Protection against Neurological Symptoms by Consuming Corn Silk Water Extract in Artery-Occluded Gerbils with Reducing Oxidative Stress, Inflammation, and Post-Stroke Hyperglycemia through the Gut-Brain Axis

Corn silk (Stigma maydis), rich in flavonoids, is traditionally used to treat edema, depression, and hyperglycemia and may alleviate ischemic stroke symptoms in Chinese medicine. This study examined whether corn silk water extract (CSW) could alleviate ischemic stroke symptoms and post-stroke hyperglycemia in Mongolian gerbils with transient cerebral ischemia and reperfusion (I/R). After being given 0.05% (I/R-LCSW) and 0.2% (I/R-HCSW), 0.02% aspirin (I/R-aspirin), and cellulose (I/R-control) in their 40 energy% fat diets for three weeks, the gerbils underwent an artery occlusion for eight minutes and reperfusion. They took the assigned diet for an additional three weeks. Sham-operated gerbils without artery occlusion had the same diet as Sham-control. CSW intake reduced neuronal cell death in gerbils with I/R and dose-dependently improved the neurological symptoms, including drooped eyes, crouched posture, flexor reflex, and walking patterns. CSW intake also alleviated the short-term memory and spontaneous alteration and grip strength compared to the I/R-control group. The protection against ischemic stroke symptoms was associated with the reduced tumor necrosis factor-α, interleukin-1β, superoxide, and lipid peroxide levels, promoting superoxide dismutase activity in the hippocampus in the CSW groups, compared to the I/R-control. The blood flow measured by Doppler was improved with CSW compared to the I/R-control. Furthermore, CSW intake prevented the post-stroke hyperglycemia related to decreasing pancreatic β-cell mass as much as the Sham-control, and it was related to protection against β-cell apoptosis, restoring the β-cell mass similar to the Sham-control. CSW intake elevated the relative abundance of Lactobacillus, Bifidobacterium, Allobaculum, and Akkermansia compared to the I/R-control. Picrust2 analysis showed that CSW increased the propionate and butyrate metabolism and the starch and glucose metabolism but reduced lipopolysaccharide biosynthesis compared to the I/R-control. In conclusion, CSW intake protects against neuronal cell death and post-hyperglycemia by reducing oxidative stress and inflammation and increasing blood flow and the β-cell mass. The alleviation was associated with promoting the gut-brain axis by changing the gut microbiome community.

Effectiveness and Safety of Electroacupuncture for Depression: a systematic review and meta-analysis

Review question / Objective: Is electroacupuncture a safe therapy for the treatment of depression? Is electroacupuncture effective for the treatment of depression, as compared with sham control, or conventional drugs？ Condition being studied: Depression is a mood disorder that causes sufferers to feel sadness, decreased interest, guilt, self-blame, loss of energy, and experience sleep disorders such as insomnia. People suffering from depression even feel they have no way out and have suicidal thoughts. In the United States, the prevalence of a major depressive disorder is 16.2%1-3. The 2010 Global Burden of Disease Study identified major depression as the second leading cause of disability worldwide and a leading cause of the burden of suicide and ischaemic heart disease. At present, depression patients are mainly treated with antidepressants, but the efficacy is extremely unstable. Studies have shown that acupuncture can help improve symptoms in patients with depression, but these clinical studies have not been systematically evaluated, and further confirmation is needed to confirm the efficacy of electroacupuncture in treating depression.

Five Different Noise Intensities Robustly Affects Corticosterone, Gastrin and Endothelin-1 Responses and Initiated Gastric Tissue Damage in Wistar Rats

Likewise other stress response noise stress is also affects the homeostasis of the biological systems and produce stress response in the form of Corticosterone to prevent the damage but if the exposure is longer with higher magnitude it may disrupt the robust ability of the homeostasis and could produce the damage to the biological systems. The goal of our study was to see how five different noise intensities affected stomach tissue damage. 42 healthy rats were divided into five different stress exposure group, normal control (NC) and sham control (SC) groups. Noise stress exposure was delivered for 1 hour per day continued for 30 days in all five noise exposed groups by specially designed noise chamber whereas sham control group of animals kept in noise chamber for 1 hour per day continued for 30 days without noise stress exposure and control group of animals neither exposed to noise stress of any intensities and nor kept in noise chamber without noise but remain in the same experimental room in their homecage for 30 days respectively. Results of the study showed that animals exposed to 60 and 80 dB noise give habituated and not significant Corticosterone, Gastrin and Endothelin-1 responses compared to NC and SC groups while animals exposed to 100, 120 and 140 dB had significantly higher Corticosterone, Gastrin and Endothelin-1 response and also chronic gastric damage was observed compared to later two noise exposed groups respectively. Study concluded that not only higher but also lower noise intensities also initiated the gastric damage even after the adaptation.

Mesenchymal Stem Cells Enhance Vascular Endothelial Growth Factor-A, Endothelial Nitric Oxide Synthetase, and HSP70 Expression in Improving Erectile Dysfunction in Streptozotocin-induced Diabetic Rats

This study investigated the therapeutic role of mesenchymal stem cells (MSCs) on erectile function in a diabetes mellitus erectile dysfunction (DMED) rat model by analyzing the expression of endothelial nitric oxide synthetase (eNOS), vascular endothelial growth factor (VEGF), and the 70 kilodalton heat shock proteins (HSP70). MSCs were isolated from umbilical cords (UCs), and their characteristics identified by flow cytometry and osteogenic differentiation analysis. Thirty 8-week-old rats were divided into four groups: sham, control, T1, and T2. After a 16 h fast, 24 rats were randomly selected and intraperitoneally injected with streptozotocin (STZ) to induce DM. At 8 weeks after STZ injection, rats with DMED were classified into four groups, sham, control group [DMED rats received 500 μL phosphate buffer saline (PBS)]; T1 [DMED rats treated with 500 μL PBS containing 1 × 106 UC-MSCs]; T2 [DMED rats treated with 500 μL PBS containing 2 × 106 UC-MSCs]. Eight weeks after MSCs administration, the rats’ erectile function was measured by cavernous nerve stimulation. The blinded histological and gene expression assessment were used to analyze the eNOS, HSP70 content, and VEGF expression on the penile tissues. MSCs administration, rats in T1 and T2 groups showed a significant enhancement of erectile response that showed a trend of increase of VEGF mRNA level expression was 2.2 ± 0.61 in T2 Group supported with the optimum recovery of eNOS, in which the value of eNOS expression was 20.66% ± 2.32%. While optimum decrease of HSP70 content, the value of HSP70 expression was 15.50% ± 0.90%. IHC results showed that the DMED induction in rats caused a significant decrease of eNOS content in corpus cavernosum tissue. MSCs could ameliorate DMED in rats by increasing VEGF and decreasing HSP70 and eNOS, indicating these cells offer a potential application for DMED patients’ treatment.

Not Quite All in Our Head: Intervention is a Better Predictor of tDCS Mind-Wandering Effects than Subjective Beliefs About Experimental Results

Background: Establishing adequate blinding for non-invasive brain stimulation research is a topic of extensive debate, especially regarding the efficacy of sham control methods for transcranial direct current stimulation (tDCS) studies. Fassi and Cohen Kadosh [1] assessed the influence of subjective participant belief regarding stimulation type (active or sham) and dosage on behaviour using data from Filmer et al. [2] who applied five stimulation protocols (anodal 1.0mA, cathodal 1.0mA, cathodal 1.5mA, cathodal 2.0mA and sham) to assess the neural substrates of mind wandering. Fassi and Cohen Kadosh [1] concluded that subjective belief drove the pattern of results observed by Filmer et al. [2]. Objective: Fassi and Cohen Kadosh [1] did not assess the key contrast between conditions in Filmer et al. (2019), 2mA vs sham, rather they examined all stimulation conditions. Here, we consider the relationship between objective and subjective intervention in this key contrast. Methods: We replicated the analysis and findings of both Filmer et al. [2] and Fassi and Cohen Kadosh [1] before assessing 2mA vs. sham via Bayesian ANOVA on subjective belief regarding stimulation type and dosage. Results: Our results support objective intervention as the strongest predictor of stimulation effects on mind-wandering when 2mA vs sham was examined, over and above that of subjective intervention. Conclusions: The conclusions made by Filmer et al. [2] are confirmed. However, it is important to control for and understand the possible effects of subjective beliefs in sham controlled studies. Best practice to prevent these issues remains the inclusion of active control conditions.

Catheter-based ultrasound renal denervation in patients with resistant hypertension: the randomized, controlled REQUIRE trial

Renal denervation is a promising new non-pharmacological treatment for resistant hypertension. However, there is a lack of data from Asian patients. The REQUIRE trial investigated the blood pressure-lowering efficacy of renal denervation in treated patients with resistant hypertension from Japan and South Korea. Adults with resistant hypertension (seated office blood pressure ≥150/90 mmHg and 24-hour ambulatory systolic blood pressure ≥140 mmHg) with suitable renal artery anatomy were randomized to ultrasound renal denervation or a sham procedure. The primary endpoint was change from baseline in 24-hour ambulatory systolic blood pressure at 3 months. A total of 143 patients were included (72 renal denervation, 71 sham control). Reduction from baseline in 24-hour ambulatory systolic blood pressure at 3 months was not significantly different between the renal denervation (−6.6 mmHg) and sham control (−6.5 mmHg) groups (difference: −0.1, 95% confidence interval −5.5, 5.3; p = 0.971). Reductions from baseline in home and office systolic blood pressure (differences: –1.8 mmHg [p = 0.488] and −2.0 mmHg [p = 0.511], respectively), and medication load, did not differ significantly between the two groups. The procedure-/device-related major adverse events was not seen. This study did not show a significant difference in ambulatory blood pressure reductions between renal denervation and a sham procedure in treated patients with resistant hypertension. Although blood pressure reduction after renal denervation was similar to other sham-controlled studies, the sham group in this study showed much greater reduction. This unexpected blood pressure reduction in the sham control group highlights study design issues that will be addressed in a new trial. Clinical trial registration NCT02918305 (http://www.clinicaltrials.gov).

Optimal Strategy for HIFU-Based Renal Sympathetic Denervation in Canines

Background: The association between the treatment efficacy and safety of high-intensity focused ultrasound (HIFU)-based renal sympathetic denervation (RDN) and the acoustic energy dose applied has not been fully studied and may provide important understanding of the mechanism that led to failure of the WAVE IV trial. The objective of this study was to externally deliver different HIFU doses to canines for RDN treatment and to investigate the optimal energy dose for HIFU-based RDN.Methods: Thirty canines were divided into five RDN groups according to dose of acoustic energy applied, and a sham control group that consisted of four canines was used for comparisons. All animals in the RDN groups underwent the RDN procedure with different acoustic energy doses, while in the sham control group, renal arteries were harvested without being subjected to acoustic energy delivery and were imaged using color Doppler flow imaging (CDFI). Blood pressure (BP) was recorded, and blood samples were collected before the RDN procedure and at 28 days after the RDN procedure. Histological examinations and measurement of renal tissue norepinephrine concentration were performed in all retrieved samples.Results: Suppression of BP was significant in the 300 W (15.17/8.33 ± 1.47/1.21 mmHg), 250 W (14.67/9.33 ± 1.21/1.37 mmHg), and 200 W (13.17/9.17 ± 2.32/1.84 mmHg) groups. Semiquantitative histological assessment of periarterial nerves around the kidney revealed that target nerves in the 300 W (9.77 ± 0.63), 250 W (9.42 ± 0.67), and 200 W (9.58 ± 0.54) groups had the highest nerve injury scores, followed by the 150 W group (5.29 ± 0.62). Furthermore, decreased renal tissue norepinephrine concentration, together with decreased expression of tyrosine hydroxylase in the 300, 250, and 200 W groups demonstrated effective sympathetic depression following sufficient acoustic energy deposition. However, the renal artery injury score in the 300 W group (0.93 ± 0.13) was significantly higher than in the other groups (p < 0.001).Conclusion: This study provides evidence that RDN effectiveness is based on the energy dose delivered and that 200–250 W is effective and safe in normal-sized canines.

Maternal Engineered Nanomaterial Inhalation During Gestation Drives Redox Dysregulation and Vascular Dysfunction Across Generations

Background Pregnancy is associated with many rapid biological adaptations that support healthy development of the growing fetus. One of which is critical to fetal health and development is the coordination between maternal liver derived substrates and vascular delivery. This crucial adaptation can be potentially derailed by inhalation of toxicants. Engineered nanomaterials (ENM) are commonly used in household and industrial products as well as in medicinal applications. As such, the potential risk of exposure remains a concern, especially during pregnancy. We have previously reported that ENM inhalation leads to upregulation in the production of oxidative species. Therefore, we aimed to determine if maternal nano-TiO2 inhalation exposure resulted in altered H2O2 production capacity and changes in downstream redox pathways. Additionally, we investigated whether this persisted into adulthood within the F1 generation and how this impacted F1 gestational outcomes and F2 fetal health and development. We hypothesized that maternal nano-TiO2 inhalation exposure during gestation would result in upregulated H2O2 in the F0 dams as well as her F1 offspring, resulting in gestational vascular dysfunction in the F1 dams yielding smaller F2 generation pups. Results Our results indicate upregulation of hepatic H2O2 production capacity in F0 dams, F1 offspring at 8 weeks and F1 females at gestational day 20. H2O2 production capacity was accompanied by a 2-fold increase in phosphorylation of the redox sensitive transcription factor NF-κB. In cell culture, naïve hepatocytes exposed to F1-nano-TiO2 plasma increased H2O2 production. Overnight exposure of these hepatocytes to F1 plasma increased H2O2 production capacity in a partially NF- κB dependent manner. Pregnant F1- nano-TiO2 females exhibited estrogen disruption (29.81 ± 8.8 pg/ml vs. 12.12 ± 3.1 pg/ml sham-control) and vascular dysfunction similar to their directly exposed mothers. F1-nano-TiO2 uterine artery H2O2 production capacity was also elevated 2-fold. Dysfunctional gestational outcomes in the F1-nano-TiO2 dams resulted in smaller F2 pups (4.93 ± 0.47 g vs. 5.78 ± 0.09 g sham-control pups). Conclusion In conclusion, this manuscript provides critical evidence of redox dysregulation across generations following maternal ENM inhalation. Furthermore, the dysfunctional gestational outcomes observed in the F1-nano-TiO2 generation impact the development of F2 offspring. In total, this data provides strong initial evidence that maternal ENM exposure has robust biological impacts that persists in at least two generations.

Secondary Cerebellar Cortex Injury in Albino Male Rats after MCAO: A Histological and Biochemical Study

The present study focused on secondary injury following the middle cerebral artery (MCA) occlusion in rats not linked to the MCA’s feeding zone. This entity has been very rarely studied. Additionally, this study investigated the rates of expression of five fundamental angiogenic biomarkers called endoglin, vascular endothelial growth factors-A (VEGF-A), endothelin-1 (ET-1), 2granulocyte colony-stimulating factor (G-CSF), and angiopoietin-using the MCA occlusion (MCAO) model. The random allocation of twelve adult male albino rats was in two groups. As a sham control group, six rats were used. This group was subjected to a sham operation without MCAO. The MCAO group consisted of six rats that were subjected to MCAO operation. After three days, the rats were sacrificed. The cerebellar specimens were immediately processed for light microscopic examination. An angiogenic biomarkers multiplex assay from multiplex was used to assess endoglin levels, VEGF-A, ET-1, angiopoietin-2, and G-CSF in serum samples. Hematoxylin and eosin-stained sections showed that the cerebellar cortex of rats of the MCAO group was more affected than the sham control group. Furthermore, Nissl stain and immunohistochemical analysis revealed an apparent increase in the number of positive immunoreactive in the cerebellar cortex and an evident decrease in Nissl granules in Purkinje cells of the MCAO rats, in contrast to the control rats. In addition, there was a significant increase in angiogenic factors VEGF-A, ET-1, angiopoietin-2, and endoglin. Interestingly, there was an increase in the G-CSF but a non-significant in the MCAO rats compared to the control rats. Furthermore, there was a significant correlation between the angiopoietin-2 and ET-1, and between G-CSF and ET-1. VEGF-A also exhibited significant positive correlations with the G-CSF serum level parameter, Endoglin, and ET-1. Rats subjected to MCAO are a suitable model to study secondary injury away from MCA’s feeding zone. Additionally, valuable insights into the association and interaction between altered angiogenic factors and acute ischemic stroke induced by MCAO in rats.

Abstract P154: Win Ratio Methodology Demonstrates Consistency Of Benefit Across Different Blood Pressure Reduction Thresholds Following Renal Denervation In The Spyral Htn-on Med Pilot Study

Objective: The win ratio is a statistical methodology to evaluate clinical trial outcomes using multiple hierarchical endpoints. We applied the win ratio to patients in SPYRAL HTN-ON MED pilot study to quantify potential differences in renal denervation (RDN) efficacy utilizing different blood pressure (BP) reduction thresholds. Methods: In the SPYRAL HTN-ON MED pilot study, patients were enrolled with office systolic BP (OSBP) ≥150 mmHg and <180 mmHg, office diastolic BP ≥90 mmHg, and mean 24-hour ambulatory systolic BP (ASBP) ≥140 mmHg and <170 mmHg despite 1 to 3 antihypertensive medications. Patients were randomized 1:1 to RDN or sham procedure. For the win ratio analysis, each RDN patient was compared with every sham control patient in the opposing group first according to ASBP to determine “win”, “lose” or “tie” with a threshold of 5 mmHg. Then, ties from the ASBP comparison underwent the comparison using OSBP with a threshold of 10 mmHg. Any tie for a pair comparing OSBP resulted in comparison of any reduction in anti-hypertensive medication burden. The win ratio analysis was repeated using thresholds of 3.5 mmHg for ASBP change, 5 mmHg for OSBP change and any net change in medication burden. Results: The calculated win ratio favored RDN: 2.78 (95% CI: 1.58, 5.48, p<0.001), using thresholds of 5 mmHg for ASBP change, 10 mmHg for OSBP change, and any net change in medication burden, all at 6 months. To test the sensitivity of the analysis, the BP thresholds were changed to 3.5 mmHg for ASBP and 5 mmHg for OSBP, and the win ratio analysis was repeated, resulting in a win ratio again in favor of RDN of 2.68 [1.58, 5.00], p<0.001. Conclusions: Win ratio methodology applied to the SPYRAL HTN-ON MED pilot study demonstrated that RDN was associated with a 2.6-2.8 times greater likelihood of BP or drug reduction compared with sham patients when evaluated across different BP reduction thresholds at 6 months.