Extraction, purification, structural features, modifications, bioactivities, structure-activity relationships, and applications of polysaccharides from garlic: A review.

Garlic is a common vegetable and spice in people's daily diets, in which garlic polysaccharide (GP) is one of the most important active components with a variety of benefits, such as antioxidant, immune-enhancing, anti-inflammatory, liver-protective and bowel-regulating properties. >20 types of GPs, mainly crude polysaccharides, have been identified. However, the exact chemical composition of GPs or the mechanism underlying their pharmacological activity is still not fully understood. The extraction and purification methods of GPs are compared in this review while providing detailed information on their structural features, identification methods, major biological activities, mechanisms of actions, structural modifications, structure-activity relationships as well as potential applications. Finally, the limitations of GP research and future issues that need to be addressed are discussed in this review. GPs are widely recognized as substances with great potential in the pharmaceutical and food industries. Therefore, this review aims to provide a comprehensive summary of the latest research progresses in the field of GPs, together with scientific insights and a theoretical support for the development of GPs in research and industrialization.

Traditional Chinese Medicine-based Treatment in Cardiovascular Disease: Potential Mechanisms of Action.

Cardiovascular Disease (CVD) is the leading cause of morbidity and death worldwide and has become a global public health problem. Traditional Chinese medicine (TCM) has been used in China to treat CVD and achieved promising results. Therefore, TCM has aroused significant interest among pharmacologists and medical practitioners. Previous research showed that TCM can regulate the occurrence and development of atherosclerosis (AS), ischemic heart disease, heart failure, myocardial injury, and myocardial fibrosis by inhibiting vascular endothelial injury, inflammation, oxidant stress, ischemia-reperfusion injury, and myocardial remodeling. It is well-known that TCM has the characteristics of multi-component, multi-pathway, and multitarget. Here, we systematically review the bioactive components, pharmacological effects, and clinical application of TCM in preventing and treating CVD.

Effects of a mixture of glycerol monolaurate and cinnamaldehyde supplementation on laying performance, egg quality, and antioxidant status in laying hens.

BACKGROUND: This study aimed to determine the effects of a mixture of glycerol monolaurate and cinnamaldehyde (GCM) supplementation on the laying performance, egg quality, antioxidant capacity, and serum parameters of laying hens. A total of 1120 14-week-old Jingfen-1 strain laying hens with similar performance were randomly allocated to four dietary treatments: control, and GCM groups supplemented with 250, 500, or 1000 mg kg-1 for 12 weeks. RESULTS: Compared with the control group, GCM-supplemented groups significantly reduced (P < 0.05) the rate of unqualified eggs of laying hens aged 17-24 weeks. Supplementation of GCM significantly increased (P < 0.05) yolk color and serum glutathione peroxidase (GSH-Px) activity but decreased (P < 0.05) the hydrogen peroxide (H2 O2 ) content in the serum of laying hens at the age of 20 weeks. Furthermore, groups supplemented with GCM showed a significant increase (P < 0.05) in Haugh unit, yolk color, activities of total superoxide dismutase and GSH-Px, and the glucose content in serum, and a decrease (P < 0.05) in the content of urea nitrogen and H2 O2 and malondialdehyde in serum of laying hens at the age of 24 weeks. 500 mg kg-1 GCM supplementation significantly increased (P < 0.05) the number of large white follicles and 1000 mg kg-1 GCM supplementation decreased the number of large yellow follicles in 28-week-old laying hens. CONCLUSION: These results indicated that GCM supplementation has positive effects on reducing egg loss and improving egg quality in the early laying period of laying hens. © 2023 Society of Chemical Industry.

Nano-selenium Antagonizes Heat Stress-Induced Apoptosis of Rainbow Trout (Oncorhynchus mykiss) Hepatocytes by Activating the PI3K/AKT Pathway.

The cold-water fish rainbow trout (Oncorhynchus mykiss) shows poor resistance to heat, which is the main factor restricting their survival and yield. With the advancement of nanotechnology, nano-selenium (nano-Se) has emerged as a key nano-trace element, showing unique advantages, including high biological activity and low toxicity, for studying the response of animals to adverse environmental conditions. However, little is still known regarding the potential protective mechanisms of nano-Se against heat stress-induced cellular damage. Herein, we aimed to investigate the mechanism underlying the antagonistic effects of nano-Se on heat stress. Four groups were assessed: CG18 (0 µg/mL nano-Se, 18 °C), Se18 (5.0 µg/mL nano-Se, 18 °C), CG24 (0 µg/mL nano-Se, incubated at 18 °C for 24 h and then transferred to 24 °C culture), and Se24 (5.0 µg/mL nano-Se, incubated at 18 °C for 24 h and then transferred to 24 °C culture). We found that after heat treatment (CG24 group), T-AOC, GPx, and CAT activities in rainbow trout hepatocytes showed a decrease of 36%, 33%, and 19%, respectively, while ROS and MDA levels showed an increase of 67% and 93%, respectively (P < 0.05). Meanwhile, the mRNA levels of the apoptosis-related genes caspase3, caspase9, Cyt-c, Bax, and Bax/Bcl-2 in the CG24 group were 41%, 47%, 285%, 65%, and 151% higher than those in the CG18 group, respectively, while those of PI3K and AKT were 31% and 17% lower, respectively (P < 0.05). Besides, flow cytometry analysis showed an increase in the level of apoptotic cells after heat exposure. More importantly, we observed that nano-Se cotreatment (Se24 group) remarkably attenuated heat stress-induced effects (P < 0.05). We conclude that heat stress induces oxidative stress and apoptosis in rainbow trout hepatocytes. Nano-Se ameliorates heat stress-induced apoptosis by activating the PI3K/AKT pathway. Our results provide a new perspective to improve our understanding of the ability of nano-Se to confer heat stress resistance.

Natural compounds from botanical drugs targeting mTOR signaling pathway as promising therapeutics for atherosclerosis: A review.

Atherosclerosis (AS) is a chronic inflammatory disease that is a major cause of cardiovascular diseases (CVDs), including coronary artery disease, hypertension, myocardial infarction, and heart failure. Hence, the mechanisms of AS are still being explored. A growing compendium of evidence supports that the activity of the mechanistic/mammalian target of rapamycin (mTOR) is highly correlated with the risk of AS. The mTOR signaling pathway contributes to AS progression by regulating autophagy, cell senescence, immune response, and lipid metabolism. Various botanical drugs and their functional compounds have been found to exert anti- AS effects by modulating the activity of the mTOR signaling pathway. In this review, we summarize the pathogenesis of AS based on the mTOR signaling pathway from the aspects of immune response, autophagy, cell senescence, and lipid metabolism, and comb the recent advances in natural compounds from botanical drugs to inhibit the mTOR signaling pathway and delay AS development. This review will provide a new perspective on the mechanisms and precision treatments of AS.

Dietary nano-selenium alleviates heat stress-induced intestinal damage through affecting intestinal antioxidant capacity and microbiota in rainbow trout (Oncorhynchus mykiss).

Heat stress-induced intestinal damage is a key event in fish pathology. Nano-selenium (nano-Se) shows remarkably high biological activity and low toxicity, making it an ideal and ecological Se formulation; however, to date, the protective effects of nano-Se against heat stress-induced intestinal injury and pertinent molecular mechanisms remain unknown. Herein, rainbow trout (Oncorhynchus mykiss) were fed either a basal diet or basal diet + 5 mg/kg nano-Se. Samples were collected before (18 °C for 9 days; CG18 and Se18 groups) and after (24 °C for 8 h; CG24 and Se24 groups) heat stress treatment. On heat stress exposure, intestinal villus height, muscularis thickness, and goblet cell number decreased, and expression of tight junction proteins (ZO-1, occludin, and claudin-8d) was downregulated; dietary supplementation with nano-Se alleviated these effects. Furthermore, in the presence of nano-Se, catalase activity was elevated, and expression of diverse heat shock proteins (Hsp70b, Hsp90α, and Hsp30), selenoproteins (Gpx1a, Gpx1b1, and Trx), and anti-inflammatory cytokine (TGF-ß) was upregulated. In contrast, nano-Se supplementation significantly alleviated the increase of the expression of pro-inflammatory cytokines (IL-1ß and TNF-α) and the malondialdehyde content. We also observed that heat stress markedly increased the relative abundance of Actinobacteria, Firmicutes, Methylobacterium, Akkermansia, and Deinococcus and decreased that of Proteobacteria; nano-Se supplementation restored these changes, making their distribution similar to that in the control group. Overall, our findings suggest that nano-Se plays a protective role against heat stress-induced intestinal damage in rainbow trout by promoting the recovery of antioxidant enzyme activity, enhancing protein repair, alleviating inflammatory responses, and restoring intestinal microbiota composition.

Transcriptome sequencing reveals the effect of selenium nanoparticles on primary hepatocytes of rainbow trout.

Heat stress is one of the important threats in rainbow trout culture, and selenium nanoparticles (SeNPs) have an important role in combating heat stress and enhancing immunity. In this study, to enable rainbow trout to survive at higher temperatures, we added 5 µg/mL SeNPs to hepatocytes to study the resistance effect and immune effect of SeNPs against heat stress, thus enabling rainbow trout to adapt to summer temperatures (Average 26 °C) in Lanzhou, Gansu Province, China. Therefore, we investigated the transcriptome expression profile of hepatocytes spiked with SeNPs when exposed to heat stress. A total of 234 differentially expressed genes (DEGs) were firmly established in SeNPs-added group when exposed to heat stress compared to non-SeNPs-added group. Of these DEGs, 156 were up-regulated and 78 were down-regulated. These DEGs were grouped into different Gene Ontology (GO) functional terms and enriched in 75 significantly different Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, of which approximately-one-third (19) were associated with immunity. STRING was used to identify 39 key immune DEGs belonging to 5 immune pathways (C-type lectin receptor signaling pathway, FoxO signaling pathway, Toll-like receptor signaling pathway, RIG-I-like receptor signaling pathway, and Rachidonic acid metabolism). These pathways interact extensively and formed a complex network to regulate heat stress. These results provided an important basis for future elucidation of the role of SeNPs in heat stress resistance and immune enhancement in rainbow trout.

Effect of selenium nanoparticles on alternative splicing in heat-stressed rainbow trout primary hepatocytes.

Alternative splicing (AS) is a ubiquitous post-transcriptional regulatory mechanism in eukaryotes that generates multiple mRNA isoforms from a single gene, increasing diversity of mRNAs and proteins that are essential for eukaryotic developmental processes and responses to environmental stress. Results showed that a total of 37,463 AS events were identified in rainbow trout hepatocytes. In addition, a total of 364 differential alternative splicing (DAS) events were identified in hepatocytes under selenium nanoparticles (SeNPs) and 3632 DAS events were identified under a combination of SeNPs and heat stress (24 °C). Gene Ontology (GO) enrichment showed that some subcategories "immune effector processes", "response to stimuli" and "antioxidant activity" were associated with immunity, abiotic stimuli and antioxidants. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment showed that differentially expressed genes (DEGs) were significantly enriched in spliceosomes by adding SeNPs in heat-stressed hepatocytes. Splicing factor family (SRSF3, SRSF7, SRSF9, U2AF1 and U2AF2) and pre-RNA splicing factors (ACIN1 and PPRF18) were significantly upregulated and promoted AS. Furthermore, addition of SeNPs activated the phosphatidylinositol signaling system and upregulated the related genes PI4KA, DGKH, ITPK1 and Ocrl, and thus attenuated the inflammatory response to heat stress and enhanced resistance to heat stress by activating the adherent plaque kinase-PI3K-Akt signaling pathway and calcium channels. Those findings suggested that AS could be an essential regulatory mechanism in adaptation of rainbow trout to heat-stressed environments.

The association between maternal tea consumption and the risk of pregnancy induced hypertension: A retrospective cohort study in Lanzhou, China.

BACKGROUND: Existing evidence on the relationship between maternal tea consumption and pregnancy induced hypertension (PIH) is inconclusive. This study aimed to evaluate the association between maternal tea consumption and the risk of PIH. METHODS: This study analysed the data of women without chronic hypertension who participated in a retrospective birth cohort study conducted from 2010 to 2012 at the Gansu Provincial Maternity and Child Care Hospital in Lanzhou, China. Multivariable logistic regression models were used to estimate the association between tea consumption and the risk of PIH and its clinical subtypes by different tea exposure time windows. RESULTS: Among the 10,452 women included in this study, tea consumption during pregnancy was significantly associated with an increased risk of PIH (odds ratio [OR] = 1.44, 95 % confidence interval [CI]: 1.01, 2.05), gestational hypertension (OR = 1.86, 95 % CI: 1.07, 3.21), and early-onset preeclampsia (OR = 2.93, 95 % CI: 1.21, 7.09). This was especially the case with black tea (OR = 3.57, 95 % CI: 1.67, 7.62). CONCLUSIONS: Tea consumption during pregnancy might be associated with an increased risk of PIH, gestational hypertension, and early-onset preeclampsia. These findings have important implications for public health in reducing the PIH.

Comprehensive proteomic analysis to elucidate the anti-heat stress effects of nano-selenium in rainbow trout (Oncorhynchus mykiss).

Because of the continuous intensification of global warming, extreme climate fluctuations, and high-density farming, cold-water rainbow trout (Oncorhynchus mykiss) are exposed to conditions of heat stress, which has severely impacted their survival and yield. Nano-selenium (nano-Se) shows higher biological activity and lower toxicity and has emerged as an ideal and ecological Se formulation. Herein rainbow trout were fed either a basal diet (control group) or basal diet plus 5 mg/kg nano-Se (treatment group). Samples were collected before (18 °C for 9 days; CG18, Se18) and after (24 °C for 8 h; CG24, Se24) heat stress. The DIA/SWATH approach was then applied to compare changes at the proteome level. We found 223 and 269 differentially abundant proteins in the CG18-CG24 and Se18-Se24 groups, respectively, which mainly included apoptosis-, heat stress-, and lipid-related proteins. In comparison with the CG18-CG24 group, the Se18-Se24 group showed higher abundance of molecular chaperone, such as Hsp70, Hsp90a.1, Hspa8, Hsp30, DNAJA4, Dnajb1, Bag2 and Ahsa1; on nano-Se supplementation, the heat stress-induced decline in the abundance of the selenoprotein MsrB2 was partially restored. Furthermore, nano-Se supplementation downregulated the abundance of lipid-related (CYP51, EBP, DHCR7, DHCR24, and APOB) and pro-apoptotic (caspase-8 and Bad) proteins. Protein-protein interaction analyses suggested that nano-Se inhibits apoptosis by upregulating the expression of Hsp70, Hsp90a.1, Hspa8, and Dnajb1; further, Hsp70/Hspa8 and MsrB2 appear to play a synergistic role in antioxidant defense under heat stress. Overall, our findings provide novel insights into nano-Se-mediated tolerance of heat stress, demonstrating that nano-Se exerts its anti-heat stress effects in rainbow trout by promoting protein repair, enhancing recovery of antioxidant enzyme activity, and alleviating lipid metabolism and apoptosis.

Dietary nanoselenium supplementation for heat-stressed rainbow trout: effects on organizational structure, lipid changes, and biochemical parameters as well as heat-shock-protein- and selenoprotein-related gene expression.

Nanoselenium (nano-Se) shows unique protective effects against environmental heat stress in rainbow trout as a selenium source additive and free radical scavenger. Accordingly, we investigated the effects of supplementation with different levels of nano-Se (0, 5, and 10 mg/kg) and before and after heat stress (24°C) for different treatment times on the dynamic changes of rainbow trout liver tissue structure, lipid changes, biochemical properties, and gene expression. The results showed that, under heat stress, the fish supplementation of 5 mg/kg nano-Se significantly increased liver glutathione peroxidase (GPx) activity and upregulated expression levels of HSP70b, HSP90a1, GPx1a, and Trx mRNAs, while liver alanine aminotransferase (ALT), aspartate aminotransferase (AST), superoxide dismutase (SOD), and malondialdehyde (MDA) levels as well as tissue structure damage and lipid accumulation were decreased. Combining the trends for the above indicators indicated that stress began to increase significantly at 8 h. It can be concluded that supplementation with 5 mg/kg nano-Se effectively alleviates stress damage in rainbow trout. Furthermore, stress at 24°C for 8 h can be thought of as a critical time point for the study of heat stress in rainbow trout, with significant changes in response but no serious damage. Thus, these results provide a reference for the addition of nano-Se to rainbow trout feed and provide theoretical and practical guidance for enhancing the resistance of rainbow trout to heat stress.

Metabonomics analysis reveals the protective effect of nano­selenium against heat stress of rainbow trout (Oncorhynchus mykiss).

Nano­selenium (nano-Se) shows high biological activity and low toxicity, and has emerged as an ideal antioxidant. Our goal was to determine the underlying mechanism of nano-Se-mediated heat stress tolerance in rainbow trout (Oncorhynchus mykiss). Using liquid chromatography-mass spectrometry (LC-MS) metabolomics, histomorphology, and conventional biochemical assays, we investigated the physiological responses of heat-stressed rainbow trout to nano-Se. Fish were fed to two levels nano-Se at 18 °C for 9 days: CG18 (0 mg/kg) and Se18 (5 mg/kg). The water temperature of all groups was increased to 24 °C and maintained for 8 h (CG24, Se24). The results showed that most glycerophospholipids and CoA levels were decreased in CG18-CG24, and pathway enrichment analysis showed that it mainly interfered with glycerophospholipids and fatty acid metabolism. Meanwhile, hematoxylin and eosin and Oil Red O staining showed significant damage to CG18-CG24, which was ameliorated by Se18-Se24. The results combining analysis of antioxidant enzymes and heat shock proteins further support the notion that nano-Se supplementation inhibited galactose metabolism and activated the glutamate-glutamine metabolic pathway as the key metabolic strategy against heat stress. These results could establish heat stress defense strategies and increase our understanding of the mechanism of nutrient participation in fish's response to adverse environments. SIGNIFICANCE: Global warming is affecting the distribution and survival of cold-water fish worldwide, through seasonal water temperature increases and an increase in the frequency of extreme heat wave events. Surprisingly, Nano­selenium (Nano-Se) with its outstanding advantages of high biological activity and low toxicity, making it a good Se nutrient supplement and free radical scavenger, and also an ideal and ecological way to supplement Se. How to utilize the metabolome to better address the complexity of the interactions that may occur with Nano-Se during the process of heat stress resistance is an important challenge. In the present study, this is the first publicly available metabonomics study of the anti-heat stress effect of Nano-Se as a nutrient on rainbow trout liver. These data indicated that Nano-Se effectively alleviated stress damage in rainbow trout, in which heat stress interfered with the metabolism of glycerophospholipids and fatty acids significantly, causing liver cell membrane damage and lipid metabolism disorders in rainbow trout. Meanwhile, supplementation of Nano-Se downregulated galactose metabolism and activated glutamate and glutamine metabolic pathways, which seems to be a key metabolic strategy to combat heat stress. The results provide a scientific basis for the development of an anti-heat-stress feed for rainbow trout that help maintain their health, productivity and welfare under unfavorable heat conditions.

Effectiveness and safety of acupuncture combined with traditional Chinese medicine in the treatment of chronic prostatitis: A systematic review and meta-analysis.

OBJECTIVE: Chronic prostatitis (CP) is a common disease in the outpatient department of males and urology. Clinical studies have found that acupuncture combined with traditional Chinese medicine (TCM) has achieved good results in treating CP, but its efficacy and safety are not completely clear. This study aimed to investigate the efficacy and safety of acupuncture combined with TCM in the treatment of CP. METHODS: Randomized controlled trials of acupuncture combined with TCM in treating CP were screened by searching PubMed, Embase, Cochrane Library, CNKI, etc. The retrieval time was from the database establishment date to March 31, 2021. The Cochrane Collaborative Risk Bias Assessment tool was used to evaluate literature's methodological quality of the literature. The RevMan5.4 software was used for the meta-analysis of outcome indicators. The TSA v0.9 software was used for sequential trial analysis (TSA) of effectiveness. RESULTS: In this study, 19 related randomized controlled trial studies were included, with a total of 1831 cases. The results of the meta-analysis showed that acupuncture combined with TCM could significantly improve the clinical efficacy of CP (OR = 3.76, 95%CI: 2.82 to 5.02, P < .00001), reduce the total score of The National Institutes of Health chronic prostatitis symptom index (MD = -4.00, 95%CI: -4.67 to 3.33, P < .00001), and improve patients' urination symptoms (MD = -1.10, 95%CI: -1.23 to -0.97, P < .00001), alleviated the pain symptoms of patients (MD = -2.38, 95%CI: -2.41 to -2.35, P < .00001), improved the quality of life of patients (MD = -1.69, 95%CI: -1.97 to -1.41, P < .00001), decreased the scores of TCM symptoms of patients (MD = -2.39, 95%CI: -3.45 to -1.33, P < .00001), and did not increase the adverse reactions of patients (MD = 1.09, 95%CI: 0.57 to 2.06, P = .8). The results of publication bias showed that this study was not affected by publication bias, and the conclusion was reliable. TSA showed that acupuncture combined with TCM was effective in treating CP. CONCLUSION: Acupuncture combined with TCM is safe and effective for alleviating CP. It can be used as an effective treatment for chronic prostatitis in the clinic.Registration number: DOI 10.17605/OSF.IO/Z8FJM.

Effects of Zinc on Cell Proliferation, Zinc Transport, and Calcium Deposition in Primary Endometrial Epithelial Cells of Laying Hens In Vitro.

For birds, the uterus is an important part for eggshell mineralization, and the establishment of the endometrial epithelial cell (EEC) model was beneficial to the study of uterine function. This study was conducted to establish a culture model of primary EECs of laying hens and explore the effects of zinc on primary EEC proliferation, zinc transport, and calcium deposition in vitro. The EECs were isolated and cultured via type I collagenase digestion, and in the logarithmic phase during 2-5 days, and then reached the plateau phase on the 7th day of inoculation. Results showed that the proliferation of EECs treated by 50 µM ZnSO4 or zinc-methionine (Zn-Met) were markedly promoted at 24-h or 48-h treating time (P < 0.05). In later experiments, the EECs were divided into three groups, involving a control group (no zinc treated), ZnSO4 group (50 µM zinc treated) and a Zn-Met group (50 µM zinc treated). Results showed the relative fluorescence intensity of Ca2+ in the Zn-Met group was significantly higher than that in the control group (P < 0.05). As for zinc transporters, it was only observed that mRNA levels of metallothionein (MT) in EECs showed a significant difference (P < 0.05) between the Zn-Met group and the control. In conclusion, the EECs of laying hens isolated by scraping and digested collagenase I were with better adherent growth. Moreover, Zn-Met can increase intracellular Ca2+ concentration and upregulate expressions of MT mRNA in the EECs of laying hens.

Compound amino acid combined with high-dose vitamin B6 attenuate traumatic coagulopathy via inhibiting inflammation by HMGB1/TLR4/NF-κB pathway.

BACKGROUND: Traumatic coagulopathy (TC) arises primarily from coagulation system failure to maintain adequate hemostasis after serious blood loss or trauma. Circulatory homeostasis restoration is the mainstay of the therapeutic approach to TC, but the effects are significantly inhibited by coagulopathy. OBJECTIVE: To identify the therapeutic effects and underlying mechanism of compound amino acid (CAA) combined with high-dosage of vitamin B6 (VB6) on TC. METHODS: Rabbit traumatic model and cellular model were used to evaluate the effect of CAA combined with high-dosage of VB6 in TC. Blood concentrations of AST and ALT were measured using the Vitros 250 device while blood APTT, PT and TT concentrations were measured using commercial diagnostics kits. Furthermore, qRT-PCR, ELISA and Western blotting were used to determine the expression of clotting factor (II, VII, IX, X and XI), inflammatory factors (TNF-α, IL-6 and IL-1ß) and HMGB1/TLR4/NF-κB signaling-related proteins, respectively. RESULTS: In the rabbit traumatic model, CAA combined with high-dosage of VB6 therapy inhibited the high expression of AST and ALT, but increased the expression of coagulation factors. Additionally, in both the rabbit trauma model and cellular injury model, CAA combined with high-dosage of VB6 inhibited the expression of inflammatory factors (IL-6, TNF-α and IL-1ß) and proteins (HMGB1, TLR4 and p-p65) in HMGB1/TLR4/NF-κB pathway. Most importantly, over-expression of HMGB1 reversed the effect of CAA and VB6 in HUVECs and EA.hy926 cells injury model. CONCLUSION: CAA combined with high-dosage of VB6 alleviated TC and inhibited the expression and secretion of inflammatory factors by inhibiting HMGB1-mediated TLR4/NF-κB pathway.

A multifunctional platform with single-NIR-laser-triggered photothermal and NO release for synergistic therapy against multidrug-resistant Gram-negative bacteria and their biofilms.

BACKGROUND: Infectious diseases caused by multidrug-resistant (MDR) bacteria, especially MDR Gram-negative strains, have become a global public health challenge. Multifunctional nanomaterials for controlling MDR bacterial infections via eradication of planktonic bacteria and their biofilms are of great interest. RESULTS: In this study, we developed a multifunctional platform (TG-NO-B) with single NIR laser-triggered PTT and NO release for synergistic therapy against MDR Gram-negative bacteria and their biofilms. When located at the infected sites, TG-NO-B was able to selectively bind to the surfaces of Gram-negative bacterial cells and their biofilm matrix through covalent coupling between the BA groups of TG-NO-B and the bacterial LPS units, which could greatly improve the antibacterial efficiency, and reduce side damages to ambient normal tissues. Upon single NIR laser irradiation, TG-NO-B could generate hyperthermia and simultaneously release NO, which would synergistically disrupt bacterial cell membrane, further cause leakage and damage of intracellular components, and finally induce bacteria death. On one hand, the combination of NO and PTT could largely improve the antibacterial efficiency. On the other hand, the bacterial cell membrane damage could improve the permeability and sensitivity to heat, decrease the photothermal temperature and avoid damages caused by high temperature. Moreover, TG-NO-B could be effectively utilized for synergistic therapy against the in vivo infections of MDR Gram-negative bacteria and their biofilms and accelerate wound healing as well as exhibit excellent biocompatibility both in vitro and in vivo. CONCLUSIONS: Our study demonstrates that TG-NO-B can be considered as a promising alternative for treating infections caused by MDR Gram-negative bacteria and their biofilms.

Dietary cadmium chloride impairs shell biomineralization by disrupting the metabolism of the eggshell gland in laying hens.

In this study, we identified cadmium (Cd) as a potential endocrine disruptor that impairs laying performance, egg quality, and eggshell deposition and induces oxidative stress and inflammation in the eggshell glands of laying hens. A total of 480 38-wk-old laying hens were randomly assigned into 5 groups that were fed a basal diet (control) or a basal diet supplemented with Cd (provided as CdCl2·2.5 H2O) at 7.5, 15, 30, and 60 mg Cd per kg feed for 9 wk. The results showed that, when compared with the control group, a low dose of dietary Cd (7.5 mg/kg) had positive effects on egg quality by improving albumen height, Haugh unit, yolk color, and shell thickness at the third or ninth week. However, with the increase in the dose and duration of Cd exposure, the laying performance, egg quality, and activities of eggshell gland antioxidant enzymes (catalase [CAT], glutathione peroxide [GSH-Px]), and ATPase (Na+/K+-ATPase, Ca2+-ATPase, and Mg2+-ATPase) deteriorated, and the activity of total nitric oxide synthase (T-NOS) and the level of malondialdehyde (MDA) increased significantly (P < 0.05). The histopathology and real-time quantitative PCR results showed that Cd induced endometrial epithelial cell proliferation accompanied by upregulation of the mRNA levels of progesterone receptor (PgR) and epidermal growth factor receptor (EGFR), downregulation of the mRNA levels of estrogen receptor α (ERα) and interleukin 6 (IL6), and inflammation of the eggshell gland accompanied by significantly increased expression of complement C3 and pro-inflammatory cytokine tumor necrosis factor α (TNFα) (P < 0.05). In addition, the ultrastructure of the eggshell showed that dietary supplementation with 7.5 mg/kg Cd increased the palisade layer and total thickness of the shell, but with the increase in dietary Cd supplementation (30 and 60 mg/kg) the thickness of the palisade layer and mammillary layer decreased significantly (P < 0.05), and the outer surface of the eggshell became rougher. Correspondingly, the expression of calbindin 1 (CALB1), ovocalyxin-32 (OCX-32), ovocalyxin-36 (OCX-36), osteopontin (SPP1), and ovocledidin-17 (OC-17) decreased significantly (P < 0.05) with increasing dietary Cd supplementation. Conclusively, the present study demonstrates that dietary supplementation with Cd negatively affects laying performance, egg quality, and eggshell deposition by disturbing the metabolism of eggshell glands in laying hens but has a positive effect on egg quality at low doses.

Reactive oxygen species-responsive dexamethasone-loaded nanoparticles for targeted treatment of rheumatoid arthritis via suppressing the iRhom2/TNF-α/BAFF signaling pathway.

Rheumatoid arthritis (RA) is an immune-mediated inflammatory disease that results in synovitis, cartilage destruction, and even loss of joint function. The frequent and long-term administration of anti-rheumatic drugs often leads to obvious adverse effects and patient non-compliance. Therefore, to specifically deliver dexamethasone (Dex) to inflamed joints and reduce the administration frequency of Dex, we developed Dex-loaded reactive oxygen species (ROS)-responsive nanoparticles (Dex/Oxi-αCD NPs) and folic acid (FA) modified Dex/Oxi-αCD NPs (Dex/FA-Oxi-αCD NPs) and validated their anti-inflammatory effect in vitro and in vivo. In vitro study demonstrated that these NPs can be effectively internalized by activated macrophages and the released Dex from NPs significantly downregulated the expression of iRhom2, TNF-α, and BAFF in activated Raw264.7. In vivo experiments revealed that Dex/Oxi-αCD NPs, especially Dex/FA-Oxi-αCD NPs significantly accumulated at inflamed joints in collagen-induced arthritis (CIA) mice and alleviated the joint swelling and cartilage destruction. Importantly, the expression of iRhom2, TNF-α, and BAFF in the joint was inhibited by intravenous injection of Dex/Oxi-αCD NPs and Dex/FA-Oxi-αCD NPs. Collectively, our data revealed that Dex-loaded ROS-responsive NPs can target inflamed joints and attenuate arthritis, and the 'iRhom2-TNF-α-BAFF' pathway plays an important role in the treatment of RA with the NPs, suggesting that this pathway may be a novel target for RA therapy.

Effects of zinc methionine supplementation on laying performance, zinc status, intestinal morphology, and expressions of zinc transporters' mRNA in laying hens.

BACKGROUND: This study was conducted to investigate effects of dietary zinc methionine (Zn-Met) supplementation on laying performance, zinc (Zn) status, intestinal morphology, and Zn transporters in laying hens compared with zinc sulfate (ZnSO4 ). A total of 384 Hyline Grey laying hens (38 weeks old) with similar performance (1.42 ± 0.07 kg) were randomly allotted to four dietary treatments and fed with a basal diet (control) or the basal diet supplemented with Zn, either as Zn-Met at 40 and 80 mg Zn/kilogram diet or as ZnSO4 at 80 mg Zn/kilogram diet, for 10 weeks. RESULTS: There was no difference in egg weight, egg production, feed intake, and feed conversation ratio among all groups (P > 0.05). Compared with the control, Zn contents were increased (P < 0.05) in the liver, duodenum, and jejunum of laying hens fed diets supplemented with different Zn sources. There was no difference (P > 0.05) in Zn contents in liver, duodenum, and jejunum between diets supplemented with Zn-Met or ZnSO4 at 80 mg Zn/kilogram diet. Compared with the control and the ZnSO4 group (80 mg Zn/kilogram diet), supplementation with Zn-Met of 80 mg Zn/kilogram diet increased (P < 0.05) villus height, villus area, and villus height/crypt depth ratio but reduced (P < 0.05) crypt depth in jejunum. Expression of metallothionein messenger RNA of jejunum in the group fed a diet containing Zn-Met (80 mg Zn/kilogram diet) was higher (P < 0.05) than that in the control. CONCLUSION: These results indicated that Zn-Met has positive effects on the Zn status of liver, duodenum, and jejunum, intestinal morphology, and metallothionein messenger RNA expression in jejunum of laying hens compared with ZnSO4 . © 2019 Society of Chemical Industry.

GRGM-13 comprising 13 plant and animal products, inhibited oxidative stress induced apoptosis in retinal ganglion cells by inhibiting P2RX7/p38 MAPK signaling pathway.

OBJECTIVE: To determine the effectiveness of GRGM-13 on oxidative stress induced apoptosis of retinal ganglion cells (RGCs) and revealed its possible mechanism. MATERIALS AND METHODS: Caspase-3 activity, MDA level, and glutathione peroxidase level were detected by Caspase-3 assay kit, Lipid Peroxidation MDA Assay Kit, and Total Glutathione Peroxidase Assay Kit, respectively. Protein levels of Bax, Bcl-2, p-p38 and p38 were observed by Western Blot. Reactive oxygen species assay kit was used to determine intracellular ROS level. Apoptotic cells were measured by flow cytometry. RESULTS: GRGM-13 inhibited apoptosis of RGCs and ROS level in rat retinal tissue and RGC-5 cells, and the decrease degree strengthened with the increase of GRGM-13 concentration. In addition, ROS upregulated p-p38 expression, while GRGM-13 reversed this effect. We also found that p38 inhibitor SB202190 did not change L-glutamate (Glu) or H2O2-induced ROS level, while SB202190 inhibited apoptosis of RGC-5 cells. Finally, we observed that P2 × 7R agonist BzATP reversed the inhibition effect of GRGM-13 on RGC-5 cell apoptosis, ROS level and p-p38 expression, while si-P2 × 7R inhibited oxidative stress-induced phosphorylation of p38. CONCLUSION: GRGM-13 could inhibit oxidative stress-induced RGCs apoptosis via inhibiting P2RX7/p38 MAPK pathway, which revealed the possible mechanism of GRGM-13 on stress-induced RGCs apoptosis and provided new Chinese medicine for the treatment of glaucoma.