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ETHNOPHARMACOLOGICAL RELEVANCE: The Sang Yu granule (SY), a traditional Chinese medicine prescription of Xijing Hospital, was developed based on the Guanyin powder in the classical prescription "Hong's Collection of Proven Prescriptions" and the new theory of modern Chinese medicine. It has been proved to have a certain therapeutic effect on drug-induced liver injury (DILI), but the specific mechanism of action is still unclear. AIM OF STUDY: Aim of the study was to explore the effect of SangYu granule on treating drug-induced liver injury induced by acetaminophen in mice. MATERIALS AND METHODS: The chemical composition of SY, serum, and liver tissue was analyzed using ultrahigh-performance liquid chromatography quadrupole time-of-flight mass spectrometry. To assess hepatic function, measurements were taken using kits for total bile acids, as well as serum AST, ALT, and ALP activity. Concentrations of IL-1ß and TNF-α in serum were quantified using ELISA kits. Transcriptome Sequencing Analysis and 2bRAD-M microbial diversity analysis were employed to evaluate gene expression variance in liver tissue and fecal microbiota diversity among different groups, respectively. Western blotting was performed to observe differences in the activation levels of FXR, SHP, CYP7A1 and PPARα in the liver, and the levels of FXR and FGF-15 genes and proteins in the ileum of mice. Additionally, fecal microbiota transplantation (FMT) experiments were conducted to investigate the potential therapeutic effect of administering the intestinal microbial suspension from mice treated with SY on drug-induced liver injury. RESULTS: SY treatment exhibited significant hepatoprotective effects in mice, effectively ameliorating drug-induced liver injury while concurrently restoring intestinal microbial dysbiosis. Furthermore, SY administration demonstrated a reduction in the concentration of total bile acids, the expression of FXR and SHP proteins in the liver was up-regulated, CYP7A1 protein was down-regulated, and the expressions of FXR and FGF-15 proteins in the ileum were up-regulated. However, no notable impact on PPARα was observed. Furthermore, results from FMT experiments indicated that the administration of fecal suspensions derived from mice treated with SY did not yield any therapeutic benefits in the context of drug-induced liver injury. CONCLUSION: The aforementioned findings strongly suggest that SY exerts a pronounced ameliorative effect on drug-induced liver injury through its ability to modulate the expression of key proteins involved in bile acid secretion, thereby preserving hepato-enteric circulation homeostasis.
Asunto(s)
Acetaminofén , Enfermedad Hepática Inducida por Sustancias y Drogas , Medicamentos Herbarios Chinos , Microbioma Gastrointestinal , Hígado , PPAR alfa , Animales , Acetaminofén/toxicidad , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Medicamentos Herbarios Chinos/farmacología , Masculino , Hígado/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Ratones , PPAR alfa/metabolismo , Microbioma Gastrointestinal/efectos de los fármacos , Factores de Crecimiento de Fibroblastos , Colesterol 7-alfa-Hidroxilasa/metabolismo , Colesterol 7-alfa-Hidroxilasa/genética , Receptores Citoplasmáticos y Nucleares/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Factor de Necrosis Tumoral alfa/sangre , Ácidos y Sales Biliares/metabolismo , Interleucina-1beta/metabolismo , Interleucina-1beta/genéticaRESUMEN
For almost five decades, the US Supreme Court had protected the right to abortion care in the United States. However, the Court's decision in 'Dobbs versus Jackson Women's Health Organization' in 2022 established that the US Constitution does not confer a right to abortion, effectively overturning the Court's own previous judgment in 'Roe versus Wade' from 1973. How could a decision that overturns the precedent for nationwide access to abortion affect women, children, and physicians? How will state laws impact healthcare equity regarding reproductive rights going forward? How will geography affect who can access care financially, and how will this shape the conditions that unwanted children are born into? This work is a systematic analysis of the impact of overturning 'Roe versus Wade' considering the scientific and medical evidence as well as the conflicting political and moral viewpoints regarding abortion. Furthermore, we make constructive recommendations with a view to detoxifying the inflammatory rhetoric surrounding this topic and protecting key stakeholders such as patients seeking abortion and their physicians. The moment 'Roe v. Wade' was overturned, several US states began to enact laws, both protecting and restricting abortion. California and New York, for example, have since enacted laws that extend protection to both patients seeking abortion and the physicians who provide it. Oklahoma and Texas, on the other hand, have enacted laws that make it more difficult for patients to have abortion access, even after fetal death or when the birthing individual's life is in danger. These differences are likely to exacerbate the healthcare access divide across the country and increase the financial burden for those who can become pregnant. As differences in healthcare access and quality of care increase across the nation, an unmatched demand for maternity care, especially in the most restrictive states, could precipitate increased maternal and fetal morbidity and mortality while physician shortages are expected to worsen. It will be up to the US Congress to address these differences while weighing competing stakeholder interests. Currently, the nation is at the center of a seismic shift surrounding health policy with laws changing rapidly. This systematic health policy analysis paper will explore what the long-term consequences of this recent Supreme Court decision might look like while considering some of the most recently reported short-term consequences after the landslide decision.
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The threshold effect in the relationship between impervious surfaces and water quality has been a focus in past decades, but little attention has been paid to how the threshold effect changes during a rapid urbanization period. This study reveals the temporal variation of threshold effect in the relationship between the percentage of total impervious area (PTIA) and water quality indicators in a reticular river network area in Shanghai, China. The PTIA was surveyed and defined using the ISC method (impervious surface coefficients). A segmented regression model was used to disclose the non-linear relationship between PTIA and water quality. It is confirmed that the threshold effect was different in terms of water quality indicators, but the effect size became smaller as the threshold increased with urbanization level during the period of 1989-2010. Meteorological conditions make influence on the threshold effect, it can be found that the effect is more significant under higher air temperature conditions, while in the lower temperature situation, there is no significant threshold effect.
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Urbanización , Calidad del Agua , Aire Acondicionado , China , RíosRESUMEN
Shanghai is one of the largest metropolitan areas in the world, during the rapid urbanization of the past decades, impervious surface expanded dramatically and became a main factor influencing surface water quality. Thus, exploring the driving forces of impervious surface has great implications in such metropolitan area. In this study, an impervious surface coefficient method (ISC) was used to measure the percentage of total impervious area (PTIA) of Shanghai; regression analysis was conducted to define the relationship between PTIA and three socio-economic factors, population density, unit area gross domestic product, and unit area industrial output at the city and district scale. Results showed that the industrial land use generated the highest ISC value, followed by high-density residential. Strong correlations were showed between PTIA and socio-economic indicators, in which population density was the most significant. Threshold effect was presented that when population density was higher than 15000 per/km2, this relationship would become less significant and PTIA remained stable. Similar effects were found when unit area gross domestic product exceeded 125 million yuan/km2. Scale effect was also discussed that the relationship was more significant at city scale than district. An improved understanding of the threshold effect and scale effect will help guide future urban planning and design new urban ecosystem policies.