Reversal Phase Research Articles

Prolonged Phase Segregation of Mixed-Halide Perovskite Nanocrystals in the Dark.

A critical issue hindering the potential applications of semiconductor mixed-halide perovskites is the phase segregation effect, wherein localized regions enriched with one type of halide anions would be formed upon continuous photogeneration of the excited-state charge carriers. These unexpected phases are capable of remixing again in the dark under the entropic driving force, the process of which is now being exclusively studied after the mixed-halide perovskites have arrived at the final stage of complete phase segregation. Here, we show that after the removal of laser excitation from a solid film of the mixed-halide perovskite nanocrystals (NCs) with partial phase segregation, the iodide- and bromide-rich regions can continuously grow in the dark for a prolonged time period of several minutes. We propose that this dark phase segregation is sustained by the local electric fields from the surface-trapped charge carriers, whose slow dissipation out of the mixed-halide perovskite NCs causes a delayed occurrence of the reversal phase remixing process.

Poly (I:C)-induced maternal immune activation generates impairment of reversal learning performance in offspring.

Maternal immune activation (MIA) induces a variety of behavioral and brain abnormalities in offspring of rodent models, compatible with neurodevelopmental disorders, such as schizophrenia or autism. However, it remains controversial whether MIA impairs reversal learning, a basic expression of cognitive flexibility that seems to be altered in schizophrenia. In the present study, MIA was induced by administration of a single dose of polyriboinosinic-polyribocytidylic acid (Poly (I:C) (5 mg/kg i.p.)) or saline to mouse pregnant dams in gestational day (GD) 9.5. Immune activation was monitored through changes in weight and temperature. The offspring were evaluated when they reached adulthood (8 weeks) using a touchscreen-based system to investigate the effects of Poly (I:C) on discrimination and reversal learning performance. After an initial pre-training, mice were trained to discriminate between two different stimuli, of which only one was rewarded (acquisition phase). When the correct response reached above 80% values for two consecutive days, the images were reversed (reversal phase) to assess the adaptation capacity to a changing environment. Maternal Poly (I:C) treatment did not interfere with the learning process but induced deficits in reversal learning compared to control saline animals. Thus, the accuracy in the reversal phase was lower, and Poly (I:C) animals required more sessions to complete it, suggesting impairments in cognitive flexibility. This study advances the knowledge of how MIA affects behavior, especially cognitive domains that are impaired in schizophrenia. The findings support the validity of the Poly (I:C)-based MIA model as a tool to develop pharmacological treatments targeting cognitive deficits associated with neurodevelopmental disorders.

Modern chromatographic method for estimating Loratadine and affections on healthcare

PurposeThe purpose of this study is to establish Loratadine [LRD] quantification in purified and capsule formulations using a precise and specific Reversal Phase with a very high-performance liquid Chromatographic [RP-HPLC] technique. The approach was evaluated in agreement with the principles of the International Conference on Harmonization [ICH]. Arcus EP-C18 Ion Pac column, 5 m, 4.6 mm, 250 mm, mobile phase Methanol: Acetonitrile (60:40) v/v. Dibasic potassium phosphate buffer, pH 7.2, flow rate 1.0 ml/min.Design/methodology/approachThe HPLC system used a 340 nm UV detector for testing. A 10-min run time was used for the analysis. At concentrations ranging from 2 to 10 g/ml, the technique was linear (R2 = 0.9998), exact (intra-day and inter-day relative standard deviation [RSD] values 1.0%), accurate (range recovery = 96%–102%), exclusive and strong.FindingsThe detecting and quantitation limits were 0.92 g/ml and 2.15 g/ml, respectively.Originality/valueThe findings demonstrated that the proposed method could accurately determine LRD in bulk and pill dose formats quickly and accurately.

Osteoclast-derived coupling factors: origins and state-of-play Louis V Avioli lecture, ASBMR 2023.

Coupling, the mechanism that controls the sequence of events in bone remodeling, is a fundamental theory for understanding the way the skeleton changes throughout life. This review is an adapted version of the Louis V Avioli lecture, delivered at the Annual Scientific Meeting of the American Society of Bone and Mineral Research in 2023. It outlines the history of the coupling concept, details how coupling is thought to occur within trabecular and cortical bone, and describes its multiple contexts and the many mechanisms suggested to couple bone-forming osteoblasts to the prior action of osteoclasts on the same bone surface. These mechanisms include signals produced at each stage of the remodeling sequence (resorption, reversal, and formation), such as factors released by osteoclasts through their resorptive action and through protein synthesis, molecules deposited in the cement line during the reversal phase, and potential signals from osteocytes within the local bone environment. The review highlights two examples of coupling factors (Cardiotrophin 1 and EphrinB2:EphB4) to illustrate the limited data available, the need to integrate the many functions of these factors within the basic multicellular unit (BMU), and the multiple origins of these factors, including the other cell types present during the remodeling sequence (such as osteocytes, macrophages, endothelial cells, and T-cells).

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Osteostaticytes: A novel osteoclast subset couples bone resorption and bone formation

BackgroundOsteomyelitis (OM) is an inflammatory condition of bone characterized by cortical bone devascularization and necrosis. Dysregulation of bone remodelling is triggered by OM. Bone remodelling is precisely coordinated by bone resorption and formation via a reversal phase. However, the cellular and molecular mechanisms underlying bone remodelling failure after osteomyelitis remain elusive. MethodsTo elucidate the cellular and molecular mechanism underlying bone healing after osteomyelitis, we employed single-cell RNA sequencing (scRNA-seq) to depict the atlas of human cortical bone in normal, infected and reconstructed states. Dimensionality reduction by t-stochastic neighbourhood embedding (t-SNE) and graph-based clustering were applied to analyse the detailed clusters of osteoclast lineages. After trajectory analysis of osteoclast lineages over pseudotime, real-time PCR and immunofluorescence (IF) staining were applied to identify marker gene expression of various osteoclast lineages in the osteoclast induction model and human bone sections, respectively. The potential function and communication of osteoclasts were analysed via gene set enrichment analysis (GSEA) and CellChat. The chemotactic ability of mesenchymal stem cells (MSCs) and osteoclast lineage cells in various differentiation states was determined by transwell assays and coculture assays. The effects of various osteoclast lineages on the osteogenic differentiation potential of MSCs were also determined by using this coculture system. A normal mouse tibia fracture model and an osteomyelitis-related tibia fracture model were generated via injection of luciferase-labelled Staphylococcus aureus to verify the relationships between a novel osteoclast lineage and MSCs. Then, the infection was detected by a bioluminescence imaging system. Finally, immunofluorescence staining was used to detect the expression of markers of MSCs and novel osteoclast lineages in different remodelling phases in normal and infected bone remodelling models. ResultsIn this study, we constructed a cell atlas encompassing normal, infected, and reconstructed cortical bone. Then, we identified a novel subset at the earlier stage of the osteoclast lineage that exhibited increased expression of IDO1, CCL3, and CCL4. These IDO1highCCL3highCCL4high cells, termed osteostaticytes (OSCs), were further regarded as the reservoir of osteoclasts in the reversal phase. Notably, OSCs exhibited the highest chemotactic activity, surpassing other lineage subsets. We also discovered that cells at the earlier stage of the osteoclast lineage play a significant role in recruiting mesenchymal stem cells (MSCs). Finally, the data revealed that OSCs might be positively related to the occurrence of bone MSCs and the contribution of bone remodelling. ConclusionCollectively, our findings revealed a novel stage (OSC) within the osteoclast lineage, potentially representing elusive bone reversal cells due to its increased chemotactic ability towards MSCs and potential contribution to bone remodelling. This study provides valuable insights into the intricate mechanisms of the reversal phase during bone remodelling and unveils potential therapeutic strategies for diseases associated with bone uncoupling. Translational potential of this articleThis study identified a new subset, referred to as IDO1(plus symbol) CCL3(plus symbol) CCL4(plus symbol) osteostaticytes which displayed the highest chemotactic activity among all osteoclast lineages and may serve as reversal cells in bone remodelling. These findings offer new insights and insights for understanding bone reversal-related diseases and may serve as novel therapeutic targets for conditions such as osteomyelitis and delayed bone healing.

Mind the ramp: Association between early life ramp use and spatial cognition in laying hen pullets.

Ramps facilitate earlier access to complex environments and increase early life voluntary exercise, which may positively affect the cognitive development of chickens. This study focused on quantifying individual differences in ramp use and its impact on spatial cognition of laying hen pullets. Sixteen identical pens were housed with Lohmann Selected Leghorn (LSL) chicks of which eight chicks from each pen were colour marked from one day of age (DoA) to serve as focal birds. We quantified overall ramp use (walk/run, wing-assisted incline running, and jump/fly to and from ramps) by scan sampling recorded videos for 6, 10, 12, 20, 27, 41, and 55 DoA for all focal birds. From 56 to 95 DoA, long and short-term spatial memory of three focal birds per pen were assessed in a holeboard test in three consecutive phases: cued, uncued and reversal. Mixed model analysis showed that the spatial cognitive abilities of the birds were linked to differences in ramp use frequency averaged across all observation days. Birds with higher ramp use made fewer reference (Estimate ± Confidence Interval = 0.94 [0.88, 0.99], p = 0.08) and working memory errors (Est ± CI = 0.77 [0.59, 1.00], p = 0.06) in the cued phase than birds with lower ramp use. In contrast, birds with higher ramp use made more reference memory errors (Est ± CI = 1.10 [1.01, 1.20], p = 0.05) in the reversal phase. Birds with higher ramp use also made more reference memory errors compared to birds with lower ramp use as the phases changed from cued to uncued (p = 0.001). Our results indicate that there might be a relationship between early life ramp use and spatial cognition of laying hens.

Better social reversal learning is associated with a more social approach across time

Flexibly updating behaviors towards others is crucial for adaptive social functioning. Previous studies have found that difficulties in flexibly updating behaviors are associated with social anxiety (SA). However, it is unclear whether such difficulties relate to actual social behaviors. The current study investigated the relationships between negative-to-positive social reversal learning, social approach behavior, and SA across time. Participants (MTurk, Time 1 = 275, Time 2 = 126, 16 weeks later) completed a performance-based social reversal-learning task. In the initial phase, participants learned that interactions with certain individuals are associated with negative outcomes, whereas interactions with other individuals are associated with positive outcomes. In the reversal phase, these associations were reversed, requiring participants to update their behaviors. The relationships between the performance in the task, SA severity, and social approach behavior reported by participants were assessed cross-sectionally and longitudinally. We found that negative-to-positive updating was negatively associated with SA severity. Furthermore, negative-to-positive updating was positively correlated with social approach behavior, both cross-sectionally and prospectively. Hence, individuals with better negative-to-positive updating at Time 1 reported significantly more social approach behaviors across time. The results support the role of negative-to-positive updating as a mechanism associated with SA and social approach, advancing and refining interpersonal and cognitive theories of SA.

The intracranial effects of flow reversal during transcarotid artery revascularization.

This study aimed to assess intraoperative cerebral hemodynamic responses and embolic events during transcarotid artery revascularization via transcranial Doppler, near-infrared spectroscopy, and bispectral index monitoring. Twelve patients (7 males, 5 females; mean age: 72.8±9.0 years; range, 63 to 91 years) undergoing transcarotid artery revascularization with simultaneous transcranial Doppler, near-infrared spectroscopy, and bispectral index monitoring were analyzed in this retrospective study between September 2017 and December 2019. The mean flow velocity and pulsatility index of the middle cerebral artery, alongside near-infrared spectroscopy and bispectral index values, before flow reversal, during flow reversal, and after flow reversal phases were investigated. The presence and frequency of high-intensity transient signals were recorded to evaluate embolic incidents. Significant reductions in middle cerebral artery mean flow velocity were noted during flow reversal (40.58±10.57 cm/sec to 20.58±14.34 cm/sec, p=0.0004), which subsequently returned to and exceeded baseline values after flow reversal cessation (53.33±17.69 cm/sec, p=0.0005). Near-infrared spectroscopy (71±4.4% to 66±6.2%) and bispectral index (45.71±8.5 to 40.14±8.1) values mirrored these hemodynamic changes, with notable decreases during flow reversal, and recoveries after flow reversal. The highest concentration of high-intensity transient signals was observed during stent deployment, signifying a critical embolic phase. No perioperative neurological complications or other significant adverse events were documented. Transcranial Doppler, near-infrared spectroscopy, and bispectral index effectively monitor cerebral hemodynamics and embolic potential during transcarotid artery revascularization, providing real-time data crucial for optimizing perioperative management. These findings underscore the clinical value of multimodal monitoring in improving patient outcomes in transcarotid artery revascularization procedures.

Cognitive flexibility in a generalist raptor: a comparative analysis along an urbanization gradient

Abstract In this study, we analyzed the variation in cognitive flexibility in the Chimango Caracara (Milvago chimango), across areas with different levels of urbanization. To assess this, we utilized the reversal learning assay which measures the ability to adapt behavior in response to changes in environmental contingencies. We also investigated the impact of neophobia on this variation. All chimangos studied succeeded in acquiring a color-reward association and reverting this learned association when the contingencies changed. Urban chimangos were faster than their rural and suburban counterparts during the initial discrimination and reversal phases. The reversal phase proved to be the most challenging task. The analysis of the errors made during this phase revealed that acquiring a new association (i.e. regressive errors) was challenging for the individuals studied, in comparison to inhibiting a previously learned one (i.e. perseverative errors). Neophobia was found to be lower in urban individuals compared to suburban and rural raptors. Moreover, neophobia showed a correlation with regressive errors during the reversal phase among rural and suburban chimangos, while no such correlation was observed among city-dwelling chimangos. We suggest that neophobia acted as a regulating factor of cognitive flexibility, mainly for individuals expressing relatively high levels of this personality trait.

2D Molecular Ferroelectric with Large Out‐of‐plane Polarization for In‐Memory Computing

Abstract2D ferroelectric materials with out‐of‐plane polarization are crucial for future nanoscale logic devices due to the increasing demand for energy‐efficient architectures in artificial intelligence. However, only a few 2D out‐of‐plane ferroelectrics are confirmed experimentally. As an important branch of ferroelectrics, organic–inorganic hybrid perovskite ferroelectrics show flexible structures, making them eligible for constructing multifunctional materials. Here, a 2D organic–inorganic hybrid perovskite ferroelectric (6‐BHA)2CdBr4 (6‐BHA is 6‐bromohexylamine) is designed, which crystallizes in polar point group Cc. It experiences the reversal phase transition at 317.8 K and possesses multiaxial ferroelectric properties. More interestingly, it exhibits a large spontaneous polarization value of 3.26 µC cm−2 in out‐of‐plane direction of the film compared with typical 2D ferroelectrics. Moreover, an inverter based on (6‐BHA)2CdBr4 is fabricated, which serves as a proof of concept for the feasibility for logic‐in‐memory devices. This work not only enriches the family of molecular ferroelectrics but also shows the potential to create the next generation of in‐memory computing devices, nanoelectronics devices, and ultra‐high‐density memories.

Dexmedetomidine Sedation in Dogs: Impact on Electroencephalography, Behavior, Analgesia, and Antagonism with Atipamezole.

This study aimed to assess the impact of dexmedetomidine constant rate infusion (CRI) on key parameters in dogs. Six dogs received a 60 µg/kg/h dexmedetomidine infusion over 10 min, followed by three 15 min decremental CRIs (3, 2, and 1 µg/kg/h). A subsequent reversal phase employed 600 µg/kg/h atipamezole over 5 min. Continuous electroencephalogram (EEG) assessment, and cardiorespiratory and analgesia monitoring (every 3 min) were conducted, including analgesia evaluation through responses to electric stimulation. Dexmedetomidine induced profound sedation, evidenced by lateral recumbency and immobility. Patient State Index (PSI) decreased from awake (90.4 ± 4.3) to Phase 1 (50.9 ± 30.7), maintaining sedation (29.0 ± 18.1 to 33.1 ± 19.1 in Phases 2-4). Bradycardia (37.8 ± 3.5 bpm, lowest at Phase 3) and hypertension (133.7 ± 17.0 mmHg, highest at Phase 1) were observed, with minimal analgesia. Atipamezole promptly reversed sedation, restoring cognitive function (tail wagging behavior), and normalizing cardiovascular parameters. During atipamezole CRI, the EEG exhibited a transition from delta waves to alpha and low beta waves. This transition was observed alongside gradual increases in PSI and electromyographic activities. Additionally, spindle activities disappeared during this process. This study's results suggest potential clinical utility for EEG-guided dexmedetomidine sedation with reversal using atipamezole, warranting further investigation.

Antipsychotic effect of diosgenin in ketamine-induced murine model of schizophrenia: Involvement of oxidative stress and cholinergic transmission

A decrease in the levels of antioxidant arsenals exacerbate generation of reactive oxygen/nitrogen species, leading to neurochemical dysfunction, with significant impact on the pathogenesis of psychotic disorders such as schizophrenia. This study examined the preventive and reversal effects of diosgenin, a phyto-steroidal saponin with antioxidant functions in mice treated with ketamine which closely replicates schizophrenia-like symptoms in human and laboratory animals. In the preventive phase, adult mice cohorts were clustered into 5 groups (n = 9). Groups 1 and 2 received saline (10 mL/kg, i.p.), groups 3 and 4 were pretreated with diosgenin (25 and 50 mg/kg), and group 5 received risperidone (0.5 mg/kg) orally for 14 days. Mice in groups 2–5 additionally received a daily dose of ketamine (20 mg/kg, i.p.) or saline (10 mL/kg/day, i.p.). In the reversal phase, mice received intraperitoneal injection of ketamine or saline for 14 consecutive days prior to diosgenin (25 and 50 mg/kg/p.o./day) and risperidone (0.5 mg/kg/p.o./day) treatment from days 8–14. Mice were assessed for behavioral changes. Oxidative, nitrergic markers, and cholinergic (acetylcholinesterase activity) transmission were examined in the striatum, prefrontal-cortex and hippocampus. Diosgenin prevented and reversed hyperlocomotion, cognitive and social deficits in mice treated with ketamine relative to ketamine groups. The increased acetylcholinesterase, malondialdehyde and nitrite levels produced by ketamine were reduced by diosgenin in the striatum, prefrontal-cortex and hippocampus, but did not reverse striatal nitrite level. Diosgenin increased glutathione, and catalase levels, except for hippocampal catalase activity when compared with ketamine controls. Conclusively, these biochemical changes might be related to the behavioral deficits in ketamine-treated mice, which were prevented and reversed by diosgenin.

A Gad2 specific Slc6a8 deletion recapitulates the contextual and cued freezing deficits seen in Slc6a8-/y mice

The creatine (Cr)-phosphocreatine shuttle is essential for ATP homeostasis. In humans, the absence of brain Cr causes significant intellectual disability, epilepsy, and language delay. Mutations of the creatine transporter (SLC6A8) are the most common cause of Cr deficiency. In rodents, Slc6a8 deletion causes deficits in spatial learning, novel object recognition (NOR), as well as in contextual and cued freezing. The mechanisms that underlie these cognitive deficits are not known. Due to the heterogeneous nature of the brain, it is important to determine which systems are affected by a loss of Cr. In this study, we generated mice lacking Slc6a8 in GABAergic neurons by crossing Slc6a8FL mice with Gad2-Cre mice. These Gad2-specific Slc6a8 knockout (cKO) mice, along with the ubiquitous Slc6a8 KO (Slc6a8-/y), Gad2-Cre+, and wild-type (WT) mice were tested in the Morris water maze, NOR, conditioned freezing, and the radial water maze. Similar to the Slc6a8-/y mice, cKO mice had reduced contextual and cued freezing compared with WT mice. The cKO mice had a mild spatial learning deficit during the reversal phase of the MWM, however they were not as pronounced as in Slc6a8-/y mice. In NOR, the Gad2-Cre mice spent less time with the novel object, similar to the reduced novel time in the cKO mice. There were no changes in radial water maze performance. Slc6a8 deletion in GABAergic neurons is sufficient to recapitulate the conditioned freezing deficits seen in Slc6a8-/y mice.

Probiotic treatment with Bifidobacterium animalis subsp. lactis LKM512 + arginine improves cognitive flexibility in middle-aged mice.

Cognitive flexibility, the ability of adapting to an ever-changing environment, declines with aging and impaired in early stages of dementia. Although recent studies have indicated there is a relationship between the intestinal microbiota and cognitive function, few studies have shown relationships between intestinal microbiota and cognitive flexibility because of limited behavioural tasks in mice. We recently established a novel cognitive flexibility task for mice using a touchscreen operant apparatus and found that probiotic treatment with a mixture of Bifidobacterium animalis subsp. lactis LKM512 and arginine improved cognitive flexibility in young adult mice. To confirm the effects of the probiotic treatment on cognitive flexibility and to determine whether it is effective even in older age, we here examined the effects of long-term treatment with Bifidobacterium animalis subsp. lactis LKM512 and arginine on cognitive flexibility in middle-aged mice. From 8 to 15 months of age, mice received LKM + Arg or vehicle (controls) orally three times per week and were subjected to the cognitive flexibility task at 13-15 months old. In one of indices of cognitive flexibility, both Bifidobacterium animalis subsp. lactis LKM512 and arginine-treated mice and vehicle-treated mice showed progressively improved performance by repeating reversal tasks, with a small trend that Bifidobacterium animalis subsp. lactis LKM512 and arginine-treated mice showed better learning performance through reversal phases. With respect to the other index of cognitive flexibility, Bifidobacterium animalis subsp. lactis LKM512 and arginine-treated mice showed significantly fewer error choices than control mice at the reversal phase, i.e. Bifidobacterium animalis subsp. lactis LKM512 and arginine improved the performance of behavioural sequencing acquired in the previous phase, which allowed Bifidobacterium animalis subsp. lactis LKM512 and arginine-treated mice to show an early onset of shift to reversal contingency. Taken together, long-term treatment with Bifidobacterium animalis subsp. lactis LKM512 and arginine was found to improve cognitive flexibility in middle-aged mice, indicating that probiotic treatment might contribute to prevention of age-related cognitive decline.

Analysis of physiological pulsating flow of fractional Maxwell fluid in a locally narrow artery

The purpose of this paper is to provide a novel reference for the early diagnosis and treatment of atherosclerosis. Two-dimensional governing equations of fractional-order Maxwell fluid flow in a local stenotic artery are established, taking real physiological pulsating blood flow at inlet into consideration. Drawing support from the finite difference method as well as the L1 formula, vorticity and stream functions are introduced to acquire numerical solutions for velocity, stream function, and pressure. The distribution of blood flow in narrowed arteries within a real physiological pulse cycle is discussed. Furthermore, the influences of the degree of stenosis δ, the stenosis length parameter L0, fractional order parameter α, and relaxation time λ on crucial medical indicators, including the time average of the wall shear stress, oscillatory shear index, relative residence time, and pressure distribution are revealed. The results show that the deceleration and reversal phases of real physiological pulsatile flow critically affect the progression of arterial stenosis, and increasing the fractional order parameter α weakens the development of stenosis, while increasing λ has the opposite effect. This study is expected to serve as a reference for formulating standards of key medical indicators in the early diagnosis of vascular stenosis.

Empowering Chinese Language Learners from Low-Income Families to Improve Their Chinese Writing with ChatGPT’s Assistance Afterschool

ChatGPT is a state-of-the-art generative artificial intelligence (AI) chatbot released by OpenAI in 2022. It simulates human conversation and has the capability to generate different texts at various levels of sophistication in near real time depending upon the user’s skill in creating prompts. While concerns have been raised about academic dishonesty and cheating among students, ChatGPT has significant academic potential for education, particularly in the field of language learning. This research explores the potential of ChatGPT in supporting and empowering Chinese language learners (CLLs) whose first language is English to enhance their writing skills, mainly focusing on the research question: Is there a functional relation between Chinese language learners from low‐income families using ChatGPT after school twice a week and improvements in their Chinese writing? Four participants with varying language proficiency levels were recruited, and their data were analyzed using an ABA design. Over three weeks, they utilized ChatGPT twice a week for approximately 20 min each after school. The students’ writing scores, writing samples, and learning reflections were used to triangulate the data and enhance the data’s trustworthiness. The findings indicate that (1) each participant made a noticeable improvement in their Chinese writing scores during the intervention and reversal phases; (2) ChatGPT played a crucial role in correcting errors and facilitating the development of complete sentence structures; and (3) the students expressed a sense of empowerment through their interactions with ChatGPT. These findings highlight that ChatGPT shows promise as a supportive tool for CLLs from low-income families, reducing educational inequality and promoting equitable access to language learning opportunities.

The Protective Effect of SLNP on Hepatic Fibrosis Induced by Thioacetamide in Rats.

The incidence of non-alcoholic fatty liver disease (NAFLD) has increased in recent years. Hepatic fibrosis (HF) is an important step in the progression of NAFLD to cirrhosis and even carcinoma and is also recognized as a possible reversal phase. We previously found that the aqueous extract of Sedum Lineare Thunb. has hepatoprotective effects. This study investigated the hepatoprotective effect and mechanism of the Sedum Lineare Thunb. n-butanol phase (SLNP) on HF in rats. Animals were intraperitoneally injected with thioacetamide solution twice a week for 8 weeks to prepare an HF model and were administered the corresponding drugs or an equal volume of normal saline by intragastric administration once a day for 8 weeks. Liver function, hydroxyproline and malondialdehyde (MDA) content, superoxide dismutase (SOD), Na+-K+-ATPase, and Ca2+-Mg2+-ATPase were analyzed using colorimetric methods. Moreover, mRNA expression and protein levels in the liver tissue were detected via quantitative polymerase chain reaction and western blotting, respectively. The results showed that SLNP could effectively improve the liver function of rats with HF and significantly reduce the content of hydroxyproline; the mRNA expression and protein levels of alpha-smooth muscle actin (α-SMA), collagen I, III, and IV, transforming growth factor beta 1 (TGF-β1), Smad2/3, and Smad4 were also significantly reduced. Simultaneously, SLNP significantly increased the activities of SOD, Na+-K+- ATPase, and Ca2+-Mg2+-ATPase in the rat liver tissues, whereas it reduced the levels of MDA and SOD in the serum and liver tissues. This study revealed that SLNP elicits an anti-fibrotic effect by inhibiting oxidative stress and stellate cell activation, thereby reducing the formation and deposition of the extracellular matrix. The TGF-β1/Smads signaling pathway may be involved in this process.

Bifidobacterium animalis subsp. lactis and arginine mixture intake improves cognitive flexibility in mice.

The relationship between intestinal microbiota and cognitive function has been investigated as one of the major topics within the intestinal microbiota-gut-brain axis. Although an increasing number of studies have demonstrated an improvement in learning and memory when using probiotics or prebiotics, to date, there are no studies that target the cognitive flexibility observed in the early stages of several neuropsychiatric diseases, including dementia. We have recently developed a novel behavioral task using the touchscreen operant system to assess cognitive flexibility. We found that the disruption of the intestinal microbiota in mice induced a decline in cognitive flexibility. In the present study, we investigated the effects of treatments consisting of Bifidobacterium animalis subsp. lactis and arginine (Bifal + Arg), which promote the production of intestinal bacterial polyamine, on cognitive flexibility in the mouse model. Male C57BL6 mice orally treated with Bifal + Arg three times a week gradually decreased the 1st-choice incorrect diagonal rate with repeated reversals compared with the control group. Furthermore, in serial reversal phases, Bifal + Arg-treated mice shifted to the behavior of choosing a new correct spot more quickly after the reversal, and this was faster with repeated reversals. These results indicate that this treatment adapts to change and improves cognitive flexibility. This is the first report to show that intestinal environmental control, including probiotics and prebiotics, improves cognitive flexibility in mice.

Effects of Na/K‐ATPase Inhibitor Marinobufagenin on Gene Expression and Cognition in a Mouse Model of Alzheimer’s Disease

AbstractBackgroundAlzheimer’s disease (AD) is characterized by brain amyloid‐β plaque formation, neuroinflammation and neurodegeneration, which lead to cognitive impairment (CI) and disruption of circadian rhythm. Bioactive steroidal Na/K‐ATPase inhibitor marinobufagenin (MBG) modulates neuroinflammation. In 16‐mo old double transgenic APPswe/PS1dE9 AD mice with advanced AD, treatment with MBG reduced mRNA expression of inflammatory markers. Here, we investigated whether treatment with MBG at early‐stage AD may impact AD manifestation in this AD mouse model.MethodsFive months old male AD mice (n = 15) and WT mice (n = 28) were administered MBG (100 µg/day/kg body weight) (AD‐MBG, n = 8; WT‐MBG, n = 14) or vehicle for control (AD‐C, n = 7; WT‐C, n = 14) via subcutaneous ALZET osmotic minipumps for 3 months. At 8‐mo of age, the mice underwent turn‐based discrimination learning in a water T‐maze (WTM) to assess procedural learning and 72‐hour home cage activity (HCA) analysis to assess circadian rhythm. The hippocampal inflammatory and AD mRNAs (by qPCR) and MBG levels (by immunoassay) were measured.ResultsMBG administration increased plasma MBG levels in WT and AD mice (Table 1). AD‐C mice exhibited greater home cage activity disruption vs. WT‐C (Fig.1a); in WTM, AD‐C required more trials to learn the turn‐based task than WT‐C (Fig. 1b). Though statistically insignificant, trends showed that MBG numerically worsened activity disruption by HCA and decreased ability to learn turn‐based task by WTM in WT mice, while numerically improving both measures in AD mice. During the reversal phase of WTM where response requirements were reversed, WT‐C mice performed significantly better than AD‐C mice, measured by the cumulative amount of time spent in the incorrect arm until reaching criterion performance (p = 0.038). Similar patterns of numerical improvement in AD‐MBG compared to AD‐C are shown (Fig. 1c). Hippocampal inflammatory and AD markers mRNAs were upregulated in AD‐C vs. WT‐C, and MBG treatment downregulated the expression of TNF and GFAP in AD mice (Table 1).ConclusionsBehavioral testing results illustrate CI and circadian impairment in 8‐mo old AD mice compared to WT. Numerical trends show a potential protective effect of MBG on AD CI likely via downregulation of hippocampal TNF and GFAP genes.0Supported by the NIH/NIA Intramural Research Program