Dietary supplements: clinical cholesterol-lowering efficacy and potential mechanisms of action.

This review aims to analyse the efficacy of dietary supplements in reducing plasma cholesterol levels. Focusing on evidence from meta-analyses of randomised controlled clinical trials, with an emphasis on potential mechanisms of action as supported by human, animal, and cell studies. Certain dietary supplements including phytosterols, berberine, viscous soluble dietary fibres, garlic supplements, soy protein, specific probiotic strains, and certain polyphenol extracts could significantly reduce plasma total and low-density lipoprotein (LDL) cholesterol levels by 3-25% in hypercholesterolemic patients depending on the type of supplement. They tended to be more effective in reducing plasma LDL cholesterol level in hypercholesterolemic individuals than in normocholesterolemic individuals. These supplements worked by various mechanisms, such as enhancing the excretion of bile acids, inhibiting the absorption of cholesterol in the intestines, increasing the expression of hepatic LDL receptors, suppressing the activity of enzymes involved in cholesterol synthesis, and activating the adenosine monophosphate-activated protein kinase signalling pathway.

Removal of ochratoxin A in wine by Cryptococcus albidus and safety assessment of degradation products.

BACKGROUND: Ochratoxin A (OTA) is a mycotoxin that contaminates grape-based products and is extremely harmful to the health of the host. It is effectively removed by yeast during the fermentation of wine, whereas the removal mechanism of OTA remains unclear. Therefore, the present study aimed to investigate the removal mechanism of ochratoxin A by yeast and to evaluate the safety of its degradation products. RESULTS: Cryptococcus albidus (20-G) with better effect on ochratoxin A (OTA) was screened out in the main fermentation stage of wine. The results showed that 20-G removed OTA through biosorption and biodegradation. Intracellular enzymes played the main role (18.44%) and yeast cell walls adsorbed a small amount of OTA (8.44%). Furthermore, the identification of proteins in 20-G revealed that the decrease in OTA content was mainly a result of the action of peroxidase, and validation tests were carried out. By analyzing the degradation products of OTA, OTα and phenylalanine with lower toxicity were obtained. Animal experiments showed that the intervention of yeast 20-G reduced the damage and adverse effects caused by OTA toxicity to the mice. CONCLUSION: The present study demonstrates the mechanism of OTA removal by 20-G and the toxicity of OTA was reduced by peroxidase in 20-G. © 2023 Society of Chemical Industry.

Missing puzzle pieces of time-restricted-eating (TRE) as a long-term weight-loss strategy in overweight and obese people? A systematic review and meta-analysis of randomized controlled trials.

The efficacy of using time restricted eating (TRE) for weight management and to mitigate metabolic disorders in overweight and obese people remains debatable. This meta-analysis quantified the impact of TRE on weight loss and metabolic health in overweight and obese people. The pooled results were subjected to a random-effects modeling using Hartung-Knapp-Sidik-Jonkman (HKSJ) method. Additionally, subgroup analysis was conducted based on study types, randomized controlled trials (RCTs) vs. non-randomized studies of interventions (NRSIs). Pooled results showed that subjects on TRE regimen (> 4 weeks) achieved a significant weight loss in comparison with unrestricted time regimen (weighted mean difference: -2.32%; 95% CI: -3.50, -1.14%; p < 0.01); however, weight loss was mainly attributed to the loss of lean mass rather than fat mass. The magnitude of weight loss was inversely correlated with daily fasting duration in RCTs. TRE significantly decreased the diastolic blood pressure and fasting insulin. An increase of low-density lipoprotein cholesterol (LDL-C) was observed in the TRE group. Favorable effect of TRE was observed on glucose metabolism but not on lipid profiles independent of weight loss. Hence TRE shall be administered with caution to overweight and obese people who have comorbidities such as dyslipidemia and sarcopenia.Supplemental data for this article is available online at https://doi.org/10.1080/10408398.2021.1974335.

Effect of IP-10/CXCR3 signaling pathway on rats with diabetic retinopathy.

This study aimed to investigate the effect of the interferon-inducible protein-10 (IP-10)/C-X-C motif chemokine receptor 3 (CXCR3) signaling pathway on rats with diabetic retinopathy. A total of 21 Sprague-Dawley rats were selected as the objects and divided into control (n=7), model (n=7) and inhibitor (n=7) groups. The rats in control group did not receive any treatment. The diabetic retinopathy model was established using streptozotocin and vascular endothelial growth factor in model group, while the rats in inhibitor group were treated with AMG 487, an inhibitor of the IP-10/CXCR3 signaling pathway, based on the treatment in model group. The changes in gene expression patterns in rats with diabetic retinopathy were screened by sequencing. After the differential genes were determined, the pathways mainly related to the complication were obtained via enrichment analysis. The expression of the IP-10/CXCR3 signaling pathway, the apoptotic cells and the expression of inflammatory molecules (IL-6, IL-12, TNF-α and IL-1ß) in each group of rats were detected. It was shown in volcano plot that there were some differentially expressed genes (fold change >1.2, P<0.01) in retinal tissues of rats in control and model groups. Meanwhile, the heatmap displayed that there were great differences in the gene expression patterns between control and model groups, and the gene expressions of IP-10 and CXCR3 in model group were higher than those in control group (P<0.05). The differential genes in control and model groupwere enriched in such processes as the cAMP metabolic regulatory pathway, chemotaxis of immunocytes, proliferation of endothelial cells, response of cytokine receptors, apoptosis, mTOR signaling pathway and TGF-ß-related signaling pathway. The mRNA expressions of IP-10 and CXCR3 in model group were higher than those in control group (P<0.05), while they were notably lower in inhibitor group than those in model group (P<0.05). Besides, the protein levels of IP-10 and CXCR3 were identical to the mRNA levels. The apoptotic cells were increased markedly in model group compared with those in control group (P<0.05) and inhibitor group (P<0.05). Model group exhibited higher expression levels of IL-6, TNF-α and IL-1ß in retinal tissues than control group (P<0.05), while inhibitor group had distinctly lower expression levels of IL-6, TNF-α and IL-1ß in retinal tissues than model group (P<0.05). The IP-10/CXCR3 signaling pathway can affect rats with diabetic retinopathy.

The Signal Characteristics of Oil and Gas Pipeline Leakage Detection Based on Magneto-Mechanical Effects.

In order to solve the problem of the quantification of detection signals in the magnetic flux leakage (MFL) of defective in-service oil and gas pipelines, a non-uniform magnetic charge model was established based on magnetic effects. The distribution patterns of magnetic charges under different stresses were analyzed. The influences of the elastic load and plastic deformation on the characteristic values of MFL signals were quantitatively assessed. The experimental results showed that the magnetic charge density was large at the edges of the defect and small at the center, and approximately decreased linearly with increasing stress. The eigenvalues of the axial and radial components of the MFL signals were compared, and it was found that the eigenvalues of the radial component exhibited a larger decline rate and were more sensitive to stress. With the increase in the plastic deformation, the characteristic values of the MFL signals initially decreased and then increased, and there was an inflection point. The location of the inflection point was associated with the magnetostriction coefficient. Compared with the uniform magnetic charge model, the accuracy of the axial and radial components of the MFL signals in the elastic stage of the improved magnetic charge model rose by 17% and 16%, respectively. The accuracy of the axial and radial components of the MFL signals were elevated by 9.15% and 9%, respectively, in the plastic stage.

Voluntary Exercise to Reduce Anxiety Behaviour in Traumatic Brain Injury Shown to Alleviate Inflammatory Brain Response in Mice.

Traumatic brain injury is a leading cause of neuroinflammation and anxiety disorders in young adults. Immune-targeted therapies have garnered attention for the amelioration of TBI-induced anxiety. A previous study has indicated that voluntary exercise intervention following TBI could reduce neuroinflammation. It is essential to determine the effects of voluntary exercise after TBI on anxiety via inhibiting neuroinflammatory response. Mice were randomly divided into four groups (sham, TBI, sham + voluntary wheel running (VWR), and TBI + VWR). One-week VWR was carried out on the 2nd day after trauma. The neurofunction of TBI mice was assessed. Following VWR, anxiety behavior was evaluated, and neuroinflammatory responses in the perilesional cortex were investigated. Results showed that after one week of VWR, neurofunctional recovery was enhanced, while the anxiety behavior of TBI mice was significantly alleviated. The level of pro-inflammatory factors decreased, and the level of anti-inflammatory factors elevated. Activation of nucleotide oligomerization domain-like thermal receptor protein domain associated protein 3 (NLRP3) inflammasome was inhibited significantly. All these alterations were consistent with reduced microglial activation at the perilesional site and positively correlated with the amelioration of anxiety behavior. This suggested that timely rehabilitative exercise could be a useful therapeutic strategy for anxiety resulting from TBI by targeting neuroinflammation.

Chemerin as an Inducer of ß Cell Proliferation Mediates Mitochondrial Homeostasis and Promotes ß Cell Mass Expansion.

Loss of the ß cell population is a crucial feature of type 2 diabetes. Restoring the ß cell mass by stimulating ß cell proliferation and preventing its apoptosis was proposed as a therapeutic approach to treating diabetes. Therefore, researchers have been increasingly interested in identifying exogenous factors that can stimulate ß cell proliferation in situ and in vitro. Adipokine chemerin, which is secreted from adipose tissue and the liver, has been identified as a chemokine that plays a critical role in the regulation of metabolism. In this study, we demonstrate that chemerin as a circulating adipokine promotes ß cell proliferation in vivo and in vitro. Chemerin serum levels and the expression of the main receptors within islets are highly regulated under a variety of challenging conditions, including obesity and type 2 diabetes. As compared to their littermates, mice overexpressing chemerin had a larger islet area and increased ß cell mass with both a normal and high-fat diet. Moreover, in chemerin-overexpressed mice, we observed improved mitochondrial homeostasis and increased insulin synthesis. In summary, our findings confirm the potential role of chemerin as an inducer of ß cell proliferation, and they provide novel insights into the helpful strategy to expand ß cell population.

Maternal high-salt diet during pregnancy impairs synaptic plasticity and memory in offspring.

Excess salt intake harms the brain health and cognitive functions, but whether a maternal high-salt diet (HSD) affects the brain development and neural plasticity of offspring remains unclear. Here, using a range of behavioral tests, we reported that the offspring of maternal HSD subjects exhibited short- and long-term memory deficits, especially in spatial memory in adulthood. Moreover, impairments in synaptic transmission and plasticity in the hippocampus were observed in adult offspring by using in vivo electrophysiology. Consistently, the number of astrocytes but not neurons in the hippocampus of the offspring from the HSD group were significantly decreased, and ERK and AKT signaling pathways involved in neurodevelopment were highly activated only during juvenile. In addition, the expression of synaptic proteins decreased both in juvenile and adulthood, and this effect might be involved in synaptic dysfunction. Collectively, these data demonstrated that the maternal HSD might cause adult offspring synaptic dysfunction and memory loss. It is possibly due to the reduction of astrocytes in juvenile.

Real wine or not? Protecting wine with traceability and authenticity for consumers: chemical and technical basis, technique applications, challenge, and perspectives.

Wine is a high-value alcoholic beverage welcomed by consumers because of its flavor and nutritional value. The key information on wine bottle label is the basis of consumers' choice, which also becomes a target for manufacturers to adulterate, including geographical origin, grape variety and vintage. With the improvement of wine adulteration technology, modern technological means are needed to solve the above mentioned problems. The chemical basis of wine determines the type of technique used. Detection technology can be subdivided into four groups: mass spectrometry techniques, spectroscopic techniques, chromatography techniques, and other techniques. Multivariate statistical analysis of the data was performed by means of chemometrics methods. This paper outlines a series of procedures for wine classification and identification, and classified the analytical techniques and data processing methods used in recent years with listing their principles, advantages and disadvantages to help wine researchers choose appropriate methods to meet the challenge and ensure wine traceability and authenticity.

Functional connectivity density alterations in children with strabismus and amblyopia based on resting-state functional magnetic resonance imaging (fMRI).

PURPOSE: To explore functional connectivity density (FCD) values of brain areas in children with strabismus and amblyopia (SA) based on blood oxygen level-dependent (BOLD) signals. METHODS: This study recruited 26 children (14 male, 12 females) with SA and 26 healthy children (14 male, 12 female) as healthy controls (HCs). Both groups matched in age, gender, educational level and socioeconomic background. While resting, all participants underwent fMRI scanning and global FCD (gFCD) and local FCD (lFCD) values were calculated. Receiver operating characteristic (ROC) curves were created to investigate whether there was a significant difference between children with SA and healthy controls. RESULTS: When compared with healthy controls, children with SA had significantly lower gFCD values in the right cerebellum, left putamen, and right superior frontal gyrus; however, the same metrics showed opposite changes in the right angular gyrus, left middle cingulate gyrus, left angular gyrus, right superior parietal gyrus, and right middle frontal gyrus. In children with SA, lFCD values were found to be remarkably decreased in regions of the middle right temporal pole, right cerebellum, left putamen, left hippocampus, right hippocampus, left thalamus, left cerebellum; values were increased in the right superior parietal gyrus as compared with healthy controls. CONCLUSION: We noted abnormal neural connectivity in some brain areas of children with SA; detailing such connectivity aberrations is useful in exploring the pathophysiology of SA and providing useful information for future clinical management.

Measuring functional connectivity in patients with strabismus using stationary functional magnetic resonance imaging: a resting-state network study.

BACKGROUND: Strabismus (STR) is a common eye disease characterized by abnormal eye movements and stereo vision. Neuroimaging studies have revealed that STR patients have impaired functional connectivity (FC) in the visual cortex and sensorimotor cortex. PURPOSE: To investigate alterations in FC and connections within and between subnetworks of the visual network (VN), sensorimotor network (SMN), and default mode network (DMN) in patients with STR. MATERIAL AND METHODS: A total of 32 patients with STR (24 men, 8 women) and 32 age- and sex-matched healthy controls (HCs) (24 men, 8 women) were recruited. Participants underwent resting-state functional magnetic resonance imaging scans. The resting-state network (RSN) was examined by independent component analysis, and differences in RSN FC between STR and HC groups were evaluated with the t test. Functional network connectivity (FNC) analysis was performed for the three RSNs. RESULTS: Compared to the HC group, the STR group showed increased FC in the VN and SMN (voxel-level P < 0.01; two-tailed Gaussian random field correction; cluster-level P < 0.05). There were no significant alterations in DMN FC between the two groups. FNC analysis of connections in the RSN revealed that one of the three connections in the VN was reduced, but no connectivity changes were observed in the SMN or DMN. FNC analysis of the connection between two RSNs showed that two had increased and one had a decreased connection value. CONCLUSION: The VN, SMN, and DMN are reorganized in patients with STR compared to HCs, providing novel insight into the neural substrates of STR.

Ectopic Expression of CsSUN in Tomato Results in Elongated Fruit Shape via Regulation of Longitudinal Cell Division.

Fruit shape, an important agronomic trait of cucumber (Cucumis sativus L.), is tightly controlled by a series of genes such as CsSUN, a homologue of SlSUN that is responsible for the tomato (Solanum lycopersicum) fruit shape via the modulation of cell division. However, the direct genetic evidence about the CsSUN-mediated regulation of fruit shape is still scarce, limiting our mechanistic understanding of the biological functions of CsSUN. Here, we introduced CsSUN into the round-fruited tomato inbred line 'SN1' (wild type, WT) via the Agrobacterium tumefaciens-mediated method. The high and constitutive expression of CsSUN was revealed by real-time PCR in all the tested tissues of the transgenic plants, especially in the fruits and ovaries. Phenotypic analyses showed that the ectopic expression of CsSUN increased fruit length while it decreased fruit diameter, thus leading to the enhanced fruit shape index in the transgenic tomato lines relative to the WT. Additionally, the reduction in the seed size and seed-setting rate and the stimulation of seed germination were observed in the CsSUN-expressed tomato. A histological survey demonstrated that the elongated fruits were mainly derived from the significant increasing of the longitudinal cell number, which compensated for the negative effects of decreased cell area in the central columellae. These observations are different from action mode of SlSUN, thus shedding new insights into the SUN-mediated regulation of fruit shape.

Quantitative evaluation of activity of thyroid-associated Ophthalmopathy using short-tau inversion recovery (STIR) sequence.

OBJECTIVE: Quantitatively staging TAO using MRI remains limited. Our study aims to identify the cut-off signal intensity value for staging TAO using STIR sequence scan. METHODS: Between June 2018 and July 2020, a number of 51 patients with TAO (102 eyes) and 19 volunteer controls (38 eyes) were recruited. The clinical and biochemical parameters were measured in each patient. Disease activity was diagnosed based on the Clinical Activity Score (CAS). The signal intensities of extraocular muscles were scanned using short-tau inversion recovery (STIR) sequences from MRI. RESULTS: Compared to the inactive TAO patients and the controls, the signal intensity ratios (SIRs) of the superior rectus, inferior rectus, medial rectus, lateral rectus on STIR images were significantly increased in the active TAO patients. After adjustment for age and smokers, the SIRs of four extraocular muscles showed strong associations with CAS. By receiver operator characteristic (ROC) curve analysis, all four muscle SIRs demonstrated good efficiency for predicting disease activity [area under curve (AUC) 0.75-0.83, all P < 0.01]. The identified cut-off SIR values were further validated in a new group of TAO patients (30 eyes) enrolled between September 2020 and January 2021. The cut-off SIR value of > 2.9 in the inferior rectus showed optimal diagnostic value for staging the active TAO. CONCLUSIONS: the signal intensity of extraocular muscles on STIR sequence was a good predictor for TAO activity. A cut-off SIR value of > 2.9 in the inferior rectus could be applied to evaluate the active stage of TAO.

Brain Functional Connectivity Changes in Patients with Acute Eye Pain: A Resting-State Functional Magnetic Resonance Imaging (fMRI) Study.

BACKGROUND By using functional magnetic resonance imaging (fMRI), we aimed to study the changes in potential brain function network activity in patients with acute eye pain. Also, by using the voxel-wise degree centrality (DC) method, we aimed to explore the relationship between spontaneous brain activity and the clinical features of patients with acute eye pain. MATERIAL AND METHODS A total of 15 patients with acute eye pain (5 women and 10 men; EP group) and 15 healthy controls (5 women and 10 men; HC group), were scanned by fMRI. The DC method was used to evaluate changes in spontaneous brain activity. Receiver operating characteristic (ROC) curves were analyzed, and Pearson correlation analysis was used to study the relationship between DC values and clinical manifestations in different regions of brain. RESULTS The area of the left limbic lobe showed a reduction in DC value in patients in the EP group. DC values were elevated in the left cerebellum posterior lobe, left inferior parietal lobule, left inferior temporal gyrus, left precuneus, and right cerebellum posterior lobe in the EP group. The visual analog scale value of the eyes in the EP group was negatively correlated with the left limbic lobe signal value and positively correlated with the left inferior parietal lobule signal value. Further, the scores of the hospital anxiety and depression scale and DC value of the left limbic lobe were negatively correlated. CONCLUSIONS Compared with the HC group, patients with acute eye pain had abnormal patterns of intrinsic brain activity in different brain regions, which may help reveal the potential neural mechanisms involved in eye pain.

Video display terminal use and other risk factors for abnormal blinking in children: gender differences.

OBJECTIVE: To explore the risk factors for abnormal blinking in children and compare these between boys and girls. METHODS: Children attending the Children's Optometry Clinic between June 2019 and June 2020 were recruited for the study. The time they had spent viewing video displays (VDTt) over the past 6 months was recorded. Incomplete blinking (IB) and blinking rate were measured and all participants were allocated to groups based on their blink rate (<20 times/min = normal blinking group, NBG; ≥20 times/min = abnormal blinking group, ABG). Tear film (TF) stability was also evaluated. The corresponding statistical methods are used to analyze the data. RESULTS: A total of 87 boys and 80 girls were enrolled in the study. No significant difference in age was found between the 2 groups. There was a significant difference in TF stability between the two groups (P<0.05). According to binary logistic analysis, VDTt and ocular protection index (OPI) are important risk factors for abnormal blinking, with cut-off values of 1.75 hours and 1.014 respectively in boys; and 1.25 hours and 1.770 respectively in girls. The average of lipid layer thickness was an important protective factor for children using VDT for long periods, with a cut-off value of 58.5 nm in boys and 53.5nm in girls. CONCLUSION: Risk factors for abnormal blinking in both boys and girls include VDTt and OPI.

Altered spontaneous brain activity patterns in dysthyroid optic neuropathy: a resting-state fMRI study.

This research investigates the characteristics of spontaneous brain activity in dysthyroid optic neuropathy patients using the regional homogeneity technique. Sixteen patients with dysthyroid optic neuropathy and 16 thyroid-associated ophthalmopathy patients without dysthyroid optic neuropathy were recruited, matched for weight, height, age, sex, and educational level. All participants underwent resting-state functional nuclear resonance imaging, and the characteristics of spontaneous brain activity were evaluated using the regional homogeneity technique. Each participant in the dysthyroid optic neuropathy group also completed the Hospital Anxiety and Depression scale. Receiver operating characteristic curves were used to compare brain activity between the two groups. Pearson correlation analysis evaluated the relationship between regional homogeneity and clinical manifestations in dysthyroid optic neuropathy patients. In addition, we analyzed the correlation between Hospital Anxiety and Depression scale and regional homogeneity. We found that the regional homogeneity values at the corpus callosum/cingulate gyrus and parietal lobe/middle frontal gyrus significantly decreased in dysthyroid optic neuropathy patients. Regional homogeneity values at the corpus callosum/cingulate gyrus and parietal lobe/middle frontal gyrus were negatively correlated with Hospital Anxiety and Depression scale and disease duration. It was found that the regional homogeneity signal values were significantly lower than in thyroid-associated ophthalmopathy without in dysthyroid optic neuropathy, which may indicate a risk of regional brain dysfunction in dysthyroid optic neuropathy. The results show that regional homogeneity has the potential for early diagnosis and prevent dysthyroid optic neuropathy. In addition, the findings suggest possible mechanisms of dysthyroid optic neuropathy optic nerve injury. They may provide a valuable basis for further research on the pathological mechanisms of dysthyroid optic neuropathy.

Voxel-based morphometry reveals altered gray matter volume related to cognitive dysfunctioning in neovascular glaucoma patients.

We used correlation analysis to examine whether changes in grey matter volume in patients correlated with clinical presentation. gray matter volume was markedly reduced in neovascular glaucoma patients than healthy controls in the following brain regions: left cingulum anterior/medial frontal gyrus; left middle frontal gyrus, orbital part; left inferior frontal gyrus, orbital part; superior temporal gyrus/right frontal inferior orbital part. VBM directly suggests that neovascular glaucoma patients have changed in the volume of multiple brain regions. These changes exist in brain areas related to the visual pathway, as well as other brain areas which are not related to vision. The alteration of specific brain areas are closely related to clinical symptoms such as increased intraocular pressure and optic nerve atrophy in neovascular glaucoma patients. In conclusion, neovascular glaucoma may cause paralgesia, anxiety, and depression in patients.

The abnormal fractional amplitude of low-frequency fluctuation changes in patients with diabetic optic neuropathy: a steady-state fMRI study.

The spontaneous changes in brain activity in patients with diabetic optic neuropathy using steady-state fMRI. The fractional amplitude of the low-frequency fluctuation method was applied to evaluate neural activity changes. The Hospital Anxiety and Depression Scale was used to assess the anxiety and depression status of participants. The independent sample t-test and chi-squared test were applied to analyze the demographics of diabetic optic neuropathy patients and healthy controls. Receiver operating characteristic curves were applied to analyze the variation in mean fractional amplitude of low-frequency fluctuation values between diabetic optic neuropathy patients and healthy controls. Pearson's correlation analysis analyzed the relationships between the fractional amplitude of low-frequency fluctuation values of brain regions and clinical behaviors in the diabetic optic neuropathy group. The fractional amplitude of low-frequency fluctuation value of diabetic optic neuropathy patients was significantly higher than healthy controls in the right precentral gyrus. However, the fractional amplitude of low-frequency fluctuation values in the right anterior cingulate gyrus and left middle cingulate gyrus were markedly decreased in diabetic optic neuropathy patients. The area under the curve of receiver operating characteristics for each brain region showed high accuracy. Pearson's correlation analysis showed that fractional amplitude of low-frequency fluctuation values of the right anterior cingulate gyrus and left middle cingulate gyrus was negatively correlated with Hospital Anxiety and Depression Scale scores. The fractional amplitude of low-frequency fluctuation values of the left middle cingulate gyrus was negatively correlated with diabetic optic neuropathy disease duration. In conclusion, we found abnormal spontaneous brain activities in regions related to cognitive and emotional dysfunction, eye movement disorder, and vision loss in patients with diabetic optic neuropathy. These results may indicate the underlying neuropathological mechanisms of diabetic optic neuropathy and show that fractional amplitude of low-frequency fluctuation may be an effective method to distinguish patients with diabetic optic neuropathy from healthy individuals.

Deficiency of Complement C3a and C5a Receptors Prevents Angiotensin II-Induced Hypertension via Regulatory T Cells.

RATIONALE: Inflammation and immunity play crucial roles in the development of hypertension. Complement activation-mediated innate immune response is involved in the regulation of hypertension and target-organ damage. However, whether complement-mediated T-cell functions could regulate blood pressure elevation in hypertension is still unclear. OBJECTIVE: We aim to determine whether C3aR (complement component 3a receptor) and C5aR (complement component 5a receptor) could regulate blood pressure via modulating regulatory T cells (Tregs). METHODS AND RESULTS: We showed that angiotensin II (Ang II)-induced hypertension resulted in an elevated expression of C3aR and C5aR in Foxp3 (forkhead box P3)+ Tregs. By using C3aR and C5aR DKO (double knockout) mice, we showed that C3aR and C5aR deficiency together strikingly decreased both systolic and diastolic blood pressure in response to Ang II compared with WT (wild type), single C3aR-deficient (C3aR-/-), or C5aR-deficient (C5aR-/-) mice. Flow cytometric analysis showed that Ang II-induced Treg reduction in the kidney and blood was also blocked in DKO mice. Histological analysis indicated that renal and vascular structure remodeling and damage after Ang II treatment were attenuated in DKO mice compared with WT mice. In vitro, Ang II was able to stimulate C3aR and C5aR expression in cultured CD4+CD25+ natural Tregs. CD3 and CD28 antibody stimuli downregulated Foxp3 expression in WT but not DKO Tregs. More important, depletion of Tregs with CD25 antibody abolished the protective effects against Ang II-induced hypertension and target-organ damage in DKO mice. Adoptive transfer of DKO Tregs showed much more profound protective effects against Ang II-induced hypertension than WT Treg transfer. Furthermore, we demonstrated that C5aR expression in Foxp3+ Tregs was higher in hypertensive patients compared with normotensive individuals. CONCLUSIONS: C3aR and C5aR DKO-mediated Treg function prevents Ang II-induced hypertension and target-organ damage. Targeting C3aR and C5aR in Tregs specifically may be an alternative novel approach for hypertension treatment.

Altered Brain Network Centrality in Patients with Diabetic Optic Neuropathy: A Resting-State FMRI Study.

OBJECTIVE: Recent studies have suggested that diabetic optic neuropathy (DON) independently increases the incidence of brain diseases like cerebral infarction and hemorrhage. In this study, voxel-level degree centrality (DC) was used to study potential changes in functional network brain activity in DON patients. METHODS: The study included 14 DON patients and 14 healthy controls (HCs) matched by age, sex, and weight. All subjects underwent resting functional magnetic resonance imaging. Receiver operating characteristic curves and Pearson correlation analysis were performed. RESULTS: The DC values of the left frontal mid-orb and right middle frontal gyrus/right frontal sup were significantly lower in DON patients compared to HCs. The DC value of the left temporal lobe was also significantly higher than in HCs. CONCLUSION: Three different brain regions show DC changes in DON patients, suggesting common optic neuropathy in the context of diabetes and providing new ideas for treating optic nerve disease in patients with long-term diabetes. ABBREVIATIONS: AUC = area under the curve; BCVA = best corrected visual acuity; DC = degree centrality; DON = diabetic optic neuropathy; fMRI = functional magnetic resonance imaging; HC = healthy control; LFMO = left frontal mid orb; LTL = left temporal lobe; RFS = right frontal sup; RMFG = right middle frontal gyrus; ROC = receiver operating characteristic.