Effects of dietary supplementation of grape seed extract in comparison with excessive level of vitamin E on growth performance and antioxidant function of broilers.

The present study was carried out to evaluate the effects of dietary vitamin E (VE) or grape seed extract (GSE) on the growth performance and antioxidant function of broilers. Two hundred sixteen broiler chicks were randomly assigned to 3 diets: diet supplemented with oxidized rice bran oil (CN group), CN group with 25 mg/kg VE or 100 mg/kg GSE. Dietary VE or GSE improved the growth performance, reverted the disturbed levels of liver antioxidant enzymes, and reduced liver damage of broilers fed oxidized rice bran oil. The mRNA data showed that supplementation of VE or GSE enhanced the antioxidant capacity of the broiler liver through activation of the Keap1-Nrf2/ARE signaling pathway. The results suggested that VE and GSE can increase weight gain, improve the oxidative status, and alleviate liver injury in broiler chicken fed oxidized rice bran oil.

A novel off-line multi-dimensional high-speed countercurrent chromatography strategy for preparative separation of bioactive neolignan isomers from Piper betle. L.

Separation and purification of naturally occurring isomers from herbs are still challenging. High-speed counter-current chromatography (HSCCC) has been applied to isolate natural products. In this study, an off-line multi-dimensional high-speed counter-current chromatography (multi-D HSCCC) strategy was developed utilizing the in situ concentration technique with online storage recycling elution to rapidly separate bioactive isomeric neolignans from chloroform-partitioned samples of the plant Piper betle L. In the procedure, the crude sample (105 mg) was implemented using the online storage recycling technique in a two-phase solvent system composed of petroleum ether-ethyl acetate-methanol-water (7: 5: 12: 3), which first simply afforded a neolignane kadsurenone (1, 5.3 mg) and its epimer (-)-denudatin B (2, 6.4 mg). Then, the remains fr a was subjected to the second-dimensional HSCCC elution using the in situ concentration technique with online storage recycling technique in another solvent system of petroleum ether-ethyl acetate-methanol-water (5: 5: 11, 15). As a result, kadsurenin I (3, 0.6 mg) and its regioisomer pibeneolignan C (4, 5.0 mg), together with the fractional remaining fr b and fr c, were obtained. Thirdly, the fr c was reloaded to allow the HSCCC for recycling elution with the former solvent system employing the in situ concentration strategy and yielded a pair of epimers, (7R,8S,1'S)-1'-allyl-5-methoxy-8-methyl-7-piperonyl-7,8,3,6-tetrahydro-2-oxobenzofuran (5, 10.2 mg), and 3-epi-(-)-burchullin (6, 2.6 mg). Finally, the three pairs of less amount and the structurally similar isomers 1-6 were isolated from the crude fraction of P. betle with a high HPLC purity of over 95.0 % for compound 2, 4-6 and 92.5 % for compound 1, 91.0 % for 3, while the purity of 1 and 3 in 1H NMR were 89.9 % and 91.1 %, respectively. The whole isolation process was quick and efficient. Compounds 1, 2, 4 and 5 showed significantly synergistic activities combining several antibiotics against five drug-resistant Staphylococcus aureus with FICIs from 0.156 to 0.375. This novel off-line multi-dimensional HSCCC strategy could be broadened to application for the rapid separation of complex natural products.

[Molecular mechanism of sleep deprivation-induced body injury and traditional Chinese medicine prevention and treatment: a review].

Sleep occupies one-third of a person's lifetime and is a necessary condition for maintaining physiological function and health. With the increase in social and economic pressures, the growing use of electronic devices and the accelerated aging process of the population, insufficient sleep and its hazards have drawn widespread attention from researchers in China and abroad. Sleep deprivation refers to a decrease in sleep or a severe lack of sleep due to various reasons. Previous studies have found that sleep deprivation can cause extensive damage to the body, including an increased incidence and mortality rate of neuropathic diseases in the brain, cardiovascular diseases, imbalances in the gut microbiota, and other multi-organ diseases. The mechanisms underlying the occurrence of multi-system and multi-organ diseases due to sleep deprivation mainly involve oxidative stress, inflammatory responses, and impaired immune function in the body. According to traditional Chinese medicine(TCM), sleep deprivation falls into the category of sleepiness, and long-term sleepiness leads to Yin-Yang imbalance, resulting in the consumption of Qi and damage to the five Zang-organs. The appropriate treatment should focus on tonifying deficiency, reinforcing healthy Qi, and harmonizing Yin and Yang. TCM is characterized by a wide variety and abundant resources, and it has minimal side effects and a broad range of applications. Numerous studies have shown that TCM drugs and prescriptions not only improve sleep but also have beneficial effects on liver nourishment, intelligence enhancement, and kidney tonification, effectively preventing and treating the body injury caused by sleep deprivation. Given the increasing prevalence of sleep deprivation and its significant impact on body health, this article reviewed sleep deprivation-mediated body injury and its mechanism, summarized and categorized TCM compound prescriptions and single drugs for preventing and treating body injury, with the aim of laying the foundation for researchers to develop effective drugs for preventing and treating body injury caused by sleep deprivation and providing references for further exploration of the molecular mechanisms underlying the body injury caused by sleep deprivation.

Supplementation with grape seed extract, onion peel extract, or rosemary extract in the diet alleviates growth inhibition, liver damage, and oxidative stress induced by diquat in Lohmann chicks.

The present study aimed to assess the impact of grape seed extract (GSE), onion peel extract (OPE), and rosemary extract (ROE) on Diquat-induced growth restriction and oxidative stress in Lohmann chicks. A total of 200 chicks were randomly assigned to 5 diets: the positive control (PC) group, the negative control (NC) group, GSE group, OPE group, and ROE group. During the first 7 d of trial, compared with NC and PC groups, the GSE group enhanced average daily feed intake (ADFI). From day 8-21, diquat injection resulted in reduced growth performance, increased platelet volume distribution width (PWD), malondialdehyde (MDA) concentration, and activities of alanine aminotransferase (ALT) in chick serum; it also decreased total protein (TP), albumin (ALB), globulin (GLB) concentration, activities of superoxide dismutase (SOD) and glutathione S-transferase (GST) in chick serum; furthermore, it increased MDA concentration while decreasing GST activities in liver. The NC group exhibited lower average daily gain (ADG) than other groups. Compared with NC group, GSE group reduced ALT activities, MDA levels, and red cell distribution width (RDW), and PDW concentration; it also increased SOD, GST activities. The ROE group lowered ALT activities and MDA concentration. The OPE group decreased ALT activities, and MDA levels, RDW, and PDW concentration, and increased SOD activities of chicks. These results suggest that supplementing antioxidants in diets alleviated oxidative stress in chicks challenged by improving antioxidant capacity and liver function.

Higher diet quality relates to better cardiac function in cancer survivors: The multi-ethnic study of atherosclerosis.

BACKGROUND: Cancer therapies induce cardiac injury and increase cardiovascular disease (CVD) risk. In non-cancer populations, higher diet quality is associated with protection against CVD, but the relationship between diet and cardiac function in cancer survivors is unknown. METHODS: This cross-sectional analysis from the Multi-Ethnic Study of Atherosclerosis (MESA) cohort included 113 cancer survivors (55 breast, 53 prostate, three lung, and three blood) and 4233 non-cancer controls. Dietary intake was reported via validated food frequency questionnaire. Alternate healthy eating index (AHEI) was calculated as a measure of quality. Cardiac function, determined as left ventricular ejection fraction (LVEF), was assessed by cardiac magnetic resonance. RESULTS: Cancer survivors had a lower LVEF compared to controls (61.3 ± 6.5% v 62.4 ± 6.1%, p = 0.04). In all participants, total fat (ß ± SE: -0.04 ± 0.01, p = 0.004), saturated fat (-0.11 ± 0.03, p < 0.001), and trans-fat (-0.36 ± 0.12, p = 0.002) intake were inversely associated with LVEF while AHEI (0.03 ± 0.01, p < 0.001) was positively associated with LVEF. Among cancer survivors only, sucrose intake was negatively related to LVEF (-0.15 ± 0.06, p = 0.02), and the ratio of unsaturated fat to saturated fat (2.7 ± 1.1, p = 0.01) and fiber intake (0.42 ± 0.14, p = 0.003) were positively related to LVEF. DISCUSSION: In cancer survivors, improved dietary fat and carbohydrate quality (i.e., greater consumption of unsaturated fatty acids and fiber) was associated with favorable cardiac function, while higher sucrose was associated with worse cardiac function. Further research is needed to confirm these findings and test whether changes in the identified dietary factors will modulate cardiac function in cancer survivors.

Compound Dihuang Granule Changes Gut Microbiota of MPTP-Induced Parkinson's Disease Mice via Inhibiting TLR4/NF-κB Signaling.

Intestinal microbiota was connected to Parkinson's Disease (PD) pathology. The ancient Chinese medication for PD is Compound Dihuang Granule (CDG), and we found a neuroprotective function in treating the constipation of PD patients. Nevertheless, the mechanism of action still needs to be clarified. We predicted the probable targets of CDG against PD through Traditional Chinese medicine (TCM) network pharmacology and verified the analysis through animal experiments in vivo. The protein-protein interaction (PPI) network analysis screened PD-related genes, including Toll-like receptor 4(TLR4), TANK-binding kinase 1(TBK1), Nuclear Factor- Kappa B (NF-κB), and Tumor necrosis factor (TNF). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses proved that the NF-κB and toll-like receptor signaling pathways serve a key function in CDG therapy of PD. Molecular docking analysis demonstrated that CDG strongly connected to TLR4/NF-κB. Experiments findings indicated that CDG improved the damage of dopaminergic neurons and gut microbial dysbiosis, ameliorated motor impairments, and suppressed the PD-associated inflammation and oxidative stress in mice induced by 1-methyl-4-phenyl-1,2,3,6-tetrahy dropyridine (MPTP). CDG suppressed the inflammatory proteins in the colon and protected the intestinal barrier. Overall, CDG improved gut microbial in PD by blocking the pathway of TLR4/NF-κB.

Unresectable hepatocellular carcinoma: transarterial chemoembolisation plus Huachansu - a single-center randomised controlled trial.

OBJECTIVE: Huachansu, a Chinese medicine derived from the dried skin glands of toad venom, has been used in China since the 1970s to treat liver cancer. Transarterial chemoembolisation (TACE) is the standard of care for patients with unresectable hepatocellular carcinoma (HCC). This study evaluated the efficacy and safety of the combination of TACE and Huachansu in unresectable HCC. METHODS: From September 2012 to September 2016, 120 patients diagnosed with unresectable HCC were prospectively enrolled. Patients were randomised at a 1:1 ratio into the combined treatment group (Huachansu-TACE) and the TACE treatment group. The primary endpoint was progression-free survival (PFS) and secondary endpoints were overall survival (OS) and safety. The exploration outcome serum Na+/K+-ATPase (NKA) α3 at baseline and 3-month follow-ups were compared for a prognostic role. All patients were subjected to 36-month follow-up. RESULTS: A total of 112 patients who completed the study were included in the analysis. PFS and OS were significantly better in the Huachansu-TACE group than in the TACE group (p=0.029 and p=0.025, respectively), with a median PFS of 6.8 and 5.3; and a median OS of 14.8 months and 10.7 months, respectively. Although no prognostic significance was found between the baseline NKA-low and NKA-high groups in the patients' OS (p=0.48), its changes after 3-month follow-up showed significant prognostic values, of which, were 8.5 months and 23.8 months, respectively (p<0.001). Treatment-related adverse events were comparable between groups. CONCLUSIONS: Huachansu-TACE is effective in prolonging the PFS and OS in patients with unresectable HCC. TRIAL REGISTRATION NUMBER: NCT01715532.

Late-Stage Functionalization for the Divergent Synthesis of Podophyllotoxin Derivatives by Rhodium Catalysis.

Invited for the cover of this issue are Chunpu Li, Hong Liu and co-workers at Shanghai Institute of Materia Medica, Nanjing University of Chinese Medicine, and Hangzhou Institute for Advanced Study. The image depicts rhodium catalysis converting the readily available podophyllotoxin into four kinds of novel derivatives. Read the full text of the article at 10.1002/chem.202300960.

The Effects of Fatty Acids on Primary Liver Cancer: A Two-Sample Mendelian Randomization Study.

Currently, it is unknown whether fatty acids (FAs) and primary liver cancer (PLC) are associated. The cause-effect association was established using a two-sample Mendelian randomization (MR) study. Eligible single nucleotide polymorphisms were selected as instrumental variables from six FAs genome-wide association studies. The outcome involved a total of 260,428 subjects and was a summary of genetic data on PLC from FinnGen biobanks. The principal method inverse variance weighted (IVW) and several other analytical approaches (MR-Egger, Weighted Median, and Maximum likelihood) were tested to determine the causal relationship between different FAs and PLC. Furthermore, sensitivity analyses were performed to determine the stability of the results. The two-sample MR analysis revealed a negative causal relationship between omega-3 FAs and PLC. It was discovered that an increase in each standard deviation (0.53 mmol/L; SD: 0.22) in the genetic levels of omega-3 FAs reduced the risk of PLC by 62.1% through the IVW method [odd ratio: 0.379; 95% confidence interval (0.176, 0.816)]. Nevertheless, other FAs were not statistically correlated with PLC. Additionally, no pleiotropy was found between the two. According to the MR study, consuming omega-3 FAs may help prevent PLC.

Guiqi Baizhu prescription ameliorates cytarabine-induced intestinal mucositis by targeting JAK2 to inhibit M1 macrophage polarization.

BACKGROUND: Intestinal mucositis (IM) is characterized by damage to the intestinal mucosa resulting from inhibition of epithelial cell division and loss of renewal capacity following anticancer chemotherapy and radiotherapy. Cytarabine (Ara-C), the main chemotherapy drug for the treatment of leukemia and lymphoma, is a frequent cause of IM. Guiqi Baizhu prescription (GQBZP) is a traditional Chinese medicine with anti-cancer and anti-inflammatory effects. PURPOSE: To determine if GQBZP can ameliorate Ara-C induced IM and identify and characterize the pharmacologic and pharmacodynamic mechanisms. STUDY DESIGN AND METHODS: IM was induced in mice with Ara-C and concurrently treated with orally administered GQBZP. Body weight and food intake was monitored, with HE staining to calculate ileal histomorphometric scoring and villus length/crypt depth. Immunoblotting was used to detect intestinal tissue inflammatory factors. M1 macrophages (M1) were labeled with CD86 by flow cytometry and iNOS + F4/80 by immunofluorescence. Virtual screening was used to find potentially active compounds in GQBZP that targeted JAK2. In vitro, RAW264.7 cells were skewed to M1 macrophage polarization by lipopolysaccharide (LPS) and interferon-γ (INF-γ) and treated orally with GQBZP or potential active compounds. M1 was labeled with CD86 by flow cytometry and iNOS by immunofluorescence. ELISA was used to detect inflammatory factor expression. Active compounds against JAK2, p-JAK2, STAT1 and p-STAT1 were identified by western blotting and HCS fluorescence. Molecular dynamics simulations and pharmacokinetic predictions were carried out on representative active compounds. RESULTS: Experimental results with mice in vivo suggest that GQBZP significantly attenuated Ara-C-induced ileal damage and release of pro-inflammatory factors by inhibiting macrophage polarization to M1. Molecular docking was used to identify potentially active compounds in GQBZP that targeted JAK2, a key factor in macrophage polarization to M1. By examining the main components of each herb and applying Lipinski's rules, ten potentially active compounds were identified. In vitro experimental results suggested that all 10 compounds of GQBZP targeted JAK2 and could inhibit M1 polarization in RAW264.7 cells treated with LPS and INF-γ. Among them, acridine and senkyunolide A down-regulated the expression of JAK2 and STAT1. MD simulations revealed that acridine and senkyunolide A were stable in the active site of JAK2 and exhibited good interactions with the surrounding amino acids. CONCLUSIONS: GQBZP can ameliorate Ara-C-induced IM by reducing macrophage polarization to M1, and acridine and senkyunolide A are representative active compounds in GQBZP that target JAK2 to inhibit M1 polarization. Targeting JAK2 to regulate M1 polarization may be a valuable therapeutic strategy for IM.

Review: Mechanisms and perspective treatment of radioresistance in non-small cell lung cancer.

Radiotherapy is the major treatment of non-small cell lung cancer (NSCLC). The radioresistance and toxicity are the main obstacles that leading to therapeutic failure and poor prognosis. Oncogenic mutation, cancer stem cells (CSCs), tumor hypoxia, DNA damage repair, epithelial-mesenchymal transition (EMT), and tumor microenvironment (TME) may dominate the occurrence of radioresistance at different stages of radiotherapy. Chemotherapy drugs, targeted drugs, and immune checkpoint inhibitors are combined with radiotherapy to treat NSCLC to improve the efficacy. This article reviews the potential mechanism of radioresistance in NSCLC, and discusses the current drug research to overcome radioresistance and the advantages of Traditional Chinese medicine (TCM) in improving the efficacy and reducing the toxicity of radiotherapy.

W/O/W emulsions stabilized with whey protein concentrate and pectin: Effects on storage, pasteurization, and gastrointestinal viability of Lacticaseibacillus rhamnosus.

Probiotics have demonstrated various bioactive functions but poor storage and application stability, and encapsulation a promising method of increasing its viability. In this study, whey protein concentrate (WPC) and pectin (PEC) formed non-covalent complexes through electrostatic interaction at pH 3.0. The formed WPC-PEC complexes showed superior particle size, absolute potential, emulsification properties, and structural changes when PEC concentration was >0.8 % (w/v). This made them appropriate as a hydrophilic emulsifier to stabilize W/O/W emulsions. Then, Lacticaseibacillus rhamnosus, one representative of probiotics, was encapsulated in the internal aqueous phase of W/O/W emulsions. We obtained higher encapsulation efficiency (78.49 %) and smaller D4,3 (9.72 µm) with 0.8 % (w/v) PEC concentration. Encapsulation of Lacticaseibacillus rhamnosus in W/O/W emulsions improved its viability under harsh conditions, including 28 days storage at 4 °C, simulated pasteurization, and simulated gastrointestinal digestion. W/O/W emulsions stabilized by WPC-PEC non-covalent complexes further improved the survival of Lacticaseibacillus rhamnosus against various adverse conditions as compared to WPC. These findings suggest that the studied W/O/W emulsions systems have the potential to deliver probiotics in food substrates to enhance their viability during production processing, storage transportation, and digestion.

Effect of Oral Nutritional Supplements on Patients with Esophageal Cancer During Radiotherapy.

Background: This study investigated the effect of oral nutritional supplements (ONS) on patients with esophageal cancer during radiotherapy. Materials and Methods: Patients with esophageal cancer undergoing radiotherapy were randomly divided into nutritional intervention (NI) and routine treatment (RT) groups. All patients received one-on-one nutritional counseling and dietary advice, and patients in the NI group received ONS. Body mass index (BMI), a patient-generated subjective global assessment (PG-SGA), serum albumin (ALB), hemoglobin (Hb), white blood cell (WBC) count, prealbumin (PA), and platelets (PLTs) were recorded before and after radiotherapy in both the NI group and the RT group. Further, the adverse reactions during the treatment were evaluated. Results: In the NI group, the BMI after radiotherapy was significantly higher than that before radiotherapy, and the PG-SGA score after radiotherapy was significantly lower than that before radiotherapy (p < 0.05). In the RT group, the levels of BMI, Hb, ALB, PA, PLTs, and WBC after radiotherapy were significantly lower than those before radiotherapy, and the PG-SGA score was worse after radiotherapy (p < 0.05). After radiotherapy, the levels of BMI, Hb, ALB, and PA in the NI group were similar to those in the RT group (p > 0.05); whereas the levels of WBC and PLTs in the NI group were lower than those in the RT group (p < 0.05). During the treatment, the toxic reactions of radiation esophagitis, myelosuppression, nausea, and vomiting were decreased in the NI group compared with the RT group. Conclusions: ONS can reduce weight loss and improve the nutritional status of patients with esophageal cancer during radiotherapy.

Combination therapy with long-acting bronchodilators and the risk of major adverse cardiovascular events in patients with COPD: a systematic review and meta-analysis.

INTRODUCTION: Accumulated high-quality data from randomised controlled trials (RCTs) indicate that long-acting muscarinic antagonist (LAMA)/long-acting ß2 agonist (LABA) combination therapy significantly improves clinical symptoms and health status in patients with chronic obstructive pulmonary disease (COPD) and reduces exacerbation risk. However, there is a growing concern that LAMA/LABA therapy may increase the risk of cardiovascular disease in patients with COPD. The aim of this paper is to determine whether the use of LAMA/LABA combination therapy modifies the risk of cardiovascular disease in patients with COPD. METHODS: Two reviewers independently searched Embase, PubMed and Cochrane Library to identify relevant RCTs of LAMA/LABA or LABA/LAMA/inhaled corticosteroids (ICS) for the management of patients with COPD that reported on cardiovascular end-points. The primary outcome was major adverse cardiovascular events (MACE), which was a composite of cardiovascular death, myocardial infarction or stroke. RESULTS: A total of 51 RCTs enrolling 91 021 subjects were analysed. Both dual LAMA/LABA (1.6% versus 1.3%; relative risk 1.42, 95% CI 1.11-1.81) and triple therapy (1.6% versus 1.4%; relative risk 1.29, 95% CI 1.03-1.61) significantly increased the risk of MACE compared with ICS/LABA. The excess risk was most evident in RCTs in which the average underlying baseline risk for MACE was >1% per year. Compared with LAMA only, LABA only or placebo, dual LAMA/LABA therapy did not significantly increase the risk of MACE, though these comparisons may have lacked sufficient statistical power. CONCLUSION: Compared with ICS/LABA, dual LAMA/LABA or triple therapy increases cardiovascular risk in patients with COPD. This should be considered in the context of the incremental benefits of these therapies for symptoms and exacerbation rates in patients with COPD, especially in those with a MACE risk of >1% per year.

Corrigendum: Compound Dihuang Granule inhibits nigrostriatal pathway apoptosis in Parkinson's disease by suppressing the JNK/AP-1 pathway.

[This corrects the article DOI: 10.3389/fphar.2021.621359.].

Cell Wall Destruction and Internal Cascade Synergistic Antifungal Strategy for Fungal Keratitis.

Fungal keratitis is one of the most common blindness-causing diseases, but clinical antifungal treatment remains a challenge. The fungal cell wall and biofilm matrix which severely confine the drug preparation are the critical obstructive factors to therapeutic effects. Herein, we report ethylenediaminetetraacetic acid (EDTA) modified AgCu2O nanoparticles (AgCuE NPs) to disrupt the cell wall and then eradicate C. albicans through the internal cascade synergistic effects of ion-released chemotherapy, chemodynamic therapy, photodynamic therapy, and mild photothermal therapy. AgCuE NPs exhibited excellent antifungal activity both in preventing biofilm formation and in destroying mature biofilms. Furthermore, AgCuE NP based gel formulations were topically applied to kill fungi, reduce inflammation, and promote wound healing, using optical coherence tomography and photoacoustic imaging to monitor nanogel retention and therapeutic effects on the infected murine cornea model. The AgCuE NP gel showed good biosafety and no obvious ophthalmic and systemic side effects. This study suggests that the AgCuE NP gel is an effective and safe antifungal strategy for fungal keratitis with a favorable prognosis and potential for clinical translation.

Lumbar Spine Bone Mineral Density Measurement: Comparison of Dual-Energy X-Ray Absorptiometry and Fat Content Evaluation by Dixon Chemical Shift MRI.

Background: To assess whether the fat signal intensity and fat fraction (FF) of the lumbar vertebrae as measured on the Dixon chemical shift magnetic resonance imaging (MRI) technique can be correlated with the lumbar vertebra bone mineral density (BMD) measured using dual-energy X-ray absorptiometry (DXA). Methods: Forty-five patients were retrospectively collected, and 180 lumbar vertebral bodies (L1-L4) were included. All patients underwent DXA and MRI examinations of the lumbar spine. Taking the T value of DXA as the gold standard and using the diagnostic criteria of the World Health Organization: T score ≥ -1.0SD as normal, -1.0 ~ -2.5SD as osteopenia, and ≤ -2.5SD as osteoporosis. Meanwhile, the signal intensity on T2WI was measured, and FF of L1-L4 vertebral bodies was calculated on MRI images. Bone marrow fat FF calculation formula: FF = [Mfat/(Mfat + Mwater)] × 100% (Mwater and Mfat refer to the total pixel signal intensity value of the region of interest in water image and lipid image, respectively). Finally, the association of signal intensity and FF with DXA was evaluated. Results: Totally 180 vertebral bodies in 45 patients were enrolled. According to the T value, they were divided into the normal group (n = 70), osteopenia group (n = 40), and osteoporosis group (n = 70). The fat signal intensity of the normal group, osteopenia group, and osteoporosis group were 96.6 ± 21.8, 154.5 ± 48.7, 216.3 ± 92.6, and the FF were 30.1 ± 6.2%, 52.6 ± 7.6%, 77.5 ± 7.9%, respectively. Among the three groups, the lumbar T2 fat signal intensity and FF had statistical differences (P < 0.01). Besides, the lumbar fat signal intensity and FF were negatively related to DXA (r =-0.65 and -0.93, P < 0.01). Conclusion: The fat content calculated using the Dixon chemical shift MRI had an inverse relation with BMD. Moreover, the Dixon chemical shift MRI might provide complementary information to osteoporosis-related research fields.

The Effects of Fatty Acids on Inflammatory Bowel Disease: A Two-Sample Mendelian Randomization Study.

Inflammatory Bowel Disease (IBD) is a severe relapsing inflammation of the gastrointestinal tract. The association between fatty acids (FAs) and IBD is controversial and it remains unclear whether there is a causal relationship between them. Mendelian randomization (MR) analysis was province/state for affiliations from the same country performed to clarify the causality. Eligible single nucleotide polymorphisms were selected as instrumental variables from six Genome-wide association studies, involving 114,999 individuals in UK Biobank. The summary-level data on IBD, including Crohn's disease (CD) and ulcerative colitis (UC), were obtained from the International Inflammatory Bowel Disease Genetics Consortium with 20,883 and 27,432 individuals involved. The primary inverse variance weighted (IVW) method as well as other supplementary analysis ones were adopted to evaluate the causal relationship between diverse FAs and IBD. The tests for heterogeneity and pleiotropy, and Leave-one-out analysis were adopted to verify the stability of the results. Omega-3 FA was found to have a causal effect on UC instead of CD. For each Standard Deviation increase in Omega-3 FA genetic levels, the risk of ulcerative colitis was found to be reduced by 39.9% by the IVW method (p = 1.766 × 10-4), by 57.8% by the MR Egger (p = 1.11 × 10-2), by 51.5% by the Weighted median estimator (p = 7.706 × 10-4), by 39% by the Maximum likelihood estimation (p = 3.262 × 10-4), and by 54.5% by the penalized weighted median estimator (p = 1.628 × 10-4). No causal relationship was found between other FAs (including total FA, saturated FA, polyunsaturated FA, monounsaturated FA and omega-6 FA) and IBD. The pleiotropic test and Leave-one-out analysis both proved the validity and reliability of these MR analyses. Omega-3 FA was observed to have a protective effect against UC, providing a new perspective on the investigation of the associations between FAs and IBD.

3D printed PCLA scaffold with nano-hydroxyapatite coating doped green tea EGCG promotes bone growth and inhibits multidrug-resistant bacteria colonization.

OBJECTIVES: 3D-printing scaffold with specifically customized and biomimetic structures gained significant recent attention in tissue engineering for the regeneration of damaged bone tissues. However, constructed scaffolds that simultaneously promote bone regeneration and in situ inhibit bacterial proliferation remains a great challenge. This study aimed to design a bone repair scaffold with in situ antibacterial functions. MATERIALS AND METHODS: Herein, a general strategy is developed by using epigallocatechin-3-gallate (EGCG), a major green tea polyphenol, firmly anchored in the nano-hydroxyapatite (HA) and coating the 3D printed polymerization of caprolactone and lactide (PCLA) scaffold. Then, we evaluated the stability, mechanical properties, water absorption, biocompatibility, and in vitro antibacterial and osteocyte inductive ability of the scaffolds. RESULTS: The coated scaffold exhibit excellent activity in simultaneously stimulating osteogenic differentiation and in situ resisting methicillin-resistant Staphylococcus aureus colonization in a bone repair environment without antibiotics. Meanwhile, the prepared 3D scaffold has certain mechanical properties (39.3 ± 3.2 MPa), and the applied coating provides the scaffold with remarkable cell adhesion and osteogenic conductivity. CONCLUSION: This study demonstrates that EGCG self-assembled HA coating on PCLA surface could effectively enhance the scaffold's water absorption, osteogenic induction, and antibacterial properties in situ. It provides a new strategy to construct superior performance 3D printed scaffold to promote bone tissue regeneration and combat postoperative infection in situ.

Microglia-derived PDGFB promotes neuronal potassium currents to suppress basal sympathetic tonicity and limit hypertension.

Although many studies have addressed the regulatory circuits affecting neuronal activities, local non-synaptic mechanisms that determine neuronal excitability remain unclear. Here, we found that microglia prevented overactivation of pre-sympathetic neurons in the hypothalamic paraventricular nucleus (PVN) at steady state. Microglia constitutively released platelet-derived growth factor (PDGF) B, which signaled via PDGFRα on neuronal cells and promoted their expression of Kv4.3, a key subunit that conducts potassium currents. Ablation of microglia, conditional deletion of microglial PDGFB, or suppression of neuronal PDGFRα expression in the PVN elevated the excitability of pre-sympathetic neurons and sympathetic outflow, resulting in a profound autonomic dysfunction. Disruption of the PDGFBMG-Kv4.3Neuron pathway predisposed mice to develop hypertension, whereas central supplementation of exogenous PDGFB suppressed pressor response when mice were under hypertensive insult. Our results point to a non-immune action of resident microglia in maintaining the balance of sympathetic outflow, which is important in preventing cardiovascular diseases.