Downregulation of miR-1388 Regulates the Expression of Antiviral Genes via Tumor Necrosis Factor Receptor (TNFR)-Associated Factor 3 Targeting Following poly(I:C) Stimulation in Silver Carp (Hypophthalmichthys molitrix).

MicroRNAs (miRNAs) are highly conserved endogenous single-stranded non-coding RNA molecules that play a crucial role in regulating gene expression to maintain normal physiological functions in fish. Nevertheless, the specific physiological role of miRNAs in lower vertebrates, particularly in comparison to mammals, remains elusive. Additionally, the mechanisms underlying the control of antiviral responses triggered by viral stimulation in fish are still not fully understood. In this study, we investigated the regulatory impact of miR-1388 on the signaling pathway mediated by IFN regulatory factor 3 (IRF3). Our findings revealed that following stimulation with the viral analog poly(I:C), the expression of miR-1388 was significantly upregulated in primary immune tissues and macrophages. Through a dual luciferase reporter assay, we corroborated a direct targeting relationship between miR-1388 and tumor necrosis factor receptor (TNFR)-associated factor 3 (TRAF3). Furthermore, our study demonstrated a distinct negative post-transcriptional correlation between miR-1388 and TRAF3. We observed a significant negative post-transcriptional regulatory association between miR-1388 and the levels of antiviral genes following poly(I:C) stimulation. Utilizing reporter plasmids, we elucidated the role of miR-1388 in the antiviral signaling pathway activated by TRAF3. By intervening with siRNA-TRAF3, we validated that miR-1388 regulates the expression of antiviral genes and the production of type I interferons (IFN-Is) through its interaction with TRAF3. Collectively, our experiments highlight the regulatory influence of miR-1388 on the IRF3-mediated signaling pathway by targeting TRAF3 post poly(I:C) stimulation. These findings provide compelling evidence for enhancing our understanding of the mechanisms through which fish miRNAs participate in immune responses.

Exploration of the correlation between superficial cerebral veins identified using susceptibility-weighted imaging findings and cognitive differences between sexes based on deep learning: a preliminary study.

Background: This study aimed to investigate the association of superficial cerebral veins (SCVs) with sex-related cognitive differences and the possible hemodynamic mechanisms underlying these associations. Methods: This investigation was a prospective case-control study. A total of 344 healthy volunteers were recruited. In all, 200 volunteers were included to establish the deep learning model, and 144 volunteers were used for the research, including 72 males (50%) and 72 females (50%). No significant differences in age (P=0.358) or education (P=0.779) were observed between the sexes. Cognitive functioning was evaluated using neuropsychological tests, including the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment-Basic (MOCA-B). Susceptibility-weighted imaging scans were acquired with a 3.0 T magnetic resonance imaging system using a 32-channel high-resolution phased array coil. Minimum intensity projection images were obtained by reconstructing susceptibility-weighted imaging data. A deep learning model was trained on the minimum intensity projection images to quantify the diameter, tortuosity index, length, and the number of SCVs in the bilateral cerebral hemispheres. Finally, the association between cognitive differences between males and females and the properties of the SCVs was analyzed. Results: The MMSE and MOCA-B scores of males were significantly higher than those of females (P<0.05). Males had more SCVs in the bilateral cerebral hemispheres than did females (right hemisphere: P<0.01; left hemisphere: P<0.05). The number of SCVs in the right cerebral hemisphere was significantly and positively correlated with the MMSE and MOCA-B scores (correlation coefficients: 0.246 and 0.201, respectively; P<0.05). The number of SCVs in the left cerebral hemisphere was positively correlated with the MMSE scores (correlation coefficient: 0.196; P<0.05) and the MOCA-B scores. In this study, no significant correlations were observed between cognition and the diameter, length, or tortuosity index of the SCVs in the bilateral cerebral hemispheres. Conclusions: The cognitive function of males was better than that of females, and the different numbers of SCVs may be one of the explanations for this phenomenon of sex-based differences in cognition.

The molecular mechanisms of alpha-lipoic acid on ameliorating aflatoxin B1-induced liver toxicity and physiological dysfunction in northern snakehead (Channa argus).

This research aimed to evaluate the protective mechanism of alpha-lipoic acid (α-LA) on the food-borne aflatoxin B1 (AFB1) exposure-induced liver toxicity and physiological dysfunction in the northern snakehead (Channa argus). 480 fish (9.24±0.01 g) were randomly assigned to four treatment groups and fed with four experimental diets for 56 d including the control group (CON), AFB1 group (200 ppb AFB1), 600 α-LA group (600 ppm α-LA+200 ppb AFB1), and 900 α-LA group (900 ppm α-LA+200 ppb AFB1). The results revealed that 600 and 900 ppm α-LA attenuated AFB1-induced growth inhibition and immunosuppression in northern snakehead. 600 ppm α-LA significantly decreased the serum aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and lactate dehydrogenase levels, and AFB1 bioaccumulation, and attenuated the changes of hepatic histopathological and ultrastructure induced by AFB1. Moreover, 600 and 900 ppm α-LA significantly up-regulated phase I metabolism genes (cytochrome P450-1a, 1b, and 3a) mRNA expression, inhibited the levels of malondialdehyde, 8­hydroxy-2 deoxyguanosine and reactive oxygen species in the liver. Notably, 600 ppm α-LA significantly up-regulated the expression levels of nuclear factor E2 related factor 2 and its related downstream antioxidant molecules (heme oxygenase 1 and NAD(P)H: quinone oxidoreductase 1, etc.), increased the phase II detoxification enzyme-related molecules (glutathione-S-transferase and glutathione), antioxidant parameters (catalase and superoxide dismutase, etc.), and the expressions of Nrf2 and Ho-1 protein in the presence of AFB1 exposure. Furthermore, 600 and 900 ppm α-LA significantly reduced the characteristic indices of AFB1-induced endoplasmic reticulum stress (glucose-regulated protein 78 and inositol requiring enzyme 1, etc.), apoptosis (caspase-3 and cytochrome c, etc.) and inflammation (nuclear factor kappa B and tumor necrosis factor α, etc.), while increased the B-cell lymphoma-2 and inhibitor of κBα in the liver after being exposed to AFB1. To summarize, the above results indicate that dietary α-LA could modulate the Nrf2 signaling pathway to ameliorate AFB1-induced growth inhibition, liver toxicity, and physiological dysfunction in northern snakehead. Although the concentration of α-LA increased to 900 ppm from 600 ppm, the protective effects of the 900 ppm α-LA do not show an advantage over the 600 ppm α-LA, and even show inferiority in some respects. So that the recommended concentration of α-LA is 600 ppm. The present study provides the theoretical foundation for developing α-LA as the prevention and treatment of AFB1-induced liver toxicity in aquatic animals.

[Preparation of luciferase-expressing mRNA and expression characteristics of mRNA delivered by electroporation in vivo].

In this study, we aimed to construct a non-replication mRNA platform and explore the side effects of electroporation-mediated delivery of mRNA on the mice as well as the expression features of the mRNA. With luciferase gene as a marker, in vitro transcription with T7 RNA polymerase was carried out for the synthesis of luciferase-expressed mRNA, followed by enzymatic capping and tailing. The mRNA was delivered in vivo by electroporation via an in vivo gene delivery system, and the expression intensity and duration of luciferase in mice were observed via an in vivo imaging system. The results demonstrated that the mRNA transcripts were successfully expressed both in vitro and in vivo. The electroporation-mediated delivery of mRNA had no obvious side effects on the mice. Luciferase was expressed successfully in all the mRNA-transduced mice, while the expression intensity and duration varied among individuals. Overall, the expression level peaked on the first day after electroporation and rapidly declined on the fourth day. This study is of great importance for the construction of non-replication mRNAs and their application in vaccine or antitumor drug development.

Dietary aflatoxin B1 caused the growth inhibition, and activated oxidative stress and endoplasmic reticulum stress pathway, inducing apoptosis and inflammation in the liver of northern snakehead (Channa argus).

The purpose of this study was to investigate the effects of dietary aflatoxin B1 (AFB1) on growth performance and AFB1 biotransformation, and hepatic oxidative stress, endoplasmic reticulum (ER) stress, apoptosis, and inflammation in northern snakehead (Channa argus). A total of 600 northern snakeheads (7.52 ± 0.02 g) were divided into five groups (three replicates/group) and fed the diets with AFB1 at concentrations of 0, 50, 100, 200, and 400 ppb for 8 weeks. The results demonstrated that dietary AFB1 (≥ 200 ppb) reduced FBW, WG, and SGR. 100, 200, and 400 ppb AFB1 treatment groups significantly decreased the PER, CRP, C3, C4, IgM, and LYS levels in northern snakehead, while FCR was significant increased. Moreover, dietary AFB1 (100, 200, and 400 ppb) increased cyp1a, cyp1b (except 400 ppb), and cyp3a mRNA expression levels, while reducing the GST enzymatic activity and mRNA expression levels in northern snakehead. Furthermore, AFB1 (≥ 100 ppb) increased ROS, MDA, and 8-OHdG levels, and grp78, ire1, perk, jnk, chop, and traf2 mRNA expression levels, and decreased SOD, CAT, GSH-Px, and GSH (except 100 ppb) levels and the gene expression levels of cat, gsh-px (except 100 ppb), and Cu/Zn sod. In addition, AFB1 (100, 200, and 400 ppb) up-regulated the cyt-c, bax, cas-3, and cas-9 mRNA levels in the liver, while down-regulating the bcl-2 expression levels. Meanwhile, the expression levels of nf-κb, tnf-α (except 100 ppb), il-1ß, and il-8 in the liver were up-regulated in AFB1 treatment groups (≥ 100 ppb), while the iκbα mRNA levels were down-regulated. In summary, dietary AFB1 reduced growth performance and humoral immunity in northern snakehead. Meanwhile, the cyclic occurrence of oxidative stress and ER stress, and induced apoptosis and inflammation, is one of the main reasons for AFB1-induced liver injury in the northern snakehead, which will provide valuable information and a fresh perspective for further research into AFB1-induced liver injury in fish.

The immuneoreaction and antioxidant status of Chinese mitten crab (Eriocheir sinensis) involve protein metabolism and the response of mTOR signaling pathway to dietary methionine levels.

To study the effects of dietary methionine on growth performance, immunity, antioxidant capacity, protein metabolism, inflammatory response and apoptosis factors in Chinese mitten crabs (Eriocheir sinensis). Five diets with different methionine levels (0.63%, 0.85%, 1.06%, 1.25% and 1.47%) were fed to E. sinensis for 8 weeks. Results showed that in the 1.25% Met group, both growth performance and feed utilization were significantly increased. The crude protein content of crab muscle in the 1.06% and 1.25% Met groups was significantly higher than that in the control group. The immune and antioxidant enzyme activities, as well as gene expression levels of anti-lipopolysaccharide factor 1 (ALF1), Crustin-1, prophenoloxidase (proPO), cap 'n' collar isoform C (CncC) in 1.25% Met group were significantly higher than other groups. The activities of adenosine deaminase (ADA) and glutamate transaminase (GPT) in serum decreased first and then increased with the increase of methionine content, while the changes of ADA and GPT in hepatopancreas increased first and then decreased. 1.25% Met group exhibited significantly increased levels of GOT, GPT, and ADA compared to the control group. 1.25% Met diet group significantly up-regulated protein synthesis and anti-apoptotic factors, and significantly down-regulated inflammatory and pro-apoptotic factors in hepatopancreas. At 1.25% in the diet, methionine was found to boost E. sinensis growth, muscle protein deposition and immunity, as well as its antioxidant capacity. Combined with the above results, based on the expression of factors involved in the mammalian target of rapamycin (mTOR) signaling pathway and the mitogen-activated protein kinase (MAPK) signaling pathway, it is proved that methionine can not only promote protein metabolism, improve feed utilization, but also alleviate the inflammatory response and apoptosis caused by oxidative stress in the body.

Case Report: TNF-Alpha Inhibitors to Rescue Pregnancy in Women With Potential Pregnancy Loss: A Report of Ten Cases.

Miscarriage poses a significant threat to pregnant women globally. Recurrent miscarriages or potential poor embryonic development indicated by early drops in serum human chorionic gonadotrophin (hCG) are even more catastrophic for pregnant women. However, these patients receive either individualized medical intervention supported by limited evidence or no treatment at all. In this study, we report ten patients who shared at least one episode of an early decline of hCG in the first trimester and were treated with compassionate use of tumor necrosis factor-alpha inhibitor (TNFi). They were then followed up regularly with caution. Their hCG trajectory all resumed a normal pattern within one week and the obstetric outcomes were promising. No adverse fetal, neonatal, or maternal health issues have been observed. This case series supports current safety evidence of TNFi and provides new insight into its use in pregnancy when the embryo is in danger. Further well-designed clinical trials should be carried out to consolidate the evidence.

Dietary α-lipoic acid alleviates deltamethrin-induced immunosuppression and oxidative stress in northern snakehead (Channa argus) via Nrf2/NF-κB signaling pathway.

The goal of the study was to determine the ameliorative effects of dietary alpha-lipoic acid (α-LA) on deltamethrin (DEL)-induced immunosuppression and oxidative stress in northern snakehead (Channa argus). The northern snakeheads (15.38 ± 0.09 g) were exposed to DEL (0.242 µg/L) and fed with diets supplemented α-LA at 300, 600, and 900 mg/kg. After the 28-day exposure test, we obtained the following results: i) α-LA alleviates DEL-induced liver injury by reversing the increase of the serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels and liver cytochrome P450 enzymes (Cytochrome P450 (cyp)1a and cyp1b) expression levels. ii) α-LA can reverse the DEL-induced reduction of serum complement 4 (C4), C3, immunoglobulin M (IgM), and lysozyme (LYS) levels and the increase of liver and intestine nuclear factor kappa B (nf-κb) p65, tumor necrosis factor (tnf)-α, interleukin (il)-1ß, il-8, and il-6 gene expressions, while il-10 expression levels showed the opposite result. iii) α-LA reversed the reduction of superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), glutathione-S-transferase (GST) and glutathione peroxidase (GSH-Px) levels in the liver and intestine induced by DEL, while malondialdehyde (MDA) showed the opposite result. iv) α-LA reversed the reduction of Cu/Zn sod, nuclear factor erythroid 2-related factor 2 (nrf2), NAD (P)H: quinone oxidoreductase (nqo)1, and heme oxygenase (ho)-1 antioxidant gene expression levels in the liver and intestine induced by DEL. Therefore, our study indicated that optimal α-LA (600 mg/kg) could attenuate DEL-induced toxicity (including liver damage, immunotoxicity, and oxidative stress) in northern snakehead via Nrf2/NF-κB signaling pathway. This is the first research that explores the alleviated effects of α-LA on DEL-induced toxicity damage in fish. This study provides a positive measure to reduce the toxicity damage caused by DEL to aquatic animals, and provides a theoretical basis for exploring the regulation mechanism of α-LA in toxic substances.

Changes in asphericity of anterior and posterior corneal surfaces for mild-moderate and high myopia after topography-guided FS-LASIK.

PURPOSE: To compare changes in asphericity of anterior and posterior corneal surfaces for different myopia patients after corneal topography-guided femtosecond-assisted laser in situ keratomileuses (FS-LASIK), and to analyze correlations between asphericity of corneal surfaces and preoperative spherical equivalence (SEQ). METHODS: In this prospective study, 59 patients who underwent corneal topography-guided FS-LASIK surgery were enrolled and divided into the mild-moderate myopia group (67 eyes) and the high myopia group (44 eyes). Postoperative follow-ups were performed at 1, 3, and 6 months. Postoperative changes in aspherical coefficient (Q values), corneal higher-order aberrations (HOAs), and spherical aberrations (Z40) were compared between the two groups. Relevance between Q value changes and SEQ, HOAs, and Z40 as well as between SEQ and changes of HOAs and Z40 was analyzed. RESULTS: There was a significant increase in Q values of the anterior (each diameter) and posterior (6-8 mm) corneal surface in both groups than before surgery (P < 0.001). Q values of corneal anterior (each diameter) and posterior (7-9 mm) surface in the high group were considerably larger than the mild-moderate group (P < 0.05). Corneal anterior surface HOAs and Z40 values in the high group largely exceeded those of the mild-moderate group (P < 0.001). The preoperative SEQ was linearly correlated with postoperative anterior Q change (ΔQ), HOAs change (ΔHOAs), and spherical aberration change (ΔZ40). CONCLUSION: The changes of corneal asphericity in patients with high myopia were greater than mild-moderate myopia, with more corneal HOAs and Z40 introduced when corneal topography-guided FS-LASIK was conducted.

The effects of dietary supplementation of α-lipoic acid on the growth performance, antioxidant capacity, immune response, and disease resistance of northern snakehead, Channa argus.

The study was the first time to explore the positive effects of α-LA on growth performance, antioxidant capability, immunity, and disease resistance of northern snakehead (Channa argus). Five hundred and forty northern snakehead fish (initial body weight: 8.74 ± 0.12 g (mean ± SE)) were randomly allocated into six groups with three replicates each. Six diets supplemented with α-LA at doses of 0 (CON), 300 (LA300), 600 (LA600), 900 (LA900), 1200 (LA1200), and 1500 (LA1500) mg/kg were fed to northern snakehead for 8 weeks. The results demonstrated that, when compared with the control group, optimal dietary α-LA increased the weight gain (WG), protein efficiency ratio (PER), and specific growth rate (SGR) and reduced the feed conversion ratio (FCR) of the fish (P < 0.05). Also, optimal dietary α-LA enhanced the immune-related parameters and antioxidant enzyme parameters levels in the head kidney, spleen, and liver of northern snakehead (P < 0.05). Dietary α-LA upregulated the mRNA expression levels of anti-inflammatory cytokines (il10 and tgfß) and antioxidant related genes (gst, gsh-px, gr and Cu/Zn sod), down-regulated the pro-inflammatory cytokines (il1ß, il8, il12 and tnfα) mRNA levels in the liver, spleen and head kidney of the northern snakehead (P < 0.05). The above results demonstrated that optimal dietary α-LA showed enhancement effects on the growth, antioxidant and anti-inflammatory capability, and immune response of northern snakehead. The survival rates in all α-LA treatments were significantly raised after the challenge with Aeromonas veronii (P < 0.05). Based on the quadratic regression analysis of WG, GSH-Px, LYS, and il1ß, the optimal dietary α-LA levels were estimated to be 737.0, 775.0, 890.0, and 916.7 mg/kg, respectively. Considering the overall responses in growth performance, antioxidant status, immune response, and inflammatory factors, the recommended dose of α-LA in the diet of fish is 737.0-916.7 mg/kg.

The effect of adding Bacillus amyloliquefaciens LSG2-8 in diets on the growth, immune function, antioxidant capacity, and disease resistance of Rhynchocypris lagowskii.

The purpose of this study was to investigate the effect of Bacillus amyloliquefaciens LSG2-8 on the growth performance, immune function, antioxidant capacity, and disease resistance of Rhynchocypris lagowskii. Fish were fed with the feed containing five levels such as 0, 1.0 × 106, 1.0 × 107, 1.0 × 108, and 1.0 × 109 CFU/g of the B. amyloliquefaciens LSG2-8 for 56 days. After 56 days of feeding, twenty four fish were randomly selected to test various growth, immune and antioxidant parameters. Ten fish were challenged with Aeromonas hydrophila for 14 days; the mortality rate was recorded 14 days after infection. The results showed that B. amyloliquefaciens LSG2-8 could significantly increase the growth parameters of R. lagowskii's, such as final body weight, weight gain rate, specific growth rate, and feed efficiency (p < 0.05). Further examination revealed the activity of antioxidant enzymes, Nrf-2 mRNA, and Keap-1 mRNA gene expression in the intestine and liver, and the serum immune index of R. lagowskii in the 1.0 × 108 CFU/g were all significantly higher compared to the other groups. Furthermore, fish fed a diet supplemented with B. amyloliquefaciens LSG2-8 had a significantly lower (p < 0.05) post-challenge mortality rate than the control fish. In summary, the research results showed that B. amyloliquefaciens LSG2-8 could improve the growth performance, immune function, antioxidant capacity, and disease resistance of R. lagowskii and be used in aquaculture.

Comparative study of objective visual quality between FS-LASIK and SMART in myopia.

AIM: To compare the changes in the objective visual quality of patients with low and moderate myopia postoperatively after transepithelial photorefractive keratectomy using the smart pulse technology (SMART) and femtosecond laser in situ keratomileusis (FS-LASIK). METHODS: Corneal higher-order aberrations (HOAs), horizontal coma, vertical coma and spherical aberration were measured using Pentacam, and cutoff for modulation transfer function (MTF cutoff), objective scatter index (OSI) and Strehl ratio (SR) was measured using an optical quality analysis system (OQAS-II), before and after operation at 1, 3, and 6mo, and data were analyzed by repeated measurement two-way analysis of variance. RESULTS: The difference in uncorrected distance visual acuity between SMART and FS-LASIK was statistically significant only 1wk postoperatively. Approximately 86.36% and 80.69% of patients with spherical equivalent (SE) in ±0.50 D were observed in the SMART and FS-LASIK groups, respectively. No significant difference was observed in SE between the two groups (P=0.509). The HOAs increased postoperatively compared with those before surgery in both groups (P<0.05). No significant difference in HOA, corneal horizontal coma, spherical aberration, ΔHOA, Δhorizontal coma, and Δspherical aberration were observed between the two group (P>0.05). Corneal vertical coma and Δcorneal vertical coma in the FS-LASIK group were higher than those in the SMART group (P<0.05). The OSI of both groups at 1mo after surgery was higher than that before surgery (P<0.05). At 3 and 6mo postoperatively, the OSI in the FS-LASIK group was slightly higher than that in the SMART group (P=0.040 and 0.047, respectively). At 6mo after surgery, the MTF cutoff was statistically significant different between the two groups (P=0.026). No significant difference in SR between the FS-LASIK and SMART groups was observed at 1, 3, and 6mo postoperatively (P>0.05). CONCLUSION: The HOAs increase and visual quality is delayed in both groups postoperatively, and the long-term objective visual quality after SMART is slightly better than that after FS-LASIK.

Corneal Asphericity and Higher-Order Aberrations after FS-LASIK and Trans-PRK for Myopia.

OBJECTIVE: To compare the corneal asphericity and higher-order aberrations (HOAs) of femtosecond laser-assisted in situ keratomileusis (FS-LASIK) with Smart Pulse Technology (SPT) assisted transepithelial photorefractive keratectomy (Trans-PRK) for myopia and myopic astigmatism correction. METHODS: This prospective study analyzed 88 eyes of 44 patients treated with FS-LASIK and 64 eyes of 32 patients treated with Trans-PRK. All eyes had low to moderate myopia with or without astigmatism (spherical equivalent (SE) <-6.00 diopters). The uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), SE, asphericity (Q value) of the anterior corneal surface, index of surface variance (ISV), corneal higher-order aberrations (HOAs), vertical coma (Z3 -1), horizontal coma (Z3 1), and spherical aberration (Z 4 0) over a 6 mm diameter central corneal zone diameter were evaluated preoperatively and 1, 3, and 6 months postoperatively. RESULTS: At 6 months, the UDVA and SE were -0.14 ± 0.06 and 0.33 ± 0.33D in FS-LASIK and -0.15 ± 0.06 and 0.35 ± 0.37D in Trans-PRK. There was no difference between the two groups in the postoperative UDVA and SE (P > 0.05). After FS-LASIK and Trans-PRK, the Q values in the 6, 7, 8, and 9 mm zones and ISV of the anterior corneal surface significantly increased (P < 0.001). At 1, 3, and 6 months after surgery, corneal HOA, Z3 -1, Z 3 1, and Z 4 0 in both groups were significantly increased compared with those before surgery, with statistically significant differences (P < 0.001). At 1, 3, and 6 months after surgery, the Z3 -1 of the Trans-PRK group was significantly lower than that of the FS-LASIK group (P < 0.001). ΔHOA and ΔZ4 0 were dramatically correlated with the ΔQ value for both FS-LASIK and Trans-PRK procedures. The ΔQ was significantly correlated with the preoperative SE, AD, and AD/CCT after both two procedures (all P < 0.001). CONCLUSIONS: Both FS-LASIK and Trans-PRK caused the anterior corneal surface to become flatter, and the morphology of the corneal surface was irregular. Corneal HOAs were significantly increased after the two procedures. Trans-PRK using SPT introduced less corneal vertical coma than FS-LASIK. Corneal asphericity changes contributed to the corneal aberrations changes following FS-LASIK and Trans-PRK.

Dietary α-lipoic acid can alleviate the bioaccumulation, oxidative stress, cell apoptosis, and inflammation induced by lead (Pb) in Channa argus.

This study aims to evaluate the effects of dietary α-lipoic acid (α-LA) on bioaccumulation, oxidative stress, apoptosis, and inflammation in Channa argus after 28 d of lead (Pb) exposure. A total of 300 fish were divided into five groups: the first group was the control group and the other four groups were exposed to waterborne Pb (800 ppb) and fed α-LA diets supplemented with 0, 300, 600, and 900 mg/kg. The results demonstrated that dietary α-LA effectively reduced the Pb accumulation in the liver, kidney, gill, intestine, and muscle of C. argus after exposure to Pb. Meanwhile, dietary α-LA reversed alterations in the biochemical parameters (Alanine aminotransferase (ALT), lactate dehydrogenase (LDH), aspartate aminotransferase (AST), blood urea nitrogen (BUN), cortisol (COR), and creatinine (CRE)) and immunity parameters (myeloperoxidase (MPO), complement 3 (C3), lysozyme (LYS), complement 4 (C4), C-reactive protein (CRP), and immunoglobulin M (IgM)) in the serum of fish caused by Pb. Pb-induced reduction of antioxidant enzyme activities (Catalase (CAT), glutathione reductase (GR), superoxide dismutase (SOD), glutathione (GSH), glutathione peroxidase (GSH-Px)) was inhibited by dietary α-LA. And malondialdehyde (MDA) and protein carbonyl (PC) content exhibited an opposite trend. Meanwhile, dietary supplemented with α-LA was found to relieve Pb-induced oxidative stress by downregulating Keap1 mRNA expression levels and upregulating the expression levels of CAT, nuclear factor erythroid 2-related factor 2 (Nrf2), GSH-Px, and Cu/Zn SOD. Furthermore, α-LA supplementation reversed Pb-induced upregulation of pro-inflammatory genes (interleukin (IL)-6, IL-1ß, tumor necrosis factor α (TNF-α), and nuclear factor kappa B (NF-κB)), Pro-apoptotic genes (Bcl-2-associated X (Bax), caspase (Cas)-3, and tumor protein p53 (p53)) and Hsp70, and downregulation of anti-inflammatory genes (IL-10, inhibitor of κBα (IκBα), and transforming growth factor ß (TGF-ß)) and anti-apoptosis gene (B-cell lymphoma-2 (Bcl-2)). Overall, dietary α-LA supplementation could enhance the innate immunity and antioxidant capacity of fish, attenuating the Pb accumulation, and cell apoptosis after being exposed to Pb. Furthermore, dietary α-LA could relieve Pb-induced inflammatory response and oxidative stress of fish via regulating NF-κB and Nrf2 signaling, respectively.

Study on Protection of Human Umbilical Vein Endothelial Cells from Amiodarone-Induced Damage by Intermedin through Activation of Wnt/ß-Catenin Signaling Pathway.

Amiodarone (AM) is one of the most effective antiarrhythmic drugs and normally administrated by intravenous infusion which is liable to cause serious phlebitis. The therapeutic drugs for preventing this complication are limited. Intermedin (IMD), a member of calcitonin family, has a broad spectrum of biological effects including anti-inflammatory effects, antioxidant activities, and antiapoptosis. But now, the protective effects of IMD against amiodarone-induced phlebitis and the underlying molecular mechanism are not well understood. In this study, the aim was to investigate the protective efficiency and potential mechanisms of IMD in amiodarone-induced phlebitis. The results of this study revealed that treatment with IMD obviously attenuated apoptosis and exfoliation of vascular endothelial cells and infiltration of inflammatory cells in the rabbit model of phlebitis induced by intravenous infusion of amiodarone compared with control. Further tests in vitro demonstrated that IMD lessened amiodarone-induced endothelial cell apoptosis, improved amiodarone-induced oxidative stress injury, reduced inflammatory reaction, and activated the Wnt/ß-catenin signal pathway which was inhibited by amiodarone. And these effects could be reversed by Wnt/ß-catenin inhibitor IWR-1-endo, and si-RNA knocked down the gene of Wnt pathway. These results suggested that IMD exerted the protective effects against amiodarone-induced endothelial injury via activating the Wnt/ß-catenin pathway. Thus, IMD could be used as a potential agent for the treatment of phlebitis.

Effects of dietary Astragalus Propinquus Schischkin polysaccharides on growth performance, immunological parameters, antioxidants responses and inflammation-related gene expression in Channa argus.

The present study investigated the effects of dietary Astragalus Propinquus schischkin polysaccharides on growth, immune responses, antioxidants responses and inflammation-related genes expression in Channa argus. Channa argus were randomly divided into 5 groups and fed 5 levels diets of A. propinquus schischkin polysaccharides (0, 250, 500, 1000 and 2000 mg/kg) for 56 days. The results showed, dietary A. propinquus schischkin polysaccharides addition can increase the final body weight, weight gain and specific growth rate, decrease the feed conversion ratio of Channa argus. And dietary A. propinquus schischkin polysaccharides supplementation can increase the levels of serum superoxide dismutase, catalase, glutathione peroxidase, lysozyme, complement 3, complement 4, immunoglobulin M and alkaline phosphatase, decrease the levels of serum malondialdehyde, cortisol, aspartate aminotransferase and glutamic-pyruvic transaminase. Furthermore, dietary A. propinquus schischkin polysaccharides can decrease the gene expression levels of interleukin-1ß, interleukin-, tumor necrosis factor-α and nuclear factor-κB, increase the gene expression levels of glucocorticoid receptor in liver, spleen, kidney, intestine. To sum up, dietary A. propinquus schischkin polysaccharides can accelerate growth, enhance immune responses and antioxidants responses, regulate inflammation-related genes expression in Channa argus and the optimum amount is 1000 mg/kg.

Experimental study on renoprotective effect of intermedin on diabetic nephropathy.

Intermedin(IMD) is a novel member of the calcitonin/calcitonin gene-related peptide (CT/CGRP) family that has anti-inflammatory, antioxidant and anti-apoptosis properties. This study aimed to evaluate the renoprotective effects of IMD on podocyte apoptotic loss and slit diaphragm protein deficiency the kidneys of rats with in streptozotocin (STZ) induced diabetes in high glucose-exposed podocytes. Our results showed that IMD significantly attenuated proteinuria, and alleviated the abnormal alterations in glomerular ultrastructure in vivo. IMD also improved the induction of slit diaphragm proteins, and restored the decreased Bcl-2 expression and suppressed Bax and caspase-3 induction in the diabetic glomeruli. In addition, IMD attenuated podocyte apoptosis and filamentous actin (F-actin) rearrangement in high glucose-exposed podocytes. Exposure to high glucose elevated the unfolded protein response (UPR) to endoplasmic reticulum (ER) stress in renal podocytes, and IMD treatment blocked such ER stress responses pertinent to podocyte apoptosis and reduced synthesis of slit diaphragm proteins in vivo and in vitro. These observations demonstrate that targeting ER stress is an underlying mechanism of IMD-mediated amelioration of diabetes-associated podocyte injury and dysfunction.

CD9, a potential leukemia stem cell marker, regulates drug resistance and leukemia development in acute myeloid leukemia.

BACKGROUND: Leukemia stem cells (LSCs) are responsible for the initiation, progression, and relapse of acute myeloid leukemia (AML). Therefore, a therapeutic strategy targeting LSCs is a potential approach to eradicate AML. In this study, we aimed to identify LSC-specific surface markers and uncover the underlying mechanism of AML LSCs. METHODS: Microarray gene expression data were used to investigate candidate AML-LSC-specific markers. CD9 expression in AML cell lines, patients with AML, and normal donors was evaluated by flow cytometry (FC). The biological characteristics of CD9-positive (CD9+) cells were analyzed by in vitro proliferation, chemotherapeutic drug resistance, migration, and in vivo xenotransplantation assays. The molecular mechanism involved in CD9+ cell function was investigated by gene expression profiling. The effects of alpha-2-macroglobulin (A2M) on CD9+ cells were analyzed with regard to proliferation, drug resistance, and migration. RESULTS: CD9, a cell surface protein, was specifically expressed on AML LSCs but barely detected on normal hematopoietic stem cells (HSCs). CD9+ cells exhibit more resistance to chemotherapy drugs and higher migration potential than do CD9-negative (CD9-) cells. More importantly, CD9+ cells possess the ability to reconstitute human AML in immunocompromised mice and promote leukemia growth, suggesting that CD9+ cells define the LSC population. Furthermore, we identified that A2M plays a crucial role in maintaining CD9+ LSC stemness. Knockdown of A2M impairs drug resistance and migration of CD9+ cells. CONCLUSION: Our findings suggest that CD9 is a new biomarker of AML LSCs and is a promising therapeutic target.

Adenovirus delivery of encoded monoclonal antibody protects against different types of influenza virus infection.

Due to the high mutation and recombination rates of the influenza virus, current clinically licensed influenza vaccines and anti-influenza drugs provide limited protection against the emerging influenza virus epidemic. Therefore, universal influenza vaccines with high efficacy are urgently needed to ensure human safety and health. Passive immunization of influenza broadly neutralizing antibodies may become an ideal option for controlling influenza infection. CR9114 isolated from the peripheral blood mononuclear cells of healthy donors is a broadly neutralizing monoclonal antibody that targets different types of influenza viruses. As the adenovirus vector is one of the most promising delivery vehicles, we employed the chimpanzee adenoviral vector, AdC68, to express CR9114 as a universal anti-influenza vaccine, termed AdC68-CR9114, and evaluated its antibody expression and its broad spectrum of prophylactic and therapeutic effects in animal models. Based on our findings, AdC68-CR9114-infected cell expressed the broadly neutralizing antibody at a high level in vitro and in vivo, exhibited biological functions, and protected mice from different types of influenza virus infection at different time points. The findings from this study shed light on a new strategy for controlling and preventing influenza infection.