Parameters In Mice Research Articles

High internal phase Pickering emulsions co-loaded with astaxanthin and ferrous gluconate improve iron deficiency anemia in mice and their applications in 3D printing

Iron deficiency anemia (IDA) is a prevalent and serious nutritional health issue that can be mitigated through dietary iron supplementation. However, only ferrous ions, prone to oxidation, can be absorbed in the gastrointestinal tract. In the current work, the effects of high internal phase Pickering emulsions (HIPPEs) co-loaded with astaxanthin (ASTA) and ferrous gluconate on Fe2+ oxidation, IDA management, and their 3D printing performance were investigated. The results demonstrated that the HIPPEs co-loaded with ASTA and ferrous gluconate effectively reduced the oxidation rate of Fe2+ during storage. Animal studies also revealed that HIPPE co-loaded with ASTA and ferrous gluconate had a therapeutic effect on IDA symptoms in mice. HIPPE co-loaded with ASTA and 400 mg/L ferrous gluconate demonstrated superior efficacy in restoring hemoglobin (Hb) levels, organ coefficients, and histological parameters in mice with IDA. Moreover, the evaluation of the adaptability of HIPPEs co-loaded with ASTA and ferrous gluconate for food 3D printing indicated a slight reduction in printing resolution. Overall printing performance was found to be acceptable and satisfactory. Co-loading ASTA and ferrous gluconate in HIPPEs offers an efficient way to address the oxidation challenge of ferrous ion supplementation, enabling customization and flexibility in the production of iron-fortified foods to mitigate IDA.

Disruption of Lipid Profile, Glucose Metabolism, and Leptin Levels following Citalopram Administration and High-Carbohydrate and High-Cholesterol Diet in Mice

Introduction: Depression therapy has been linked to negative effects on energy metabolism, which can be attributed to various factors, including an ongoing inflammatory process commonly seen in metabolic disorders. Unhealthy lifestyle choices of patients and the impact of antidepressants on body weight and lipid and glucose metabolism also contribute to these metabolic side effects. Although not as pronounced as other psychopharmaceuticals, the increasing use of antidepressants raises concerns about their potential impact on public health. The study aimed to evaluate the short- and long-term effects of the antidepressant citalopram and its long-term combination with a special diet on metabolic parameters in mice. Methods: Animals were randomly divided into 5 groups – control, control + special diet, citalopram (10 mg/kg for 35 days), citalopram + special diet (10 mg/kg for 35 days), and citalopram (10 mg/kg for 7 days). After a described time of administration, animals were anesthetized, blood and fat and liver tissues were collected. Biochemical parameters of lipid metabolism (total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides) and glucose were analyzed using spectrophotometry and relevant adipokines and cytokines were evaluated by ELISA. Results: After a week of application of citalopram, we observed dyslipidemia that persisted even at the end of the 5-week experiment. Furthermore, after 5 weeks of citalopram administration, we observed a significant decrease in body weight gain and decreased leptin levels. Changes in lipid metabolism, higher levels of adipokines leptin and PAI-1 were observed due to the special diet after 5 weeks. Conclusions: Our research suggests that the effects of citalopram and a diet on the metabolism of mice can be significant, both in the short term (1 week) and in the long term (5 weeks).

Subchronic Chloroform Exposure Causes Intestinal Damage and Induces Gut Microbiota Disruption and Metabolic Dysregulation in Mice.

Chloroform is a prevalent toxic environmental pollutant in urban settings, posing risks to human health through exposure via various mediums such as air and tap water. The gut microbiota plays a pivotal role in maintaining host health. However, there is a paucity of research elucidating the impact of chloroform exposure on the gut microbiota. In this investigation, 18 SPF Kunming female mice were stratified into three groups (n = 6) and subjected to oral gavage with chloroform doses equivalent to 0, 50, and 150 mg/kg of body weight over 30 days. Our findings demonstrate that subchronic chloroform exposure significantly perturbs hematological parameters in mice and induces histopathological alterations in cecal tissues, consequently engendering marked disparities in the functional composition of cecal microbiota and metabolic equilibrium of cecal contents. Ultimately, our investigation revealed a statistically robust correlation, exhibiting a high degree of significance, between the intestinal microbiome composition and the metabolites that were differentially expressed consequent to chloroform exposure.

Silymarin mitigates toxic effects of cyclophosphamide on testicular tissue and sperm parameters in mice

Cyclophosphamide, a chemotherapy drug, increases oxidative stress in sperm and testicular tissue. This study evaluated the effect of silymarin, a potent antioxidant, on the quality of sperm and testicular tissue in mice treated with cyclophosphamide. NMRI adult male mice were divided into four groups: control; cyclophosphamide (intraperitoneal injection, 100 mg/kg, once a week); cyclophosphamide + silymarin; and silymarin (intraperitoneal injection, 200 mg/kg, every other day). After a 35-day treatment period, the caudal region of the epididymis was examined for sperm parameters, the right testis was used for stereological studies, and the left testis was used to assess biochemical factors. The data were statistically analyzed using SPSS software, one-way ANOVA and Tukey's test. In the cyclophosphamide group, there was a significant reduction in the mean total volume of testicular tissue, the average volume of seminiferous tubules and their components, and the average volume of interstitial tissue. Additionally, there was a notable decrease (p < 0.001) in the average number of Leydig cells, Sertoli cells, and sperm parameters. The mean concentration of testosterone hormone (p < 0.05) and total antioxidant capacity (TAC) level (p < 0.01) also significantly decreased, while the malondialdehyde (MDA) level increased significantly (p < 0.05). However, these adverse changes were mitigated in the cyclophosphamide + silymarin group compared to the cyclophosphamide group. Our results showed that silymarin as an antioxidant can mitigate the adverse effects of cyclophosphamide on testicular tissue and sperm parameters.

Pharmacokinetics of Oleandrin Following Administration of a Nerium oleander Extract in Mice

Background. Nerium oleander Linn is native of Mediterranean regions of Africa and Europe, where it is used in folk medical practices. The whole plant is known to be toxic. Various studies have shown its antimicrobial and anticancer properties. Oleandrin, the main toxic component in Nerium oleander is an inhibitor of P-glycoprotein. Cardiac glycosides, including oleandrin, are substrates of P-glycoprotein. The presence of other inhibitors in the alcoholic extract may potentially modify the pharmacokinetics of oleandrin. Given the therapeutic potential and the associated toxicity of the alcoholic extract, it is important to investigate the kinetics of oleandrin within this extract. Purpose. The objective of this study was to determine the pharmacokinetic parameters in mice following oral and I.V. administrations of a hydroalcoholic extract of Nerium oleander. Methods. Pharmacokinetic investigations of oleandrin, a cardiotonic glycoside and main active compound in Nerium oleander, were conducted in mice following intravenous administration (30 mg/kg) and oral administration (150 mg/kg) of the hydrolcoholic extract of Nerium oleander. For the oral route, seven times were chosen for the mice sampling. Four times were chosen for the intravenous route. Three mice per group were used at each time point. In the excretion study, seven mice were housed in a mouse urine collection device and a dose of 150 mg/g was administered. A urine sample was collected after 48 hours. Oleandrin was measured by LC-MS/MS validated method. MS data were acquired in the positive ion electrospray ionization (ESI) mode. Two deuterated internal standards, cocaine-d3 and digoxin-d3, were used. The retention times were 8.47 min for oleandrin, 4.78 min for deuterated internal standard cocaine d3 and 5,37 min for deuterated internal standard digoxin d3. Results. The equivalent doses of oleandrin administred to mice were 1710 ug/kg for the oral route and 342 ug/kg for the intravenous route. Oleandrin was rapidly absorbed after oral administration (Cmax at 10 min). The AUC0-inf (ug/L*min) values obtained after intravenous and oral dosing were 34797.7 and 107222 respectively, resulting in an oral bioavailability of 61.6 %. The apparent volume of distribution (Vss) was 0.55 L/kg and Clearance ClT was 0.01 kg* L/min.

Investigation of the Hepatitis-B Vaccine's Immune Response in a Non-Alcoholic Fatty Liver Disease Mouse Model.

This study aimed to investigate the immunogenicity of the hepatitis B virus (HBV) vaccine by applying a normal and high-dose hepatitis B virus vaccination program in the mice modeling of non-alcoholic fatty liver disease (NAFLD). NAFLD was induced in mouse livers via diet. At the 10-week mark, both groups were divided into 3 subgroups. While the standard dose vaccination program was applied on days 0, 7, and 21, two high-dose programs were applied: one was applied on days 0 and 7, and the other was applied on days 0, 7, and 21. All mice were euthanized. Blood samples from anti-HB titers; T follicular helper, T follicular regulatory, CD27+, and CD38+ cells; and the liver, spleen, and thymus were taken for histopathologic evaluation. NAFLD subgroups receiving high doses showed higher hepatocyte ballooning scores than normal-dose subgroup. There were differences in CD27+ and CD27+CD38+ cells in animals fed on different diets, without any differences or interactions in terms of vaccine protocols. In the NAFLD group, a negative correlation was observed between anti-HB titers and T helper and CD27+ cells, while a positive correlation was observed with CD38+ cells. NAFLD induced changes in immune parameters in mice, but there was no difference in vaccine efficacy among the applied vaccine protocols. Based on this study's results, high-dose vaccination protocols are not recommended in cases of NAFLD, as they do not enhance efficacy and may lead to increased liver damage.

Impact of gastrointestinal inoculation and benznidazole treatment on infection by Trypanosoma cruzi (Y strain, DTU TcII) in Swiss mice

In Brazil, where Chagas disease is endemic, the most frequent form of transmission of the parasite is the oral route, associated with greater severity and worse response to benznidazole (BZ), the drug used in its treatment. This study aimed to evaluate the impact of gastrointestinal infection (GI) and BZ treatment on the parasitological and histopathological parameters in mice inoculated with a strain of T. cruzi II. Swiss mice were inoculated by GI and intraperitoneal (IP) routes with 2x106 culture-derived metacyclic trypomastigotes of the Y strain (TcII) of T. cruzi and were treated with BZ in the acute phase of the infection. Fresh blood examination, qPCR, histopathological and biochemical evaluations (enzymatic dosages and oxidative stress-OS) were performed. BZ treatment of uninfected animals caused changes in the liver, increased the activity of aspartate aminotransferase and alanine aminotransferase enzymes and OS, showing that the drug alone affects this organ. Inflammation and necrosis in the cardiac tissue were less intense and deaths occurred later in animals inoculated via the GI route than the animals inoculated via the IP route. BZ reduced the intensity of tissue lesions and avoided lethality in animals inoculated via the GI route, and decreased parasitemia and OS in those inoculated via both routes. Although BZ alone caused liver damage, it was less intense than that caused by both routes of inoculation. Infection with the Y strain of T. cruzi II via the GI route proved to be less virulent and pathogenic and responded better to treatment than the infection acquired via the IP route.

Helicobacter pylori infection exacerbates metabolic dysfunction-associated steatotic liver disease through lipid metabolic pathways: a transcriptomic study

BackgroundThe relationship between Helicobacter pylori (H. pylori) infection and metabolic dysfunction-associated steatotic liver disease (MASLD) has attracted increased clinical attention. However, most of those current studies involve cross-sectional studies and meta-analyses, and experimental mechanistic exploration still needs to be improved. This study aimed to investigate the mechanisms by which H. pylori impacts MASLD.MethodsWe established two H. pylori-infected (Cag A positive and Cag A negative) mouse models with 16 weeks of chow diet (CD) or high-fat diet (HFD) feeding. Body weight, liver triglyceride, blood glucose, serum biochemical parameters, inflammatory factors, and insulin resistance were measured, and histological analysis of liver tissues was performed. Mouse livers were subjected to transcriptome RNA sequencing analysis.ResultsAlthough H. pylori infection could not significantly affect serum inflammatory factor levels and serum biochemical parameters in mice, serum insulin and homeostatic model assessment for insulin resistance levels increased in CD mode. In contrast, H. pylori Cag A + infection significantly aggravated hepatic pathological steatosis induced by HFD and elevated serum inflammatory factors and lipid metabolism parameters. Hepatic transcriptomic analysis in the CD groups revealed 767 differentially expressed genes (DEGs) in the H. pylori Cag A + infected group and 1473 DEGs in the H. pylori Cag A- infected group, and the “nonalcoholic fatty liver disease” pathway was significantly enriched in KEGG analysis. There were 578 DEGs in H. pylori Cag A + infection combined with the HFD feeding group and 820 DEGs in the H. pylori Cag A- infected group. DEGs in the HFD groups were significantly enriched in “fatty acid degradation” and “PPAR pathway.” Exploring the effect of different Cag A statuses on mouse liver revealed that fatty acid binding protein 5 was differentially expressed in Cag A- H. pylori. DEG enrichment pathways were concentrated in the “PPAR pathway” and “fatty acid degradation.”ConclusionsClinicians are expected to comprehend the impact of H. pylori on MASLD and better understand and manage MASLD. H. pylori infection may exacerbate the development of MASLD by regulating hepatic lipid metabolism, and the H. pylori virulence factor Cag A plays a vital role in this regulation.

Optimization of spermatozoa analysis in mice: A comprehensive protocol

Sperm quality is critical to predict reproductive alterations caused by immunological factors or toxicant agents. Yet, no detailed protocol has been published focusing on analyses of sperm parameters in mice. Our aim was to evaluate the most efficient diluent for mice sperm analyses and to optimize the sperm morphology classification, through the comparison of different staining methods. The diluents assessed were PBS (baseline), HTF, DMEM, 1 % BSA in PBS and 9 % skimmed powdered milk diluted in PBS. Spermatozoa were evaluated for vitality, motility, and morphology, smears were stained with Papanicolaou, HE, Giemsa, and Rapid staining. Sperm vitality and total motility reached better scores in milk based and DMEM diluents. HE raised up as an effective option since its combination with any of the diluents we tested, resulted in a fair staining, which was appropriated to evaluate mice spermatozoa. Finally, based on WHO manual, we have updated the current morphological classification for mice sperm, since we have detailed the head defects as well as included midpiece and tail defects on it. Taken together, we presented a useful, low cost, and reliable method to assess sperm morphology that could be employed worldwide by laboratories dedicated to study reproductive biology on mice model.

Analysis of the effect of hypusination in myeloid cells on colitis and colitis-associated cancer

Hypusine is an amino acid synthesized by the enzyme deoxyhypusine synthase (DHPS). It is critical for the activity of eukaryotic translation initiation factor 5A (EIF5A). We reported that hypusination i) in macrophages supports the innate response towards pathogenic bacteria and ii) in epithelial cells maintains intestinal homeostasis. Herein, we investigated the effect of myeloid hypusination on the outcome of colitis and colitis-associated cancer. We found that patients with Crohn's disease exhibit increased levels of DHPS and EIF5AHyp in cells infiltrating the colon lamina propria. However, the specific deletion of Dhps in myeloid cells had no impact on clinical, histological, or inflammatory parameters in mice treated with dextran sulfate sodium (DSS). Further, tumorigenesis and level of dysplasia were not affected by myeloid deletion of Dhps in the azoxymethane-DSS model. The composition of the fecal and the mucosa-associated microbiome was similar in animals lacking or not DHPS in myeloid cells. Thus, hypusination in myeloid cells does not regulate colitis associated with epithelial injury and colitis-associated cancer. Enhancement of the DHPS/hypusine pathway in patients with inflammatory bowel disease could have therapeutic impact through epithelial effects, but modulation of hypusination in myeloid cells will be unlikely to affect the disease.

The Comparison of Long-term Effect Between Intermittent Fasting and Calorie Restriction on Neurological Parameters of Mice

Intermittent fasting (IF) and calorie restriction (CR) were purported to have health benefits. This research aimed to determine the long-term effect of IF and CR on selected neurological parameters in mice. Swiss Webster male mice were divided into 3 groups: ad libitum feeding (AL), IF, and CR. Mice in each group received the treatment for 16 weeks. They were then tested for anhedonia, depression, aggressiveness, and social approach. They were also subjected to contextual fear conditioning tests to model PTSD. Compared to AL, sucrose intake in the IF group was lower, while the CR group showed higher intake (p&lt;0.01). This anhedonia characteristic shown in the IF group was confirmed not related to depression, as shown by significantly lower immobility time in the forced swimming test compared to AL (p&lt;0.05). In the resident-intruder test, attack numbers in the IF group were fewer than in the AL group (p&lt;0.05). As demonstrated by the results of the three-chamber test, the reduced aggressiveness in IF mice was unrelated to a deficit in sociability. In the fear extinction test (PTSD model), mice in the IF group showed lower freezing compared to those in AL (p&lt;0.001). Although both IF and CR caused a reduction in total food intake, in the mice model tested, IF was shown to have favorable impacts on neurological parameters.

Effects of Acute Exposure to Methylglyoxal or/and A Diet Rich in Advanced Glycation End Products on Sperm Parameters in Mice.

Advanced glycation end products (AGEs) that accompany many metabolic disorders including diabetes, obesity, and a wide range of dyslipidemia conditions, are strongly associated with adverse effects on cell and tissue homeostasis. Accordingly, our objective was to investigate the impact of AGE-promoting diets on mouse models, considering both scenarios with and without methylglyoxal (MGO) as a primary precursor of AGEs. In this experimental study, 5-week-old C57BL/6 mice were split into four groups as a control group (n=5), AGE (n=5), MGO (n=8), and AGE-MGO-diets (n=8). After five weeks the level of fasting blood sugar (FBS), body weight, food intake, sperm parameters, and functional tests were evaluated. Furthermore, testicular superoxide dismutase (SOD) activity, malondialdehyde, and total antioxidant capacity (TAC) were assessed. After five weeks, AGE, AGE-MGO, and MGO groups showed the highest level of body weight and FBS in comparison to the control group. Mean sperm concentration, sperm malondialdehyde, testicular lipid peroxidation, and TAC did not differ significantly among the study groups. While, AGE, MGO, and AGE-MGO groups showed a significant reduction in sperm motility and progressive motility compared to the control group (P<0.05). The greatest increases in abnormal sperm morphology and intracytoplasmic reactive oxygen species (ROS) were observed in the MGO and AGE-MGO groups than in the control group (P<0.05). Sperm protamine deficiency and residual histone were significantly increased in the three treatment groups compared to the control group (P<0.05). Regarding the DNA damage, the AGE and AGE-MGO groups showed the most severe damage. The lowest amount of testicular superoxide dismutases (SOD, P<0.001) was observed in the AGE-MGO group. AGEs and MGO have a negative influence on sperm function and reproductive potential. These effects could be possibly attributed to both increased oxidative stress (OS) and inflammation.

Berberine attenuates obesity-induced insulin resistance by inhibiting miR-27a secretion.

Berberine (BBR) is an alkaloid found in plants. It has neuroprotective, anti-inflammatory and lipid-lowering activity. However, the efficacy of treatment with BBR and the mechanisms through which it acts need further study. This study investigated the therapeutic effects and the mechanism of action of BBR on obesity-induced insulin resistance in peripheral tissues. High-fat-fed C57BL/6J mice and low-fat-fed C57BL/6J mice with miR-27a overexpression were given BBR intervention (100 mg/kg, po), and the oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) were performed. Palmitic acid-stimulated hypertrophic adipocyte models were treated with BBR (10 μM). Related indicators and protein expression levels were examined. The AUCs of the OGTT and the ITT in the BBR intervention group were reduced significantly (p < 0.01) (p < 0.05), and the serum biochemical parameters, including FBG, TC, TG and LDL-C were significantly reduced after BBR intervention. In the invitro experiments, the triglyceride level and volume of lipid droplets decreased significantly after BBR intervention (p < 0.01) (p < 0.05). Likewise, BBR ameliorates skeletal muscle and pancreas insulin signalling pathways invivo and invitro. The results showed that BBR significantly ameliorated insulin resistance, reduced body weight and percent body fat and improved serum biochemical parameters in mice. Likewise, BBR reduced triglyceride level and lipid droplet volume in hypertrophic adipocytes, BBR improved obesity effectively. Meanwhile, BBR ameliorated the histomorphology of the pancreas, and skeletal muscle and pancreas insulin related signalling pathways of islets in invitro and invivo experiments. The results further demonstrated that BBR inhibited miR-27a levels in serum from obese mice and supernatant of hypertrophic adipocytes. miR-27a overexpression in low-fat fed mice indicated that miR-27a caused insulin resistance, and BBR intervention significantly improved the miR-27a induced insulin resistance status. This study demonstrates the important role of BBR in obesity-induced peripheral insulin resistance and suggest that the mechanism of its effect may be inhibition of miR-27a secretion.

Noise and Vibration Generation and Response of Mice (Mus musculus) to Routine Intrafacility Transportation Methods.

Intrafacility transport of mice is an essential function for both laboratory and husbandry personnel. However, transport may induce a stress response that can alter research findings and negatively impact animal welfare. To determine minimally adverse intrafacility transport methods, in-cage noise and vibration exposure during transport on a variety of transport vehicles (hand carrying, stainless steel rack, flatbed cart, metal teacart, plastic teacart, and a cart with pneumatic wheels) were measured. Under-cage and in-cage padding was tested for its ability to decrease noise and vibration on each vehicle. Behavioral (open field test and elevated plus maze) and corticosterone responses of mice were then measured following transport on the most adverse (metal teacart) and least adverse (pneumatic cart) methods of multicage transport. Behavioral measures showed no difference between transported mice and untransported mice in both single- and group-housed settings. Plasma corticosterone was significantly elevated in mice transported on the metal teacart immediately following transport and continued to have elevated trends in circadian peaks during the 48h of sampling. The cart with pneumatic wheels was most effective at reducing noise and vibration, reflected in posttransport corticosterone readings that remained equivalent to those in untransported mice. This study demonstrates that mitigation of noise and vibration during cart transport may decrease the impact of transport on certain stress parameters in mice.

Noni enhances the anticancer activity of cyclophosphamide and suppresses myelotoxicity and hepatotoxicity in tumor-bearing mice

Background and aimMorinda citrifolia fruit juice (noni) is an herbal remedy documented to have antioxidant properties. It has been suggested that prevention of carcinogen-DNA adduct formation and the antioxidant activity of NJ may contribute to the cancer preventive effect. In the present study, the antitumor activity of noni was investigated in the presence of cyclophosphamide (CYL) in vitro and in vivo.MethodsIn vitro breast cancer cells (MDA-MB-468) were used to measure the percentage of inhibition and the IC50. The in vivo antitumor activity of noni was studied by monitoring the mean survival time (MST), percentage increase in life span (%ILS), viable and non-viable cell count, tumor volume, body weight, and hematological and serum biochemical parameters in mice. Treatment with noni and CYL exhibited dose- and time-dependent cytotoxicity toward breast cancer cells.ResultsIndividual treatment of noni and CYL exhibited dose- and time-dependent cytotoxicity on breast cancer cell lines, while in combination therapy of noni and CYL, noni enhances cytotoxic effect of CYL at 48 h than that at 24 h. Similar result was found in in vivo studies, the results of which revealed that alone treatment of CYL and noni suppressed tumor growth. However, combination treatment with CYL and noni presented better tumor inhibition than that of alone treatment of CYL and noni. On the contrary, CYL alone drastically attenuated hematological parameters, i.e., RBC, WBC, and Hb compared to normal and control groups, and this change was reversed and normalized by noni when given as combination therapy with CYL. Moreover, the levels of serum biochemical markers, i.e., AST, ALP, and ALT, were significantly increased in the control and CYL-treated groups than those in the normal group. In the combination treatment of noni and CYL, the above biochemical marker levels significantly decreased compared to CYL alone-treated group.ConclusionsThe present study suggested that CYL treatment can cause serious myelotoxicity and hepatic injury in cancer patients. In conclusion, the combined use of noni with CYL potentially enhances the antitumor activity of CYL and suppresses myelotoxicity and hepatotoxicity induced by CYL in tumor-bearing mice.

Coal-Derived Humic Substances: Insight into Chemical Structure Parameters and Biomedical Properties.

An investigation was carried out on humic substances (HSs) isolated from the coal of the Kansk-Achinsk basin (Krasnoyarsk Territory, Russia). The coal HSs demonstrate the main parameters of molecular structure inherent to this class of natural compounds. An assessment was performed for the chemical, microbiological, and pharmacological safety parameters, as well as the biological efficacy. The HS sample meets the safety requirements in microbiological purity, toxic metals content (lead, cadmium, mercury, arsenic), and radionuclides. The presence of 11 essential elements was determined. The absence of general, systemic toxicity, cytotoxicity, and allergenic properties was demonstrated. The coal HS sample was classified as a Class V hazard (low danger substances). High antioxidant and antiradical activities and immunotropic and cytoprotective properties were identified. The ability of the HS to inhibit hydroxyl radicals and superoxide anion radicals was revealed. Pronounced actoprotective and nootropic activities were also demonstrated in vivo. Intragastric administration of the HS sample resulted in the improvement of physical parameters in mice as assessed by the "swim exhaustion" test. Furthermore, intragastric administration in mice with cholinergic dysfunction led to a higher ability of animals with scopolamine-induced amnesia to form conditioned reflexes. These findings suggest that the studied HS sample is a safe and effective natural substance, making it suitable for use as a dietary bioactive supplement.

Initial Characterization of a Transgenic Mouse with Overexpression of the Human H1-Histamine Receptor on the Heart.

There is a debate on whether H1-histamine receptors can alter contractility in the mammalian heart. We studied here a new transgenic mouse model where we increased genetically the cardiac level of the H1-histamine receptor. We wanted to know if histamine could augment or decrease contractile parameters in mice with cardiac-specific overexpression of human H1-histamine receptors (H1-TG) and compared these findings with those in littermate wild-type mice (WT). In H1-TG mice, we studied the presence of H1-histamine receptors by autoradiography of the atrium and ventricle using [3H]mepyramine. The messenger RNA for human H1-histamine receptors was present in the heart from H1-TG and absent from WT. Using in situ hybridization, we noted mRNA for the human H1-histamine receptor in cardiac cells from H1-TG. We noted that histamine (1 nM-10 µM) in paced (1 Hz) left atrial preparations from H1-TG, exerted at each concentration of histamine initially reduced force of contraction and then raised contractile force. Likewise, in spontaneously beating left atrial preparations from H1-TG, we noted that histamine led to a transient reduction in the spontaneous beating rate followed by an augmentation in the beating rate. The negative inotropic and chronotropic and the positive inotropic effects on histamine in isolated atrial muscle strips from H1-TG were attenuated by the H1-histamine receptor antagonist mepyramine. Histamine failed to exert an increased force or reduce the heartbeat in atrial preparations from WT. We concluded that stimulation of H1-histamine-receptors can decrease and then augment contractile force in the mammalian heart and stimulation of H1-histamine receptors exerts a negative chronotropic effect. SIGNIFICANCE STATEMENT: We made novel transgenic mice with cardiomyocyte-specific high expressional levels of the human H1-histamine receptor to contribute to the clarification of the controversy on whether H1-histamine receptors increase or decrease contractility and beating rate in the mammalian heart. From our data, we conclude that stimulation of H1-histamine receptors first decrease and then raise contractile force in the mammalian heart but exert solely negative chronotropic effects.

Is mouse dynamics information credible for user behavior research? An empirical investigation

Mouse dynamics, information on user’s interaction with a computer mouse, are in vogue in machine learning for purposes such as recommendations, personalization, prediction of user characteristics and behavioral biometrics. We point out a blind spot in current works involving mouse dynamics that originates in underestimating the gravity of the characteristics of the mouse device and configuration on the data that mouse dynamics are inferred from. In a controlled study with N=32 participants, across three kinds of mouse interaction activities, we collect data for mouse dynamics utilizing a variety of mouse parameter configurations. We show that mouse dynamics commonly used in studies can be significantly altered by differences in mouse parameters. Out of 108 evaluated mouse dynamics metrics, 95 and 84 are affected between two conducted studies. A machine learning model’s performance can be warped by the mouse parameters being used. We demonstrate on a prediction task that mouse parameters cannot be approached uniformly and without consideration. We discuss methodological implications — how mouse dynamics studies should account for the diversity of mouse-related conditions.

Nutritional strategies cause memory damage and alter biochemical parameters without causing neuroinflammation.

Obesity results from an energy imbalance and has been considered an epidemic due to its increasing rates worldwide. It is classified as a low-grade chronic inflammatory disease and has associated comorbidities. Different nutritional strategies are used for the purpose of weight loss, highlighting low-carbohydrate (LC) diets, ketogenic diets, and intermittent fasting (IF). These strategies can lead to metabolic and behavioral changes as they stimulate different biochemical pathways. Therefore, this study evaluated memory, energy metabolism, neuroinflammation, oxidative stress, and antioxidant defense parameters in mice subjected to an LC diet, ketogenic diet (KD), or IF. Eighty male Swiss mice, 60 days old, were divided into 4 groups: control, LC, KD, or IF. Body weight was measured weekly, and food intake every 48h. After 15 days of nutritional interventions, the animals were subjected to the behavioral object recognition test and subsequently euthanized. Then, visceral fat was removed and weighed, and the brain was isolated for inflammatory and biochemical analysis. We concluded from this study that the LC and KD strategies could damage memory, IF improves the production of adenosine triphosphate (ATP), and the LC, KD, and IF strategies do not lead to neuroinflammatory damage but present damage at the level of oxidative stress.

Ultrasound diagnosis and treatment of heterotopic ossification

Heterotopic ossification (HO), or the presence of bone in soft tissues, can occur after musculoskeletal trauma, causing pain and reduced mobility. However, even the most sensitive diagnostic modality requires 2–3 weeks after initiation to detect HO, and the only treatment is surgical resection after HO matures (&amp;gt;2 years). Here, we evaluate the color Doppler ultrasound twinkling artifact for early diagnosis of HO and focused ultrasound (fUS) for treatment of early HO. We began by evaluating twinkling and fUS parameters in ossified cell culture. We then evaluated imaging and treatment parameters in mice with HO. Results show that twinkling correlated well with the presence of ossified cells; although the exact size/number of ossified cells required for twinkling was unclear. In mice, twinkling was found to detect HO in some mice as early as 3 days-post-injection, which is earlier than other imaging modalities. For treatment, fUS at 1.07-MHz and 0.2% duty-cycle with p + /p− = 17/7 MPa was found to be most successful at disrupting mineralizations with little damage to surrounding cells. Mice treated with fUS were found to have less advanced HO compared to sham mice. These results highlight the promise of ultrasound for the diagnosis and treatment of early HO. [Work supported by CDMRP PR201164].