Mice In Normal Group Research Articles

Synthesis and biological evaluation of a novel 68Ga-labeled GalNAc-PET probe for asialoglycoprotein receptor imaging

PurposeThe asialoglycoprotein receptor (ASGPR), expressed exclusively on mammalian hepatocyte membranes, recognizes ligands terminated with β-D-galactose (Gal) and N-acetylglucosamine (GalNAc). This study aims to develop a 68Ga-labeled monovalent GalNAc derivative that particularly interacts with ASGPR. It also aims to assess the potential utility of this derivative in visualizing ASGPR-related liver dysfunction using positron emission tomography (PET)/ computed tomography (CT) imaging. MethodsThe PET imaging probe 68Ga-NOTA-GalNAc was developed and characterized with regard to radiochemical purity, biocompatibility, biodistribution patterns, and specific ASGPR-targeting ability. Groups of normal mice, mice with acute liver injury (ALI) induced by CCl4, mice with early-stage liver fibrosis induced by CCl4, mice with nonalcoholic fatty liver disease (NAFLD), and orthotopic HepG2 hepatoma-bearing mice were imaged with 68Ga-NOTA-GalNAc PET to evaluate the potential of this technique in monitoring ASGPR-related liver dysfunction. Results68Ga-NOTA-GalNAc, a hydrophilic compound with high radiochemical purity (>99 %) and good liver targeting ability, particularly binds ASGPR on the surface of hepatocytes with moderate affinity (KD = 6.82 μM). Compared with control, ASGPR-related liver dysfunction groups, even the group of mice with ALI (P <0.0001), revealed sensitive distinctions in the liver uptake value of 68Ga-NOTA-GalNAc. The 68Ga-NOTA-GalNAc absorbed in the livers of mice with early-stage liver fibrosis and NAFLD group is significantly less than that absorbed in the livers of mice in the normal group (P <0.0001). Hepatoma can be visualized in orthotopic HepG2 hepatoma-bearing mice because of different radioactivity accumulated in the nontumor region and lesion region, corresponding to the ASGPR expression confirmed with immunohistochemical staining. Conclusion68Ga-NOTA-GalNAc has the potential to be a specific, noninvasive, and sensitive PET imaging agent for ASGPR-related liver dysfunction.

Experimentally Histological Assessment for the Effect of Resveratrol in the Liver of Mice

Resveratrol a major Polyphenolic compound is a non-flavonoid stilbene, was isolated and purified as a first time in Iraq from the skin of black grape had grown in this country. Many studies confirmed the biological importance of this substance in different disorders, beside the protective properties specially towered the hepatic cells against free radicals and drugs toxic effects as histological level. In this study the purified resveratrol from Iraqi black grape was administered to groups of normal mice in three doses to investigate if there is any unwanted or harmful effects which may appear on the mice liver after fifteen days and thirty days administrated as intrapretoneal single dose a day Results showed that the extraction method estimated resveratrol in two stereo isomer mixture cis and trance forms. The different doses within two intervals affected the hepatocytes in different manner. The harmful properties of this substance appeared to be more potent in relation with dose and exposure time increasing. The study concluded that there must be an extensive studies that bridge the gap of available information with what is required regarding the Iraqi purified resveratrol as a safe therapeutic substance, not only for treating liver disorders, but in all it's therapeutic purposes

Study the Effective Role of Metronidazole Nanoemulsion for the Treatment of Skin Lesions in Mice Induced by Entamoeba Histolytica

The current study aimed to create a metronidazole nanoemulsion and then use it in the treatment of skin lesions in mice caused by Entamoeba histolytica. We used parasite isolates which taken from the Department of Biology, College of Science, University of Kirkuk. It was rediagnosed by conventional methods. After prepared metronidazole nanoemulsion. We selected 24 healthy males Mus musculus with an average weight of 20-25 grams mice aged 9-12 weeks from, the animals were randomly divided into four groups, with six animals in each group, as follows Control group which injected with normal saline in a volume of 0.1 ml. The second group was injected with a suspension of E. histolytica in a volume of 0.1 ml and at a concentration of 1 x 108 CFU. The third group was injected with Mt-nanoemulsion 0.1 ml. The fourth group was injected with a suspension of E. histolytica and treated with Mt-nanoemulsion. The solubility investigation was conducted using a variety of vehicles to determine the optimal solvent for isradipine's dissolution. Pseudo ternary phase diagrams are created at surfactant and co-surfactant mix related ratios of (1:1, 1:2, 1:3, 1:4, and 2:1). Eight nano emulsions were created by combining several amounts of (Transcutol, Tween20, and Triacetin). The findings indicated that Triacetin was included in the formulations to preserve the medication in a solubilized state and prevent precipitation of the drug because Triacetin had a better solubility of metronidazole. The results of the in vitro study showed that the levels of Malondialdehyde were substantially greater (P &gt;0.05) in the E. histolytica group than in the normal mouse group. Glutathione and catalase levels in the E. histolytica group were substantially lower (P&gt;0.05) than those of normal mice. MDA, GSH, and catalase levels did not differ significantly between the Mt-nanoemulsion-treated group and the control group (P&lt;0.05).

Hyperbaric oxygen as an immunosuppressant in mouse model of lupus nephritis

Lupus nephritis (LN) is the main cause of morbidity and death due to the most severe complications of the kidney organ in Systemic Lupus Erythematosus (SLE). Immunosuppressive drugs are needed to control this disease, but currently available immunosuppressive drugs do not provide optimal results. This research used 21 Mus Musculus BALB/c mice, female, body weight 25 – 30 grams, 8-12 weeks old, healthy and active, divided into 3 groups. The group of normal mice (G1) was the negative control group, the group of lupus nephritis mice without Hyperbaric Oxygen (HBO) therapy (G2) was the positive control group and the group of lupus nephritis mice with HBO therapy (G3) was the treatment group. The results showed a significant reduction in anti-dsDNA Ab levels p = 0.002 (p&lt;0.05) and proteinuria levels p = 0.005 (p&lt;0.05) in the group given HBO (G3) compared to the group not given HBO (G2). Repair of kidney tissue damage was characterized by a decrease in inflammatory cells, a decrease in tubular constriction and a decrease in immune complex deposits in the group given HBO (G3) compared to the group not given HBO (G2). So HBO can reduce anti-dsDNA Ab levels and proteinuria, and repair damaged kidney tissue. HBO as an immunosuppressive can be used as additional therapy in lupus nephritis.

In vitro alpha-amylase and alpha-glucosidase inhibitory activity and in vivo antidiabetic activity of Quercus coccifera (Oak tree) leaves extracts

Quercus species are group of plants known as oak which represent important genus of Fagaceae family. These species are widely distributed in Mediterranean countries. Many of those species used in traditional medicine to treat and prevent various human disorders such as diabetes. Exhausted extraction for Quercus coccifera leaves were carried out using n-hexane, chloroform, methanol, boiled water and microwaved water. Extracts were subjected to phytochemical screening, acute toxicity study, and in vitro and in vivo animal model to evaluate antidiabetic activity of the produced extracts. The highest in vitro activity against α-amylase and α-glucosidase activity was obtained from methanolic extract with an IC50 of 0.17 and 0.38 µg/ml respectively and better than the positive control acarbose. While the rest of the extract was either with moderate or low activity. Similarly, in the in vivo study, methanolic extract with a concentration of 200 mg/kg/day was able to reduce the blood glucose level for the diabetic mice to 146.8 mg/dL with normal bodyweight and biochemical signs when compared to the normal mice group. While the rest of the extracts were either with moderate or low ability to maintain blood glucose level for diabetic mice with few signs of hepatic and renal toxicity and weight loss. All data were statistically significantly different with p-value of less than 0.001 at confidence interval of 95% with high variance homogeneity. In conclusion, methanolic plant leaves extract of Q. coccifera can possibly be used alone to control the elevation of blood glucose level with a renal and hepatic protective property.

Mechanism of Yanghe Decoction against subcutaneous tumor in pulmonary metastasis from breast cancer through HIF-1α signaling pathway regulating glycolysis:based on network pharmacology and animal experiment

This study aims to explore the mechanism of Yanghe Decoction(YHD) against subcutaneous tumor in pulmonary metastasis from breast cancer, which is expected to lay a basis for the treatment of breast carcinoma with YHD. The chemical components of medicinals in YHD, and the targets of the components were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and SwissTargetPrediction. The disease-related targets were searched from GeneCards and Online Mendelian Inheritance in Man(OMIM). Excel was employed to screen the common targets and plot the Venn diagram. The protein-protein interaction network was constructed. R language was used for Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment. A total of 53 female SPF Bablc/6 mice were randomized into normal group(same volume of normal saline, ig), model group(same volume of normal saline, ig), and low-dose and high-dose YHD groups(YHD, ig, 30 days), with 8 mice in normal group and 15 mice in each of the other groups. Body weight and tumor size was measured every day. Curves for body weight variation and growth of tumor in situ were plotted. In the end, the subcutaneous tumor sample was collected and observed based on hematoxylin and eosin(HE) staining. The mRNA and protein levels of hypoxia inducible factor-1α(HIF-1α), pyruvate kinase M2(PKM2), lactate dehydrogenase A(LDHA), and glucose transporter type 1(GLUT1) were detected by PCR and Western blot. A total of 213 active components of YHD and 185 targets against the disease were screened out. The hypothesis that YHD may regulate glycolysis through HIF-1α signaling pathway to intervene in breast cancer was proposed. Animal experiment confirmed that the mRNA and protein levels of HIF-1α, PKM2, LDHA, and GLUT1 in the high-and low-dose YHD groups were lower than those in the model group. YHD has certain inhibitory effect on subcutaneous tumor in pulmonary metastasis from breast cancer in the early stage, which may intervene pulmonary metastasis from breast cancer by regulating glycolysis through HIF-1α signaling pathway.

Effect of Recombinant Human Thrombopoietin (rhTPO) on Long-term Hematopoietic Recovery in Mice with Acute Radiation Sickness and Relative Mechanism

To investigate the effect and relative mechanism of Recombinant Human Thrombopoietin (rhTPO) on long-term hematopoietic recovery in mice with acute radiation sickness. Mice were intramuscularly injected with rhTPO (100 μg/kg) 2 hours after total body irradiation with 60Co γ-rays (6.5 Gy). Moreover, six months after irradiation, peripheral blood, hematopoietic stem cells (HSC) ratio, competitive transplantation survival rate and chimerization rate, senescence rate of c-kit+ HSC, and p16 and p38 mRNA expression of c-kit+ HSC were detected. Six months after 6.5 Gy γ-ray irradiation, there were no differences in peripheral blood white blood cells, red blood cells, platelets, neutrophils and bone marrow nucleated cells in normal group, irradiated group and rhTPO group (P>0.05). The proportion of hematopoietic stem cells and multipotent progenitor cells in mice of irradiated group was significantly decreased after irradiation (P<0.05), but there was no significant changes in rhTPO group (P>0.05). The counts of CFU-MK and BFU-E in irradiated group were significantly lower than that in normal group, and rhTPO group was higher than that of the irradiated group(P<0.05). The 70 day survival rate of recipient mice in normal group and rhTPO group was 100%, and all mice died in irradiation group. The senescence positive rates of c-kit+ HSC in normal group, irradiation group and rhTPO group were 6.11%, 9.54% and 6.01%, respectively (P<0.01). Compared with the normal group, the p16 and p38 mRNA expression of c-kit+ HSC in the irradiated mice were significantly increased (P<0.01), and it was markedly decreased after rhTPO administration (P<0.01). The hematopoietic function of mice is still decreased 6 months after 6.5 Gy γ-ray irradiation, suggesting that there may be long-term damage. High-dose administration of rhTPO in the treatment of acute radiation sickness can reduce the senescence of HSC through p38-p16 pathway and improve the long-term damage of hematopoietic function in mice with acute radiation sickness.

Hyperbaric Oxygen Ameliorates The Expression of Tumor Growth Factor-β and Malondialdehyde in Pristane-induced Lupus Nephritis Mice Model

BACKGROUND: Lupus nephritis (LN) is associated with chronic renal failure and a high mortality rate. Tumor growth factor-β (TGF-β) plays a basic part in keeping up immune homeostasis, meanwhile extensive oxidation of the lipid membrane in LN causes the arrangement of malondialdehyde (MDA). Up to date, the mechanism of hyperbaric oxygen (HBO) therapy in LN has not been elucidated well. Hence this study was conducted to assess the impact of HBO therapy on TGF-β and MDA expression in the pristane-induced LN mice model.METHODS: Thirty-two mice aged 8-12 old weeks were isolated into 4 groups: normal saline-injected mice (group 1); pristane-injected mice (group 2); as well as pristane-injected followed by HBO-exposured with 2.4 (group 3) and 1.5 (group 4) atmosphere absolute (ATA) pressure. Pristane were injected intraperitoneal to initiate LN. Two months after pristane injection, the mice were placed within 24 hours in the special cage for metabolic examination to determined that pristane-induced LN mice model was successfully formed and marked by the occurring proteinuria. Oxidative stress was assessed by examining MDA, while systemic inflammation was assessed by examining by TGF-β. MDA and TGF-β serum were measured by enzyme-linked immunosorbent assay (ELISA).RESULTS: A significantly lower (p&lt;0.050) MDA expression was found in group 3 in comparison with group 2. The results also showed that TGF-β level was significantly increased (p&lt;0.050) in group 3 compared to group 2.CONCLUSION: HBO therapy ameliorates inflammation in LN by diminishing MDA and expanding TGF-β levels through activating antioxidants.KEYWORDS: lupus nephritis, hyperbaric oxygen, malondialdehyde, tumor growth factor-β

Mechanism of Huangjing Qianshi Decoction in treatment of prediabetic mice based on transcriptome sequencing

Based on transcriptome sequencing technology, the mouse model of prediabetes treated with Huangjing Qianshi Decoction was sequenced to explore the possible mechanism of treating prediabetes. First of all, transcriptome sequencing was performed on the normal BKS-DB mouse group, the prediabetic model group, and the Huangjing Qianshi Decoction treatment group(treatment group) to obtain differentially expressed genes in the skeletal muscle samples of mice. The serum biochemical indexes were detected in each group to screen out the core genes of Huangjing Qianshi Decoction in prediabetes. Gene Ontology(GO) database and Kyoto Encyclopedia of Genes and Genomes(KEGG) database were used to conduct signaling pathway enrichment analysis of differentially expressed genes, and real-time quantitative polymerase chain reaction(RT-qPCR) was used to verify them. The results showed that the levels of fasting blood glucose(FBG), fasting insulin(FINS), insulin resistance index(HOMA-IR), total cholesterol(TC), triglycerides(TG), and low-density lipoprotein cholesterol(LDL-C) in the mouse model were significantly decreased after treatment with Huangjing Qianshi Decoction. In the results of differential gene screening, there were 1 666 differentially expressed genes in the model group as compared with the normal group, and there were 971 differentially expressed genes in the treatment group as compared with the model group. Among them, interleukin-6(IL-6) and NR3C2 genes, which were closely related to the regulation of insulin resis-tance function, were significantly up-regulated between the model group and the normal group, and vascular endothelial growth factor A(VEGFA) genes were significantly down-regulated between the model group and the normal group. However, the expression results of IL-6, NR3C2, and VEGFA genes were adverse between the treatment group and the model group. GO functional enrichment analysis found that the biological process annotation mainly focused on cell synthesis, cycle, and metabolism; cell component annotation mainly focused on organelles and internal components; and molecular function annotation mainly focused on binding molecular functions. KEGG pathway enrichment analysis found that it involved the protein tyrosine kinase 6(PTK6) pathway, CD28-dependent phosphoinositide 3-kinase/protein kinase B(PI3K/AKT) pathway, p53 pathway, etc. Therefore, Huangjing Qianshi Decoction can improve the state of prediabetes, and the mechanism may be related to cell cycle and apoptosis, PI3K/AKT pathway, p53 pathway, and other biological pathways regulated by IL-6, NR3C2, and VEGFA.

Targeted ferroptotic potency of ferrous oxide nanoparticles-diethyldithiocarbamate nanocomplex on the metastatic liver cancer.

Existing treatments are frequently ineffective in combating liver cancer (LC) due to its rapid growth, high metastatic potential, and chemoresistance. Thus, inducing ferroptosis, a new non-apoptotic regulated cell death-dependent massive iron overload-mediated lipid peroxidation, is an alternative effective approach for treating LC. The efficient trigger of ferroptosis requires blocking cellular antioxidant (anti-ferroptosis) response and selectivity to avoid harming other healthy tissues. In this study, green chemically synthesized ferrous oxide nanoparticles (F(II) NPs) were used for enhancing selective iron accumulation in tumor tissue, while diethyldithiocarbamate (DE) was for inhibiting the antioxidant system (glutathione and aldehyde dehydrogenase (ALDH) 2) which protects the tumor from damage-dependent lipid peroxides. Thus, F(II) NPs were used with DE as nanocomplex (DF(II) NPs) and its anti-LC activity compared to ferrous oxide DF(II). DF(II) NPs outperformed the typical complex of DF(II) in eradicating metastatic LC cells in HepG2 cells and a chemically induced metastatic LC animal model, as evidenced by flow cytometry, histological and immunohistochemical analyses, and α-fetoprotein depletion. The superior therapeutic potency-dependent ferroptotic activity of DF(II) NPs, attributed to their higher selective accumulation (∼77%) than DF(II) in tumor tissues (liver and lung), resulted in a strong elevation of cellular lipid peroxidation with extreme suppression of nuclear related factor 2 (Nrf2) transcriptional activity, glutathione (GSH), glutathione peroxidase 4, and ALDH2. Subsequently, a severe inhibition in the expression of oncogenes and metastatic cancer stem cell genes was recorded in DF(II) NPs-treated LC animal group. In contrast to DF(II), DF(II) NPs were able to normalize liver functions and did not show any variations in hematological and histological parameters in the blood and tissues of DF(II) NPs-treated normal mouse group. These findings validate the potency and safety of DF(II) nanocomplex as a promising nanodrug for combating metastatic LC.

Immunological Effect of Goat Bile on The Immunity of Mice Infected with Plasmodium berghei

Goat bile (GB) has been used traditionally as antimalarial medicine. Toxicity and antimalarial activity as well as the suppressive effect of GB have been reported previously. This study aimed to find out the immunological effect of GB on the serum level of IgG, TNF-α, and IL-10 in Plasmodium berghei ANKA. Fifty male BALB/c mice were infected with P. berghei ANKA and were divided into 5 groups. Groups 1-3 were treated with GB at a concentration of 25% (GB25), 50% (GB50), and 100% (GB100), respectively. Group 4 was a negative control and was given only sterile water. Group 5 was a positive control group, which was given 187.2 mg/kg body weight of the dihydroartemisinin-piperaquine antimalarial drug. Simultaneously, 3 groups of uninfected mice were treated with GB as above. Additionally, a group of normal mice without any treatment was used as a comparison control group. Treatments were given for four consecutive days. Parasitemia was observed daily on Giemsa-stained blood smears. Sera were collected on day five before the measurement of IgG anti P. berghei ANKA, TNF-α, and IL-10 levels by ELISA kit. Data were analyzed using one-way ANOVA, Mann Whitney, and Pearson correlation tests. Temporary mild diarrhea was seen in GB100-treated mice. All GB concentrations suppressed IgG production. The GB100 was more therapeutic, but GB50 and GB25 increased IL-10 levels as an antiinflammation response against infection. The pro-inflammatory effect of GB in normal mice caused TNF-α levels in GB-treated uninfected mice to be high. Both the toxicity and benefit of GB could be considered potential sources for the development of new anti-malarial candidates. The toxicity of GB should be considered seriously as the contradictive effect.

NEUROPROTECTIVE AND ANTIOXIDANT ACTIVITIES OF AQUEOUS EXTRACT MORINGA OLEIFERA LEAVES

Objective: To investigate the neuroprotective and antioxidant effects of leaves aqueous extract Moringa oleifera (MW) in chronic stress mouse models.&#x0D; Methods: Water immersion and stress restraint for 16 d to obtain a chronic stress model animal. Moringa extract flour dissolved in Aquades, dose 800 mg/kg for 23 d, for chronic Stress+MOW group. Fluoxetine in aquades at a dose of 18 mg/kg BW for 23 d for chronic stress group+Fluoxetine. Aquades were given to normal mice (group N), and mice under chronic stress conditions (chronic stress control group). Furthermore, measure behavioral abnormalities by testing depressive behavior and oxidative stress parameters such as anxiety, Brain-derived neurotrophic factors (BDNF).&#x0D; Results: Moringa oleifera water extract administration can improve behavioral disorders caused by stress by decreasing immobility time on the Force swim test, increasing time in the middle area, and increasing the number of returns to center areas on the Open field test. When chronically stressed mice were given fluoxetine and MOW, their MDA levels (p=0.008 and 0.041, respectively) and SOD activity (p=0.001 and 0.004) decreased significantly compared to the chronic stress control group. In contrast, Catalase activity increased significantly in chronically stressed mice given fluoxetine and MOW compared to the chronic stress control group (p=0.010 and 0.013). Administration of fluoxetine and MOW may increase the expression of mRNA BDNF compared to the chronic stress control group (p=0.000 and 0.013).&#x0D; Conclusion: The study found that MOW can improve behavioral abnormalities, namely anxiety and depression behavior caused by chronic stress exposure, through antioxidant pathways and oxidant systems, and also BDNF

Effects of adipokine chemerin on the improvement of islet function in diabetic mice by aerobic exercise and its mechanisms

Objective: To investigate the effects of adipokines chemerin on the improvement of islet function caused by exercise in mice with diabetes, and the possible mechanism of glucagon-like peptide 1 (GLP-1). Methods: Male ICR mice were randomly divided into a control group fed with normal diet (Con, n=6) and a diabetic modeling group fed with 60% kcal high-fat diet (n=44). After 6 weeks, the diabetic modeling group was once given a fasting intraperitoneal injection of streptozotocin (100 mg/kg). The successfully modeled mice were divided into diabetes group (DM), diabetes plus exercise group (EDM), and diabetes plus exercise and exogenous chemerin group (EDMC), 6 in each group. Mice in exercise groups participated in a six-week modest intensity treadmill running exercise with a gradually increased load. Mice in the EDMC group were intraperitoneally injected with exogenous chemerin (8 μg/kg) from the 4th week of the exercise period, six days per week, and one time per day. And the other groups were untreated. Adipose chemerin knockout mice were constructed. Then they and the control mice were divided into 6 groups (n=4): Normal diet control group (Con-ND), Normal diet chemerin knockout heterozygote mice group (Chemerin(+/-)-ND), Normal diet chemerin knockout homozygotes mice group(Chemerin(-/-)-ND), High-fat diet control group (Con-HFD), High-fat diet chemerin knockout heterozygote mice group (Chemerin(+/-)-HFD), High-fat diet chemerin knockout homozygotes mice group (Chemerin(-/-)-HFD). They were fed with normal or high-fat diet for 11 weeks and oral glucose tolerance test (OGTT) was conducted. After the mice of each group were executed under anesthesia, the samples such as pancreas and colon were collected. Fasting blood glucose (FBG) and fasting insulin (FINS) levels in mice were measured, and the insulin resistance index (HOMA-IR) was calculated. HE staining was used to observe the structure of islets. ELISA was used to detect the GLP-1 level in serum. The mRNA levels of proglucagon (GCG) and chemerin in the colon were measured by real-time PCR. And the protein levels of GCG and chemerin in the colon were detected by Western blot. Results: Compared with the DM group, the vacuolar degeneration and shrinkage of islet cells in the EDM group were reduced, the islet structure was improved, while the levels of FINS, HOMA-IR and FBG were decreased significantly (P＜0.05 or P＜0.01). The colon and serum chemerin levels were decreased significantly(P＜0.05), while the colonic GCG mRNA and protein levels were increased significantly (P＜0.05 or P＜0.01). Compared with the EDM group, the islet cells in the EDMC group were shrunken, with unclear borders. The structure of the islets was damaged, and the levels of FINS, HOMA-IR and FBG were increased significantly (P＜0.01), while the mRNA and protein levels of GCG were decreased significantly (P＜0.05 or P＜0.01). Compared with the Con-HFD group, the blood glucose at 30, 90 and 120 min after oral glucose in the chemerin (-/-)-HFD group was significantly lower (P＜0.01), and the area under the blood glucose time curve was significantly lower (P＜0.01). The islets had clear structure, regular shape and well-defined boundaries, while the serum GLP-1 and colonic GCG protein levels were increased significantly(P＜0.05). Conclusion: Aerobic exercise improves the structure and function of pancreatic islets by reducing the level of chemerin in diabetes mice, which is related to the negative regulation of chemerin on GLP-1 level.

INVESTIGATING ACUTE ORAL TOXICITY OF YOUNG MANGO (Mangifera indica L.) LEAVES ON MICROLOGY OF LIVER AND KIDNEYS OF Mus muscular L.

Histopathology is the most important issue in research pharmacy and clinical medicine. Microdiagnosis is a method of identifying and orienting treatment as well as disease prognosis. In testing acute toxicity, the youngleaves of mangoe extract (Mangifera indica L., MIL) was investigated based on analysis and comparison of liver/kidney microstructure of normal mice (Mus musculus L.) and mice that drank at high doses of MIL. The liver and kidney of laboratory mice were separated from groups of normal mice drinking distilled water (physiological control), normal mice drinking 1000 mg/kg, normal mice taking 2500 mg/kg and rats taking5000 mg/kg b.w., only one time. The observed results showed that the microstructure of the liver/kidney of rats drinking methanol extract MIL were damaged when compared to physiological control mice. This means that high doses of MIL have adverse effects on the liver/kidney of normal mice. From these results, it is concluded that MIL extract should not be taken arbitrarily not only in the body with any pathogenesis but also in the healthy body without the guidance of the pharmacist.

Regulatory mechanism of deferoxamine on macrophage polarization and wound healing in mice with deep tissue injury

Regulatory mechanism of deferoxamine on macrophage polarization and wound healing in mice with deep tissue injury

Antitumor effect and metabonomics of niclosamide micelles.

Polymer micelles now have promising applications in the treatment of cancer, increasing the water solubility and bioavailability of drugs. Previous studies have found that micelles of niclosamide have good anti‐liver cancer effect. In view of the poor water solubility of niclosamide (NIC), we decided to prepare niclosamide micelles. However, its therapeutic mechanism is not clear, so this paper conducted a preliminary study on its vitro anti‐tumour mechanism and metabonomics to find out its impact. It was found that the drug‐loaded micelles (PEG2K‐FIbu/NIC) had an inhibitory effect on HepG2 cells. Moreover, it can promote apoptosis of HepG2 cells and block S and G2/M phase of cell cycle. The plasma and liver metabolomics of mice in normal group, model group and administration group were studied by UPLC‐MS and 1H‐NMR. Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS‐DA) were used to process the data and find the relevant metabolites. metaboanalyst 5.0 was used to integrate the relevant metabolites to find the main related metabolic pathways. Thus, the anti‐tumour mechanism of PEG2K‐FIbu/NIC was analysed. Fifty‐one biomarkers were detected in plasma, and 43 biomarkers were detected in liver. After comprehensive biomarker and metabolic pathway analysis, it was found that PEG2K‐FIbu/NIC micelles could affect the changes of many metabolites, mainly affecting amino acid metabolism. This article is an in‐depth study based on the published Preparation and pharmacodynamics of niclosamide micelles (DOI: 10.1016/j.jddst.2021.103088).

An aqueous extract of Syzygium cumini protects against kainate-induced status epilepticus and amnesia: evidence for antioxidant and anti-inflammatory intervention.

Temporal lobe epilepsy is the most common drug-resistant epilepsy. To cure epilepsy, drugs must target the mechanisms at the origin of seizures. Thus, the present investigation aimed to evaluate the antiepileptic- and anti-amnesic-like effects of an aqueous extract of Syzygium cumini against kainate-induced status epilepticus in mice, and possible mechanisms of action. Mice were divided into 7 groups and treated as follows: normal group or kainate group received po distilled water (10 mL/kg), four test groups received Syzygium cumini (28.8, 72, 144, and 288mg/kg, po), and the positive control group treated intraperitoneally (ip) with sodium valproate (300mg/kg). An extra group of normal mice was treated with piracetam (200mg/kg, po). Treatments were administered 60min before the induction of status epilepticus with kainate (15mg/kg, ip), and continued daily throughout behavioral testing. Twenty-four hours after the induction, T-maze and Morris water maze tasks were successively performed. The animals were then sacrificed and some markers of oxidative stress and neuroinflammation were estimated in the hippocampus. The extract significantly prevented status epilepticus and mortality. In the T-maze, the aqueous extract markedly increased the time spent and the number of entries in the discriminated arm. In the Morris water maze, the extract significantly increased the time spent in the target quadrant during the retention phase. Furthermore, the aqueous extract induced a significant reduction of oxidative stress and neuroinflammation. These results suggest that the aqueous extract of Syzygium cumini has antiepileptic- and anti-amnesic-like effects, likely mediated in part by antioxidant and anti-inflammatory activities.

Modulation of Gut Microbiota and Metabolites by Berberine in Treating Mice With Disturbances in Glucose and Lipid Metabolism.

Introduction: Glucose and lipid metabolism disturbances has become the third major disease after cancer and cardio-cerebrovascular diseases. Emerging evidence shows that berberine can effectively intervene glucose and lipid metabolism disturbances, but the underlying mechanisms of this remain unclear. To investigate this issue, we performed metagenomic and metabolomic analysis in a group of normal mice (the NC group), mice with disturbances in glucose and lipid metabolism (the MC group) and mice with disturbances in glucose and lipid metabolism after berberine intervention (the BER group). Result: Firstly, analysis of the clinical indicators revealed that berberine significantly improved the blood glucose and blood lipid of the host. The fasting blood glucose level decreased by approximately 30% in the BER group after 8 weeks and the oral glucose tolerance test showed that the blood glucose level of the BER group was lower than that of the MC group at any time. Besides, berberine significantly reduced body weight, total plasma cholesterol and triglyceride. Secondly, compared to the NC group, we found dramatically decreased microbial richness and diversity in the MC group and BER group. Thirdly, LDA effect size suggested that berberine significantly altered the overall gut microbiota structure and enriched many bacteria, including Akkermansia (p < 0.01), Eubacterium (p < 0.01) and Ruminococcus (p < 0.01). Fourthly, the metabolomic analysis suggested that there were significant differences in the metabolomics signature of each group. For example, isoleucine (p < 0.01), phenylalanine (p < 0.05), and arbutin (p < 0.05) significantly increased in the MC group, and berberine intervention significantly reduced them. The arbutin content in the BER group was even lower than that in the NC group. Fifthly, by combined analysis of metagenomics and metabolomics, we observed that there were significantly negative correlations between the reduced faecal metabolites (e.g., arbutin) in the BER group and the enriched gut microbiota (e.g., Eubacterium and Ruminococcus) (p < 0.05). Finally, the correlation analysis between gut microbiota and clinical indices indicated that the bacteria (e.g., Eubacterium) enriched in the BER group were negatively associated with the above-mentioned clinical indices (p < 0.05). Conclusion: Overall, our results describe that the changes of gut microbiota and metabolites are associated with berberine improving glucose and lipid metabolism disturbances.

Potensi Ubi Jalar Ungu dan Kuning (Ipomoea batatas) Sebagai Terapi Penurunan Kadar Gula Darah

The aim of this study was to measure the potential of purple sweet potato and yellow sweet potato (lpomoea batatas) juice in reducing blood sugar levels in mice strain BALB/c (Mus musculus) conditioned by hyperglycemia. This study was required 30 mice and divided into 3 groups placed in cages. Each groups consisted of 10 female mice (Mus musculus) weighing 25-30 g and 2.5 months. The results showed that there were differences in the value of blood sugar levels in mice. The group of normal mice, blood sugar levels did not increase or decrease, the group of mice with dextrose treatment had an increase in blood sugar values, the group of mice with dextrose treatment and sweet potato therapy had a decrease in blood sugar values. The results of statistical calculations obtained a significance value of 0.00 which means that the value of blood sugar levels has a significant difference after administration of purple sweet potato and yellow sweet potato juice. The conclusion of this study that purple and yellow sweet potatoes juice (lpomoea batatas) could lower blood sugar levels in mice (Mus musculus) which were previously hyperglicemia conditioned, so it could be continued as candidates to be tested in further research purple and yellow sweet potatoes can be candidats for blood sugar lowering foods.

MicroRNA Expression Analysis of Mice Retinas with Oxygen-Induced Retinopathy by RNA Sequencing.

Purpose To characterize the microRNA (miRNA) expression profiles in the retinas of mice with oxygen-induced retinopathy by RNA sequencing and to ascertain miRNAs associated with retinal neovascularization. Methods Retina samples were obtained from 3 groups (6 retinas/group) of OIR mice and normal mice at P17. RNA was isolated from 24 retina samples and then detected on an Illumina HiSeq. Twelve retina samples were used for quantitative polymerase chain reaction to validate the RNA sequencing. Bioinformatics analyses were performed. Result The RNA sequence showed that 565 miRNAs were detected in the retina of OIR mice and 583 miRNAs in the retina of normal control mice. A total of 553 miRNAs were expressed in both groups. Thirty-eight miRNAs showed altered expression in both groups (p ≤ 0.05). Compared with the control group, 2 miRNAs were significantly upregulated in the OIR group, while 36 miRNAs were significantly downregulated. Meanwhile, 2 candidate miRNAs (miR-181a-5p and miR-21a-5p) with significant differences in miRNA expression (p < 0.01) were selected for validation. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to confirm the relative expression of the two miRNAs. Bioinformatics analyses showed that pathways involved in ischemic retinopathy (such as TGF-β, Ras, Hippo, PI3K-Akt, VEGF, and HIF-1 signaling pathways) were enriched. Conclusions Our study provided an overall view of miRNA profiling in the OIR retina. These miRNA profiles provide a valuable framework for the potential therapy of retinal angiogenesis.