Jasminoidin and ursodeoxycholic acid exert synergistic effect against cerebral ischemia-reperfusion injury via Dectin-1-induced NF-κB activation pathway.

BACKGROUND: Jasminoidin (JA) and ursodeoxycholic acid (UA) were shown to act synergistically against ischemic stroke (IS) in our previous studies. PURPOSE: To investigate the holistic synergistic mechanism of JA and UA on cerebral ischemia. METHODS: Middle cerebral artery obstruction reperfusion (MCAO/R) mice were used to evaluate the efficacy of JA, UA, and JA combined with UA (JU) using neurological function testing and infarct volume examination. High-throughput RNA-seq combined with computational prediction and function-integrated analysis was conducted to gain insight into the comprehensive mechanism of synergy. The core mechanism was validated using western blotting. RESULTS: JA and UA synergistically reduced cerebral infarct volume and alleviated neurological deficits and pathological changes in MCAO/R mice. A total of 1437, 396, 1080, and 987 differentially expressed genes were identified in the vehicle, JA, UA, and JU groups, respectively. A strong synergistic effect between JA and UA was predicted using chemical similarity analysis, target profile comparison, and semantic similarity analysis. As the 'long-tail' drugs, the top 20 gene ontology (GO) biological processes of JA, UA, and JU groups primarily reflected inflammatory response and regulation of cytokine production, with specific GO terms of JU revealing enhanced regulation on immune response and tumor necrosis factor superfamily cytokine production. Comparably, the Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling of common targets of JA, UA, and JU focused on extracellular matrix organization and signaling by interleukins, immune system, phagosomes, and lysosomes, which interlock and interweave to produce the synergistic effects of JU. The characteristic signaling pathway identified for JU highlighted the crosstalk between autophagy activation and inflammatory pathways, especially the Dectin-1-induced NF-κB activation pathway, which was validated by in vivo experiments. CONCLUSIONS: JA and UA can synergistically protect cerebral ischemia-reperfusion injury by attenuating Dectin-1-induced NF-κB activation. The strategy integrating high throughput data with computational models enables ever-finer mapping of 'long-tail' drugs to dynamic variations in condition-specific omics to clarify synergistic mechanisms.

Bioaccumulation determines the toxicity of carbon dots to two marine dinoflagellates.

With the ever-increasing application of carbon dots (CDs), a substantial amount will be released and assemble in the aquatic environment. Nevertheless, potential photodegradation of CDs in the aquatic environment, their accumulation and impacts in aquatic organisms remain unclear. Our study examined the toxicity of CDs to two marine dinoflagellates Prorocentrum micans and Prorocentrum donghaiense. Their bioaccumulation including the uptake and elimination kinetics was also determined. Significant photodegradation of CDs in seawater was observed. Moreover, both the degraded CDs and their photodegradation products were toxic to the dinoflagellates. Although P. donghaiense was more sensitive to CDs than P. micans with the median effect concentration 17.0 and 99.0 mg L-1, respectively, such sensitivity difference disappeared when the toxicity data were plotted against cellularly accumulated CDs instead of their concentration in the experimental medium. Therefore, the higher sensitivity of P. donghaiense was attributable to its higher accumulation of CDs. Overall, the photodegradation and bioaccumulation of CDs should be considered when evaluating their environmental risks.

The role of traditional herbal medicine for ischemic stroke: from bench to clinic-A critical review.

BACKGROUND: Ischemic stroke (IS) is a leading cause of death and severe long-term disability worldwide. Over the past few decades, considerable progress has been made in anti-ischemic therapies. However, IS remains a tremendous challenge, with favourable clinical outcomes being generally difficult to achieve from candidate drugs in preclinical phase testing. Traditional herbal medicine (THM) has been used to treat stroke for over 2,000 years in China. In modern times, THM as an alternative and complementary therapy have been prescribed in other Asian countries and have gained increasing attention for their therapeutic effects. These millennia of clinical experience allow THM to be a promising avenue for improving clinical efficacy and accelerating drug discovery. PURPOSE: To summarise the clinical evidence and potential mechanisms of THMs in IS. METHODS: A comprehensive literature search was conducted in seven electronic databases, including PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, the Chinese National Knowledge Infrastructure, the VIP Information Database, the Chinese Biomedical Literature Database, and the Wanfang Database, from inception to 17 June 2022 to examine the efficacy and safety of THM for IS, and to investigate experimental studies regarding potential mechanisms. RESULTS: THM is widely prescribed for IS alone or as adjuvant therapy. In clinical trials, THM is generally administered within 72 h of stroke onset and are continuously prescribed for over 3 months. Compared with Western medicine (WM), THM combined with routine WM can significantly improve neurological function defect scores, promote clinical total effective rate, and accelerate the recovery time of stroke with fewer adverse effects (AEs). These effects can be attributed to multiple mechanisms, mainly anti-inflammation, antioxidative stress, anti-apoptosis, brain blood barrier (BBB) modulation, inhibition of platelet activation and thrombus formation, and promotion of neurogenesis and angiogenesis. CONCLUSIONS: THM may be a promising candidate for IS management to guide clinical applications and as a reference for drug development.

Redox-Mediated Artificial Non-Enzymatic Antioxidant MXene Nanoplatforms for Acute Kidney Injury Alleviation.

Acute kidney injury (AKI), as a common oxidative stress-related renal disease, causes high mortality in clinics annually, and many other clinical diseases, including the pandemic COVID-19, have a high potential to cause AKI, yet only rehydration, renal dialysis, and other supportive therapies are available for AKI in the clinics. Nanotechnology-mediated antioxidant therapy represents a promising therapeutic strategy for AKI treatment. However, current enzyme-mimicking nanoantioxidants show poor biocompatibility and biodegradability, as well as non-specific ROS level regulation, further potentially causing deleterious adverse effects. Herein, the authors report a novel non-enzymatic antioxidant strategy based on ultrathin Ti3 C2 -PVP nanosheets (TPNS) with excellent biocompatibility and great chemical reactivity toward multiple ROS for AKI treatment. These TPNS nanosheets exhibit enzyme/ROS-triggered biodegradability and broad-spectrum ROS scavenging ability through the readily occurring redox reaction between Ti3 C2 and various ROS, as verified by theoretical calculations. Furthermore, both in vivo and in vitro experiments demonstrate that TPNS can serve as efficient antioxidant platforms to scavenge the overexpressed ROS and subsequently suppress oxidative stress-induced inflammatory response through inhibition of NF-κB signal pathway for AKI treatment. This study highlights a new type of therapeutic agent, that is, the redox-mediated non-enzymatic antioxidant MXene nanoplatforms in treatment of AKI and other ROS-associated diseases.

[Research Status of Application of Gold Nanoparticles in Medical Biotechnology].

In recent years, gold nanoparticles (GNPs) have attracted more and more attention for their unique physical, chemical and biological properties, and are emerging as optical probes and biocompatibility materials for use. With the application of nanogold labeling technology in the medical field, detection techniques using GNPs as immune markers will become a major labeling technique, and will have wide applications in basic and clinical medicine. In this article, recent research progress on the applications of GNPs in the detection of pathogens, nucleic acids, and proteins and in the preparation of biosensors is reviewed.

[Seroepidemiology investigation of neutralizing antibody against enterovirus 71 among healthy people in Tianjin].

OBJECTIVE: To investigate the latent infection caused by enterovirus 71 (EV71) among healthy people in Tianjin and to provide evidence on prevention and control hand-food and mouth diseases (HFMD). METHODS: 1611 sera specimens were collected from healthy people in Tianjin while EV71 antibody was detected by neutralization test, and then the results were analyzed statistically. RESULTS: For determining positivity, the cut-point was set at 1:4. The positive rate was 66.79% (1076/1611) for EV71 neutralizing antibody. The lowest positive rate was 32.71% in the 0 - 5 age group while the highest rate was 76.67% in the 16 - 25 age group. Significant difference was seen in the positive rates among different age groups. The lowest positive rate (59.05%) was seen in the city areas while the highest rate (72.35%) was seen in the surrounding counties. 5.71% of the people being tested showed their neutralizing antibody as ≥ 1:256. The difference was statistically significant on positive rates among different areas. We constructed logistic regression models with the EV71 neutralizing antibody positive rate as the dependent variable and age, sex, floating population, area etc. as independent variables. There appeared statistical significances in all the independent variables. CONCLUSION: Age seemed a risk factor for recessive infection of EV71, and the neutralizing antibody against EV71 might not be kept permanently. In order to prevent and control the HFMD, more attention should be paid to the areas where more floating population were resided.

[Safety and immunogenicity on three lots of influenza split vaccines among adults].

OBJECTIVE: To evaluate the immunogenicity, safety and stability of the manufacture process regarding three consecutive lots of influenza split vaccines (Anflu). METHODS: A double-blind, randomized and controlled clinical trial was conducted in healthy volunteers. A total of 566 subjects aged 18 to 60 years were recruited and stratified into four age groups before randomly assigned into four groups. Each group would receive one dose of influenza vaccine from either one of the three lots of Anflu or one lot of the licensed control vaccine. Each dose of the vaccines contained 15 microg of each of the H1N1, H3N2 and B type antigen. Safety was assessed through 30-minute observation for immediate allergic reaction and three-day observation after vaccination. HI antibody titers were determined before vaccination and on day 21, after vaccination. RESULTS: Mild adverse reaction was reported and the overall incidence rates on fever of the four groups were from 1.4% to 2.8% but no significant difference was observed between groups. Seroconversion rates of the three viral strains in four groups were 80.3% and above with fold increase as > or = 11.1 and protection rate was > or = 93.4%. For the three lots of investigated vaccines, all of the indexes of the three viral strains in four groups exceeded the standards on EMEA and FDA for influenza vaccine. CONCLUSION: The three consecutive lots of Anflu appeared to be good, with both consistent immunogenicity and safety, indicating the stability of manufacture process.

[An applied multilevel model used in the study on behavior of smoking].

OBJECTIVE: To introduce the nature and its application of a multilevel model. METHODS: Data was analyzed from a baseline survey of smoking behavior among middle school students sponsored by a WHO smoking controll project. Multilevel analysis was used on available data and to compare the results from logistic regression. RESULTS: The outcomes of null multilevel model approved that there was hierarchical structure on data. The influencing factors of middle school students smoking appeared to be gender, age, attitude, environment and public education at schools. When the variable of public education by classes was not included, the standard errors by multilevel analysis became smaller than the corresponding standard errors through logistic regression method. CONCLUSION: Multilevel model seemed a good method for analyzing data with hierarchical or cluster structure, it could be applied in stratified or cluster sampling of epidemiological or community-based investigation.

[Multilevel model analysis on the influence of smoking among university students in Tianjin].

OBJECTIVE: To study the influencing factors of smoking among university students on individual and classes level by multilevel model and to identify high risk groups in order to develop pertinent prevention measures which can decrease smoking behavior among university students. METHODS: Self-reported data on knowledge, attitude and behavior on smoking coming from a randomly clustered sampling of 24 classes in students from 12 universities in Tianjin. RESULTS: Through analyses of 743 questionnaires from university students, we learned that the occasional smoking rate was 10.0% , the regular smoking rate was 7.4% and 5.9% had given up smoking. The influencing factors for students who smoked occasionally and regularily were gender (OR values were 0.243 and 0. 186), moods (OR values were 0.071 and 0.078) and environment (OR values were 2.722 and 19.075). Gender (OR value was 0. 180), age (OR value was 1.567), moods (OR value was 0.221) and environment (OR value was 2.776) had positive influences on students in giving up their smoking behavior. CONCLUSION: According to the different status of university students, different measures should be taken to prevent smoking and to change thier smoking behavior.