Injectable, Antioxidative, and Tissue-Adhesive Nanocomposite Hydrogel as a Potential Treatment for Inner Retina Injuries.

Reactive oxygen species (ROS) have been recognized as prevalent contributors to the development of inner retinal injuries including optic neuropathies such as glaucoma, non-arteritic anterior ischemic optic neuropathy, traumatic optic neuropathy, and Leber hereditary optic neuropathy, among others. This underscores the pivotal significance of oxidative stress in the damage inflicted upon retinal tissue. To combat ROS-related challenges, this study focuses on creating an injectable and tissue-adhesive hydrogel with tailored antioxidant properties for retinal applications. GelCA, a gelatin-modified hydrogel with photo-crosslinkable and injectable properties, is developed. To enhance its antioxidant capabilities, curcumin-loaded polydopamine nanoparticles (Cur@PDA NPs) are incorporated into the GelCA matrix, resulting in a multifunctional nanocomposite hydrogel referred to as Cur@PDA@GelCA. This hydrogel exhibits excellent biocompatibility in both in vitro and in vivo assessments, along with enhanced tissue adhesion facilitated by NPs in an in vivo model. Importantly, Cur@PDA@GelCA demonstrates the potential to mitigate oxidative stress when administered via intravitreal injection in retinal injury models such as the optic nerve crush model. These findings underscore its promise in advancing retinal tissue engineering and providing an innovative strategy for acute neuroprotection in the context of inner retinal injuries.

Exploring Inter-Brain Electroencephalogram Patterns for Social Cognitive Assessment During Jigsaw Puzzle Solving.

Social interaction enables the smooth progression of our daily lives. Mounting evidence from recent hyperscanning neuroimaging studies indicates that key components of social behavior can be evaluated using inter-brain oscillations and connectivity. However, mapping out inter-brain networks and developing neurocognitive theories that explain how humans co-create and share information during social interaction remains challenging. In this study, we developed a jigsaw puzzle-solving game with hyperscanning electroencephalography (EEG) signals recorded to investigate inter-brain activities during social interactions involving cooperation and competition. Participants were recruited and paired into dyads to participate in the multiplayer jigsaw puzzle game with 32-channel EEG signals recorded. The corresponding event-related potentials (ERPs), brain oscillations, and inter-brain functional connectivity were analyzed. The results showed different ERP morphologies of P3 patterns in competitive and cooperative contexts, and brain oscillations in the low-frequency band may be an indicator of social cognitive activities. Furthermore, increased inter-brain functional connectivity in the delta, theta, alpha, and beta frequency bands was observed in the competition mode compared to the cooperation mode. By presenting comparable and valid hyperscanning EEG results alongside those of previous studies using traditional paradigms, this study demonstrates the potential of utilizing hyperscanning techniques in real-life game-playing scenarios to quantitatively assess social cognitive interactions involving cooperation and competition. Our approach offers a promising platform with potential applications in the flexible assessment of psychiatric disorders related to social functioning.

Promote lipolysis in white adipocytes by magnetic hyperthermia therapy with Fe3O4microsphere-doped hydrogel.

Obesity has become an ongoing global crisis, since it increases the risks of cardiovascular disease, type 2 diabetes, fatty liver, cognitive decline, and some cancers. Adipose tissue is closely associated with the disorder of lipid metabolism. Several efforts have been made toward the modulation of lipid accumulation, but have been hindered by poor efficiency of cellular uptake, low safety, and uncertain effective dosage. Herein, we design an Fe3O4microsphere-doped composite hydrogel (Fe3O4microspheres @chitosan/ß-glycerophosphate/collagen), termed as Fe3O4@Gel, as the magnetocaloric agent for magnetic hyperthermia therapy (MHT), aiming to promote lipolysis in white adipocytes. The experimental results show that the obtained Fe3O4@Gel displays a series of advantages, such as fast sol-gel transition, high biocompatibility, and excellent magneto-thermal performance. MHT, which is realized by Fe3O4@Gel subjected to an alternating magnetic field, leads to reduced lipid accumulation, lower triglyceride content, and increased mitochondrial activity in white adipocytes. This work shows that Fe3O4@Gel-mediated MHT can effectively promote lipolysis in white adipocytesin vitro, which provides a potential approach to treat obesity and associated metabolic disorders.

Methotrexate Chemotherapy Causes Growth Impairments, Vitamin D Deficiency, Bone Loss, and Altered Intestinal Metabolism-Effects of Calcitriol Supplementation.

Vitamin D deficiency or insufficiency is prevalent in childhood cancer patients and survivors after chemotherapy; further studies are needed to investigate the underlying aetiology and effectiveness of vitamin D supplementation in preventing chemotherapy-induced bone loss. This study used a rat model of treatment with antimetabolite methotrexate to investigate whether methotrexate chemotherapy causes vitamin D deficiency and if vitamin D supplementation attenuates the resultant bone loss. Methotrexate treatment (five daily injections) decreased serum vitamin D levels (from 52 to <30 ng/mL), reduced body and bone lengthening and tibial trabecular bone volume, and altered intestinal vitamin D metabolism, which was associated with intestinal mucosal damage known to cause malabsorption of nutrients, including dietary vitamin D and calcium. During the early stage after chemotherapy, mRNA expression increased for vitamin D activation enzyme CYP27B1 and for calcium-binding protein TRPV6 in the intestine. During the intestinal healing stage, expression of vitamin D catabolism enzyme CYP24 increased, and that of TRPV6 was normalised. Furthermore, subcutaneous calcitriol supplementation diminished methotrexate-induced bone loss due to its effect suppressing methotrexate-induced increased bone resorption. Thus, in young rats, methotrexate chemotherapy causes vitamin D deficiency, growth impairments, bone loss, and altered intestinal vitamin D metabolism, which are associated with intestinal damage, and vitamin D supplementation inhibits methotrexate-induced bone loss.

[Processing Magnoliae Officinalis Cortex with ginger juice: process optimization based on AHP-CRITIC weighting method and composition changes after processing].

The weight coefficients of appearance traits, extract yield of standard decoction, and total content of honokiol and magnolol were determined by analytic hierarchy process(AHP), criteria importance though intercrieria correlation(CRITIC), and AHP-CRITIC weighting method, and the comprehensive scores were calculated. The effects of ginger juice dosage, moistening time, proces-sing temperature, and processing time on the quality of Magnoliae Officinalis Cortex(MOC) were investigated, and Box-Behnken design was employed to optimize the process parameters. To reveal the processing mechanism, MOC, ginger juice-processed Magnoliae Officinalis Cortex(GMOC), and water-processed Magnoliae Officinalis Cortex(WMOC) were compared. The results showed that the weight coefficients of the appearance traits, extract yield of standard decoction, and total content of honokiol and magnolol determined by AHP-CRITIC weighting method were 0.134, 0.287, and 0.579, respectively. The optimal processing parameters of GMOC were ginger juice dosage of 8%, moistening time of 120 min, and processing at 100 ℃ for 7 min. The content of syringoside and magnolflorine in MOC decreased after processing, and the content of honokiol and magnolol followed the trend of GMOC>MOC>WMOC, which suggested that the change in clinical efficacy of MOC after processing was associated with the changes of chemical composition. The optimized processing technology is stable and feasible and provides references for the modern production and processing of MOC.

Effects of Neurofeedback on Cognitive Function, Productive Activity, and Quality of Life in Patients With Traumatic Brain Injury: A Randomized Controlled Trial.

BACKGROUND: Cognitive impairment is common in patients with traumatic brain injury (TBI). Studies that have examined the effectiveness of neurofeedback (NFB) on cognitive function following TBI have had poor study designs and small sample sizes. OBJECTIVES: This randomized controlled trial assessed the effects of low-resolution tomography Z-score NFB (LZNFB) and theta/beta NFB on cognitive impairment, return to productive activity, and quality of life in patients with TBI. METHODS: We randomly assigned 87 patients with TBI with cognitive impairment to LZNFB, theta/beta NFB, or usual care (UC) groups. Patients in both NFB groups received weekly 60-minute treatment for 10 weeks, and those in the control group received UC and telephone interviews for 10 weeks. The primary outcome was cognitive function as measured by performance on cognitive tasks; the secondary outcomes included productive activity and quality of life based on the Community Integration Questionnaire-revised (CIQ-R) and the Quality of Life after Brain Injury (QOLIBRI), respectively, at baseline and immediately after the last intervention. RESULTS: The LZNFB group exhibited significantly greater improvements in immediate recall, delayed recall, recognition memory, and selective attention compared with the UC group; the theta/beta NFB group exhibited improvements in only immediate memory and selective attention (P < .05). The total CIQ-R scores of the LZNFB group after treatment were significantly improved than those of the UC group were. CONCLUSION: Consecutive LZNFB achieved therapeutic effects in memory, attention, and productive activity, whereas theta/beta NFB improved memory and attention in patients with TBI.This trial was prospectively registered at ClinicalTrial.gov (registration number: NCT03515317; https://clinicaltrials.gov/ct2/show/NCT03515317).

Analysis of the Influencing Factors of Tumor Volume, Body Immunity, and Poor Prognosis after 125I Particle Therapy for Differentiated Thyroid Cancer.

Objective: To analyze the influencing factors of tumor volume, body immunity, and poor prognosis after 125I particle therapy for differentiated thyroid cancer. Methods: A total of 104 patients with differentiated TC who were treated with 125I particles during January 2020 to January 2021 was picked. These subjects were graded as low-dose group (80Gy-110Gy) and high-dose group (110Gy-140Gy) according to the minimum dose received by 90% of the target volume (D90) after surgery. The tumor volume before and after treatment was compared, and fasting venous blood was collected before and after treatment. The content of thyroglobulin (Tg) was detected by electrochemiluminescence immunoassay. The levels of absolute lymphocyte count (ALC), lymphocytes, neutrophils, and monocytes were detected on automatic blood cell analyzer. The lymphocyte to monocyte ratio (LMR), neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ration (PLR) were calculated. The changes in the condition of patients were closely observed, and the occurrence of adverse reactions in the two groups were compared. The risk factors influencing the efficacy of 125I particle therapy for differentiated TC were analyzed through multivariate logistic regression analysis. Results: The total effective rate of patients in the low- and high-dose groups was 78.85% and 82.69%, respectively (P > 0.05). Compared with the pretreatment period, the tumor volume and Tg level in both groups were much lower (P < 0.05), and the differences in tumor volume and Tg level had no statistically significant difference between the two groups before and after treatment (P > 0.05). At 1 week of the treatment, the total incidence of adverse reactions such as nausea, radiation gastritis, radiation parotitis, and neck discomfort was obviously higher in the high-dose group than in the low-dose group (P < 0.05). At 1 month of treatment, the incidence of adverse reactions such as nausea was markedly higher in the high-dose group than in the low-dose group (P < 0.05). After treatment, serum NLR and PLR contents were memorably elevated and LMR level was sharply decreased in both groups, and serum NLR and PLR contents were higher and LMR content was lower in the high-dose group than in the low-dose group (P < 0.05). Multivariate logistic regression analysis showed that the pathological type of follicular adenocarcinoma, tumor size ≥ 2 cm, clinical stage of III~IV, distant metastasis, and high TSH level before 125I particle treatment were all risk factors related to the efficacy of 125I particle treatment of TC (P < 0.05). Conclusion: The efficacy of low-dose and high-dose 125I particles in the treatment of differentiated thyroid cancer is comparable, among which low-dose 125I particles have fewer adverse effects and have less impact on the immunity of the body, which is well tolerated by patients and can be widely used in clinical practice. In addition, the pathological type of follicular adenocarcinoma, tumor size ≥ 2 cm, clinical stage III~IV, distant metastasis, and high TSH level before 125I particle treatment are all risk factors that affect the poor effect of 125I particles on thyroid cancer treatment, and early monitoring of the above index changes can help evaluate the prognosis.

Geranylated or prenylated flavonoids from Cajanus volubilis.

Five new flavonoid derivatives, cajavolubones A-E (1-5), along with six known analogues (6-11) were isolated from Cajanus volubilis, and their structures were elucidated by spectroscopic analysis and quantum chemical calculations. Cajavolubones A and B (1 and 2) were identified as two geranylated chalcones. Cajavolubone C (3) was a prenylated flavone, while cajavolubones D and E (4 and 5) were two prenylated isoflavanones. Compounds 3, 8, 9 and 11 displayed cytotoxicity against HCT-116 cancer cell line.

Effectiveness and Safety of Lianhua Qingwen Capsules for COVID-19: A Propensity-Score Matched Cohort Study.

As a traditional Chinese medicine, Lianhua Qingwen capsules have been widely used to treat Coronavirus Disease 2019 (COVID-19). This study was aimed to demonstrate the association between treatment with Lianhua Qingwen capsules and the clinical outcomes of hospitalized patients with COVID-19. This retrospective study was conducted at four hospitals in Central China. Data of hospitalized COVID-19 patients were collected between December 19, 2019 and April 26, 2020. Based on whether Lianhua Qingwen capsules were used, patients were classified into Lianhua Qingwen and non-Lianhua Qingwen (control) groups. To control for confounding factors, we used conditional logistic regression in a propensity-score matched (PSM) cohort (1 : 1 balanced), as well as logistic regression without matching as sensitivity analysis. A total of 4918 patients were included, 2760 of whom received Lianhua Qingwen capsules and 2158 of whom did not. In the PSM model, after adjusting for confounders, the in-hospital mortality was similar between the Lianhua Qingwen group and the control group (6.8% vs. 3.3%, adjusted OR, 0.66 [95% CI, 0.38-1.15], p = 0.138). The negative conversion rate of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection was higher in the Lianhua Qingwen group (88.3% vs. 96.1%, adjusted OR, 4.02 [95% CI, 2.58-6.25], p < 0.001). The incidence of acute liver injury was comparable between the two groups (14.0% vs. 11.5%, adjusted OR: 0.85 [95% CI, 0.71-1.02], p = 0.083), and the incidence of acute kidney injury was lower in the Lianhua Qingwen group (5.3% vs. 3.0%, adjusted OR: 0.71 [95% CI, 0.50-1.00], p = 0.048). Treatment with Lianhua Qingwen capsules was not significantly associated with in-hospital mortality in COVID-19 patients. In the Lianhua Qingwen group, the negative conversion rate of SARS-CoV-2 infection was higher and the incidence of acute kidney injury was lower than in the control group.

Association between Selenium Intake and Optimal Sleep Duration: A National Longitudinal Study.

Inconsistent findings have been discovered in studies examining the link between dietary selenium (Se) and sleep. Data were obtained from 17,176 people aged 20 and over who participated in the China Health and Nutrition Survey (CHNS) from 2004 to 2011. Face-to-face interviews were used to measure sleep duration in 2004, 2006, 2009, and 2011. To track dietary Se consumption, a 3-day, 24-h recall was undertaken. In the analysis, multilevel mixed-effects logistic regression was employed. The odds ratios (95% confidence intervals) of optimal sleep duration (7-9 h/day) in the regression of Model 4 were 1.00, 1.01 (0.89-1.15) and 1.19 (1.02-1.38) for the three tertiles of selenium consumption, respectively. Only overweight patients displayed a substantial positive connection between Se intake and the optimal sleep duration in the subgroup analysis. In summary, Se intake was significantly associated with optimal sleep duration.

[Mineralization Characteristics of Soil Organic Carbon and Its Relationship with Organic Carbon Components in Artificial Robinia pseudoacacia Forest in Loess Hilly Region].

In order to explore the characteristics of organic carbon mineralization and the variation law of organic carbon components of an artificial forest in a loess hilly area, an artificial Robinia pseudoacacia forest restored for 13 years and the adjacent slope farmland were selected as the research objects, and indoor culture experiments under three different temperature treatments (15, 25, and 35℃) were carried out. The results indicated that the mineralization rate of soil organic carbon decreased sharply at first and then stabilized. The cumulative release of organic carbon increased rapidly in the initial stage of culture and gradually slowed in the later stage. Soil organic carbon mineralization in sloping farmland was more sensitive to temperature change, and its temperature sensitivity coefficient Q10 was 1.52, whereas that in R. pseudoacacia forest land was only 1.38. According to the fitting of the single reservoir first-order dynamic equation, the soil mineralization potential Cp of R. pseudoacacia forest land and slope farmland was between 2.02-4.32 g·kg-1 and 1.25-3.17 g·kg-1, respectively, that is, the mineralization potential of the R. pseudoacacia forest was higher. During the cultivation period, the content of various active organic carbon components decreased with time, and that in the R. pseudoacacia forest land was greater than that in the slope land. The cumulative carbon release of soil was significantly positively correlated with the contents of MBC and DOC (P<0.05), and Q10 (15-25℃) was negatively correlated with the contents of SOC, EOC, and SWC (P<0.05). These results could provide some reference for the study of soil carbon sequestration in loess hilly regions under climate change.

Interaction among dietary n-3 and n-6 polyunsaturated fatty acid intake, fatty acid desaturase 2 genetic variants, and low-density lipoprotein cholesterol levels in type 2 diabetes patients.

AIMS/INTRODUCTION: Fatty acid desaturase (FADS) genetic polymorphisms are strongly correlated with the risk of dyslipidemia and cardiovascular disease. In this study, we examined the impact of FADS1 and FADS2 genetic variants on plasma lipid status, and assessed interactions between FADS genetic polymorphisms and plasma n-3/n-6 fatty acids regarding lipid status within a population of 816 Taiwanese patients with type 2 diabetes. MATERIALS AND METHODS: Selected tag single-nucleotide polymorphisms (FADS1 rs174546 [T/C]; FADS2 rs174602 [A/G] and rs2072114 [A/G]) were genotyped (n = 816). RESULTS: The distribution of genotypes were compared with reports publicly available in the Genome Aggregation Database for East Asian populations (https://gnomad.broadinstitute.org). In the subgroup of patients not taking lipid-lowering medications (n = 192), we observed that the G allele of FADS2 rs174602 was statistically significantly correlated with lower low-density lipoprotein cholesterol (LDL-C) concentrations (P = 0.001), whereas the G allele of rs2072114 was marginally associated with LDL-C concentrations (P = 0.091). Using a general linear model adjusted for confounding factors, statistically significant interactions (P = 0.016) between single-nucleotide polymorphisms in rs2072114 and a low alpha-linolenic acid (18:3n-3)/linoleic acid (18:2n-6) ratio; the G allele correlated with lower LDL-C levels among individuals with a low alpha-linolenic acid/linoleic acid ratio. Interaction between rs174602 single-nucleotide polymorphisms and low alpha-linolenic acid/linoleic acid values on LDL-C was only marginally significant (P = 0.063). CONCLUSIONS: Our results show the role of n-3/n-6 dietary polyunsaturated fatty acids in modifying the effects of genetic susceptibility on lipoprotein concentrations in patients with type 2 diabetes. Our findings highlight the potential of interventions with dietary polyunsaturated fatty acids regarding developing individualized prevention strategies for type 2 diabetes presenting with co-occurring dyslipidemia and cardiovascular diseases.

CD8 + T cell memory is sustained in mice by hepatic stellate cells.

BACKGROUND AND AIMS: Long-lasting immunological memory is the ultimate goal of vaccination. Homeostatic maintenance of memory CD8 + cytotoxic T cells (MemCD8TCs) is thought to be mediated by IL-15/IL-15R heterodimer (15HD)-expressing myeloid cells. Nonmyeloid hepatic stellate cells (HSCs) also express 15HD, but their role in maintaining MemCD8TC homeostasis is unknown. APPROACH AND RESULTS: We engineered a genetically engineered mouse in which IL-15R complementary DNA (cDNA) had been inserted in-frame with lecithin-retinol acyltransferase gene and bred onto an IL-15R-KO (15R-KO) genetic background (L15R) that expressed IL-15R in HSCs at normal levels, but not in other liver cells. Outside of the liver of L15R mice, IL-15R expression was found in a number of organs, but not in dendritic cells and macrophages. The low IL-15R expression in the bone marrow (BM) of L15R mice was eliminated by the reconstitution of lethally-irradiated L15R mice with 15R-KO BM to generate L15RC mice. Because MemCD8TC maintenance is mediated by 15HD, not empty IL-15R, 15HD content in L15R mice was determined and found for liver, lung, kidney, and heart. L15R and L15RC mice developed and maintained long-lasting, systemic antigen-specific MemCD8TCs that were efficacious against tumor growth and Listeria monocytogenes infection in an antigen-specific manner. Among the four organs with 15HD content, liver-associated MemCD8TCs were different from those found in the lung, kidney, and heart in two ways: (1) they were quantitatively the most numerous, and (2) they appeared uniquely in the form of clusters in a specialized structure, sinusoidal niches of the liver. CONCLUSIONS: The liver, the largest organ of the body, is endowed with the capability of effectuating long-lasting functional cytotoxic T cell memory.

Interactions between folate intake and genetic predictors of gene expression levels associated with colorectal cancer risk.

Observational studies have shown higher folate consumption to be associated with lower risk of colorectal cancer (CRC). Understanding whether and how genetic risk factors interact with folate could further elucidate the underlying mechanism. Aggregating functionally relevant genetic variants in set-based variant testing has higher power to detect gene-environment (G × E) interactions and may provide information on the underlying biological pathway. We investigated interactions between folate consumption and predicted gene expression on colorectal cancer risk across the genome. We used variant weights from the PrediXcan models of colon tissue-specific gene expression as a priori variant information for a set-based G × E approach. We harmonized total folate intake (mcg/day) based on dietary intake and supplemental use across cohort and case-control studies and calculated sex and study specific quantiles. Analyses were performed using a mixed effects score tests for interactions between folate and genetically predicted expression of 4839 genes with available genetically predicted expression. We pooled results across 23 studies for a total of 13,498 cases with colorectal tumors and 13,918 controls of European ancestry. We used a false discovery rate of 0.2 to identify genes with suggestive evidence of an interaction. We found suggestive evidence of interaction with folate intake on CRC risk for genes including glutathione S-Transferase Alpha 1 (GSTA1; p = 4.3E-4), Tonsuko Like, DNA Repair Protein (TONSL; p = 4.3E-4), and Aspartylglucosaminidase (AGA: p = 4.5E-4). We identified three genes involved in preventing or repairing DNA damage that may interact with folate consumption to alter CRC risk. Glutathione is an antioxidant, preventing cellular damage and is a downstream metabolite of homocysteine and metabolized by GSTA1. TONSL is part of a complex that functions in the recovery of double strand breaks and AGA plays a role in lysosomal breakdown of glycoprotein.

Cupping Therapy as an Adjunctive Therapy for Side Effects of Colorectal Cancer Treatment: A Prospective Observational Study.

Objective: The purpose of this study was to assess the effects of moving cupping therapy in people with colorectal cancer (CRC) experiencing chemotherapy-related side effects. Methods: A prospective observational study was conducted in people diagnosed with CRC who were treated for the side effects of their chemotherapy. Participants received cupping therapy 3 times a week for 10 consecutive weeks at our traditional Chinese medicine ward. Their quality of life and meridian energies were evaluated both at baseline and at 3 months after the treatment course. Results: Forty-six individuals with CRC were enrolled and 34 completed the study. The average number of cycles of chemotherapy during the study was 4.5. The mean number of moving cupping treatments was 25.7. After the moving cupping treatment program, participants exhibited significant improvements in quality of life, physical function, fatigue, nausea/vomiting, sleep disturbance, and pain. Conclusion: For the participants in this study, moving cupping therapy relieved some chemotherapy-related side effects and improved quality of life in people with CRC.

Short-Term Hyperuricemia Leads to Structural Retinal Changes That Can be Reversed by Serum Uric Acid Lowering Agents in Mice.

Purpose: Metabolic disorders have been implicated in ocular diseases, such as age-related macular degeneration (AMD) and diabetic retinopathy (DR). Recently, hyperuricemia (HUA) has been proposed as another risk factor for AMD, although no cause-and-effect experimental data have been published. In this study, we investigated whether HUA would initiate AMD or related retinal damages in hyperuricemic mice. Methods: HUA was induced in male ICR mice by dietary supplements of uric acid and oxonic acid potassium salt, with or without treatments by allopurinol or benzbromarone for various durations. Serum uric acid and angiotensin II concentrations were measured by enzyme-linked immunosorbent assay (ELISA) at regular intervals. The retinal damages were assessed by hematoxylin and eosin staining, immunostaining, and TUNEL assay. The cause-and-effect of HUA was compared among the study groups. Results: The results showed that the total thickness of photoreceptor inner and outer segments, as well as the thickness of the photoreceptor outer segment alone, were reduced under HUA. Furthermore, HUA elevated serum angiotensin II, which indicated activation of the renin-angiotensin system (RAS), leading to higher matrix metalloproteinase-2 (MMP-2) expression, and glial activation in the ganglion cell layer. HUA also led to the reduction of retinal pigment epithelium gap junction protein connexin-43 and apoptosis. Uric acid lowering agents, allopurinol or benzbromarone, were effective in ameliorating the impairments. Conclusions: HUA may pose as a causative factor of retinal injuries. The reduction of serum uric acid may reduce the detrimental effects caused by HUA.

Ursolic acid silences CYP19A1/aromatase to suppress gastric cancer growth.

INTRODUCTION: Gastric cancer (GCa) is a malignancy with few effective treatments. Ursolic acid (UA), a bioactive triterpenoid enriched in Hedyotis diffusa Willd, known to suppress GCa without identified target. CYP19A1 (cytochrome P450 family 19A1; also known as aromatase, Ar) was correlated to GCa prognosis. Relatedly, Ar silencers, which halt the expression of Ar exhibited anti-GCa effects in experimental models, are currently being investigated. METHOD: The docking simulation score of UA was compared with Ar inhibitors, e.g., letrozole, exemestane, in Ar protein crystallization. Hedyotis diffusa Willd ethanol extract, UA, or 5-fluracil were applied onto AGS, SC-M1, MKN45 GCa cells for cancer inhibition tests. Immunoblot for measuring gene expressions upon drug treatments, or gene knockdown/overexpression. Treatments were also applied in a MKN45 implantation tumor model. A web-based GCa cohort for Ar expression association with prognosis was performed. RESULT: The ethanol extracts of Hedyotis diffusa Willd, enrich with UA, exhibited cytotoxic activity against GCa cells. Molecular docking simulations with the 3D Ar structure revealed an excellent fitting score for UA. UA increase cytotoxic, and suppressed colony, in addition to its Ar silencing capacity. Moreover, UA synergistically facilitated 5-FU, (a standard GCa treatment) regimen in vitro. Consistent with those results, adding estradiol did not reverse the cancer-suppressing effects of UA, which confirmed UA acts as an Ar silencer. Furthermore, UA exhibited tumor-suppressing index (TSI) score of 90% over a 6-week treatment term when used for single dosing in xenograft tumor model. In the clinical setting, Ar expression was found to be higher in GCa tumors than normal parental tissue from the TCGA (The Cancer Genome Atlas) cohort, while high Ar expression associated with poor prognosis. Together, the results indicate UA could be used to treat GCa by silencing Ar expression in GCa. Hedyotis diffusa Willd ethanol extract could be an functional food supplements.

Sensory and autonomic innervation of the local tissues at traditional acupuncture point locations GB14, ST2 and ST6.

OBJECTIVE: To visualize and compare the sensory and autonomic innervation of the local tissues at the sites of different traditional acupuncture points in the rat forehead and face by histochemical examination. METHODS: GB14 (Yangbai), ST2 (Sibai) and ST6 (Jiache) were selected as the representative traditional acupuncture points in this study, and the local tissues at these sites were dissected in rats after perfusion followed by double or triple fluorescent histochemical staining. Here, calcitonin gene-related peptide (CGRP), tyrosine hydroxylase (TH) and vesicular acetylcholine transporter (VAChT) were used to label the sensory, sympathetic and parasympathetic nerve fibers, respectively. RESULTS: The CGRP+ sensory, TH+ sympathetic and VAChT+ parasympathetic nerve fibers were simultaneously demonstrated in the local tissues at GB14, ST2 and ST6. Although the three kinds of nerve fibers ran in parallel or intermingled with each other, by the analysis from the view of three-dimensional reconstruction, it was clear that each of them distributed in an independent pattern to their corresponding target tissues including the blood vessels, hair follicles, arrector pili and subcutaneous muscles, as well as sebaceous glands. CONCLUSION: Our study demonstrated the sensory and autonomic innervation of the local tissues at GB14, ST2 and ST6, providing neurochemical evidence indicating that the CGRP+ sensory, TH+ sympathetic and VAChT+ parasympathetic nerve fibers form a neural network at these point locations that may respond to acupuncture stimulation.

Association of fish oil containing lipid emulsions with retinopathy of prematurity: a retrospective observational study.

BACKGROUND: Retinopathy of prematurity (ROP) remains a leading cause of childhood blindness worldwide. This study aimed to investigate whether supplementation of n-3 polyunsaturated fatty acids (n-3 PUFAs) in parenteral nutrition may have beneficial effects on ROP in preterm infants. METHODS: A total of 89 preterm infants, admitted to Neonatal Intensive Care Unit (NICU) in Anhui Provincial Children's Hospital from September 2017 to August 2020, were recruited in the study. Based on the medical documents, the subjects were categorised into two groups: administration of the fish oil emulsion (n=43) containing soy oil, medium-chain-triglycerides (MCT), olive oil and fish oil (6g/dL, 6g/dL, 5g/dL and 3g/dL respectively), and the soy oil emulsion (n=46) containing 10g/dL of soy oil and MCT each. At 4 weeks of hospitalization, ROP was screened and diagnosed. Fatty acids in erythrocytes were determined using gas chromatography. RESULTS: The averaged birth weight and gestational age were 1594±296 g and 31.9±2.3 wk, 1596±263 g and 31.6±2.3 wk respectively for preterm infants in the fish oil group and soy oil group. After 4 to 6 weeks of hospitalization, among all the preterm infants, 52 developed ROP (all stages) indicating an incidence of ROP at 58.43%. Although the incidence of ROP with any stages showed no differences between the two groups, the severe ROP incidence in the group with fish oil emulsions (2.33%) was significantly lower than that in the group with soy oil emulsions (23.91%) (P<0.05). After 14 days of nutrition support, the preterm infants administered fish oil emulsions had an increase in erythrocyte DHA content, with a reduction in ratio of arachidonic acid (AA) to DHA and an increase of n-3 index. CONCLUSION: Supplementation of n-3 PUFAs through parenteral fish oil containing lipid emulsions resulted in an increase in erythrocyte DHA, and this might have beneficial effects on prevention of severe ROP in preterm infants.

Geranyl phenyl ethers from Illicium micranthum and their anti-HBV activity.

Fourteen new geranyl phenyl ethers (1-14) along with three known compounds (15-17) were isolated from Illicium micranthum, and their structures were elucidated by comprehensive spectroscopic methods. Illimicranins A-H (1-8) were characterized as geranyl vanillin ethers, while 9 and 10 were dimethyl acetal derivatives. Illimicranins I and J (11 and 12) were rare geranyl isoeugenol ethers. Illimicranins K and L (13 and 14) represented the first example of geranyl guaiacylacetone ether and geranyl zingerone ether, respectively. Compounds 1, 2 and 15 exhibited anti-HBV (hepatitis B virus) activity against HBsAg (hepatitis B surface antigen) and HBeAg (hepatitis B e antigen) secretion, and HBV DNA replication.