Dietary vitamin A modifies the gut microbiota and intestinal tissue transcriptome, impacting intestinal permeability and the release of inflammatory factors, thereby influencing Aß pathology.

Background: Alzheimer's disease (AD) is an age-related neurodegenerative disorder with no effective interventions for curing or modifying its progression. However, emerging research suggests that vitamin A in the diet may play a role in both the prevention and treatment of AD, although the exact mechanisms are not fully understood. Objectives: This study aims to investigate the dietary vitamin A modifies the gut microbiota and intestinal tissue transcriptome, impacting intestinal permeability and the release of inflammatory factors, thereby influencing Aß pathology shedding light on its potential as a dietary intervention for AD prevention and treatment. Methods: The APP/PS1-AD mouse model was employed and divided into three dietary groups: vitamin A-deficient (VAD), normal vitamin A (VAN), and vitamin A-supplemented (VAS) for a 12-week study. Neurobehavioral functions were assessed using the Morris Water Maze Test (MWM). Enzyme-linked immunosorbent assay (ELISA) was used to quantify levels of Diamine Oxidase (DAO), D-lactate, IL-6, IL-1ß, and TNF-a cytokines. Serum vitamin A levels were analyzed via LC-MS/MS analysis. Immunohistochemical analysis and morphometry were performed to evaluate the deposition of Aß in brain tissue. The gut microbiota of APP/PS1 mice was analyzed using 16S rRNA sequencing analysis. Additionally, transcriptomic analysis was conducted on intestinal tissue from APP/PS1 mice. Results: No significant changes in food intake and body weight were observed among the groups. However, the VAD and VAS groups showed reduced food intake compared to the VAN group at various time points. In terms of cognitive function, the VAN group performed better in the Morris Water Maze Test, indicating superior learning and memory abilities. The VAD and VAS groups exhibited impaired performance, with the VAS group performing relatively better than the VAD group. Serum vitamin A concentrations differed significantly among the groups, with the VAS group having the highest concentration. Aß levels were significantly higher in the VAD group compared to both the VAN and VAS groups. Microbial analysis revealed that the VAS and VAN groups had higher microbial diversity than the VAD group, with specific taxa characterizing each group. The VAN group was characterized by taxa such as Actinohacteriota and Desulfovibrionaceae, while the VAD group was characterized by Parabacteroides and Tannerellaceae. The VAS group showed similarities with both VAN and VAD groups, with taxa like Desulfobacterota and Desulfovibrionaceae being present. The VAD vs. VAS, VAD vs. VAN, and VAS vs. VAN comparisons identified 571, 313, and 243 differentially expressed genes, respectively, which associated with cellular and metabolic processes, and pathway analysis revealed enrichment in pathways related to chemical carcinogenesis, drug metabolism, glutathione metabolism, and immune-related processes. The VAD group exhibited higher levels of D-lactate, diamine oxidase, and inflammatory cytokines (TNF-a, IL-1ß, IL-6) compared to the VAN and VAS groups. Conclusion: Dietary vitamin A supplementation modulates the gut microbiota, intestinal permeability, inflammatory factors, and Aß protein formation, offering insights into the pathogenesis of AD and potential therapeutic avenues for further exploration. This research highlights the intricate interplay between diet, gut microbiota, and neurodegenerative processes, emphasizing the importance of dietary interventions in managing AD-related pathologies.

Development and evaluation of short-form version of the Constitution in Chinese Medicine Questionnaire: study a new and best brief instrument of Chinese medicine for health management.

BACKGROUND: More efficient instruments for body constitution identification are needed for clinical practice. We aimed to develop the short-form version of the Constitution in Chinese Medicine Questionnaire (CCMQ) and evaluate for health management. METHODS: First, the short forms were developed through expert survey, classical test theory (CTT), and modern item response (IRT) based on the CCMQ. A combination of e-mail and manual methods was used in expert survey. Then, five indexes of CTT including criteria value-critical ratio, correlation coefficient, discrete tendency, internal consistency, and factor loading were used. And, IRT method was used through analyzing the discrimination and difficulty parameters of items. Second, the three top-ranked items of each constitution scale were selected for the simplified CCMQ, based on the three combined methods of different conditions and weights. Third, The psychometric properties such as completion time, validity (Construct, criterion, and divergent validity), and reliability (test-retest and internal consistency reliability) were evaluated. Finally, the diagnostic validity of the best short-form used receiver operating characteristic (ROC) curve. RESULTS: Three short-form editions were developed, and retained items 27, 23 and 27, which are named as WangQi nine body constitution questionnaire of Traditional Chinese Medicine (short-form) (SF-WQ9CCMQ)- A, B, and C, respectively. SF-WQ9CCMQ- A is showed the best psychometric property on Construct validity, Criterion validity, test-retest reliability and internal consistency reliability. The diagnostic validity indicated that the area under the ROC curve was 0.928 (95%CI: 0.924-0.932) for the Gentleness constitution scale, and were 0.895-0.969 and 0.911-0.981 for unbalance constitution scales using the cut-off value of the original CCMQ as 40 ("yes" standard) and 30 ("tendency" standard), respectively. CONCLUSIONS: Our study successfully developed a well short-form which has good psychometric property, and excellent diagnostic validity consistent with the original. New and simplified instrument and opportunity are provided for body constitution identification, health management and primary care implementation.

Selenium (Se) recovery for technological applications from environmental matrices based on biotic and abiotic mechanisms.

Selenium (Se) is an essential element with application in manufacturing from food to medical industries. Water contamination by Se is of concern due to anthropogenic activities. Recently, Se remediation has received increasing attention. Hence, different types of remediation techniques are listed in this work, and their potential for Se recovery is evaluated. Sorption, co-precipitation, coagulation and precipitation are effective for low-cost Se removal. In photocatalytic, zero-valent iron and electrochemical systems, the above mechanisms occur with reduction as an immobilization and detoxification process. In combination with magnetic separation, the above techniques are promising for Se recovery. Biological Se oxyanions reduction has been widely recognized as a cost-effective method for Se remediation, simultaneously generating biosynthetic Se nanoparticles (BioSeNPs). Increasing the extracellular production of BioSeNPs and controlling their morphology will benefit its recovery. However, the mechanism of the microbial production of BioSeNPs is not well understood. Se containing products from both microbial reduction and abiotic methods need to be refined to obtain pure Se. Eco-friendly and cost-effective Se refinery methods need to be developed. Overall, this review offers insight into the necessity of shifting attention from Se remediation to Se recovery.

Appraisal of China's Response to the Outbreak of COVID-19 in Comparison With SARS.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2, was first reported in Wuhan, China, in December 2019 and has since become a pandemic. The COVID-19 containment measures were comparable to those used with severe acute respiratory syndrome (SARS), although these were stricter and more organized, and were initiated earlier and on a larger scale. Based on the lessons learned from SARS, the Chinese government acted aggressively in response to COVID-19, through a unified and effective commanding system, using law-based and science-driven strategies, and coordinated deployment of medical resources. Additionally, the application of high-tech measures, traditional Chinese medicine, and hierarchical medical systems also played an important role in control measures. Despite the remarkable performance, the initial delay in response suggests that the coordination between public health and medical services, reserve and coordination of emergency materials, and capacity for disease control and prevention need to be strengthened.

Benzothiophene-2-carboxamide derivatives as SENPs inhibitors with selectivity within SENPs family.

The SUMO (small ubiquitin-related modifier)-specific proteases (SENPs) are responsible for the cleavage of SUMO from its target proteins, thus play important roles in the dynamic SUMOylation and deSUMOylation processes. SENPs are related to a variety of human diseases including cancer and represent a new class of potential therapeutic targets with mechanism of action that is likely to be different from that of current clinically used drugs. However, potent inhibitors that are selective within the SENPs family members still remain a challenge due to their high homology. In order to demonstrate the feasibility of developing selective inhibitors within the SENPs family, we chose SENP1/2/5 as representatives, aiming to identify inhibitors with selectivity among the members. Starting from a hit compound ZCL951 from virtual screening, a series of benzothiophene-2-carboxamide inhibitors were designed based on the protein structures of SENP1, 2, and 5. First, an unoccupied hydrophobic pocket was first identified which led to IC50 as low as 0.56 µM. Furthermore, the ethylacetate 77 gave both submicromolar inhibitory activity and 33-fold selectivity for SENP2 versus SENP5. They are the most potent and selective nonpeptidic inhibitor reported so far for the SENPs family, as far as we are aware. Their structure-activity relationship was also discussed.

Pharmacokinetic Characterizations of Ginsenoside Ocotillol, RT5 and F11, the Promising Agents for Alzheimer's Disease from American Ginseng, in Rats and Beagle Dogs.

BACKGROUND: Ocotillol, RT5 and F11, the main active components of ocotillol type ginsenosides, have attracted a lot of attention due to their beneficial effects on neurodegenerative disease models of Alzheimer's disease. Pharmacokinetic (PK) is a bridge linking the herbal medicines and their pharmacological responses. However, few data are available regarding PK behaviors of ocotillol type ginsenosides. METHODS: The liquid chromatography-tandem mass spectrometry methods were developed and validated to calculate the concentrations of 3 ginsenosides in different biological matrices. Rat and beagle dog plasma samples were deproteinized with methanol and separated on Shim-pack GIST C18 column. All of the analytes were detected in positive ion mode using multiple reaction monitoring. RESULTS: The methods showed good linearity (r > 0.996) in the established concentration range. All validated data, such as specificity, intra- and inter-day precision, accuracy, extraction recovery, matrix effect, and stability were within required limits. The values of Cmax and AUC(0-t) indicated ocotillol type ginsenosides had low systemic exposure and poor absorption into blood. T1/2 and MRT(0-t) demonstrated the elimination process of ocotillol type ginsenosides might be slow. Double peaks were observed in the mean plasma concentration versus time profiles of ocotillol, RT5, and F11 after oral intake. CONCLUSIONS: This was the first PK investigation of the ocotillol type ginsenosides in rats and beagle dogs. The results we found here were helpful to our understanding of the absorption mechanism of ocotillol type ginsenosides and provided the scientific basis for further pre-clinical research.

Sevoflurane anesthesia alters cognitive function by activating inflammation and cell death in rats.

The present study was designed to investigate the effects of sevoflurane inhalation anesthesia on the cognitive function of rats and to investigate the molecular mechanisms mediating this effect. A total of 100 healthy male Sprague-Dawley rats were divided into four groups: i) Control (air inhalation), ii) low-dose (1.5% sevoflurane inhalation for 2 h), iii) high-dose (3% sevoflurane inhalation for 2 h), and iv) nimodipine group (3% sevoflurane inhalation for 2 h + nimodipine). Sevoflurane inhalation anesthesia resulted in cognitive dysfunction in a dose-dependent manner. Sevoflurane also upregulated the expression of tumour necrosis factor-α (TNF-α), interleukin (IL) -6, -8, and Caspase-3 in the hippocampus. The intervention with nimodipine partially recovered the cognitive function and the abnormal expression of TNF-α, IL-6, IL-8, and Caspase-3 induced by sevoflurane. The results showed that the cognitive dysfunction caused by sevoflurane inhalation in rats may be related to the activation of inflammatory and apoptotic pathways. The neuroprotective effect of nimodipine suggests that abnormal calcium transport is partially responsible for the sevoflurane toxicity.

Identification of SENP1 inhibitors through in silico screening and rational drug design.

The small ubiquitin-related modifier (SUMO)-specific proteases (SENPs) catalyze the deconjugation of SUMO from their substrate proteins. SENP1 which is the most studied isoform is closely related to many cancers such as prostate cancer and colon cancer, thus representing a potential therapeutic target for cancer treatment. In the present study, we identified eleven SENP1 inhibitors representing a variety of scaffolds through in silico screening. Based on these scaffolds, a series of new compounds were designed and synthesized in order to improve their SENP1 inhibitory potency. As a result, compounds with IC50 as low as 3.5 µM (compound 13m) were obtained and a preliminary structure-activity relationship was discussed.

Osthole inhibits histamine-dependent itch via modulating TRPV1 activity.

Osthole, an active coumarin isolated from Cnidium monnieri (L.) Cusson, has long been used in China as an antipruritic herbal medicine; however, the antipruitic mechanism of osthole is unknown. We studied the molecular mechanism of osthole in histamine-dependent itch by behavioral test, Ca(2+) imaging, and electrophysiological experiments. First, osthole clearly remitted the scratching behaviors of mice induced with histamine, HTMT, and VUF8430. Second, in cultured dorsal root ganglion (DRG) neurons, osthole showed a dose-dependent inhibitory effect to histamine. On the same neurons, osthole also decreased the response to capsaicin and histamine. In further tests, the capsaicin-induced inward currents were inhibited by osthole. These results revealed that osthole inhibited histamine-dependent itch by modulating TRPV1 activity. This study will be helpful in understanding how osthole exerts anti-pruritus effects and suggests that osthole may be a useful treatment medicine for histamine-dependent itch.

Preventive effects of ginsenoside Rg1 on post-traumatic stress disorder (PTSD)-like behavior in male C57/B6 mice.

We investigated the preventive effects of Rg1 on a model of mouse post-traumatic stress disorder (PTSD) induced by electric shock combined with situation reminder and explored the underlying mechanism. In the experiment, before the PTSD animal model was developed, Rg1 (10, 5, and 2.5mg/kg) was orally administered for one week. After the animal model was established, PTSD-like behavior was observed using elevated plus maze, black and light box, and open field tests. One hour after the behavior test, all mice were sacrificed, and then serum corticosterone (CORT) and hypothalamus corticotrophin-releasing hormone (CRH) assays were performed. Results showed that Rg1 (5mg/kg) treatments relieved PTSD-like behavior by altering elevated serum corticosterone and hypothalamus CRH levels. By contrast, fluoxetine (3mg/kg) treatment reversed the behavior changes and had no effect on increased CORT and CRH levels. These findings confirmed the preventive effect of Rg1 in PTSD model. Decreasing CORT and CRH levels may be one of the underlying mechanisms.

Effects of electroacupuncture combined with clean intermittent catheterization on urinary retention after spinal cord injury: a single blind randomized controlled clinical trial.

PURPOSE: This study aimed to evaluate the therapeutic effects of electroacupuncture (EA) combined with clean intermittent catheterization (CIC) on spinal cord injury (SCI) induced urinary retention. METHODS: A total of 107 patients with SCI induced urinary retention were randomly divided into 3 groups, including group 1 (CIC treatment), group 2 (EA combined with CIC treatment), and group 3 (sham acupuncture combined with CIC treatment). After different treatments, the residual urine volume, voided volume (each time), number of bladder balance patients, and frequency of CIC were recorded and compared. RESULTS: There were no significant differences between group 1 and 3 in number of bladder balance patients and voided volume (ml) at the 1(st) month. The rate of patients reaching bladder balance was significantly higher in group 2 than group 1 and 3 (P<0.05). The frequency of CIC was significantly less in group 2 than the other groups (P<0.001). The voided volume at the 1(st) and the 3(rd) month after surgery was significantly higher in group 2 than that in group 1 and 3 (P<0.001). Meanwhile, after 1 month and 3 months of treatment, residual urine volume was significantly reduced in group 2 compared with that in group 1 and 3 (P<0.001). CONCLUSION: The therapeutic effects of EA were effective for SCI induced urinary retention by reducing residual urine volume and the frequency of CIC, increasing voided volume, and promoting the balance of vesical function.

Determination of total ginsenosides in ginseng extracts using charged aerosol detection with post-column compensation of the gradient.

AIM: Variation in structure-related components in plant products prompted the trend to establish methods, using multiple or total analog analysis, for their effective quality control. However, the general use of routine quality control is restricted by the limited availability of reference substances. Using an easily available single marker as a reference standard to determine multiple or total analogs should be a practical option. METHOD: In this study, the Ultra-HPLC method was used for the baseline separation of the main components in ginseng extracts. Using a plant chemical component database, ginsenosides in ginseng extracts were identified by Ultra-HPLC-MS analysis. The charged aerosol detection (CAD) system with post-column compensation of the gradient generates a similar response for identical amounts of different analytes, and thus, the content of each ginsenoside in ginseng extracts was determined by comparing the analyte peak area with the reference standard (determination of total analogs by single marker, DTSM). The total ginsenoside content was determined by the summation of reference standard and other ginsenoside components. RESULTS: The results showed that DTSM approaches were available for the determination of total ginsenosides in a high purity ginseng extract because of the removal of impurities. In contrast, DTSM approaches might be suitable for determination of multiple ginsenosides without interference from impurities in the crude ginseng extract. CONCLUSION: Future practical studies similar to the present study should be conducted to verify that DTSM approaches based on CAD with post-column inverse gradient for uniform response are ideal for the quality control of plant products.

The antidepressant effects of ginseng total saponins in male C57BL/6N mice by enhancing hippocampal inhibitory phosphorylation of GSK-3ß.

Ginseng total saponins (GTS) are principal bioactive ingredients of Panax ginseng. In this study, we investigated the antidepressant effect of GTS on the corticosterone-induced mouse depression model and explored the underlying mechanism. Corticosterone (20 mg kg(-1) d(-1)) was subcutaneously administered for 22 d to induce the model, before doses of GTS (12.5, 25, and 50 mg kg(-1) d(-1)) or fluoxetine (10 mg kg(-1) d(-1)) were subsequently given by gavage. On day 20 and 21, depression-like behavior was observed via a forced swimming test and a tail suspension test respectively. At 6 h after the last dose of corticosterone (day 22), all mice were sacrificed followed by serum corticosterone assays and Western blot analysis. The results showed that GTS (25 and 50 mg kg(-1) d(-1))treatments relieved depression-like behavior without altering the elevated serum corticosterone levels. Furthermore, GTS treatments raised the down-regulated levels of hippocampal glycogen synthase kinase-3ß (GSK-3ß) inhibitory phosphorylation. In contrast, fluoxetine (10 mg kg(-1) d(-1)) treatment reversed the increased corticosterone level and had no effect on the decreased GSK-3ß inhibitory phosphorylation. These findings confirmed the antidepressant effect of GTS in the corticosterone-induced mouse depression model. Enhancing GSK-3ß inhibitory phosphorylation may be one of the underlying mechanisms.

Preparation and quality assessment of high-purity ginseng total saponins by ion exchange resin combined with macroporous adsorption resin separation.

AIM: To prepare high-purity ginseng total saponins from a water decoction of Chinese ginseng root. METHOD: Total saponins were efficiently purified by dynamic anion-cation exchange following the removal of hydrophilic impurities by macroporous resin D101. For quality control, ultrahigh-performance liquid chromatography with a charged aerosol detector (CAD) was applied to quantify marker components. The total saponin content was estimated by a colorimetric method using a vanillin-vitriol system and CAD response. RESULTS: D201, which consisted of a cross-linked polystyrene matrix and -N(+)(CH3)3 functional groups, was the best of the four anion exchange resins tested. However, no significant difference in cation exchange ability was observed between D001 (strong acid) and D113 (weak acid), although they have different functional groups and matrices. After purification in combination with D101, D201, and D113, the estimated contents of total saponins were 107% and 90% according to the colorimetric method and CAD response, respectively. The total amount of representative ginsenosides Re, Rd, Rg1, and compound K was approximately 22% based on ultrahigh-performance liquid chromatography-CAD quantitative analysis. CONCLUSION: These findings suggest that an ion exchange resin, combined with macroporous adsorption resin separation, is a promising and feasible purification procedure for neutral natural polar components.

Ginseng Total Saponins Reverse Corticosterone-Induced Changes in Depression-Like Behavior and Hippocampal Plasticity-Related Proteins by Interfering with GSK-3 ß -CREB Signaling Pathway.

This study aimed to explore the antidepressant mechanisms of ginseng total saponins (GTS) in the corticosterone-induced mouse depression model. In Experiment 1, GTS (50, 25, and 12.5 mg kg(-1) d(-1), intragastrically) were given for 3 weeks. In Experiment 2, the same doses of GTS were administrated after each corticosterone (20 mg kg(-1) d(-1), subcutaneously) injection for 22 days. In both experiments, mice underwent a forced swimming test and a tail suspension test on day 20 and day 21, respectively, and were sacrificed on day 22. Results of Experiment 1 revealed that GTS (50 and 25 mg kg(-1) d(-1)) exhibited antidepressant activity and not statistically altered hippocampal protein levels of brain-derived neurotrophic factor (BDNF) and neurofilament light chain (NF-L). Results of Experiment 2 showed that GTS (50 and 25 mg kg(-1) d(-1)) ameliorated depression-like behavior without normalizing hypercortisolism. The GTS treatments reversed the corticosterone-induced changes in mRNA levels of BDNF and NF-L, and protein levels of BDNF NF-L, phosphor-cAMP response element-binding protein (Ser133), and phosphor-glycogen synthase kinase-3 ß (Ser9) in the hippocampus. These findings imply that the effect of GTS on corticosterone-induced depression-like behavior may be mediated partly through interfering with hippocampal GSK-3 ß -CREB signaling pathway and reversing decrease of some plasticity-related proteins.

Preventive action of Panax ginseng roots in hypercortisolism-induced Impairment of hippocampal neurons in male C57BL/6N mice.

An increasing number of people suffering from hypercortisolism are at risk of developing hippocampus impairment and mental disorders. The aim of this study was to investigate whether the water extract of Panax ginseng roots (GWE) could prevent hypercortisolism-induced adverse consequences. Hypercortisolism was experimentally induced by repeated corticosterone injection in male mice. Treatment with corticosterone alone resulted in a significant decrease in hippocampus neurofilament light chain (NF-L) protein expression and induced depression-like behavior. Serum corticosterone was significantly increased in the corticosterone-treated mice. Treatment with GWE (800 and 400 mg/kg) during corticosterone treatment reduced or partially antagonized the effects induced by corticosterone toward the normal values of the controls; however, it failed to normalize increased corticosterone levels in corticosterone-treated mice. Overall, ginseng conclusively exhibited a protective action against hypercortisolism-induced impairment of hippocampal neurons.