Repeated Low-Level Red-Light Therapy for Controlling Onset and Progression of Myopia-a Review.

Repeated low-level red-light (RLRL), characterized by increased energy supply and cellular metabolism, thus enhancing metabolic repair processes, has gained persistent worldwide attention in recent years as a new novel scientific approach for therapeutic application in myopia. This therapeutic revolution led by RLRL therapy is due to significant advances in bioenergetics and photobiology, for instance, enormous progresses in photobiomodulation regulated by cytochrome c oxidase, the primary photoreceptor of the light in the red to near infrared regions of the electromagnetic spectrum, as the primary mechanism of action in RLRL therapy. This oxidase is also a key mitochondrial enzyme for cellular bioenergetics, especially for the nerve cells in the retina and brain. In addition, dopamine (DA)-enhanced release of nitric oxide may also be involved in controlling myopia by activation of nitric oxide synthase, enhancing cGMP signaling. Recent evidence has also suggested that RLRL may inhibit myopia progression by inhibiting spherical equivalent refraction (SER) progression and axial elongation without adverse effects. In this review, we provide scientific evidence for RLRL therapy as a unique paradigm to control myopia and support the theory that targeting neuronal energy metabolism may constitute a major target for the neurotherapeutics of myopia, with emphasis on its molecular, cellular, and nervous tissue levels, and the potential benefits of RLRL therapy for myopia.

Escin avoids hemorrhagic transformation in ischemic stroke by protecting BBB through the AMPK/Cav-1/MMP-9 pathway.

BACKGROUND: Hemorrhagic transformation (HT) seriously affects the clinical application of recombinant tissue plasminogen activator (rt-PA). The main strategy for combating HT is to keep the blood-brain barrier (BBB) stable. Escin is the active ingredient of Aesculus hippocastanum and a natural mixture of triterpene saponins, and may play a part in mitigation of HT. PURPOSE: This study sought to investigate the effect of Escin in improving rt-PA-induced HT, explore possible mechanisms, and provide new ideas for the treatment of clinical HT. STUDY DESIGN AND METHODS: In in vivo experiments, transient middle cerebral artery occlusion (tMCAO) was undertaken in 6-week-old and 12-month-old mice, and rt-PA was administered to induce HT injury. The inhibitory effect of Escin on HT and its protective effect on neurobehavior, the BBB, and cerebrovascular endothelial cells was determined. In in vitro experiments, bEnd.3 cells were injured by oxygen-glucose deprivation/reperfusion (OGD/R) and rt-PA. The protective effect of Escin was measured by the CCK8 assay, release of lactate dehydrogenase (LDH), and expression of tight junction (TJ) proteins. In mechanistic studies, the effect of Escin on the adenosine monophosphate-activated kinase / caveolin-1 / matrix metalloprotease-9 (AMPK/Cav-1/MMP-9) pathway was investigated by employing AMPK inhibitor and Cav-1 siRNA. RESULTS: In mice suffering from ischemia, rt-PA caused HT as well as damage to the BBB and cerebrovascular endothelial cells. Escin reduced the infarct volume, cerebral hemorrhage, improved neurobehavioral deficits, and maintained BBB integrity in rt-PA-treated tMCAO mice while attenuating bEnd.3 cells damage caused by rt-PA and OGD/R injury. Under physiological and pathological conditions, Escin increased the expression of p-AMPK and Cav-1, leading to decreased expression of MMP-9, which further attenuated damage to cerebrovascular endothelial cells, and these effects were verified with AMPK inhibitor and Cav-1 siRNA. CONCLUSION: We revealed important details of how Escin protects cerebrovascular endothelial cells from HT, these effects were associated with the AMPK/Cav-1/MMP-9 pathway. This study provides experimental foundation for the development of new drugs to mitigate rt-PA-induced HT and the discovery of new clinical application for Escin.

Effects of a online brief modified mindfulness-based stress reduction therapy for anxiety among Chinese adults: A randomized clinical trial.

The COVID-19 pandemic has exacerbated anxiety and related symptoms among the general population. In order to cope with the mental health burden, we developed an online brief modified mindfulness-based stress reduction (mMBSR) therapy. We performed a parallel-group randomized controlled trial to evaluate the efficacy of the mMBSR for adult anxiety with cognitive-behavioral therapy (CBT) as an active control. Participants were randomized to mMBSR, CBT or waitlist group. Those in the intervention arms performed each therapy for 6 sections in 3 weeks. Measurements were conducted at baseline, post-treatment and 6 months post-treatment by Generalized Anxiety Disorder-7, Patient Health Questionnaire-9, Patient Health Questionnaire-15, reverse scored Cohen Perceived Stress scale, Insomnia Severity Index, and Snaith-Hamilton Pleasure Scale. 150 participants with anxiety symptoms were randomized to mMBSR, CBT or waitlist group. Post intervention assessments showed that mMBSR improved the scores of all the six mental problem dimensions (anxiety, depression, somatization, stress, insomnia, and the experience of pleasure) significantly compared to the waitlist group. During 6-month post treatment assessment, the scores of all six mental problem dimensions in the mMBSR group still showed improvement compared to baseline and showed no significant difference with the CBT group. Our results provide positive evidence for the efficacy and feasibility of an online brief modified MBSR program to alleviate anxiety and related symptoms of individuals from the general population, and the therapeutic benefits of mMBSR persisted for up to six months. This low resource-consuming intervention could facilitate the challenges of supplying psychological health therapy to large scale of population.

Association between Micronutrient-Related Dietary Pattern and Cognitive Function among Persons 55 Years and Older in China: A Longitudinal Study.

Appropriate dietary patterns for preserving cognitive function in China remains unknown. This study explored the association between dietary pattern and cognitive function in the Chinese population. A total of 6308 adults aged 55 and above who participated in the China Health and Nutrition Survey at least two waves from 1997 to 2018 were selected. The dietary pattern was determined using the reduced rank regression method with responses regarding vitamin C, vitamin E, zinc, iron, copper, and selenium intakes. We used a three-level random coefficient model to evaluate the association. A "vegetable-pork" dietary pattern characterized by high intakes of Legume products, vegetables, fruits, nuts, pork, fish, and plant oil was identified. Compared to the first quartile (Q1) of dietary scores, the regression coefficients (p value) for the global cognitive score across Q2, Q3, and Q4 were 0.27 (p = 0.030), 0.45 (p < 0.001), and 0.50 (p < 0.001), respectively. The adjusted odds ratios (ORs) and the 95% confidence intervals (CIs) for poor cognition across Q2, Q3, and Q4 were 0.82 (0.73 to 0.93), 0.79 (0.69 to 0.91), and 0.74 (0.63 to 0.86), respectively. The relationship appeared to be stronger among people who were 65 years and older, women, people from the south, and smokers. Higher adherence to the "vegetable-pork" diet is associated with better cognitive function among Chinese elders.

Abdominal Massage Improves the Symptoms of Irritable Bowel Syndrome by Regulating Mast Cells via the Trypase-PAR2-PKCε Pathway in Rats.

Background: Irritable bowel syndrome (IBS) is a clinical disease mainly characterized as a syndrome of abdominal pain and discomfort, which frequently occurs in humans aged 20-50. Abdomen massage is of great medical significance for the health of the human body, including promoting intestinal peristalsis, relieving constipation, and facilitating weight loss. However, its potential benefits in alleviating IBS and the underlying mechanisms remain elusive. Methods: In this study, we established an IBS model in rats to evaluate the effects of abdomen massage. Forty male Sprague Dawley (SD) rats were randomly assigned into 4 groups: the normal (control) group, IBS group, abdominal massage group, and abdominal massage + ketotifen treatment group (n = 10 rats in each group). Abdominal massage was performed once a day for 5 minutes for 14 days. On day 14, the rats were euthanized and the tissues were analyzed by transmission electron microscopy (TEM), immunohistochemistry or immunofluorescence staining, and laser confocal focus to visualize the micromorphology of the intestinal mucosa. The expression of TRPV1 and the release of trypase were determined by RT-qPCR and western blot. Results: We found that compared with the control group, the mast cells in the IBS group were significantly increased and the increased MC was partially decreased by an abdominal massage with or without ketotifen treatment. We also found that TRPV1 was upregulated in the IBS group. Abdominal massage with or without ketotifen treatment could attenuate the upregulation of TRPV1 in IBS. Mechanically, results of IHC and western Blot suggested that abdominal massage reduces the sensitivity of IBS by regulating the trypase-PAR2-PKCε pathway. Conclusion: Overall, our results suggested that abdominal massage produces a beneficial effect in improving the symptoms of IBS through reducing mast cell recruitment and attenuating the trypase-PAR2-PKCε pathway. Ketotifen could promote the effect of abdominal massage on IBS treatment, which can serve as a potential therapeutic strategy for IBS.

[Fat intake from pre-packaged foods among Chinese residents of 16 provinces in 2018].

OBJECTIVE: To investigate the impact of prepackaged food consumption on fat intake in 16 provinces of China in 2018. METHODS: Data used in present study was derived from the eleventh round of China Health and Nutrition Survey(CHNS), 17312 residents aged 6 and over were selected and their consumed information of pre-packaged food was collected. The consumption of pre-packaged food and fat intake from pre-packaged food in urban and rural areas, different age groups, different regions and different genders were calculated and compared. RESULTS: The median intake of fat from pre-packaged food among subjects and consumers were 33.6 g/d and 34.7 g/d, respectively.73.5% of the intake of fat from pre-packaged food comes from vegetable oil. CONCLUSION: Vegetable oil was the main source of fat from pre-packaged food for Chinese residents.

Effect of aniline and antimony on anaerobic-anoxic-oxic system with novel amidoxime-modified polyacrylonitrile adsorbent for wastewater treatment.

There has been increasing concern over the mixed discharge of municipal-textile composite wastewater, which remains challenging for typical wastewater treatment plant (WWTP) using anaerobic-anoxic-oxic process (AAO). Highly-toxic aniline and antimony, typical co-contaminants in textile wastewater, usually lead to increased chemical oxygen demand (COD) in influent and deteriorated effluent quality. Amidoxime-modified polyacrylonitrile (amPAN) adsorbent was prepared and added to adsorb antimony and facilitate substrate removal. With amPAN dosage at 6.0 g L-1 in oxic bioreactor, 64.2 ± 5.6% of antimony was removed from influent. Extracellular polymeric substance release was simultaneously changed with residual antimony concentration. Meanwhile, amPAN promoted the proliferation of Proteobacteria, Bacteroidetes and Epsilonbacteraeota serving as microorganism carrier. As a result, removal efficiencies of COD (94.4 ± 0.6%), ammonium (NH4+-N, 92.6 ± 3.3%), total nitrogen (TN, 76.4 ± 6.3%) and total phosphorus (TP, 93.4 ± 2.1%) were enhanced to meet Class 1A discharge standard in China. These results indicate that AAO with amPAN is promising for municipal-textile composite wastewater treatment.

Multi-Trajectories of Macronutrient Intake and Their Associations with Obesity among Chinese Adults from 1991 to 2018: A Prospective Study.

Studies on macronutrient intake and obesity have been inconclusive. This study examined the associations between multi-trajectories of macronutrients and the risk of obesity in China. We used data from 7914 adults who participated in the China Health and Nutrition Survey at least three times from 1991 to 2018. We collected detailed dietary data by conducting three 24 h dietary recalls and weighing foods and condiments in household inventories. We identified multi-trajectories using group-based multi-trajectory models and examined their associations with the risk of obesity with multiple Cox regression models. We found four multi-trajectories in rural areas: balanced macronutrient intake (BM), moderate protein, increasing low fat, and decreasing high carbohydrate (MP&ILF&DHC); decreasing moderate protein, decreasing high fat, and increasing moderate carbohydrate (DMP&DHF&IMC); increasing moderate protein, increasing high fat, and decreasing low carbohydrate (IMP&IHF&DLC)-35.1%, 21.3%, 20.1%, and 23.5% of our rural participant population, respectively. Compared with the BM trajectory, the hazard ratios of obesity in the DMP&DHF&IMC and the IMP&IHF&DLC groups were 0.50 (95% confidence interval (CI): 0.27-0.95) and 0.48 (95% CI: 0.28-0.83), respectively, in rural participants. Relatively low carbohydrate and high fat intakes with complementary dynamic trends are associated with a lower risk of obesity in rural Chinese adults.

Chinese medicine GeGen-DanShen extract protects from myocardial ischemic injury through promoting angiogenesis via up-regulation of VEGF/VEGFR2 signaling pathway.

HEADINGS ETHNOPHARMACOLOGICAL RELEVANCE: Coronary heart disease (CHD) usually refers to myocardial ischemia or myocardial necrosis caused by coronary artery stenosis. GeGen and DanShen (GD) are popular Chinese herbs for the treatment of angina pectoris and myocardial infarction (MI). This sentence needs to be a separate paragraph. AIM OF THE STUDY: This study was to investigate the role of GD extract in promoting ischemic myocardial angiogenesis, and to explore its signaling mechanism, so as to provide a more reliable scientific basis for the clinical treatment of ischemic cardiovascular disease. MATERIALS AND METHODS: GD extract was initially analyzed by HPLC-Q-TOF MS. In vitro, migration assay and tube formation assay were subsequently used to detect the angiogenesis activity of GD extract in human umbilical vein endothelial cells (HUVECs). Following the in vitro study, an MI rat model was established by ligating the left anterior descending coronary artery (LAD), immediately followed by a 4-week daily GD extract treatment by intragastric administration. After the animal sacrifice, hematoxylin-eosin (HE) staining was conducted to observe the pathological changes of the infarct margin. Besides, the MI area was measured by 2,3,5-triphenyltetrazoliumchloride (TTC) staining. The microvascular density (MVD) was also quantified through CD31 immunohistochemistry. Moreover, the levels of VEGF, TXB2 and 6-keto-PGF1α in serum were detected by enzyme-linked immunosorbent assay. The expression of VEGFR2 and ERK were detected by immunohistochemistry as well. RESULTS: In vitro study, GD extract was found to induce significant angiogenesis in HUVECs. In vivo, smaller infarct size was found in treatment groups than that of the model group, and the protein expression of VEGFR2 as well as ERK in the marginal zone of MI in treatment groups were significantly increased. The morphological changes of myocardium were observed with a significant growth in the number of new blood vessels. Regarding the effect of GD extract, the serum levels of CK, LDH and TXB2 were consequently reduced, whereas the levels of VEGF, 6-keto-PGF1α were significantly increased. CONCLUSIONS: Based on the findings of this study, GD extract had a protective effect against MI in rats. The possible mechanism is to promote angiogenesis by regulating the VEGF/VEGFR2 signaling pathway after MI occurrence.

The Advances on the Protective Effects of Ginsenosides on Myocardial Ischemia and Ischemia-Reperfusion Injury.

Ginseng is a traditional medicine with a complex chemical composition, wide bioactivity and unique pharmacological action. Many studies have confirmed that ginsenosides are the active ingredients of ginseng, and ginsenosides have always been the focus of different researchers. With the development of modern separation and analysis technology, more than 150 kinds of ginsenosides have been isolated. The ginsenosides Rb1, Rb2, Rc, Rg1 and Re account for more than 80% of total ginsenosides, and other saponins, such as Rd, Rg3 and Rh2, which are minor constituents, accounting for only a small portion of the total amount. In recent years, ginsenosides have been found to possess strong pharmacological activities, such as antioxidation, clearing of oxygen free radicals, reducing calcium overload and anti-apoptosis. Ginsenosides play a protective role in ischemia-reperfusion injury. This paper reviews the protective effects of ginsenosides on myocardial ischemia and ischemiareperfusion injury.

Dairy Intake Would Reduce Nutrient Gaps in Chinese Young Children Aged 3-8 Years: A Modelling Study.

Dairy foods are under-consumed among Chinese children. We modeled the impact of increased dairy consumption on nutrient inadequacy and assessed whether the consumption of formulated milk powder for children ≥3 years (FMP3+) is useful for reducing nutrient gaps. Data from 3-8-year-old children, with completed socio-demographic and dietary measurements from the China Health and Nutrition Survey 2015, were used (n = 1122). Dietary intakes were modeled in two scenarios: Scenario 1 added FMP3+ or cow's milk to reported diet to reach recommended dairy intakes; Scenario 2 replaced the currently consumed milk with an equal volume of FMP3+. Reported nutrient intakes were compared with each model. Only 32.5% of children consumed dairy products; the average intake amount in total was 48.6 g/day. Most children (97.6%) did not meet dairy intake recommendation. Inadequate nutrient intakes were observed for calcium, potassium, thiamin, riboflavin, vitamin C and selenium. In Scenario 1, both FMP3+ and cow's milk improved the intake of all analyzed nutrients. In Scenario 2, FMP3+ substitution increased the intake of most nutrients, and reduced the proportion of children with an inadequate intake of vitamin C, thiamin, vitamin A, iron, zinc and potassium. Thus, increasing dairy consumption would reduce nutrient gaps, and FMP3+ is a good food source to help children meet nutrient requirements.

Arginase promotes immune evasion of Echinococcus granulosus in mice.

BACKGROUND: Cystic echinococcosis is a chronic disease caused by infection with the larvae of Echinococcus granulosus. The parasite's ability to establish persistent infection is partly due to its evolving immune evasion strategies. One strategy may involve the protective effect of arginase, which impedes the control of pathogens or tumors, whereas it remains largely unknown during E. granulosus infection. Here, we analyzed whether arginase was produced in peritoneal cells and assessed its role in immunosuppression in mice infected with protoscoleces of E. granulosus. METHODS: BALB/c mice injected with protoscoleces of E. granulosus were used to evaluate the expression of arginase (ARG) in mRNA and protein levels. The profiles of ARG-1 expression in peritoneal cells and CD3ζ expression in T cells from spleens were assessed at different time points (3, 6, 9 and 12 months post-infection) by flow cytometry. In vitro, peritoneal cells were co-cultured with purified T cells in a transwell system, and the levels of CD3ζ re-expression were compared by flow cytometry. Meanwhile, the changes of L-arginine and its related metabolites in serum were tested. RESULTS: Compared to the control group, the peritoneal cells from infected mice showed higher levels of ARG-1 mRNA and protein, unchanged ARG-2 and iNOS. Enhanced ARG-1 expression was present in SSClowCD11b+F4/80+, CD11b+CD11c+, CD11b+Gr-1+Ly-6C+Ly-6G-, CD11b+Gr-1+Ly-6C-Ly-6G+, CD11b+Gr-1+ and CD11b+Ly-6G+ cells. The proportion of cells and the proportion of ARG-1 expression in corresponding cells exhibited a rising trend along with the extension of infection time, except for fluctuations in SSClowCD11b+F4/80+ and CD11b+CD11c+ cells at 12 months post-infection, whereas the expression of CD3ζ chain in CD4+ and CD8+ T cells showed a descending trend. Purified T cells showed declined re-expression of CD3ζ when co-cultured with peritoneal cells from infected mice, and CD3ζ was regenerated by supplement of L-arginine or arginase inhibitor BEC, rather than NOS inhibitor L-NMMA or catalase. Meanwhile, the concentrations of L-arginine, L-citrulline and NO decreased, and those of L-ornithine and urea increased in serum post-infection. CONCLUSIONS: Our findings demonstrated that ARG-1 expression is enhanced in multiple myeloid cells from peritoneum and promotes immune evasion of E. granulosus in mice by inhibiting the expression of T cell receptor CD3ζ chain and antagonism against iNOS.

Chinese Medicine She-Xiang-Xin-Tong-Ning, Containing Moschus, Corydalis and Ginseng, Protects from Myocardial Ischemia Injury via Angiogenesis.

The Chinese patent medicine She-Xiang-Xin-Tong-Ning (SXXTN) is a clinical medication for coronary heart disease (CHD) and angina pectoris. This study aimed to investigate pharmacological effects of SXXTN and elucidate the role in angiogenesis on human umbilical vein endothelial cells (HUVECs) and acute myocardial ischemia (AMI) rats. We prepared SXXTN to treat the cells to reveal their effects on oxidative stress-damaged cell viability, as well as cell proliferation, migration, and tube formation processes. SXXTN was also used to treat coronary artery ligation-induced acute myocardial ischemia rats to confirm whether it had positive effect on myocardial issues by hematoxylin and eosin (HE), 2,3,5-triphenyltetrazolium chloride (TTC) staining and immunohistochemical staining. We measured the levels of peroxidative damage-related enzymes in cytoplasm and serum by biochemical kits and detected vascular endothelial growth factor (VEGF), angiotensin II (Ang II), thromboxane B2 (TXB2), and 6-keto-prostaglandin F1 alpha (6-keto-PGF1α) levels in cells and rats by enzyme-linked immunosorbent assay (ELISA) kits. The results showed that SXXTN protects HUVECs against oxidative stress damage and reversed the decrease of superoxide dismutase (SOD), glutathione (GSH) and increase of creatine kinase (CK), lactate dehydrogenase (LDH) caused by oxidative stress. SXXTN promoted angiogenesis through stimulating cell migration, tube formation, and activating VEGF/VEGFR2 and ERK1/2 pathways. Furthermore, SXXTN reduced infarct size and inhibited PGI2/TXA2 imbalance, preventing atherosclerosis plaque rupture leading to worsening coronary heart disease. Taken together, we report the first in vivo and in vitro evidence that SXXTN reduced oxidative stress-mediated damage and enhanced angiogenesis, which might be useful in treatment of myocardial infarction.

Baicalin Alleviates Nitroglycerin-induced Migraine in Rats via the Trigeminovascular System.

Migraine is a common neurological disorder with a serious impact on quality of life. The aim of this study was to explore the effect of baicalin on nitroglycerin-induced migraine rats. We carried out a behavioral research within 2 h post-nitroglycerin injection, and blood samples were drawn for measurements of nitric oxide (NO), calcitonin gene-related peptide, and endothelin (ET) levels. Immunohistochemistry was adopted to detect the activation of C-fos immunoreactive neurons in periaqueductal gray. The number, area size, and integrated optical density of C-fos positive cells were measured using Image-Pro Plus. As a result, baicalin administration (0.22 mm/kg) alleviated pain responses of migraine rats. It profoundly decreased NO and calcitonin gene-related peptide levels, increased ET levels, and rebuilt the NO/ET balance in migraine rats. Besides, baicalin pretreatment significantly reduced the number, the stained area size, and integrated optical density value of C-fos positive cells. In brief, this paper supports the possibility of baicalin as a potential migraine pharmacotherapy. Copyright © 2017 John Wiley & Sons, Ltd.

Fusing Heterogeneous Features From Stacked Sparse Autoencoder for Histopathological Image Analysis.

In the analysis of histopathological images, both holistic (e.g., architecture features) and local appearance features demonstrate excellent performance, while their accuracy may vary dramatically when providing different inputs. This motivates us to investigate how to fuse results from these features to enhance the accuracy. Particularly, we employ content-based image retrieval approaches to discover morphologically relevant images for image-guided diagnosis, using holistic and local features, both of which are generated from the cell detection results by a stacked sparse autoencoder. Because of the dramatically different characteristics and representations of these heterogeneous features (i.e., holistic and local), their results may not agree with each other, causing difficulties for traditional fusion methods. In this paper, we employ a graph-based query-specific fusion approach where multiple retrieval results (i.e., rank lists) are integrated and reordered based on a fused graph. The proposed method is capable of combining the strengths of local or holistic features adaptively for different inputs. We evaluate our method on a challenging clinical problem, i.e., histopathological image-guided diagnosis of intraductal breast lesions, and it achieves 91.67% classification accuracy on 120 breast tissue images from 40 patients.