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2022 ◽  
Vol 12 (4) ◽  
pp. 834-840
Author(s):  
Peng Xu ◽  
Fang Sun ◽  
Ming Xiong ◽  
Qun Li ◽  
Peng Tu ◽  
...  

Purpose: To discuss the effects and mechanisms of improvement of Hydroxysafflor yellow A in pulmonary fibrosis by in vivo study. Material and Methods: In this study, dividing the C57BL/6 mice as 4 group, there were 10 mice in every group. Collecting the serum of difference groups and measuring the Hyp, SOD, MDA, TNF-α and IL-6 levels. Lung tissues were taken out and evaluating the pathology by HE staining and fibrosis degree by Masson staining. The relative proteins (α-SMA and E-cadherin) were measured by IHC and WB in lung tissues of difference groups. Results: With HSYA or DXM supplement, the Hyp, MDA, TNF-α and IL-6 concentrations significantly suppressed and SOD concentration significantly enhanced (P < 0.05, respectively). Compared with Sham group, the pathology injury and fibrosis degree of Model group were significantly up-regulation (P < 0.001, respectively); With HSYA or DXM treatment, the pathology injury and fibrosis degree of HSYA and DXM groups were significantly improved (P < 0.05, respectively). By IHC and WB assay, the α-SMA and E-cadherin proteins expressions of Model group were significantly differences (P < 0.001, respectively); however, the α-SMA and E-cadherin proteins expressions of HSYA and DXM groups were significantly improved with HSYA or DXM supplement (P < 0.05, respectively). Conclusion: HSYA improves pulmonary fibrosis by regulation α-SMA and E-cadherin in vivo study.


2022 ◽  
Vol 2022 ◽  
pp. 1-7
Author(s):  
Shuaidong Mao ◽  
Huan Huang ◽  
Xianzheng Chen

Objective. To explore the effect of long noncoding RNA H19 (lncRNA H19) on brain injury in rats following experimental intracerebral hemorrhage (ICH). Methods. Rat ICH model was established with type IV collagenase. The neurological function scores were evaluated, and the water content in brain tissue was measured. The nerve injury indexes, inflammatory factors, and oxidative stress indexes were also measured. Moreover, the expression of lncRNA H19 was determined by qRT-PCR, and Western blot detected NF-κB pathway-related protein expression. Results. Compared with the sham group, the neurological function scores, the water content in brain tissue, and levels of injury indicators myelin basic protein (MBP), S-100B, and neuron-specific enolase (NSE) in the ICH rats were significantly increased. Meanwhile, the levels of TNF-α, IL-6, IL-1β, ROS, and MDA were significantly increased, but the levels of SOD were significantly decreased. In addition, the expression of lncRNA H19 in the brain tissue in the ICH group was significantly higher than that in the sham group. After further interference with lncRNA H19 expression (sh-H19 group), the levels of all the above indicators were reversed and the neurological damage was improved. Western blot results showed that the expression of NF-κBp65 and IKKβ was significantly higher, and IκBα expression was lower in the perivascular hematoma tissue in the ICH group compared with the sham group. Compared with the sh-NC group, NF-κBp65 and IKKβ expression were significantly lower and IκBα was significantly higher in the sh-H19 group. Conclusion. lncRNA H19 exacerbated brain injury in rats with ICH by promoting neurological impairment, brain edema, and releasing inflammatory responses and oxidative stress. This may be related to the activation of NF-κB signaling pathway.


2022 ◽  
Vol 12 ◽  
Author(s):  
Lu Xia ◽  
Lu Liu ◽  
Qiang Wang ◽  
Jing Ding ◽  
Xin Wang

PurposeThis study aimed to analyse the correlation between the pyroptosis pathway and epilepsy using bioinformatics analysis technology. We analyzed the expression of gasdermin D (GSDMD) and gasdermin E (GSDME), the key molecules of pyroptosis, in kainic acid-induced epileptic mice.MethodsWeighted gene co-expression network analysis (WGCNA) was used to construct a signed co-expression network from expression data to screen gene sets closely related to epilepsy. The correlation between the module and epilepsy was verified through module conservative analysis, gene ontology (GO) annotation analysis, and correlation analysis with known epilepsy genes. We obtained currently recognized pyroptosis-related molecules through literature review, and correlation analysis was used to evaluate their correlation with epilepsy. Differentially expressed gene (DEG) analysis was used to analyse expression changes of pyroptosis-related molecules at the transcriptome level, compared to the sham group. We subsequently established a kainic acid-induced status epilepticus (SE) model in mice and validated the mRNA and protein expression of GSDMD and GSDME, the key molecules of pyroptosis, by quantitative reverse transcription PCR (qRT-PCR) and western blotting (WB).ResultsUsing WGCNA, module conservative analysis, and correlation analysis with known epilepsy genes, we screened out a module (a gene set of interest) closely related to epilepsy that was prominently enriched in immune and inflammatory-related biological processes. Correlation analysis results suggest that pyroptosis-related molecules are closely related to this module, but have no obvious correlation with others. DEG analysis of molecules associated with pyroptosis suggests that most of the pyroptosis-related molecules had significantly increased expression after SE, such as IL1b, Casp1, Casp4, Pycard, Gsdmd, Nlrp3, Aim2, Mefv, Tlr2, Tlr3, and Tlr4. qRT-PCR and WB analysis confirmed that the mRNA and protein levels of GSDMD in the mouse hippocampus were significantly upregulated after SE. The mRNA expression of GSDME was not different between the epilepsy group and sham group. However, the WB results showed that the expression of full-length GSDME was decreased and GSDME-N-terminus were significantly increased after SE.ConclusionsOur study highlights that the pyroptosis pathway may be closely related to epilepsy. GSDMD and GSDME, the key executive molecules of pyroptosis, will help to understand the pathogenesis of epilepsy and aid in discovering new targets for anti-epileptic drug treatments.


2022 ◽  
Author(s):  
David Martín-Caro Álvarez ◽  
Diego Serrano-Muñoz ◽  
Juan José Fernández-Pérez ◽  
Julio Gómez-Soriano ◽  
Juan Avendaño-Coy

Abstract BackgroundFormer studies investigated the application, both transcutaneous and with implanted electrodes, of high frequency alternating currents (HFAC) in humans for blocking the peripheral nervous system. The present trial aimed to assess the effect of HFAC on motor response, somatosensory thresholds, and peripheral nerve conduction, when applied percutaneously with ultrasound-guided needles at frequencies of 10 kHz and 20 kHz in healthy volunteers. MethodsA parallel, placebo-controlled, double-blind, randomized clinical trial was conducted. Ultrasound-guided HFAC at 10 kHz and 20 kHz and sham stimulation were delivered to the median nerve of 60 healthy volunteers (n=20 per group) for 20 minutes. The main assessed variables were maximum isometric flexion strength (MFFS) of the index finger, myotonometry, pressure pain threshold (PPT), mechanical detection threshold (MDT), and antidromic sensory nerve action potential (SNAP). Measurements were recorded pre-intervention, during the intervention 15 minutes after its commencement, immediately post-intervention, and at 15 minutes post-intervention.ResultsA decrease in the MFFS was observed immediately post-intervention compared to baseline, both in the 10 kHz group [-8.5 %; 95% confidence interval (CI) -14.9 to -2.1] and the 20 kHz group (-12.0%; 95%CI -18.3 to -5.6). At 15 minutes post-intervention, the decrease in the MFFS was -9.5% (95%CI -17.3 to -1.8) and -11.5% (95%CI -9.3 to -3.8) in the 10 kHz and 20 kHz groups, respectively. No changes over time were found in the sham group. The between-group comparison of changes in MFFS showed a greater reduction of -10.8% (95%CI -19.8 to -1.8) immediately post-intervention in the 20 kHz compared to the sham stimulation group. Muscle tone increased over time in both the 10 kHz and 20 kHz groups, but not in the sham group. The intergroup comparison of myotonometry showed a superior effect in the 20 kHz (6.7%, 95%CI 0.5 to 12.9) versus the sham group. No significant changes were observed in the rest of the assessed variables. ConclusionsThe ultrasound-guided percutaneous stimulation applying 10 kHz and 20 kHz HFAC to the median nerve produced reversible reductions in strength and increases in muscle tone with no adverse effects.


2022 ◽  
Vol 13 ◽  
Author(s):  
Ting-Yu Chou ◽  
Jia-Chi Wang ◽  
Mu-Yun Lin ◽  
Po-Yi Tsai

BackgroundAlthough low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) has shown promise in the treatment of poststroke aphasia, the efficacy of high-frequency rTMS (HF-rTMS) has yet to be determined.PurposeWe investigated the efficacy of intermittent theta burst stimulation (iTBS) in ameliorating chronic non-fluent aphasia and compared it with that of LF-rTMS.MethodsWe randomly assigned patients with poststroke non-fluent aphasia to an ipsilesional iTBS (n = 29), contralesional 1-Hz rTMS (n = 27), or sham (n = 29) group. Each group received the rTMS protocol executed in 10 daily sessions over 2 weeks. We evaluated language function before and after the intervention by using the Concise Chinese Aphasia Test (CCAT).ResultsCompared with the sham group, the iTBS group exhibited significant improvements in conversation, description, and expression scores (P = 0.0004–0.031), which characterize verbal production, as well as in auditory comprehension, reading comprehension, and matching scores (P &lt; 0.01), which characterize language perception. The 1-Hz group exhibited superior improvements in expression, reading comprehension, and imitation writing scores compared with the sham group (P &lt; 0.05). The iTBS group had significantly superior results in CCAT total score, matching and auditory comprehension (P &lt; 0.05) relative to the 1-Hz group.ConclusionOur study findings contribute to a growing body of evidence that ipsilesional iTBS enhances the language recovery of patients with non-fluent aphasia after a chronic stroke. Auditory comprehension was more preferentially enhanced by iTBS compared with the 1-Hz protocol. Our findings highlight the importance of ipsilesional modulation through excitatory rTMS for the recovery of non-fluent aphasia in patients with chronic stroke.Clinical Trial Registration:[www.ClinicalTrials.gov], identifier [NCT03059225].


Cephalalgia ◽  
2022 ◽  
pp. 033310242110688
Author(s):  
Umer Najib ◽  
Timothy Smith ◽  
Nada Hindiyeh ◽  
Joel Saper ◽  
Barbara Nye ◽  
...  

Aim Evaluate the efficacy and safety of non-invasive vagus nerve stimulation for migraine prevention. Methods After completing a 4-week diary run-in period, adults who had migraine with or without aura were randomly assigned to receive active non-invasive vagus nerve stimulation or sham therapy during a 12-week double-blind period. Results Of 336 enrolled participants, 113 (active, n = 56; sham, n = 57) completed ≥70 days of the double-blind period and were ≥66% adherent with treatment, comprising the prespecified modified intention-to-treat population. The COVID-19 pandemic led to early trial termination, and the population was ∼60% smaller than the statistical target for full power. Mean reduction in monthly migraine days (primary endpoint) was 3.12 for the active group and 2.29 days for the sham group (difference, −0.83; p = 0.2329). Responder rate (i.e. the percentage of participants with a ≥50% reduction in migraine days) was greater in the active group (44.87%) than the sham group (26.81%; p = 0.0481). Prespecified subgroup analysis suggested that participants with aura responded preferentially. No serious device-related adverse events were reported. Conclusions These results suggest clinical utility of non-invasive vagus nerve stimulation for migraine prevention, particularly for patients who have migraine with aura, and reinforce the well-established safety and tolerability profile of this therapy. Trial Registration: ClinicalTrials.gov (NCT03716505).


2022 ◽  
Vol 2022 ◽  
pp. 1-10
Author(s):  
Lan Zhan ◽  
Yu Pang ◽  
Hao Jiang ◽  
Shicun Zhang ◽  
Hongwei Jin ◽  
...  

Stroke is a disease with the highest incidence rate and the highest mortality rate in the world. The study aims to verify the neuroprotective effect of Butylphthalide. The mice were divided into sham group, MCAO group, and MCAO + Butylphthalide-treated group. The mice in MCAO + Butylphthalide-treated group were administered with 70 mg/kg Butylphthalide injection intraperitoneally after cerebral ischemia-reperfusion. The normal saline with the same volume was administered intraperitoneally for the mice in the MCAO group and sham group. The levels of miR-21 in brain tissue and cells were detected by qPCR. The OGD/R injury model of Neuro2A cells was used to simulate the hypoxic-ischemic environment of neurons in vitro. The proliferation rate of Neuro2A cells was detected with CCK-8. The production of ROS was detected with DCFH-DA. Compared with the mice in MCAO group, a decrease ( P < 0.01 ) was observed in the functional neurologic impairment scoring, cerebral infarction volume, and brain loss volume in the mice treated with MCAO + Butylphthalide, but an increase ( P < 0.01 ) was observed in the level of miR-21, which was positively correlated with functional neurologic impairment scoring (r = −0.8933, P < 0.001 ). MTT assay showed that the cell viability of OGD/R + Butylphthalide group was significantly higher than that of other groups ( P < 0.001 ), and the activity of ROS was significantly decreased ( P < 0.001 ). The WB results showed that, compared with OGD/R + miR-NC and control groups, the ratio of Bcl-2/Bax in OGD/R + Butylphthalide group and OGD/R + miR-21 mimics group was significantly higher ( P < 0.05 ), while the ratio of caspase-3/GAPDH was significantly lower ( P < 0.05 ). In conclusion, Butylphthalide has neuroprotective effect on the mouse model of MCAO. It may upregulate the level of miR-21 to inhibit neuronal apoptosis and ROS production and improve the proliferation activity. The specific mechanism may lie in inhibiting TLR4/NF-κB pathway.


2022 ◽  
Vol 12 ◽  
Author(s):  
Kaitlin E. Burch ◽  
Kelly McCracken ◽  
Daniel J. Buck ◽  
Randall L. Davis ◽  
Dusti K. Sloan ◽  
...  

Although increasing research focuses on the phenomenon of body weight gain in women after menopause, the complexity of body weight regulation and the array of models used to investigate it has proven to be challenging. Here, we used ovariectomized (OVX) rats, which rapidly gain weight, to determine if receptors for ghrelin, insulin, or leptin in the dorsal vagal complex (DVC), arcuate nucleus (ARC), or paraventricular nucleus (PVN) change during post-ovariectomy weight gain. Female Sprague-Dawley rats with ad libitum access to standard laboratory chow were bilaterally OVX or sham OVX. Subgroups were weighed and then terminated on day 5, 33, or 54 post-operatively; blood and brains were collected. ELISA kits were used to measure receptors for ghrelin, insulin, and leptin in the DVC, ARC, and PVN, as well as plasma ghrelin, insulin, and leptin. As expected, body weight increased rapidly after ovariectomy. However, ghrelin receptors did not change in any of the areas for either group, nor did circulating ghrelin. Thus, the receptor:hormone ratio indicated comparable ghrelin signaling in these CNS areas for both groups. Insulin receptors in the DVC and PVN decreased in the OVX group over time, increased in the PVN of the Sham group, and were unchanged in the ARC. These changes were accompanied by elevated circulating insulin in the OVX group. Thus, the receptor:hormone ratio indicated reduced insulin signaling in the DVC and PVN of OVX rats. Leptin receptors were unchanged in the DVC and ARC, but increased over time in the PVN of the Sham group. These changes were accompanied by elevated circulating leptin in both groups that was more pronounced in the OVX group. Thus, the receptor:hormone ratio indicated reduced leptin signaling in the DVC and PVN of both groups, but only in the OVX group for the ARC. Together, these data suggest that weight gain that occurs after removal of ovarian hormones by ovariectomy is associated with selective changes in metabolic hormone signaling in the CNS. While these changes may reflect behavioral or physiological alterations, it remains to be determined whether they cause post-ovariectomy weight gain or result from it.


2022 ◽  
Vol 12 (1) ◽  
pp. 19-27
Author(s):  
Xiaocheng Jiang ◽  
Yuxiang Ren ◽  
Xintao Zhang ◽  
Tian You ◽  
Shiyou Ren ◽  
...  

This study was aim to investigate the effect of type 1 collagen (Col I) bioactive scaffold on regeneration and repair of motor cartilage injury. Fifteen New Zealand rabbits were randomly divided into sham operation group (Sham group, only cartilage was exposed, no defect was made), model group Focal cortical dysplasias (FCD) group, cartilage defect model], and treatment group (Col I group, cartilage defect + Col I bioactive scaffold treatment). The cartilage tissue of each group was detected 16 weeks after the operation. Immunohistochemistry and Western Blot were adopted to detect the expression of cartilage related proteins in each group. The results showed that Col I bioactive scaffold could repair the gross morphology of cartilage defect, promote the regeneration and repair of chondrocytes in defect area, and reduce the mast cells in defect area. Western Blot detection of the expression of signal pathway marker proteins showed that expression of Wnt protein, β-catenin protein, and phosphofructokinase-1 (PFK-1) protein in the FCD group were significantly reduced than Sham group (P < 0.05), while the expression of phosphoenolpyruvate carboxykinase 1 (PEPCK1) protein was significantly increased (P < 0.05). Expression of Wnt protein, β-catenin protein, and PFK-1 protein in Col I group increased significantly versus FCD group (P < 0.05), while the expression of PEPCK1 protein significantly decreased (P < 0.05). In conclusion, Col I bioactive scaffolds could regenerate and repair cartilage defects, and the mechanism may be related to Wnt signaling pathway and glycolysis/gluconeogenesis pathway.


Pharmacology ◽  
2021 ◽  
pp. 1-6
Author(s):  
Masashi Tawa ◽  
Takashi Shimosato ◽  
Keisuke Nakagawa ◽  
Tomio Okamura ◽  
Mamoru Ohkita

Soluble guanylate cyclase (sGC) plays an important role in nitric oxide (NO)-mediated regulation of vascular tone; however, NO bioavailability is often reduced in diseased blood vessels. Accumulating evidence suggests that a shift of sGC from the NO-sensitive form to the NO-insensitive form could be an underlying cause contributing to this reduction. Herein, we investigated the impact of renovascular hypertension on NO-sensitive and NO-insensitive sGC-mediated relaxation in rat aortas. Renovascular hypertension was induced by partially clipping the left renal artery (2-kidneys, 1-clip; 2K1C) for 10 weeks. Systolic, diastolic, and mean arterial pressures were significantly increased in the 2K1C group when compared with the sham group. In addition, plasma thiobarbituric acid reactive substances and aortic superoxide generation were significantly enhanced in the 2K1C group when compared with those in the sham group. The vasorelaxant response of isolated aortas to the sGC stimulator BAY 41-2272 (NO-sensitive sGC agonist) was comparable between the sham and 2K1C groups. Likewise, the sGC activator BAY 60-2770 (NO-insensitive sGC agonist)-induced relaxation did not differ between the sham and 2K1C groups. In addition, the cGMP mimetic 8-Br-cGMP (protein kinase G agonist) induced similar relaxation in both groups. Furthermore, there were no differences in BAY 41-2272-stimulated and BAY 60-2770-stimulated cGMP generation between the groups. These findings suggest that the balance between NO-sensitive and NO-insensitive forms of sGC is maintained during renovascular hypertension. Therefore, sGC might not be responsible for the reduced NO bioavailability observed during renovascular hypertension.


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