Abstract The colonization ability of Limosilactobacillus fermentum DALI02 and the promoting effect of fermented prebiotics have been studied. This study aims to evaluate the systemic immunomodulatory effects of DALI02 and DALI02 + Prebiotics on cyclophosphamide‐induced immunosuppressed rats. We found that DALI02 and DALI02 + Prebiotics, especially DALI02 + Prebiotics, exhibited significant restorative effects on the immunocompromised state in rats ( p < .05). Specifically, both of them promoted the recovery of body weight and immune organ function, enhanced the proliferative capacity of immune cells, and effectively reduced the levels of interleukin 6 (IL‐6) and tumor necrosis factor‐α (TNF‐α). Furthermore, both of them significantly reduced the levels of lipopolysaccharide (LPS) and D‐lactic acid in the blood ( p < .05). Principal coordinate analysis (PCoA), principal component analysis (PCA), and unsupervised cluster analysis revealed that DALI02 and DALI02 + Prebiotics group were more similar to the blank group at the genus level of the gut microbiota. At the level of short‐chain fatty acids (SCFAs), DALI02 + Prebiotics and blank group belonged to Cluster 3. These results suggested that the intervention with DALI02 and DALI02 + Prebiotics effectively modulated the structure of the gut microbiota, and DALI02 + Prebiotics restored the dysregulation of SCFAs. In summary, DALI02 and DALI02 + Prebiotics possess immunomodulatory functions, with the latter showing superior effects.
Aims:To investigate the effect of euonymus fortune drugcontaining serum on cytokines damaged rat islet cell of glutathione (GSH) and nitric oxide (NO)content as well as the expression of inducible nitric oxide synthase (iNOS).Methods: The isolated SD rat islet cells were randomly divided into three groups (n = 8 in each group), including the control group (islets were cultured with bovine serum), model group(islets were cultured with bovine serum and cytokines (IL-1β 50 U/mL + TNF-α 250 U/ mL)) and test group (islet cells were cultured with euonymus fortune drug-containing serum and cytokines (IL-1β 50 U/mL + TNF-α 250 U/mL)).The detection of GSH and NO content in islet cells was determined by ELISA kits.The iNOS mRNA levels of islet cell were quantified with RT-PCR.The iNOS protein expression was investigated through Western blot.Results: In the study, we found that compared with the model group, the GSH contents in control and test islet cells were considerably increased, the level of NO was significantly decreased.The expression of iNOS mRNA and iNOS in control group and test group was significantly down-regulated compared with model group (all P < 0.05).Conclusions: Euonymus fortune may reduce cytokineinduced pancreas damage and improve activity of islet cells by down-regulating the expression of iNOS, suppressing the NO production and improving the content of GSH.
Abstract Renal clearable nanoparticles have been drawing much attention as they can avoid prolonged accumulation in the body by efficiently clearing through the kidneys. While much effort has been made to understand their interactions within the kidneys, it remains unclear whether their transport could be influenced by other organs, such as the liver, which plays a crucial role in metabolizing and eliminating both endogenous and exogenous substances through various biotransformation processes. Here, by utilizing renal clearable IRDye800CW conjugated gold nanocluster (800CW 4 ‐GS 18 ‐Au 25 ) as a model, we found that although 800CW 4 ‐GS 18 ‐Au 25 strongly resisted serum‐protein binding and exhibited minimal accumulation in the liver, its surface was still gradually modified by hepatic glutathione‐mediated biotransformation when passing through the liver, resulting in the dissociation of IRDye800CW from Au 25 and biotransformation‐generated fingerprint message of 800CW 4 ‐GS 18 ‐Au 25 in urine, which allowed us to facilely quantify its urinary biotransformation index (UBI) via urine chromatography analysis. Moreover, we observed the linear correlation between UBI and hepatic glutathione concentration, offering us a noninvasive method for quantitative detection of liver glutathione level through a simple urine test. Our discoveries would broaden the fundamental understanding of in vivo transport of nanoparticles and advance the development of urinary probes for noninvasive biodetection.
Infection with severe acute respiratory syndrome coronavirus 2 Omicron variants still causes neurological complications in elderly individuals. However, whether and how aging brains are affected by Omicron variants in terms of neuroinvasiveness and neurovirulence are unknown. Here, we utilize resected paracarcinoma brain tissue from elderly individuals to generate primary brain spheroids (BSs) for investigating the replication capability of live wild-type (WT) strain and Omicron (BA.1/BA.2), as well as the mechanisms underlying their neurobiological effects. We find that both WT and Omicron BA.1/BA.2 are able to enter BSs but weakly replicate. There is no difference between Omicron BA.1/BA.2 and WT strains in neurotropism in aging BSs. However, Omicron BA.1/BA.2 exhibits ameliorating neurological damage. Transcriptional profiling indicates that Omicron BA.1/BA.2 induces a lower neuroinflammatory response than WT strain in elderly BSs, suggesting a mechanistic explanation for their attenuated neuropathogenicity. Moreover, we find that both Omicron BA.1/BA.2 and WT strain infections disrupt neural network activity associated with neurodegenerative disorders by causing neuron degeneration and amyloid-β deposition in elderly BSs. These results uncover Omicron-specific mechanisms and cellular immune responses associated with severe acute respiratory syndrome coronavirus 2-induced neurological complications.
Gastrointestinal (GI) disorders are one of the main adverse events by mycophenolic acid (MPA). The aim of this preliminary study was to evaluate the GI side-effects of mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS) in rat, discover the mechanism of MPA drugs inducing GI side effects. Forty male Sprague Dawley rats were randomized into five groups: control, MMF (100 mg/Kg.d), N-(2-Hydroxyethyl)morpholine(60mg/kg.d), EC-MPS (144 mg/Kg.d), N-(2-Hydroxyethyl)morpholine +EC-MPS. Each group was intragastric administration with MMF or EC-MPS once a day for seven days. Diarrhea grade and weight loss were significantly increased in MMF group.Figure: No Caption available.Figure: No Caption available.After the last visit, the rats were sacrificed and GI tissue including stomach, duodenum, jejunum, ileum, colon and rectum were prepared for pathological Analysis. MMF group were significantly pathological injury especially in mucosa. On the last experiment day, following the daily dose of drugs, blood was collected by tail nick for determination of MPA and MPAG pharmacokinetic profiles. Blood collection times were 0, 15, 30, 60, 120, 240 min. MPA and MPAG in blood are detected by liquid chromatography. Area under the plasma time-concentration curve (AUC) values were calculated from 0 to 240 min. AUC of MPA and MPAG, MMF group was not significant higher than EC-MPS group. In conclusion, EC-MPS showed more advantages in Diarrhea grade and weight loss, less GI pathologic injury than MMF. Meanwhile, AUC of MPA and MPAG between EC-MPS and MMF were not significant differences.
Visual biofeedback and force plate systems are often used for treatment of balance and mobility disorders following neurological injury. Conventional Physical Therapy techniques have been shown to improve balance, mobility and gait. The training program encourages patients to transfer weight onto the impaired limb in order to improve weight shift in standing and during gait. Researchers and therapists have been exploring the use of video game consoles such as the Nintendo® WiiFitTM as rehabilitation tools. Initial case studies have demonstrated that the use of video games has some promise for balance rehabilitation. However, initial usability studies and anecdotal evidence has indicated that the commercial games that are currently available are not necessarily suitable for the controlled, specific exercise required for therapy. Based on focus group data and observations with patients, a game has been developed to specifically target weight shift training using an open source game engine and the WiiFit balance board. The prototype underwent initial usability testing with a sample of four Physical Therapists and four patients with neurological injury or disease. Overall, feedback was positive and areas for improvement were identified. This preliminary research provides support for the development of a game that caters specifically to the key requirements of balance rehabilitation.
Renal clearable nanoparticles have been drawing much attention as they can avoid prolonged accumulation in the body by efficiently clearing through the kidneys. While much effort has been made to understand their interactions within the kidneys, it remains unclear whether their transport could be influenced by other organs, such as the liver, which plays a crucial role in metabolizing and eliminating both endogenous and exogenous substances through various biotransformation processes. Here, by utilizing renal clearable IRDye800CW conjugated gold nanocluster (800CW
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