) may be a candidate for the treatment or prevention of amyloid-β (Aβ)-induced Alzheimer's disease (AD). An in vitro Alzheimer's model was created with Aβ-induced toxicity in mouse hippocampal neuronal cells (HT-22). Aβ(1-42)-exposed cells were treated with different concentrations of CDELNs (1-50 μg/ml) and the viability of cells was analyzed. The change in the mitochondrial membrane potential (ΔΨm) of cells was also determined. CDELNs treatment increased the viability of Aβ(1-42 )-toxicity-induced HT-22 cells significantly. The increase in the viability of Aβ(1-42)-toxicity-induced cells was correlated with an improvement in ΔΨm. CDELNs treatment restored the dissipated ΔΨm. These results suggested that CDELNs protect neuronal cells against Aβ(1-42)-induced neurotoxicity by repairing mitochondrial dysfunction. CDELNs might be a useful neuroprotective agent for the treatment or prevention of Aβ-induced AD. Further animal and clinical studies should be carried out to investigate the neuroprotective potential of CDELNs against Aβ-induced AD.

High mobility group box 1 (HMGB1) has the capability of activating the immune response and taking part in macrophage polarization. Despite this, there is significant scope for exploration into how HMGB1 regulates macrophage polarization phenotype and influences intestinal epithelial barrier function. Investigating the role of HMGB1 in the creation of neutrophil extracellular traps (NETs) and the mechanism of its impact on macrophages could provide novel insights into intervening in intestinal inflammation and barrier damage. Therefore, the research examined the relationship between the macrophage polarization phenotype and HMGB1. Additionally, we analyzed how cell proliferation and cytokines changed in CaCo-2 cells following co-culture with HMGB1-influenced macrophages and intestinal epithelial CaCo-2 cells. We discovered that up-regulation of HMGB1 expression enhanced the creation of NETs, whereas inhibition of NETs formation led macrophages to switch from the anti-inflammatory M2 phenotype to the pro-inflammatory M1 phenotype. Additionally, we observed that macrophages induced by NETs containing HMGB1 can prompt CaCo-2 cell apoptosis and exacerbate the inflammatory response. HMGB1-containing NETs hinder tight junction protein expression in CaCo-2 cells by inducing macrophage M1 polarization, thereby impairing intestinal epithelial barrier function. Therefore, our findings indicate that by inhibiting the expression of HMGB1, the formation of NETs can be inhibited. This, in turn, mediates macrophage polarization and offers potential new therapies for intestinal diseases.

We aimed to investigate whether pulsed magnetic fields (PMFs) (1 mT) may have preventive effects on myocardial damage and apoptosis in rats with sepsis. Twenty-eight adult Wistar albino rats were evenly distributed among four experimental groups, each consisting of seven rats: SH, LF-PMF, HF-PMF, and CLP. Sepsis induction was carried out via the cecal ligation and puncture (CLP) method, while rats in the LF-PMF and HF-PMF groups were exposed to 7.5 Hz and 15 Hz PMF, respectively, for duration of 24 hours. Following the removal of heart tissue, histological techniques were employed for the analysis. Histological scoring of apoptosis-related Bax, Bcl-2, and Acas-3 proteins as well as cTnI were performed in the heart tissue. The myocardial damage score significantly increased in the CLP group compared to the SH group (p < 0.05). Significant decreases were observed in Bcl-2 and cTnI protein levels in the CLP group, while significant increases were detected in the PMF groups (p < 0.05). An increase in Bax and Acas-3 protein levels, as well as the Bax/Bcl-2 ratio, was observed in the CLP group, with a decrease in the PMF groups (p < 0.05). The results demonstrate that PMF application has anti-apoptotic and therapeutic effects on septic heart tissue damage.