The Effect of Iron–Vitamin C Co-supplementation on Biomarkers of Oxidative Stress in Iron-Deficient Female Youth

There is no study that assessed the effect of co-supplementation of iron and vitamin C on biomarkers of oxidative stress in non-anemic iron-deficient females. We investigated the effects of iron vs. iron?+?vitamin C co-supplementation on biomarkers of oxidative stress in iron-deficient girls. In a double-blind randomized controlled clinical trial, performed among 60 non-anemic iron-deficient girls, participants were randomly assigned to receive either 50 mg/day elemental iron supplements or 50 mg/day elemental iron?+?500 mg/day ascorbic acid for 12 weeks. Fasting blood samples were taken at baseline, weeks 6 and 12 for assessment of biomarkers of oxidative stress. Compared with the baseline levels, both iron and iron?+?vitamin C supplementation resulted in a significant reduction in serum malondialdehyde (MDA) levels (P _time?<?0.001) and remarkable elevation in serum total antioxidant capacity (TAC; P _time?<?0.001) and vitamin C levels (P _time?=?0.001); however, comparing the two groups we failed to find an additional effect of iron?+?vitamin C supplementation to that of iron alone on serum TAC and MDA levels (P _group was not statistically significant). Iron?+?vitamin C supplementation influenced serum vitamin C levels much more than that by iron alone (P _group?<?0.01). We also found a significant interaction term between time and group about serum vitamin C levels while this interaction was not significant about serum TAC and MDA levels. In conclusion, we found that iron supplementation with/without vitamin C improve biomarkers of oxidative stress among non-anemic iron-deficient females and may strengthen the antioxidant defense system by decreasing reactive oxygen species. Co-supplementation of iron?+?vitamin C has no further effect on oxidative stress compared with iron alone.     

Betaine Elevates Ovarian Antioxidant Enzyme Activities and Demonstrates Methyl Donor Effect in Non-Pregnant Rats

Chronic alcoholism leads to infertility in male and female rats, and antioxidant enzymes form the first line against oxidative stress in organisms. In recent years, betaine has shown beneficial effects on various tissues, and this study has attempted to clarify antioxidant and methyl donor properties of betaine in the rat ovary. For this purpose, the sexually matured Sprague-Dawley female rats were divided into Control, Ethanol (EtOH), Betaine, and Betaine?+?EtOH groups. Administration of betaine in Betaine?+?EtOH group significantly increased CAT activity when compared to the other groups (P?<?0.05). GPx activity increased significantly in Betaine and Betaine?+?EtOH groups as compared to controls (P?<?0.05). Interestingly, GPx and CAT activities insignificantly increased (in order compensatory) in EtOH group to suppress oxidative stress. In contrast, SOD activity decreased insignificantly in EtOH group compared to Betaine?+?EtOH and control groups (P?>?0.05). TBARS concentration (as a lipid peroxidation marker) significantly increased in ethanol-treated rats as compared to controls, while total homocysteine concentration significantly decreased in betaine-treated rats in comparison with EtOH group. Regarding to oestrous cycles, ethanol-treated animals had irregular estral cycle and persistent oestrous phase compared to controls and betaine-treated rats. In conclusion, these results demonstrate for the first time the antioxidant and methyl donor properties of betaine in the rat ovary. Thus, betaine might be used as a potential therapy in hyperhomocysteinemia and partial infertility mediated by oxidative stress in females.     

A Comparative Study of the Oxidative Profile in Graves’ Disease, Hashimoto’s Thyroiditis, and Papillary Thyroid Cancer

The aim of this study was to evaluate and compare the oxidative profiles of three thyroid disorders: Graves’ disease (GD), Hashimoto thyroiditis (HT), and papillary thyroid cancer (PTC). Malondialdehyde levels (MDA), glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) activities were examined in the plasma of 52 patients (29 untreated HT, 16 untreated GD, and 7 PTC who underwent surgical therapy). Results were compared with those of 30 healthy controls and among the three groups of patients. The GD, HT, and PTC patients exhibited increased plasma MDA levels and SOD activities compared with the controls (p?<?0.05, p?<?0.05, and p?<?0.001, respectively). CAT activities significantly increased only for the PTC and HT patients (p?<?0.001 and p?<?0.05, respectively), whereas GPx activities significantly decreased only in the GD and PTC (p?<?0.05 and p?<?0.01, respectively). The comparison among the three groups of patients has shown increased MDA level and SOD activity for the PTC patients as compared to the GD patients (p?<?0.01 and p?<?0.001, respectively). Compared with HT, PTC patients exhibited significant higher MDA level, SOD, and CAT activities and a significant lower GPx activity (p?<?0.01, p?<?0.001, p?<?0.05, and p?<?0.05, respectively). No significant discrepancies were noted between the GD and HT patients. Our results have clearly shown an oxidative profile that is highly disturbed for the PTC patients as compared to those of autoimmune disorders. Future studies are needed to determine whether or not the oxidative stress has a prognostic value in this pathology.     

Triptolide improves spinal cord injury by promoting autophagy and inhibiting apoptosis

We investigated the effect of triptolide (TP) on spinal cord injury (SCI), and its underlying mechanism. Following the establishment of the SCI model using YFP H‐line transgenic mice, TP was intraperitoneally injected at a dose of 0.2 mg/kg once daily for 7 days. Behavioral tests, Nissl staining, and hematoxylin–eosin staining were employed to assess motor function recovery and neuronal cell death. Western blot and immunofluorescence staining were used to assess autophagy‐associated proteins (LC3B, p62, Beclin‐1) and the apoptosis‐associated proteins (Bcl‐2, caspase‐3, Bax). The TP‐treated group showed improved motor functions, and reduced neuronal cell death. Also, significant upregulation of Bcl‐2 and LC3B expressions, with the downregulation of p62, Bax and caspase‐3 expressions were found in the TP‐treated group. Additionally, phosphorylation of extracellular signal‐regulated protein kinases 1 and 2 (ERK1 and ERK2) was decreased in the TP‐treated group. TP mediates its protective effect in SCI by promoting the autophagic pathway while inhibiting the MAPK/ERK1/2 signaling pathway. These results demonstrate the therapeutic potential of TP in SCI.     

The Beneficial Effect of Probiotics Supplementation on Penicillin-Induced Focal Seizure in Rats

The focal epilepsy is a chronic neurological brain disorder which affects millions of people in the world. There is emerging evidence that changes in the gut microbiota may have effects on epileptic seizures. In the present study, we examined the effect of probiotics on penicillin-induced focal seizure model in rats. Male Wistar Albino rats (n: 21) were randomly divided into three groups: control (no medication), penicillin and penicillin?+?probiotic. Probiotic VSL#3 (12.86 bn living bacteria/kg/day) was given by gavage for 30 days. The seizures were induced by intracortical injection of penicillin G (500 IU) into the cortex. An ECoG recordings were made for 180 min after penicillin G application. The spike frequency and the amplitude were used to assess the severity of seizures. Tumor necrosis factor (TNF-α), nitric oxide (NO) and interleukin (IL-6) levels in the brain were studied biochemically. Our results indicated that probiotic supplementation improved focal seizures through increasing the latency (p?<?0.001) and decreasing the spike frequency (p?<?0.01) compared to the penicillin group. Penicillin-induced seizure in rats significantly enhanced TNF-α (p?<?0.01), NO (p?<?0.01) and IL-6 (p?<?0.05) compared to the control. Probiotic supplementation significantly decreased IL-6 (p?<?0.05), TNF-α (p?<?0.01) and NO (p?<?0.001) compared to the penicillin group. When the body weights were compared before and after the experiment, there was no difference between the control and penicillin groups, but it was observed that the body weight decreased after probiotic supplementation in the penicillin?+?probiotic group. Probiotic supplementation may have anti-seizure effect by reducing proinflammatory cytokine and NO levels in epileptic rat brain.

     

Betanin alleviates oxidative stress through the Nrf2 signaling pathway in the liver of STZ-induced diabetic rats

Background

Continuing hyperglycemia causes and exacerbate oxidative stress. Betanin as the principal pigment of red beet root has antioxidant, anti-inflammatory, and anti-diabetic properties. The purpose of this study was to investigate the potency of betanin on antioxidant defense in STZ-induced diabetic rats’ livers.

Methods

STZ at a single dose of 60 mg/kg body weight was intraperitoneally injected and betanin (10, 20, and 40 mg/kg/day) was administered orally for 28 days. Malondialdehyde (MDA), total antioxidant capacity (TAC), protein carbonyl (PC) levels, and the enzyme activity of superoxide dismutase (SOD), catalases and glutathione peroxidases (GPx) were evaluated in the liver. Furthermore, gene expression of Nrf2 and mentioned antioxidant enzymes were measured by Real-time PCR.

Results

Betanin (10 and 20 mg/kg) significantly reduced PC levels and increased antioxidant enzyme activity in diabetic rats compared to the control diabetic group (P?<?0.01). In comparison to the diabetic control group, all studied genes expression in diabetic rats were increased significantly with betanin at doses of 10 and 20 mg/kg (P?<?0.02). The increase in gene expression at 20 mg/kg of betanin was significantly stronger than others (P?<?0.015) except for the catalase (P?=?0.201), that was almost the same. Moreover, treatment of diabetic rats with 20 mg/kg of betanin could significantly increase TAC levels (P?<?0.05) and decrease MDA levels (P?<?0.001) compared to diabetic control group.

Conclusions

Betanin could increase the antioxidant capacity of liver tissue associated with the Nrf2-mediated pathway in a dose-dependent manner.

     

Selenomethionine administration decreases the oxidative stress induced by post mortem ischemia in the heart,liver and kidneys of rats

Selenium is an essential element in human and animal metabolism integrated into the catalytic site of glutathione peroxidase (GPX1), an antioxidant enzyme that protects cells from damage caused by reactive oxygen species (ROS). Oxidative stress refers the imbalance between ROS and antioxidant defense systems. It generates alterations of DNA, proteins and lipid peroxidation. The imbalance occurs particularly during ischemia and lack of postmortem perfusion. This mechanism is of relevance in transplant organs, affecting their survival. The aim of this research is to evaluate the effect of seleno-methionine (SeMet) as a protective agent against postmortem ischemia injury in transplant organs. Wistar rats were orally administered with SeMet. After sacrifice, liver, heart and kidney samples were collected at different postmortem intervals (PMIs). SeMet administration produced a significant increase of Se concentration in the liver (65%, p?<?0.001), heart (40%, p?<?0.01) and kidneys (45%, p?<?0.05). Levels of the oxidative stress marker malondialdehyde (MDA) decreased significantly compared to control in the heart (0.21?±?0.04 vs. 0.12?±?0.02 mmol g^?1) and kidneys (0.41?±?0.02 vs. 0.24?±?0.03 mmol g^?1) in a PMI of 1–12 h (p?<?0.01). After SeMet administration for 21 days, a significant increase in GPX1 activity was observed in the liver (80%, p?<?0.001), kidneys (74%, p?<?0.01) and heart (35%, p?<?0.05). SeMet administration to rats significantly decreased the oxidative stress in the heart, liver and kidneys of rats generated by postmortem ischemia.

     

Circadian Variation in the Response to Experimental Endotoxemia and Modulatory Effects of Exogenous Melatonin

Disturbances in circadian rhythms are commonly observed in the development of several medical conditions and may also be involved in the pathophysiology of sepsis. Melatonin, with its antioxidative and anti-inflammatory effects, is known to modulate the response to endotoxemia. In this paper, we investigated the circadian variation with or without melatonin administration in an experimental endotoxemia model based on lipopolysaccharide (LPS). Sixty male Sprague-Dawley rats were assigned to six groups receiving an intraperitoneal injection of either LPS (5?mg/kg), LPS?+?melatonin (1?mg/kg), or LPS?+?melatonin (10?mg/kg) at either daytime or nighttime. Superoxide dismutase (SOD) was analyzed in liver samples collected after decapitation. Furthermore, inflammatory plasma markers (cytokines interleukin [IL]-6, IL-10) and oxidative plasma markers (ascorbic acid [AA], dehydroascorbic acid [DHA], and malondialdehyde [MDA]) were analyzed before and 5?h after the onset of endotoxemia. There were significant higher levels of SOD (p?<?0.05), IL-6 (p?<?0.01), and IL-10 (p?<?0.05) during nighttime endotoxemia compared with daytime. At daytime, melatonin 1 and 10?mg reduced the levels of MDA and increased SOD, IL-6, IL-10, and DHA (p?<?0.05). At nighttime, melatonin reduced the levels of MDA and increased DHA (p?<?0.05). Additionally, 10?mg melatonin resulted in lower levels of AA during daytime (p?<?0.05). No dose relationship of melatonin was observed. The results showed that the response induced by experimental endotoxemia was dependent on time of day. Melatonin administration modulated the inflammatory and oxidative stress responses induced by endotoxemia and also resulted in higher levels of antioxidants during daytime. The effect of circadian time on the endotoxemia response and possible modulatory effects of melatonin need further investigations in a human endotoxemia model.     

Regulation of Zinc Transporter 1 Expression in Dorsal Horn of Spinal Cord After Acute Spinal Cord Injury of Rats by Dietary Zinc

Zinc concentrations in the dorsal horn of spinal cord are important for wound healing, neurological function, and reproduction. However, the response of the spinal cord to alterations in dietary zinc is unknown in rats after spinal cord injury (SCI). The current study explored cellular zinc levels and zinc transporter 1 (ZnT1) expression in the dorsal horn of spinal cord with different dietary zinc after SCI. A hundred and forty-four male Wistar rats were randomly divided into four groups: sham-operated group (30?mg Zn/kg), zinc-high dietary SCI model group (ZH, 180?mg Zn/kg), zinc-adequate dietary SCI model group (30?mg Zn/kg), and marginal zinc-deficient dietary SCI model group (MZD, 5?mg Zn/kg). To test the hypothesis that dietary zinc may regulate role of ZnT1 expression in dorsal horn after acute SCI, we traced ZnT1 proteins and zinc ions with immunohistochemistry, western blot, and autometallography. Zinc and ZnT1 levels of the dorsal horn in ZH significantly increased after surgery (P?<?0.05), reached peak level (P?<?0.05) on the seventh day, and subsequently levels of their expression began to decrease. But zinc levels and ZnT1 expression of spinal cord in MZD dietary groups decreased (P?<?0.05) in SCI. There was a positive correlation between ZnT1 protein and zinc content in spinal cord (R?=?0.49880, P?=?0.0492). We found that both zinc and ZnT1 expressions in spinal cord are regulated by dietary zinc. These results indicate that dietary zinc may regulate the expression of ZnT1 in the dorsal horn of spinal cord after SCI. ZnT1 may, at the same time, play a significant role in the maintenance of zinc homeostasis in SCI.     

Thiamine deficiency induces oxidative stress in brain mitochondria of Mus musculus

The present investigation evaluates the changes in the levels of antioxidant enzymes, lipid peroxidation (LPO), and protein carbonyl content (PCC) in brain mitochondria following thiamine deficiency (TD). The study was carried out on Mus musculus allocated into three groups, namely control and thiamine-deficient group for 8 (TD 8) and 10 (TD 10) days. The LPO was measured in terms of reduced glutathione (GSH) and thiobarbituric acid reactive substance (TBARS). Antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were measured biochemically. A significant increase in the TBARS (p?<?0.0001) and PCC (p?<?0.001) levels in group II (TD 8) and group III (TD 10) animals was observed in comparison to controls. The GSH levels were found to be reduced in both the treated groups compared to the control. A significant reduction in the activities of SOD was also observed in group II (p?<?0.01) and group III (p?<?0.0001) animals in comparison to the control. Enzymatic activities of CAT (p?<?0.001) and GPx (p?<?0.05) were found to be significantly reduced in group III (TD 10) in comparison to the control. In conclusion, reduction in the activities of antioxidant enzymes as well as an increase in LPO and PCC following TD implies oxidative stress in brain mitochondria that may further leads to neurodegeneration.     

Effects of Aluminum and Extremely Low Frequency Electromagnetic Radiation on Oxidative Stress and Memory in Brain of Mice

This study was aimed to investigate the effect of aluminum and extremely low-frequency magnetic fields (ELF-MF) on oxidative stress and memory of SPF Kunming mice. Sixty male SPF Kunming mice were divided randomly into four groups: control group, ELF-MF group (2 mT, 4 h/day), load aluminum group (200 mg aluminum/kg, 0.1 ml/10 g), and ELF-MF?+?aluminum group (2 mT, 4 h/day, 200 mg aluminum/kg). After 8 weeks of treatment, the mice of three experiment groups (ELF-MF group, load aluminum group, and ELF-MF?+?aluminum group) exhibited firstly the learning memory impairment, appearing that the escaping latency to the platform was prolonged and percentage in the platform quadrant was reduced in the Morris water maze (MWM) task. Secondly are the pathologic abnormalities including neuronal cell loss and overexpression of phosphorylated tau protein in the hippocampus and cerebral cortex. On the other hand, the markers of oxidative stress were determined in mice brain and serum. The results showed a statistically significant decrease in superoxide dismutase activity and increase in the levels of malondialdehyde in the ELF-MF group (P?<?0.05 or P?<?0.01), load aluminum group (P?<?0.01), and ELF-MF?+?aluminum group (P?<?0.01). However, the treatment with ELF-MF?+?aluminum induced no more damage than ELF-MF and aluminum did, respectively. In conclusion, both aluminum and ELF-MF could impact on learning memory and pro-oxidative function in Kunming mice. However, there was no evidence of any association between ELF-MF exposure with aluminum loading.     

Long-term Therapeutic Effects of Extracorporeal Shock Wave-Assisted Melatonin Therapy on Mononeuropathic Pain in Rats

We evaluated the ability of extracorporeal shock wave (ECSW)-assisted melatonin (Mel) therapy to offer an additional benefit for alleviating the neuropathic pain (NP) in rats. Left sciatic nerve was subjected to chronic constriction injury (CCI) to induce NP. Animals (n?=?30) were randomized into group 1 (sham-operated control), group 2 (CCI only), group 3 (CCI?+?ECSW), group 4 (CCI?+?Mel) and group 5 (CCI?+?ECSW?+?Mel). By days 15, 22 and 29 after CCI, the thermal paw withdrawal latency (TPWL) and mechanical paw withdrawal threshold (MPWT) were highest in group 1, lowest in group 2, significantly higher in group 5 than in groups 3 and 4, but they showed no difference between the later two groups (all p?<?0.0001). The protein expressions of inflammatory (TNF-α, NF-κB, MMP-9, IL-1ß), oxidative-stress (NOXs-1, -2, -4, oxidized protein), apoptotic (cleaved-caspase3, cleaved-PARP), DNA/mitochondrial-damaged (γ-H2AX/cytosolic-cytochrome C), microglia/astrocyte activation (ox42/GFAP), and MAPKs [phosphorylated (p)-p38, p-JNK, p-ERK] biomarkers in dorsal root ganglia neurons (DRGs) and in spinal dorsal horn were exhibited an opposite pattern of TPWL among the five groups (all p?<?0.0001). Additionally, protein expressions of Nav.1.3, Nav.1.8 and Nav.1.9 in sciatic nerve exhibited an identical pattern to inflammation among the five groups (all p?<?0.0001). The numbers of cellular expressions of MAPKs (p-ERK1/2+/peripherin?+?cells, p-ERK1/2+/NF200?+?cells and p-JNK+/peripherin?+?cells, p-JNK+/NF200?+?cells) and voltage-gated sodium channels (Nav.1.8+/peripherin?+?cells, Nav.1.8+/NF200?+?cells, Nav.1.9+/peripherin?+?cells, Nav.1.9+/NF200?+?cells) in small and large DRGs displayed an identical pattern to inflammation among the five groups (all p?<?0.0001). In conclusion, the synergistic effect of combined ECSW-Mel therapy is superior to either one alone for long-term improvement of mononeuropathic pain-induced by CCI in rats.

     

The Effect of Enriched Milk with Selenium and Vitamin E on Growth Rate, Hematology, Some Blood Biochemical Factors, and Immunoglobulins of Newborn Goat Kids

Thirty male and female (n?=?15 for each one) Markhoz newborn goat kids (aged 7?±?3 days) were distributed in a randomized block design in a 2?×?2?+?1 factorial arrangement: two levels of sodium selenite as a source of selenium (0.2 or 0.3 ppm Se), two levels of α-tocopherol acetate as a source of vitamin E (150 or 200 IU Vit E), and one control treatment with six repetitions per treatment (each replicate included three male and three female kids). Animals were fed daily by Se-Vit E-enriched milk (Se-Vit E treatments) or non-enriched milk (control treatment). Growth rate, hematology, and serum biological parameters were measured. The levels of serum albumin (P?<?0.01), serum globulin (P?<?0.05), total serum protein levels (P?<?0.01), erythrocyte counts (RBC) (P?<?0.001), hemoglobin (P?<?0.001), hematocrit (P?<?0.001), leukocyte counts (WBC) (P?<?0.001), IgA (P?<?0.05), IgG (P?<?0.01), and IgM (P?<?0.01) significantly differed among treatments, while no significant differences were observed for calcium, lymphocyte, neutrophil average daily gain and body weight among treatments. Kids feeding by enriched milk with 0.3 ppm Se and 200 IU Vit E had significantly higher serum total protein, globulin, RBC, IgA, IgG, and IgM compared to control and those fed by enriched milk to 0.2 ppm Se and 200 IU Vit E had significantly higher WBC counts.     

The Effects of Zinc Treatment on the Blood–Brain Barrier Permeability and Brain Element Levels During Convulsions

We evaluated the effect of zinc treatment on the blood–brain barrier (BBB) permeability and the levels of zinc (Zn), natrium (Na), magnesium (Mg), and copper (Cu) in the brain tissue during epileptic seizures. The Wistar albino rats were divided into four groups, each as follows: (1) control group, (2) pentylenetetrazole (PTZ) group: rats treated with PTZ to induce seizures, (3) Zn group: rats treated with ZnCl₂ added to drinking water for 2 months, and (4) Zn?+?PTZ group. The brains were divided into left, right hemispheres, and cerebellum?+?brain stem regions. Evans blue was used as BBB tracer. Element concentrations were analyzed by inductively coupled plasma optical emission spectroscopy. The BBB permeability has been found to be increased in all experimental groups (p?<?0.05). Zn concentrations in all brain regions in Zn-supplemented groups (p?<?0.05) showed an increase. BBB permeability and Zn level in cerebellum?+?brain stem region were significantly high compared to cerebral hemispheres (p?<?0.05). In all experimental groups, Cu concentration decreased, whereas Na concentrations showed an increase (p?<?0.05). Mg content in all the brain regions decreased in the Zn group and Zn?+?PTZ groups compared to other groups (p?<?0.001). We also found that all elements’ levels showed hemispheric differences in all groups. During convulsions, Zn treatment did not show any protective effect on BBB permeability. Chronic Zn treatment decreased Mg and Cu concentration and increased Na levels in the brain tissue. Our results indicated that Zn treatment showed proconvulsant activity and increased BBB permeability, possibly changing prooxidant/antioxidant balance and neuronal excitability during seizures.     

Protective effects of vitamins (C and E) and melatonin co-administration on hematological and hepatic functions and oxidative stress in alloxan-induced diabetic rats

The present study aimed to investigate the potential effects of vitamins (C and E)/melatonin co-administration on the hematologic and hepatic functions and oxidative stress in alloxan-induced diabetic rats. The intraperitoneal injection of alloxan (120 mg/kg b.w. for 2 days) induced a significant increase of blood glucose levels (hyperglycemia) associated with serious hematologic disorders (P?<?0.01) evidenced by the decrease in the levels of red blood cell count (RBC) (?18 %), hematocrit (Ht) (?18 %), hemoglobin content (Hb) (?36 %), mean corpuscular hemoglobin (MCH) (?17 %), and mean corpuscular hemoglobin concentration (MCHC) (?16 %). The activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), and the plasmatic levels of total cholesterol and triglyceride contents of diabetic rats were, however, noted to undergo significant increases by 42 % (P?<?0.01), 134 % (P?<?0.001), 27.5 % (P?<?0.01), 147 % (P?<?0.001), and 67 % (P?<?0.01), respectively, as compared to the control animals. Furthermore, a significant increase in malondialdehyde (MDA) content and a significant decrease in superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities were observed in the plasma and hepatic tissues of diabetic rats when compared to the controls. Interestingly, the treatment with vitamins (C, E) in combination with melatonin was noted to reduce the plasma levels of glucose, lower the MDA levels, and restore the hematologic parameters and biochemical and antioxidant levels of diabetic rats back to normal values, alleviating diabetes metabolic disorders in rats.     

Effects of Oligoelements Se,Zn, and Mn plus Lachesis Muta Venom in Experimental Scleroderma

Scleroderma, sclerosis of the skin, is a severe autoimmune disease refractant to all kind of treatments. To study the in vivo effects of a combination of three oligoelements selenium (Se), zinc (Zn), and manganese (Mn) plus Lachesis muta venom (O-LM) on the bleomycin (BLM)-induced scleroderma mouse experimental model. C3H mice were randomly divided into four groups: control (phosphate-buffered saline (PBS)), O-LM, BLM, and BLM?+?O-LM. All administrations were performed subcutaneously into the back of mice. BLM was injected 5 days per week for three consecutive weeks and O-LM was administered simultaneously with BLM from the beginning of the experiments and lasted for 3 weeks after the final BLM or PBS injection (for O-LM and BLM?+?O-LM groups), when animals were sacrificed and histopathological, immunohistochemical, thiobarbituric acid reactive species (TBARS) evaluation, and autoantibodies detection were determined. O-LM significantly reduced BLM-induced enhanced dermal thickness (605?±?47 vs. 956?±?59 μm, P?<?0.01), collagen deposition, and mast cells infiltration (43.1?±?1.0 vs. 102?±?14.1 mast cells, P?<?0.05). O-LM administration significantly blocked BLM-induced oxidative damage and the enhanced immunoreactive fibroblasts for α-smooth muscle actin while reduced BLM-induced autoantibodies that strongly react mainly with skin and spleen. O-LM significantly reduced BLM-induced scleroderma through the modulation of antioxidant and immunological pathways.     

The diagnostic value of serum DSA-TRF in hepatocellular carcinoma

TRF is a glycoprotein mainly secreted by hepatocytes, The aim of this study was to explore the diagnostic value of aberrant glycosylated serum transferrin (TRF) especially containing multi-antennary glycans in hepatocellular carcinoma (HCC).A total of 581 subjects including HCC patients, liver cirrhosis (LC) patients, chronic hepatitis (CHB) patients and healthy controls (HC) were recruited. All the subjects were randomly assigned to training group (n?=?411) and validation group (n?=?170). We firstly analyzed the serum protein N-glycome profiling of HCC, LC, and HC by DNA sequencer–assisted fluorophore-assisted carbohydrate electrophoresis (DSA-FACE) technology. We established a lectin-antibody sandwich ELISA (Lectin-ELISA) method to detect multi-antennary glycans-contained TRF (DSA-TRF) in serum, in which Datura stramonium Agglutinin (DSA) was used for specific recognition. Levels of serum DSA-TRF and TRF were analyzed respectively. The diagnostic efficacies of DSA-TRF and TRF of differentiating HCC patients from CHB, LC patients and HC within the training group were evaluated using receiver operating characteristic (ROC) curve and tested in the validation group.The result found that in training group, serum TRF and DSA-TRF levels differed significantly between HCC (1.86?±?0.50, g/L, 0.285?±?0.06), CHB?+?LC (2.39?±?0.74, g/L, 0.189?±?0.07) and HC (1.92?±?0.69, g/L, 0.249?±?0.09) (HCC vs. CHB?+?LC, P?<?0.001; HCC vs. HC, P?<?0.001; CHB?+?LC vs. HC, P?<?0.001). The area under the ROC curve (AUC) of DSA-TRF was significantly superior to AFP (0.880, 95%CI: 0.834–0.925 vs. 0.776, 95%CI: 0.725–0.827, P?=?0.003) in differentiating HCC from CHB?+?LC. The AUC of diagnostic model GlycoTRF1 (0.981, 95%CI: 0.969–0.993) was higher than DSA-TRF and AFP alone (P<0.001) in differentiating HCC from CHB?+?LC, which was verified in validation group.The results indicated that the serum DSA-TRF might serve as a potential glycan biomarker for distinguishing HCC from CHB and LC.

     

Baicalin effects on rats with spinal cord injury by anti‐inflammatory and regulating the serum metabolic disorder

Baicalin had neuroprotective effects on inhibiting neuronal cell apoptosis induced by spinal cord ischemic injury. This study aimed to explore the protective effects of Baicalin on rats with spinal cord injury (SCI) and its mechanism of action. The recovery of spinal cord nerve function in rats was evaluated by the Basso, Beattie, and Bresnahan (BBB) score and the combine behavioral score (CBS). The expressions of cytokines tumor necrosis factor α (TNF‐α), interleukin‐1β (IL‐1β), and IL‐6 were detected by the enzyme‐linked immunosorbent assay method. Expressions of inflammation‐related proteins were detected by Western blot. Multivariate statistical analysis was performed for serum metabolites. The BBB and CBS score results showed that Baicalin had a certain improvement on rats with SCI. SCI symptoms were significantly improved in low‐dose and high‐dose groups. The levels of TNF‐α, IL‐1β, and IL‐6 in the SCI group were significantly increased. The expressions of NF‐κB p65, NF‐κB p50, p‐IκBα, and IKKα in the SCI group showed the opposite trend compared with the low‐dose and high‐dose groups. Compared with the sham group, glutamine, levels of 3‐OH‐butyrate, N‐acetylaspartate, and glutathione were significantly reduced, and the levels of glutamate and betaine were significantly increased in the SCI group. When Baicalin was administered, the contents of glutamine synthase (GS) and glutaminase (GLS) were significantly reduced, indicating that Baicalin had the effect of improving GS and GLS. Baicalin has protective effects on improving SCI and lower extremity motor function, has a significant anti‐inflammatory effect, and regulates the serum metabolic disorder caused by SCI in rats.