Melatonin Attenuates Imiquimod-Induced Psoriasis-Like Inflammation and Restores the Th17/Treg Immune Balance.

Psoriasis is a common immune-mediated skin disease characterized by abnormally reactive inflammation and epidermal hyperplasia. Previous studies have shown melatonin (MLT) has powerful anti-inflammatory effects. The mechanisms that MLT regulates psoriasis-associated skin inflammation remain unclear. Here, in imiquimod-induced psoriasis-like mice, MLT supplementation reduced skin inflammation and corrected the Th17/Treg cell imbalance. Network pharmacology and proteome sequencing analyses revealed that MLT attenuates the inflammatory response in the skin of psoriatic mice by inhibiting the PI3K/Akt signaling pathway. Overall, the data suggest that MLT has a protective effect against psoriasis-like inflammation.

Comprehensive HRMS Screening and Risk Assessments of Aristolochic Acid Analogues in Asari Radix et Rhizoma and Related Commercial Health Products.

Aristolochic acid analogues (AAAs) are well-known toxins. We performed the first comprehensive screening on AAAs in Asari Radix et Rhizoma (underground part of Asarum heterotropoides Schmidt), the only Aristolochiaceae plant widely used in clinical practice. LC-HRMS revealed 70 trace AAAs using polygonal mass defect filtering and precursor ion list strategies, 38 of which were newly discovered in A. heterotropoides. UHPLC-QTrap-MS/MS was then utilized for quantitative/semiquantitative analysis of 26 abundant compounds. Seventeen AAAs were detected from 91 batches of A. heterotropoides and 20 AAAs from 166 consumable products. For 141 Asari-containing proprietary products, aristolactam I and aristolactam II-glucoside exhibited the widest distribution, present in 98% products. AA IVa was the most abundant, detected in 91%. Notably, 60% of the products contained AA I (0.03-0.79 ppm). The safety was assessed using linear extrapolation, permitted daily exposure, cumulative amount, and the margin of exposure. It is recommended that AA I content be limited to 3 ppm.

Integrating cfDNA liquid biopsy and organoid-based drug screening reveals PI3K signaling as a promising therapeutic target in colorectal cancer.

BACKGROUND: The current precision medicine relies on biomarkers, which are mainly obtained through next-generation sequencing (NGS). However, this model failed to find effective drugs for most cancer patients. This study tried to combine liquid biopsy with functional drug tests using organoid models to find potential drugs for cancer patients. METHODS: Colorectal cancer (CRC) patients were prospectively enrolled and blood samples were collected from patients before the start of treatment. Targeted deep sequencing of cfDNA samples was performed using a 14-gene panel. Gastrointestinal (GI) cancer organoids were established and PI3K and mTOR inhibitors were evaluated on organoid models. RESULTS: A total of 195 mutations were detected across 58 cfDNA samples. The most frequently mutated genes were KRAS, TP53, PIK3CA, and BRAF, all of which exhibited higher mutation rates than tissue biopsy. Although 81% of variants had an allele frequency of less than 1%, certain mutations in KRAS, TP53, and SMAD4 had high allele frequencies exceeding 10%. Notably, among the seven patients with high allele frequency mutations, six had metastatic tumors, indicating that a high allele frequency of ctDNA could potentially serve as a biomarker of later-stage cancer. A high rate of PIK3CA mutation (31 out of 67, or 46.3%) was discovered in CRC patients, suggesting possible tumor progression mechanisms and targeted therapy opportunities. To evaluate the value of anti PI3K strategy in GI cancer, different lines of GI cancer organoids were established. The organoids recapitulated the morphologies of the original tumors. Organoids were generally insensitive to PI3K inhibitors. However, CRC-3 and GC-4 showed response to mTOR inhibitor Everolimus, and GC-3 was sensitive to PI3Kδ inhibitor Idelalisib. The CRC organoid with a PIK3CA mutation showed greater sensitivity to the PI3K inhibitor Alpelisib than wildtype organoids, suggesting potential treatment options for the corresponding patients. CONCLUSION: Liquid biopsy holds significant promise for improving precision treatment and tumor prognosis in colorectal cancer patients. The combination of biomarker-based drug prediction with organoid-based functional drug sensitivity assay may lead to more effective cancer treatment.

Hierarchically decorated magnetic nanoparticles amplify the oxidative stress and promote the chemodynamic/magnetic hyperthermia/immune therapy.

Magnetic nanoparticles (MNPs) are promising in tumor treatments due to their capacity for magnetic hyperthermia therapy (MHT), chemodynamic therapy (CDT), and immuno-related therapies, but still suffer from unsatisfactory tumor inhibition in the clinic. Insufficient hydrogen peroxide supply, glutathione-induced resistance, and high-density extracellular matrix (ECM) are the barriers. Herein, we hierarchically decorated MNPs with disulfide bonds (S-S), dendritic L-arginine (R), and glucose oxidase (GOx) to form a nanosystem (MNPs-SS-R-GOx). Its outer GOx layer not only enhanced the H2O2 supply to produce .OH by Fenton reaction, but also generated stronger oxidants (ONOO-) together with the interfaced R layer. The inner S-S layer consumed glutathione to interdict its reaction with oxidants, thus enhancing CDT effects. Importantly, the generated ONOO- tripled the MMP-9 expression to induce ECM degradation, enabling much deeper penetration of MNPs and benefiting CDT, MHT, and immunotherapy. Finally, the MNPs-SS-R-GOx demonstrated a remarkable 91.7% tumor inhibition in vivo. STATEMENT OF SIGNIFICANCE: Magnetic nanoparticles (MNPs) are a promising tumor therapeutic agent but with limited effectiveness. Our hierarchical MNP design features disulfide bonds (S-S), dendritic L-arginine (R), and glucose oxidase (GOx), which boosts H2O2 supply for ·OH generation in Fenton reactions, produces potent ONOO-, and enhances chemodynamic therapy via glutathione consumption. Moreover, the ONOO- facilitates the upregulation of matrix metalloprotein expression beneficial for extracellular matrix degradation, which in turn enhances the penetration of MNPs and benefits the antitumor CDT/MHT/immuno-related therapy. In vivo experiments have demonstrated an impressive 91.7% inhibition of tumor growth. This hierarchical design offers groundbreaking insights for further advancements in MNP-based tumor therapy. Its implications extend to a broader audience, encompassing those interested in material science, biology, oncology, and beyond.

A radiomics approach based on MR imaging for classification of deficiency and excess syndrome of traditional Chinese medicine in prostate cancer.

Objective: To explore the potential imaging biomarkers for predicting Traditional Chinese medicine (TCM) deficiency and excess syndrome in prostate cancer (PCa) patients by radiomics approach based on MR imaging. Methods: A total of 121 PCa patients from 2 centers were divided into 1 training cohort with 84 PCa patients and 1 validation cohort with 37 PCa patients. The PCa patients were divided into deficiency and excess syndrome group according to TCM syndrome differentiation. Radiomic features were extracted from T2-weighted imaging (T2WI), diffusion-weighted imaging and apparent diffusion coefficient images originated from diffusion-weighted imaging. A radiomic signature was constructed after reduction of dimension in training group by the minimum redundancy maximum relevance and the least absolute shrinkage and selection operator. The performance of the model was evaluated by receiver operating characteristic (ROC) curve and calibration curve. Results: The radiomic scores of PCa with TCM excess syndrome group were statistically higher than those of PCa with TCM deficiency syndrome group among T2WI, diffusion-weighted imaging and apparent diffusion coefficient imaging models. The area under ROC curves for T2WI, diffusion-weighted imaging and apparent diffusion coefficient imaging models were 0.824, 0.824, 0.847 in the training cohort and 0.759, 0.750, 0.809 in the validation cohort, respectively. The apparent diffusion coefficient imaging model had the best discrimination in separating patients with TCM excess syndrome and deficiency syndrome, and its accuracy was 0.788, 0.778 in the training and validation cohort, respectively. The calibration curve demonstrated that there was a high consistency between the prediction of radiomic scores and the actual classification of TCM's deficiency and excess syndrome in PCa. Conclusion: The radiomic signature based on MR imaging can be performed as a non-invasive, potential approach to discriminate TCM deficiency syndrome from excess syndrome in PCa, in which apparent diffusion coefficient imaging model has the best diagnostic efficiency.

Olfactory Three-Needle Electroacupuncture Improved Synaptic Plasticity and Gut Microbiota of SAMP8 Mice by Stimulating Olfactory Nerve.

OBJECTIVE: To investigate the effects and mechanisms of olfactory three-needle (OTN) electroacupuncture (EA) stimulation of the olfactory system on cognitive dysfunction, synaptic plasticity, and the gut microbiota in senescence-accelerated mouse prone 8 (SAMP8) mice. METHODS: Thirty-six SAMP8 mice were randomly divided into the SAMP8 (P8), SAMP8+OTN (P8-OT), and SAMP8+nerve transection+OTN (P8-N-OT) groups according to a random number table (n=12 per group), and 12 accelerated senescence-resistant (SAMR1) mice were used as the control (R1) group. EA was performed at the Yintang (GV 29) and bilateral Yingxiang (LI 20) acupoints of SAMP8 mice for 4 weeks. The Morris water maze test, transmission electron microscopy, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining, Nissl staining, Golgi staining, Western blot, and 16S rRNA sequencing were performed, respectively. RESULTS: Compared with the P8 group, OTN improved the cognitive behavior of SAMP8 mice, inhibited neuronal apoptosis, increased neuronal activity, and attenuated hippocampal synaptic dysfunction (P<0.05 or P<0.01). Moreover, the expression levels of synaptic plasticity-related proteins N-methyl-D-aspartate receptor 1 (NMDAR1), NMDAR2B, synaptophysin (SYN), and postsynaptic density protein-95 (PSD95) in hippocampus were increased by OTN treatment (P<0.05 or P<0.01). Furthermore, OTN greatly enhanced the brain-derived neurotrophic factor (BDNF)/cAMP-response element binding (CREB) signaling and phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) signaling compared with the P8 group (P<0.05 or P<0.01). However, the neuroprotective effect of OTN was attenuated by olfactory nerve truncation. Compared with the P8 group, OTN had a very limited effect on the fecal microbial structure and composition of SAMP8 mice, while specifically increased the genera Oscillospira and Sutterella (P<0.05). Interestingly, the P8-N-OT group showed an abnormal fecal microbiota with higher microbial α-diversity, Firmicutes/Bacteroidetes ratio and pathogenic bacteria (P<0.05 or P<0.01). CONCLUSIONS: OTN improved cognitive deficits and hippocampal synaptic plasticity by stimulating the olfactory nerve and activating the BDNF/CREB and PI3K/AKT/mTOR signaling pathways. Although the gut microbiota was not the main therapeutic target of OTN for Alzheimer's disease, the olfactory nerve was essential to maintain the homeostasis of gut microbiota.

Suggested Electroacupuncture for Postoperative Nausea and Vomiting: A Comprehensive Meta-Analysis and Systematic Review of Randomized Controlled Trials.

BACKGROUND The purpose of this meta-analysis was to evaluate the effectiveness of electroacupuncture in preventing and treating postoperative nausea and vomiting (PONV) after general anesthesia. MATERIAL AND METHODS We searched for papers on randomized controlled trials on electroacupuncture for PONV prevention after general anesthesia published in PubMed, Web of Science, and China National Knowledge Infrastructure (CNKI) since October 1, 2016. Primary outcome was incidence of PONV; secondary outcomes were incidence of postoperative nausea (PON) at 6 h, postoperative vomiting (POV) at 6 h, and postoperative antiemetic requirement. Data were combined and analyzed using RevMan 5.4.1 software. RESULTS Eight randomized controlled trials, with 899 total participants, were included. Findings showed (1) there was no significant difference in occurrence rate of PONV between electroacupuncture and control groups (OR=0.31, 95% CI [0.06, 1.49], P=0.14, I²=82%); (2) electroacupuncture reduced incidence of PON at 6 h postoperatively, compared with controls (OR=0.43, 95% CI [0.27, 0.67], P=0.0002, I²=0%); (3) compared with control group, electroacupuncture reduced POV incidence 0-6 h postoperatively (OR=0.38, 95% CI [0.23, 0.63], P=0.0001, I²=0%); (4) electroacupuncture group demonstrated a significant reduction in postoperative requirement for antiemetic medications (OR=0.44, 95% CI [0.25, 0.78], P=0.005, I²=61%); (5) one study reported adverse reactions during observation, with 3 patients experiencing pain and itching at acupuncture site and 2 patients refusing a second acupuncture treatment; all symptoms lasted less than 2 h. CONCLUSIONS Based on current evidence, electroacupuncture significantly reduces the occurrence rate of PON and POV at 6 h after surgery and the use of antiemetic medication postoperatively. However, more high-quality, large-sample randomized controlled trials are needed to further validate its efficacy.

Could long-term dialysis vintage and abnormal calcium, phosphorus and iPTH control accelerate aging among the maintenance hemodialysis population?

OBJECTIVE: Aging is a complex process of physiological dysregulation of the body system and is common in hemodialysis patients. However, limited studies have investigated the links between dialysis vintage, calcium, phosphorus, and iPTH control and aging. The purpose of the current study was to examine these associations. METHODS: During 2020, a cross-sectional study was conducted in 3025 hemodialysis patients from 27 centers in Anhui Province, China. Biological age was calculated by a formula using chronological age and clinical indicators. The absence of the target range for serum phosphorus (0.87-1.45 mmol/L), corrected calcium (2.1-2.5 mmol/L) and iPTH (130-585 pg/mL) were identified as abnormal calcium, phosphorus, and iPTH control. RESULTS: A total of 1131 hemodialysis patients were included, 59.2% of whom were males (669/1131). The mean (standard deviation) of actual age and biological age were 56.07 (12.79) years and 66.94 (25.88), respectively. The median of dialysis vintage was 4.3 years. After adjusting for the confounders, linear regression models showed patients with abnormal calcium, phosphorus, and iPTH control and on hemodialysis for less than 4.3 years (B = 0.211, p = .002) or on hemodialysis for 4.3 years or more (B = 0.302, p < .001), patients with normal calcium, phosphorus, and iPTH control and on hemodialysis for 4.3 years or more (B = 0.087, p = .013) had a higher biological age. CONCLUSION: Our findings support the hypothesis that long-term hemodialysis and abnormal calcium, phosphorus, and iPTH control may accelerate aging in the hemodialysis population. Further studies are warrant to verify the significance of maintaining normal calcium-phosphorus metabolism in aging.

Baicalin promotes antiviral IFNs production and alleviates type I IFN-induced neutrophil inflammation.

Type I and III interferons (IFNs) both serve as pivotal components of the host antiviral innate immune system. Although they exert similar antiviral effects, type I IFNs can also activate neutrophil inflammation, a function not born by type III IFNs. Baicalin, the main bioactive component of Scutellariae radix, has been shown to exert therapeutic effects on viral diseases due to its anti-viral, anti-inflammatory and immunomulatory activities. There is uncertainty, however, on the association between the antiviral effects of baicalin and the modulation of anti-viral IFNs production and the immunological effects of type I IFNs. Here, a Poly (I:C)-stimulated A549 cell line was established to mimic a viral infection model. Our results demonstrated that baicalin could elevate the expression of type I and III IFNs and their receptors in Poly (I:C)-stimulated A549 cells. Moreover, the potential regulation effects of baicalin for type I IFN-induced neutrophil inflammation was further explored. Results showed that baicalin diminished the production of the pro-inflammatory cytokines (IL-1ß, IL-6, IL-17 and TNF-α), ROS, and neutrophil extracellular traps and suppressed chemotaxis. Collectively, all these data indicated that baicalin had a dual role on IFNs production and effects: (1) Baicalin was able to elevate the expression of type I and III IFNs and their receptors, (2) and it alleviated type I IFN-mediated neutrophil inflammatory response. This meant that baicalin has the potential to act as an eximious immunomodulator, exerting antiviral effects and reducing inflammation.

Biotransformation of ginsenoside Rb1 and Rd to four rare ginsenosides and evaluation of their anti-melanogenic effects.

Improving physiological activity of primary ginsenosides through biotransformation is of great significance for food applications. In this study, gynostapenoside XVII, gynostapenoside LXXV, ginsenoside F2, and ginsenoside CK were obtained by enzymolysis of an accessible extract composed of ginsenoside Rb1 and Rd. Their effects on melanin content and tyrosinase activity were compared in vitro, and molecular docking simulation was employed to elucidate the interaction between tyrosinase and individual saponin. The results indicated that four rare ginsenosides decreased tyrosinase activity, melanin content and microphthalmia-associated transcription factor (MITF) expression level, more greatly than their primary ginsenosides, and they were more readily to bind with ASP10 and GLY68 at active site of tyrosinase to inhibit tyrosinase activity as well. These findings suggested that the rare ginsenosides obtained by enzymolysis had excellent anti-melanogenic effect, which could expand the application of ginsenosides in the field of functional foods and health supplements.

Baicalin Antagonizes Prostate Cancer Stemness via Inhibiting Notch1/NF-κB Signaling Pathway.

OBJECTIVE: To investigate the molecular mechanisms underlying the effect of baicalin on prostate cancer (PCa) progression both in vivo and in vitro. METHODS: The in situ PCa stem cells (PCSCs)-injected xenograft tumor models were established in BALB/c nude mice. Tumor volume and weight were respectively checked after baicalin (100 mg/kg) treatment. Hematoxylin-eosin (HE) staining was used to observe the growth arrest and cell necrosis. mRNA expression levels of acetaldehyde dehydrogenase 1 (ALDH1), CD44, CD133 and Notch1 were determined by reverse transcription-polymerase chain reaction. Protein expression levels of ALDH1, CD44, CD133, Notch1, nuclear factor κB (NF-κB) P65 and NF-κB p-P65 were detected by Western blot. Expression and subcellular location of ALDH1, CD44, CD133, Notch1 and NF-κB p65 were detected by immunofluorescence analysis. In vitro, cell cycle distribution and cell apoptosis of PC3 PCSCs was assessed by flow cytometry after baicalin (125 µmol/L) treatment. The migration and invasion abilities of PCSCs were assessed using Transwell assays. Transmission electron microscopy scanning was utilized to observe the structure and autophagosome formation of baicalin-treated PCSCs. In addition, PCSCs were infected with lentiviruses expressing human Notch1. RESULTS: Compared with the control group, the tumor volume and weight were notably reduced in mice treated with 100 mg/kg baicalin (P<0.05 or P<0.01). Histopathological analysis showed that baicalin treatment significantly inhibited cell proliferation and promoted cell apoptosis. Furthermore, baicalin treatment reduced mRNA and protein expression levels of CD44, CD133, ALDH1, and Notch1 as well as the protein expression of NF-κB p-P65 in the xenograft tumor (P<0.01). In vitro, the cell proliferation of PCSCs was significantly attenuated after treatment with 125 µmol/L baicalin for 72 h (P<0.01). The cell migration and invasion rates were decreased following treatment with baicalin for 48 and 72 h (P<0.01). Baicalin notably induced cell apoptosis and seriously damaged the structure of PCSCs. The mRNA and protein expressions of CD133, CD44, ALDH1 and Notch1 in PCSCs were significantly downregulated following baicalin treatment (P<0.01). Importantly, the inhibitory effects of baicalin on PCa progression and stemness were reversed by Notch1 overexpression (P<0.05 or P<0.01). CONCLUSION: Mechanistically, baicalin exhibited a potential therapeutic effect on PCa via inhibiting the Notch1/NF-κB signaling pathway and its mediated cancer stemness.

Association between type of drinking water and upper gastrointestinal cancer incidence in the Linxian General Population.

BACKGROUND: This study aimed to explore the association between drinking water source and risk of upper gastrointestinal (UGI) cancer, including esophageal cancer (EC) and gastric cancer (GC), in the Linxian General Population Nutrition Intervention Trial (NIT) cohort. METHODS: In this study, we used data from the Linxian NIT cohort, which included 29,584 healthy adults aged 40 to 69 years. Subjects were enrolled in April 1986 and followed up until March 2016. Tap water drinking status and demographic characteristics were collected at baseline. Subjects who drank tap water were treated as the exposed group. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were estimated using the Cox proportional hazard model. RESULTS: A total of 5,463 cases of UGI cancer were identified during the 30-year follow-up period. After adjusting for multiple factors, the incidence rate of UGI cancer in participants who drank tap water was significantly lower compared with individuals in the control (HR = 0.91, 95% CI: 0.86-0.97). A similar association was observed between tap water drinking and EC incidence (HR = 0.89, 95% CI: 0.82-0.97). The association between drinking tap water and risk of UGI cancer and EC incidence did not vary across the subgroup by age and gender (All Pinteraction > 0.05). For EC incidence, an interaction effect was observed for riboflavin/niacin supplements and drinking water source (Pinteraction = 0.03). No association was observed between drinking water source and GC incidence. CONCLUSIONS: In this prospective cohort study in Linxian, participants who drank tap water had a lower risk of EC incidence. As a source of drinking water, use of tap water may reduce the risk of EC by avoiding exposure to nitrate/nitrite. Measures should be taken to improve the quality of drinking water in high-incidence areas of EC. TRIAL REGISTRATION: The trial is registered with ClinicalTrials.gov (NCT00342654, 21/06/2006), and the trial name is Nutrition Intervention Trials in Linxian Follow-up Study.

Multidisciplinary strategies to enhance therapeutic effects of flavonoids from Epimedii Folium: Integration of herbal medicine, enzyme engineering, and nanotechnology.

Flavonoids such as baohuoside I and icaritin are the major active compounds in Epimedii Folium (EF) and possess excellent therapeutic effects on various diseases. Encouragingly, in 2022, icaritin soft capsules were approved to reach the market for the treatment of hepatocellular carcinoma (HCC) by National Medical Products Administration (NMPA) of China. Moreover, recent studies demonstrate that icaritin can serve as immune-modulating agent to exert anti-tumor effects. Nonetheless, both production efficiency and clinical applications of epimedium flavonoids have been restrained because of their low content, poor bioavailability, and unfavorable in vivo delivery efficiency. Recently, various strategies, including enzyme engineering and nanotechnology, have been developed to increase productivity and activity, improve delivery efficiency, and enhance therapeutic effects of epimedium flavonoids. In this review, the structure-activity relationship of epimedium flavonoids is described. Then, enzymatic engineering strategies for increasing the productivity of highly active baohuoside I and icaritin are discussed. The nanomedicines for overcoming in vivo delivery barriers and improving therapeutic effects of various diseases are summarized. Finally, the challenges and an outlook on clinical translation of epimedium flavonoids are proposed.

Electroacupuncture Improves Blood-Brain Barrier and Hippocampal Neuroinflammation in SAMP8 Mice by Inhibiting HMGB1/TLR4 and RAGE/NADPH Signaling Pathways.

OBJECTIVE: To investigate the molecular mechanisms underlying the beneficial effect of electroacupuncture (EA) in experimental models of Alzheimer's disease (AD) in vivo. METHODS: Senescence-accelerated mouse prone 8 (SAMP8) mice were used as AD models and received EA at Yingxiang (LI 20, bilateral) and Yintang (GV 29) points for 20 days. For certain experiments, SAMP8 mice were injected intravenously with human fibrin (2 mg). The Morris water maze test was used to assess cognitive and memory abilities. The changes of tight junctions of blood-brain barrier (BBB) in mice were observed by transmission electron microscope. The expressions of fibrin, amyloid- ß (Aß), and ionized calcium-binding adapter molecule 1 (IBa-1) in mouse hippocampus (CA1/CA3) were detected by reverse transcription-quantitative polymerase chain reaction (qRT-PCR), Western blot or immunohistochemical staining. The expression of fibrin in mouse plasma was detected by enzyme-linked immunosorbent assay. The expressions of tight junction proteins zonula occludens-1 and claudin-5 in hippocampus were detected by qRT-PCR and immunofluorescence staining. Apoptosis of hippocampal neurons was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. RESULTS: Fibrin was time-dependently deposited in the hippocampus of SAMP8 mice and this was inhibited by EA treatment (P<0.05 or P<0.01). Furthermore, EA treatment suppressed the accumulation of Aß in the hippocampus of SAMP8 mice (P<0.01), which was reversed by fibrin injection (P<0.05 or P<0.01). EA improved SAMP8 mice cognitive impairment and BBB permeability (P<0.05 or P<0.01). Moreover, EA decreased reactive oxygen species levels and neuroinflammation in the hippocampus of SAMP8 mice, which was reversed by fibrin injection (P<0.05 or P<0.01). Mechanistically, EA inhibited the promoting effect of fibrin on the high mobility group box protein 1 (HMGB1)/toll-like receptor 4 (TLR4) and receptor for advanced glycation end products (RAGE)/nicotinamide adenine dinucleotide phosphate (NADPH) signaling pathways (P<0.01). CONCLUSION: EA may potentially improve cognitive impairment in AD via inhibition of fibrin/A ß deposition and deactivation of the HMGB1/TLR4 and RAGE/NADPH signaling pathways.

Optimization of C50 Carotenoids Production by Open Fermentation of Halorubrum sp. HRM-150.

C50 carotenoids, as unique bioactive molecules, have many biological properties, including antioxidant, anticancer, and antibacterial activity, and have a wide range of potential uses in the food, cosmetic, and biomedical industries. The majority of C50 carotenoids are produced by the sterile fermentation of halophilic archaea. This study aims to look at more cost-effective and manageable ways of producing C50 carotenoids. The basic medium, carbon source supplementation, and optimal culture conditions for Halorubrum sp. HRM-150 C50 carotenoids production by open fermentation were examined in this work. The results indicated that Halorubrum sp. HRM-150 grown in natural brine medium grew faster than artificial brine medium. The addition of glucose, sucrose, and lactose (10 g/L) enhanced both biomass and carotenoids productivity, with the highest level reaching 4.53 ± 0.32 µg/mL when glucose was added. According to the findings of orthogonal studies based on the OD600 and carotenoids productivity, the best conditions for open fermentation were salinity 20-25%, rotation speed 150-200 rpm, and pH 7.0-8.2. The up-scaled open fermentation was carried out in a 7 L medium under optimum culture conditions. At 96 h, the OD600 and carotenoids productivity were 9.86 ± 0.51 (dry weight 10.40 ± 1.27 g/L) and 7.31 ± 0.65 µg/mL (701.40 ± 21.51 µg/g dry weight, respectively). When amplified with both universal bacterial primer and archaeal primer in the open fermentation, Halorubrum remained the dominating species, indicating that contamination was kept within an acceptable level. To summarize, open fermentation of Halorubrum is a promising method for producing C50 carotenoids.

The impact of lactating Hu sheep's dietary protein levels on lactation performance, progeny growth and rumen development.

This study aimed to investigate whether lactating Hu sheep's dietary protein levels could generate dynamic effects on the performance of their offspring. Twelve ewes with similar parity were fed iso-energy diets which contained different protein levels (P1: 9.82%, P2: 10.99%) (n = 6), and the corresponding offspring were divided into SP1 and SP2 (n = 12). At 60 days, half of the lambs were harvested for further study: the carcass weight (p = 0.043) and dressing percentage (p = 0.004) in the SP2 group were significantly higher than SP1. The acetic acid (p = 0.007), propionic acid (p = 0.003), butyric acid (p < 0.001) and volatile fatty acids (p < 0.001) in rumen fluid of SP2 were significantly lower than SP1. The expression of MCT2 (p = 0.024), ACSS1 (p = 0.039) and NHE3 (p = 0.006) in the rumen of SP2 was lower than SP1, while the HMGCS1 (p = 0.026), HMGCR (p = 0.024) and Na+/K+-ATPase (p = 0.020) was higher than SP1. The three dominant phyla in the rumen are Bacteroidetes, Proteobacteria and Firmicutes. The membrane transport, amino acid metabolism and carbohydrate metabolism of SP1 were relatively enhanced, the replication and repair function of SP2 was relatively enhanced. To sum up, the increase of dietary protein level significantly increased the carcass weight and dressing percentage of offspring and had significant effects on rumen volatile fatty acids, acetic acid activation and cholesterol synthesis related genes. HIGHLIGHTSIn the early feeding period, the difference in ADG of lambs was mainly caused by the sucking effect.The increase in dietary protein level of ewes significantly increased the carcass weight and dressing percentage of offspring.The dietary protein level of ewes significantly affected the volatile fatty acids (VFAs) and genes related to acetic acid activation and cholesterol synthesis in the rumen of their offspring.The membrane transport, amino acid metabolism and carbohydrate metabolism of the offspring of ewes fed with a low protein diet were relatively enhanced.The replication and repair function of the offspring of ewes fed with a high protein diet was relatively strengthened.

A multi-center study on the association between serum magnesium levels and allostatic load in hemodialysis patients.

Objective: Serum magnesium (Mg2+) levels are associated with insulin resistance, hypertension, lipid abnormalities, and inflammation. However, limited studies have indicated the relationship between Mg2+ and multiple system indexes. The purpose of this study was to investigate the association between Mg2+ and allostatic load (AL) in hemodialysis patients. Methods: A cross-sectional survey was conducted on hemodialysis patients from different centers in Anhui Province, China, between January and December 2020. A total of 3,025 hemodialysis patients were recruited. Their clinical data were measured before hemodialysis. Information was collected by an online self-reported questionnaire and medical record. Serum Mg2+ was divided into three groups by tertiles. A score of AL greater than or equal to 3 was defined as high AL. A binary logistic regression model was applied to examine the relationship between serum Mg2+ and AL. Results: A total of 1,222 patients undergoing hemodialysis were included, 60% of whom were males (733/1,222). The mean (standard deviation) age of patients was 55.90 (12.75). The median level of serum Mg2+ was 1.22 mmol/L. The rate of high AL levels was 23.4%. Serum Mg2+ was negatively correlated with body mass index, fasting blood glucose (Glu), and C-reactive protein and positively correlated with high-density lipoprotein, low-density lipoprotein, total cholesterol, diastolic blood pressure (DBP), and serum phosphorus. After adjusting for gender, anxiety, diabetes, family residence, lipid-lowering agents, antihypertensive medications, albumin, and Glu, the binary logistic regression model showed that patients with lower levels of serum Mg2+ were more likely have high AL (OR for the T1 group of serum Mg2+:1.945, 95% CI: 1.365-2.773, and OR for the T2 group of serum Mg2+:1.556, 95% CI: 1.099-2.201). Conclusion: Our data support the hypothesis that higher serum Mg2+ concentrations may contribute to lower health risk in hemodialysis populations. Further randomized controlled trials and cohort studies are warranted to verify whether Mg2+ supplementation could be part of routine examinations in hemodialysis populations.

Association of Folic Acid Supplementation in Early Pregnancy with Risk of Gestational Diabetes Mellitus: A Longitudinal Study.

BACKGROUND: Gestational diabetes mellitus (GDM) may lead to many adverse effects on women and their offspring. METHOD: 24,429 pregnant women were enrolled during early pregnancy from January 2018 to December 2021. The self-reported intake of folic acid supplements was assessed via a questionnaire. Oral glucose tolerance tests were used for the diagnosis of GDM. The association between intake or not, dose, and duration of folic acid and GDM risk was assessed. RESULTS: 6396 (26.18%) women were diagnosed with GDM. In the univariate models, folic acid was found to be correlated with total GDM risk (OR = 0.82, 95% CI: 0.70~0.95, p = 0.009). After adjusting for potential confounders, the association with total GDM risk was not significant, but the association of folic acid with 2-h PBG diagnosed GDM risk was consistently significant (OR = 0.75, 95% CI: 0.63~0.90, p = 0.002). No significant association between the dose and duration of folic acid supplementation and GDM risk was observed in the analyses. CONCLUSION: Folic acid supplementation might be a protective factor for the risk of GDM caused by the high level of postprandial blood glucose, but the dose or duration-related association between folic acid supplementation and GDM risk is not clear.

Keratin-Based Composite Bioactive Films and Their Preservative Effects on Cherry Tomato.

In this study, keratins were extracted from pig nail waste through the reduction method using L-cysteine as a reductant. Curcumin was successively incorporated in a mixed solution including keratin, gelatin, and glycerin to prepare different kinds of keratin/gelatin/glycerin/curcumin composite films. The morphology of the keratin/ gelatin/glycerin/curcumin composite films were examined using scanning electron microscopy. The structures and the molecular interactions between curcumin, keratin, and pectin were examined using Fourier transform infrared spectroscopy and X-ray diffraction, and the thermal properties were determined through thermogravimetric analysis. The tensile strengths of keratin/gelatin/glycerin/curcumin and keratin/gelatin/curcumin composite films are 13.73 and 12.45 MPa, respectively, and their respective elongations at break are 56.7% and 4.6%. In addition, compared with the control group (no film wrapped on the surface of tomato), the ratio of weight loss of the keratin (7.0%)/gelatin (10%)/glycerin (2.0%)/curcumin (1.0%) experimental groups is 8.76 ± 0.2%, and the hardness value of the tomatoes wrapped with composite films is 11.2 ± 0.39 kg/cm3. Finally, the composite films have a superior antibacterial effect against Staphylococcus aureus and Escherichia coli because of the addition of curcumin. As the concentration of curcumin reaches 1.0%, the antibacterial activity effect of the film is significantly improved. The diameter of the inhibition zone of E. coli is (12.16 ± 0.53) mm, and that of S. aureus is (14.532 ± 0.97) mm. The multifunctional keratin/gelatin/glycerin/curcumin bioactive films have great potential application in the food packaging industry.

Moxibustion attenuates inflammation and alleviates axial spondyloarthritis in mice: Possible role of APOE in the inhibition of the Wnt pathway.

Background and aim: Moxibustion is widely used in China and other East Asian countries to manage the symptom of ankylosing spondylitis (AS). This study investigated the effects of moxibustion intervention on protein expression through proteomics analysis in AS mice. Experimental procedure: Proteoglycan-induced spondylitis (PGISp) was established in Balb/c mice. PGISp mice were intervened with daily moxibustion at ST36, BL23, and DU4 for four weeks. Various biochemical (including pro-inflammatory cytokines and bone metabolism indexes) and histopathological parameters were determined. The effects of moxibustion on protein changes in AS mice were analyzed using data-independent acquisition-mass spectrometry (DIA-MS). The target proteins were then confirmed by Western blot analysis. Results: Moxibustion significantly decreased pro-inflammatory cytokine expression including IL-1ß, TNF-α, IL-17, and IL-6, reduced the mRNA expression of RANKL, RANK, ALP, and OCN, and improved the histopathological examination in AS mice. DIA-MS proteomic technique has identified 25 candidate proteins involved in the mechanisms of moxibustion for AS mice, most of which are mainly associated with the regulation of Wnt/ß-catenin. Integrated pathway analysis revealed that glycine, serine and threonine metabolism together with lipid metabolism were the most important canonical pathways involved in the anti-AS effect of moxibustion. In line with the multi-omic data, the levels of BPGM, APOC2, APOE, and GPD1 modified in the AS mice, intervened with moxibustion as confirmed by Western blot. In particular, APOE may play a key role in linking the lipid metabolism and the Wnt/ß-catenin pathway of new bone formation. Conclusion: In conclusion, moxibustion may reduce pro-inflammatory cytokines and improve bone erosion for AS mice. The regulation of APOE by moxibustion may have a potential inhibitory effect on the Wnt/ß-catenin pathway in AS mice. However, due to the lack of silencing or overexpression of key molecules of the signal pathway, whether the beneficial and positive effect of moxibustion involved in the regulation of Wnt/ß-catenin signaling pathway by APOE or other aspects, needed to be explored in further study.