Early administration of Wumei Wan inhibit myeloid-derived suppressor cells via PI3K/Akt pathway and amino acids metabolism to prevent Colitis-associated Colorectal Cancer.

ETHNOPHARMACOLOGICAL RELEVANCE: Wumei Wan (WMW), a traditional Chinese medicine prescription, has been proved to be effective in treating Colitis-associated colorectal cancer (CAC), but it has not been proven to be effective in different stages of CAC. AIM OF THE STUDY: The purpose of our study is to investigate the therapeutic effect and mechanism of WMW on the progression of CAC. MATERIALS AND METHODS: Azioximethane (AOM) and dextran sulfate sodium (DSS) were used to treat mice for the purpose of establishing CAC models. WMW was administered in different stages of CAC. The presentative chemical components in WMW were confirmed by UHPLCQTOF/MS under the optimized conditions. The detection of inflammatory cytokines in the serum and colon of mice were estimated by qRT-PCR and ELISA. The changes of T cells and myeloid-derived suppressor cells (MDSCs) in each group were detected by flow cytometry. The metabolic components in serum of mice were detected by UPLC-MS/MS. Expression of genes and proteins were detected by eukaryotic transcriptomics and western blot to explore the key pathway of WMW in preventing CAC. RESULTS: WMW had significant effect on inhibiting inflammatory responses and tumors during the early development stage of CAC when compared to other times. WMW increased the length of mice's colons, reduced the level of IL-1ß, IL-6, TNF-α in colon tissues, and effectively alleviated colonic inflammation, and improved the pathological damage of colon tissues. WMW could significantly reduce the infiltration of MDSCs in the spleen, increase CD4+ T cells and CD8+ T cells in the spleen of CAC mice, and effectively reform the immune microenvironment in CAC mice. Transcriptomics analysis revealed that 2204 genes had different patterns of overlap in the colon tissues of mice between control group, AOM+DSS group, and early administration of WMW group. And KEGG enrichment analysis showed that PI3K/Akt signaling pathway, ECM-receptor interaction, IL-17 signaling pathway, MAPK signaling pathway, pancreatic secretion, thermogenesis, and Rap1 signaling pathway were all involved. The serum metabolomics results of WMW showed that the metabolic compositions of the control group, AOM+DSS group and the early stage of WMW were different, and 42 differential metabolites with the opposite trends of changes were screened. The metabolic pathways mainly included pyrimidine metabolism, glycine, serine and threonine metabolism, tryptophan metabolism, and purine metabolism. And amino acids and related metabolites may play an important role in WMW prevention of CAC. CONCLUSION: WMW can effectively prevent the occurrence and development of CAC, especially in the initial stage. WMW can reduce the immune infiltration of MDSCs in the early stage. Early intervention of WMW can improve the metabolic disorder caused by AOM+DSS, especially correct the amino acid metabolism. PI3K/Akt signaling pathway was inhabited in early administration of WMW, which can regulate the amplification and function of MDSCs.

Household fuel and direct carbon emission disparity in rural China.

Universal access to clean fuels in household use is one explicit indicator of sustainable development while currently still billions of people rely on solid fuels for daily cooking. Despite of the recognized clean transition trend in general, disparities in household energy mix in different activities (e.g. cooking and heating) and historical trends remain to be elucidated. In this study, we revealed the historical changing trend of the disparity in household cooking and heating activities and associated carbon emissions in rural China. The study found that the poor had higher total direct energy consumption but used less modern energy, especially in cooking activities, in which the poor consumed 60 % more energy than the rich. The disparity in modern household energy use decreased over time, but conversely the disparity in total residential energy consumption increased due to the different energy elasticities as income increases. Though per-capita household CO2 and Black Carbon (BC) emissions were decreasing under switching to modern energies, the disparity in household CO2 and BC deepened over time, and the low-income groups emitted âˆ¼ 10 kg CO2 more compared to the high-income population. Relying solely on spontaneous clean cooking transition had limited impacts in reducing disparities in household energy and carbon emissions, whereas improving access to modern energy had substantial potential to reduce energy consumption and carbon emissions and its disparity. Differentiated energy-related policies to promote high-efficiency modern heating energies affordable for the low-income population should be developed to reduce the disparity, and consequently benefit human health and climate change equally.

An optimized short-term steroid therapy for chronic drug-induced liver injury: A prospective randomized clinical trial.

BACKGROUND AND AIMS: The use of corticosteroids in chronic drug-induced liver injury (DILI) is an important issue. Our previous randomized controlled trial showed that patients with chronic DILI benefited from a 48-week steroid stepwise reduction (SSR) regimen. However, it remains unclear whether a shorter course of therapy can achieve similar efficacy. In this study, we aimed to assess whether a 36-week SSR can achieve efficacy similar to that of 48-week SSR. METHODS: A randomized open-label trial was performed. Eligible patients were randomly assigned to the 36- or 48-week (1:1) SSR group. Liver biopsies were performed at baseline and at the end of treatment. The primary outcome was the proportion of patients with relapse rate (RR). The secondary outcomes were improvement in liver histology and safety. RESULTS: Of the 90 participants enrolled, 84 (87.5%) completed the trial, and 62 patients (68.9%) were women. Hepatocellular damage was observed in 53.4% of the cohort. The RR was 7.1% in the 36-week SSR group but 4.8% in the 48-week SSR group, as determined by per-protocol set analysis (p = 1.000). Significant histological improvements in histological activity (93.1% vs. 92.9%, p = 1.000) and fibrosis (41.4% vs. 46.4%, p = .701) were observed in both the groups. Biochemical normalization time did not differ between the two groups. No severe adverse events were observed. CONCLUSIONS: Both the 36- and 48-week SSR regimens demonstrated similar biochemical response and histological improvements with good safety, supporting 36-week SSR as a preferable therapeutic choice (ClinicalTrials.gov, NCT03266146).

Estimated health effects from domestic use of gaseous fuels for cooking and heating in high-income, middle-income, and low-income countries: a systematic review and meta-analyses.

BACKGROUND: Exposure to household air pollution from polluting domestic fuel (solid fuel and kerosene) represents a substantial global public health burden and there is an urgent need for rapid transition to clean domestic fuels. Gas for cooking and heating might possibly affect child asthma, wheezing, and respiratory health. The aim of this review was to synthesise the evidence on the health effects of gaseous fuels to inform policies for scalable clean household energy. METHODS: In this systematic review and meta-analysis, we summarised the health effects from cooking or heating with gas compared with polluting fuels (eg, wood or charcoal) and clean energy (eg, electricity and solar energy). We searched PubMed, Scopus, Web of Science, MEDLINE, Cochrane Library (CENTRAL), Environment Complete, GreenFile, Google Scholar, Wanfang DATA, and CNKI for articles published between Dec 16, 2020, and Feb 6, 2021. Studies eligible for inclusion had to compare gas for cooking or heating with polluting fuels (eg, wood or charcoal) or clean energy (eg, electricity or solar energy) and present data for health outcomes in general populations. Studies that reported health outcomes that were exacerbations of existing underlying conditions were excluded. Several of our reviewers were involved in screening studies, data extraction, and quality assessment (including risk of bias) of included studies; 20% of studies were independently screened, extracted and quality assessed by another reviewer. Disagreements were reconciled through discussion with the wider review team. Included studies were appraised for quality using the Liverpool Quality Assessment Tools. Key health outcomes were grouped for meta-analysis and analysed using Cochrane's RevMan software. Primary outcomes were health effects (eg, acute lower respiratory infections) and secondary outcomes were health symptoms (eg, respiratory symptoms such as wheeze, cough, or breathlessness). This study is registered with PROSPERO, CRD42021227092. FINDINGS: 116 studies were included in the meta-analysis (two [2%] randomised controlled trials, 13 [11%] case-control studies, 23 [20%] cohort studies, and 78 [67%] cross-sectional studies), contributing 215 effect estimates for five grouped health outcomes. Compared with polluting fuels, use of gas significantly lowered the risk of pneumonia (OR 0·54, 95% CI 0·38-0·77; p=0·00080), wheeze (OR 0·42, 0·30-0·59; p<0·0001), cough (OR 0·44, 0·32-0·62; p<0·0001), breathlessness (OR 0·40, 0·21-0·76; p=0·0052), chronic obstructive pulmonary disease (OR 0·37, 0·23-0·60; p<0·0001), bronchitis (OR 0·60, 0·43-0·82; p=0·0015), pulmonary function deficit (OR 0·27, 0·17-0·44; p<0·0001), severe respiratory illness or death (OR 0·27, 0·11-0·63; p=0·0024), preterm birth (OR 0·66, 0·45-0·97; p=0·033), and low birth weight (OR 0·70, 0·53-0·93; p=0·015). Non-statistically significant effects were observed for asthma in children (OR 1·04, 0·70-1·55; p=0·84), asthma in adults (OR 0·65, 0·43-1·00; p=0·052), and small for gestational age (OR 1·04, 0·89-1·21; p=0·62). Compared with electricity, use of gas significantly increased risk of pneumonia (OR 1·26, 1·03-1·53; p=0·025) and chronic obstructive pulmonary disease (OR 1·15, 1·06-1·25; p=0·0011), although smaller non-significant effects were observed for higher-quality studies. In addition, a small increased risk of asthma in children was not significant (OR 1·09, 0·99-1·19; p=0·071) and no significant associations were found for adult asthma, wheeze, cough, and breathlessness (p>0·05). A significant decreased risk of bronchitis was observed (OR 0·87, 0·81-0·93; p<0·0001). INTERPRETATION: Switching from polluting fuels to gaseous household fuels could lower health risk and associated morbidity and mortality in resource-poor countries where reliance on polluting fuels is greatest. Although gas fuel use was associated with a slightly higher risk for some health outcomes compared with electricity, gas is an important transitional option for health in countries where access to reliable electricity supply for cooking or heating is not feasible in the near term. FUNDING: WHO.

Phytoplankton in headwater streams: spatiotemporal patterns and underlying mechanisms.

Phytoplankton are key members of river ecosystems wherein they influence and regulate the health of the local environment. Headwater streams are subject to minimal human activity and serve as the sources of rivers, generally exhibiting minimal pollution and strong hydrodynamic forces. To date, the characteristics of phytoplankton communities in headwater streams have remained poorly understood. This study aims to address this knowledge gap by comparing phytoplankton communities in headwater streams with those in plain rivers. The results demonstrated that within similar watershed sizes, lower levels of spatiotemporal variability were observed with respect to phytoplankton community as compared to plain rivers. Lower nutrient levels and strong hydrodynamics contribute to phytoplankton growth limitation in these streams, thereby reducing the levels of spatiotemporal variation. However, these conditions additionally contribute to greater phytoplankton diversity and consequent succession towards Cyanophyta. Overall, these results provide new insights into the dynamics of headwater stream ecosystems and support efforts for their ecological conservation.

Indoor exposure to polycyclic aromatic hydrocarbons associated with solid fuel use in rural China.

Polycyclic aromatic hydrocarbons (PAHs) are widespread environmental contaminants associated with various health risks including lung cancer. Indoor exposure to PAHs, particularly from the indoor burning of fuels, is significant; however, long-term large-scale assessments of indoor PAHs are hampered by high costs and time-consuming in field sampling and laboratory experiments. A simple fuel-based approach and statistical regression models were developed as a trial to predict indoor BaP, as a typical PAH, in China, and consequently spatiotemporal variations in indoor BaP and indoor exposure contributions were discussed. The results show that the national population-weighted indoor BaP concentration has decreased substantially from 46.1 ng/m3 in 1992 to 6.60 ng/m3 in 2017, primarily due to the increased use of clean energies for cooking and heating. Indoor BaP exposure contributed to > 70% of the total inhalation exposure in most cities, particularly in regions where solid fuels are widely utilized. With limited experimental observation data in building statistical models, quantitative results of the study are associated with high uncertainties; however, the study undoubtedly supports effective countermeasures on indoor PAHs from solid fuel use and the importance of promoting clean household energy usage to improve household air quality.

Trends in air pollutants emissions in the Qinghai-Tibet Plateau and its surrounding areas under different socioeconomic scenarios.

The Qinghai-Tibetan Plateau (QTP) and its surrounding areas are undergoing rapid changes in socioeconomic conditions, activity sectors, and emission levels. These changes underscore the significance of conducting local environmental assessments in the future and generating air pollutant emission forecasts necessary for effective evaluation. Current pollutants emissions pathways exhibit regional limitation since their based historical inventory could not accurately reflect the emission characteristics in QTP. This study constructed a high spatial resolution (0.1° × 0.1°) atmospheric pollutant emissions dataset in the Qinghai-Tibet Plateau and its surrounding Areas (QTPA) based on updated emission inventory and various socioeconomic scenarios. We found that the pollutant emissions levels are distinct among different social development scenarios, with SSP3-7.0 demonstrating the highest magnitude of emissions. Regional and sectoral contributions exhibit substantial variations. Notably, solid fuel combustion originating from residential sectors in Northeast India and open fires in Myanmar are identified as high-density sources of PM2.5 emissions. Current pollutant emission patterns in the QTPA are more akin to SSP2-4.5, however, specific regions such as Qinghai and Tibet have exhibited more pronounced trends of emission reduction. The comparison with previous datasets reveals that the predicted pollutant emissions in this study are lower than Scenario Model Intercomparison Project (SMIP) dataset but higher than Asian-Pacific Integrated Model (AIM) dataset due to the revised inventory data and model variations, in which the latter might be the main obstacle to accurate emissions prediction.

Interpreting Highly Variable Indoor PM2.5 in Rural North China Using Machine Learning.

Household air pollution associated with solid fuel use is a long-standing public concern. The global population mainly using solid fuels for cooking remains large. Besides cooking, large amounts of coal and biomass fuels are burned for space heating during cold seasons in many regions. In this study, a wintertime multiple-region field campaign was carried out in north China to evaluate indoor PM2.5 variations. With hourly resolved data from ∼1600 households, key influencing factors of indoor PM2.5 were identified from a machine learning approach, and a random forest regression (RFR) model was further developed to quantitatively assess the impacts of household energy transition on indoor PM2.5. The indoor PM2.5 concentration averaged at 120 µg/m3 but ranged from 16 to ∼400 µg/m3. Indoor PM2.5 was ∼60% lower in families using clean heating approaches compared to those burning traditional coal or biomass fuels. The RFR model had a good performance (R2 = 0.85), and the interpretation was consistent with the field observation. A transition to clean coals or biomass pellets can reduce indoor PM2.5 by 20%, and further switching to clean modern energies would reduce it an additional 30%, suggesting many significant benefits in promoting clean transitions in household heating activities.

Pyroptotic MAITs link microbial translocation with severity of alcohol-associated liver disease.

BACKGROUND: Mucosal-associated invariant T cells (MAITs) are markedly reduced in patients with alcohol-associated liver disease (ALD); however, the potential mechanism underlying MAITs' loss remains elusive. Hence, we aimed to explore what induced MAITs' loss and its clinical significance. METHODS: The characteristics of pyroptotic MAITs were evaluated in a cohort of patients with ALD, including 41 patients with alcohol-associated liver cirrhosis (ALC) and 21 patients with ALC complicated with severe alcoholic hepatitis (ALC + SAH). RESULTS: In patients with ALD, blood MAITs were significantly decreased, hyperactivated, and displayed enhanced cell death through pyroptosis. The frequencies of pyroptotic MAITs increased with disease severity in patients with ALC and patients with ALC + SAH. These frequencies were negatively associated with the frequencies of MAITs and positively correlated with the levels of MAITs' activation, plasma levels of intestinal fatty acid-binding protein (a marker of intestinal enterocyte damage), soluble CD14, lipopolysaccharide-binding protein, and peptidoglycan recognition proteins (surrogate markers of microbial translocation). Pyroptotic MAITs were also found in the liver of patients with ALD. Interestingly, MAITs underwent further activation and pyroptosis in vitro under stimulation by Escherichia coli or direct bilirubin. Notably, blocking IL-18 signaling reduced the activation and frequencies of pyroptotic MAITs. CONCLUSIONS: The loss of MAITs in patients with ALD is, at least in part, due to cell death from pyroptosis and is associated with the severity of ALD. Such increased pyroptosis may be affected by dysregulated inflammatory responses to intestinal microbial translocation or direct bilirubin.

Divergent Energy-Climate Nexus in the Global Fuel Combustion Processes.

Fuel combustion provides basic energy for the society but also produces CO2 and incomplete combustion products that threaten human survival, climate change, and global sustainability. A variety of fuels burned in different facilities expectedly have distinct impacts on climate, which remains to be quantitatively assessed. This study uses updated emission inventories and an earth system model to evaluate absolute and relative contributions in combustion emission-associated climate forcing by fuels, sectors, and regions. We showed that, from 1970 to 2014, coal burned in the energy sector and oil used in the transportation sector contributed comparable energies consumed (24 and 20% of the total) but had distinct climate forcing (1 and 40%, respectively). Globally, coal burned for energy production had negative impacts on climate forcing but positive effects in the residential sector. In many developing countries, coal combustion in the energy sector had negative radiative forcing (RF) per unit energy consumed due to insufficient controls on sulfur and scattering aerosol levels, but oils in the transportation sector had high positive RF values. These results had important implications on the energy transition and emission reduction actions in response to climate change. Distinct climate efficiencies of energies and the spatial heterogeneity implied differentiated energy utilization strategies and pollution control policies by region and sector.

Identification of Factors Determining Household PM2.5 Variations at Regional Scale and Their Implications for Pollution Mitigation.

Indoor PM2.5, particulate matter no more than 2.5 µm in aerodynamic equivalent diameter, has very high spatiotemporal variabilities; and exploring the key factors influencing the variabilities is critical for purifying air and protecting human health. Here, we conducted a longer-term field monitoring campaign using low-cost sensors and evaluated inter- and intra-household PM2.5 variations in rural areas where energy or stove stacking is common. Household PM2.5 varied largely across different homes but also within households. Using generalized linear models and dominance analysis, we estimated that outdoor PM2.5 explained 19% of the intrahousehold variation in indoor daily PM2.5, whereas factors like the outdoor temperature and indoor-outdoor temperature difference that was associated with energy use directly or indirectly, explained 26% of the temporal variation. Inter-household variation was lower than intrahousehold variation. The inter-household variation was strongly associated with distinct internal sources, with energy-use-associated factors explaining 35% of the variation. The statistical source apportionment model estimated that solid fuel burning for heating contributed an average of 31%-55% of PM2.5 annually, whereas the contribution of sources originating from the outdoors was ≤10%. By replacing raw biomass or coal with biomass pellets in gasifier burners for heating, indoor PM2.5 could be significantly reduced and indoor temperature substantially increased, providing thermal comforts in addition to improved air quality.

Variabilities in Primary N-Containing Aromatic Compound Emissions from Residential Solid Fuel Combustion and Implications for Source Tracers.

Nitroaromatic compounds (NACs) not only are strongly absorbing chromophores but also adversely affect human health. NACs can be emitted from incomplete combustions and can derive secondarily through photochemical reactions. Here, emission experiments were conducted for 31 fuel-stove combinations to elucidate variations in, and influencing factors of, NAC emission factors (EF∑NACs) and to explore potential tracers for different combustion sources. EF∑NACs varied by 2 orders of magnitude among different combinations. Differences in fuel type contributed more than the stove difference to the observed variation. EF∑NACs for biomass pellets was approximately 66% lower than that for raw biomass, although the bulk organic and brown carbon EFs were 95% lower. 2-Nitro-1-naphthol was the most abundant individual compound, followed by 4-nitrocatechol, while acid compounds (salicylic acid and benzoic acid) were low in abundance (<1%). Substantially different profiles were observed between coal and biomass burning emissions. Biomass burning had more single-ring-based phenolic compounds with more 4-nitrocatechol, while in coal combustion, more two-ring products were produced. This study demonstrated much lower ratios of 2-nitro-1-naphthol/4-nitrocatechol for biomass in both traditional (2.0 ± 3.5) and improved stoves (3.0 ± 2.1) than for coals (15 ± 6). Coal and biomass burning differed in not only EF∑NACs but also compound profile, consequently leading to distinct health and climate impacts; moreover, the ratio of 2-nitro-1-naphthol/4-nitrocatechol may be used in source apportionment of NACs.

Mesenchymal Stromal Cell Therapy in Spinal Cord Injury: Mechanisms and Prospects.

Spinal cord injury (SCI) often leads to severe motor, sensory, and autonomic dysfunction in patients and imposes a huge economic cost to individuals and society. Due to its complicated pathophysiological mechanism, there is not yet an optimal treatment available for SCI. Mesenchymal stromal cells (MSCs) are promising candidate transplant cells for use in SCI treatment. The multipotency of MSCs, as well as their rich trophic and immunomodulatory abilities through paracrine signaling, are expected to play an important role in neural repair. At the same time, the simplicity of MSCs isolation and culture and the bypassing of ethical barriers to stem cell transplantation make them more attractive. However, the MSCs concept has evolved in a specific research context to encompass different populations of cells with a variety of biological characteristics, and failure to understand this can undermine the quality of research in the field. Here, we review the development of the concept of MSCs in order to clarify misconceptions and discuss the controversy in MSCs neural differentiation. We also summarize a potential role of MSCs in SCI treatment, including their migration and trophic and immunomodulatory effects, and their ability to relieve neuropathic pain, and we also highlight directions for future research.

[Effect of elevated atmospheric CO2 concentration and temperature on volatile halogenated organic compound content in soils of Schima superba and Cunninghamia lanceolata seedlings.] / 大气CO2浓度和温度升高对木荷和杉木幼苗土壤卤代烃含量的影响.

Global changes caused by the increases of atmospheric CO2 concentration and temperature have important effects on soil biogeochemical processes. The synthesis and release of volatile halogenated organic compounds (VOXs) is an important pathway for soil to participate in the global material cycle and energy flow. In this study, Schima superba and Cunninghamia lanceolata seedlings in the southern subtropics were selected as the research objects. Four treatments, including control (CK), elevated CO2 concentration (EC), elevated temperature (ET) and elevated both factors (EC+ET) were set up. The effects of EC and ET on soil VOXs formation were studied by an open-top chamber system coupled with a purging and trapping gas chromatography/mass spectrometry. The results showed that VOXs content in the soil of S. superba seedlings was 0.065-0.252 ng·g-1, which was higher than that of C. lanceolata (0.038-0.136 ng·g-1). At the EC, ET and EC+ET treatments, VOXs contents were reduced in soils of both species. The effect of ET was the most significant, with the decrease rates of 74.2% and 72.1% in both soils, respectively. The change of VOXs content with increasing temperature mainly attributed to the changes of soil moisture and nitrogen content. The content of VOXs in the soils of S. superba seedlings decreased more than that of C. lanceolata under different treatments. In CK, EC, ET and EC+ET treatment, bromodichloromethane (BDCM) (27.5%, 36.7%, 32.9%, 32.6%) and tetrachloromethane (TCM) (9.0%, 16.8%, 22.7%, 15.8%) were the main VOXs in the soil of S. superba seedlings, respectively, while BDCM and dibromomethane (DBM) were the main VOXs in the soil of C. lanceolata seedlings. BDCM accounted for 31.9%, 38.2%, 40.9% and 37.2% of the VOXs content in each treatment, and DBM accounted for 17.9%, 16.5%, 19.2% and 16.0% of the VOXs content, respectively. Simulating elevated atmospheric CO2 concentration and temperature was conducive to more comprehensive reflection of the ecological effect of global climate change, and it could provide data support for improving the VOCs flux model.

Impacts of Household Coal Combustion on Indoor Ultrafine Particles-A Preliminary Case Study and Implication on Exposure Reduction.

Ultrafine particles (UFPs) significantly affect human health and climate. UFPs can be produced largely from the incomplete burning of solid fuels in stoves; however, indoor UFPs are less studied compared to outdoor UFPs, especially in coal-combustion homes. In this study, indoor and outdoor UFP concentrations were measured simultaneously by using a portable instrument, and internal and outdoor source contributions to indoor UFPs were estimated using a statistical approach based on highly temporally resolved data. The total concentrations of indoor UFPs in a rural household with the presence of coal burning were as high as 1.64 × 105 (1.32 × 105-2.09 × 105 as interquartile range) #/cm3, which was nearly one order of magnitude higher than that of outdoor UFPs. Indoor UFPs were unimodal, with the greatest abundance of particles in the size range of 31.6-100 nm. The indoor-to-outdoor ratio of UFPs in a rural household was about 6.4 (2.7-16.0), while it was 0.89 (0.88-0.91) in a home without strong internal sources. A dynamic process illustrated that the particle number concentration increased by ~5 times during the coal ignition period. Indoor coal combustion made up to over 80% of indoor UFPs, while in an urban home without coal combustion sources indoors, the outdoor sources may contribute to nearly 90% of indoor UFPs. A high number concentration and a greater number of finer particles in homes with the presence of coal combustion indicated serious health hazards associated with UFP exposure and the necessity for future controls on indoor UFPs.

Mechanism of Bushen Zhuyun Prescription on Improving Luteal Function of Brown Norway Rats Based on MAPKs Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the possible mechanism of Bushen Zhuyun prescription （BSZYP） to reduce the level of ovarian apoptosis in Brown Norway （BN） rats with luteal phase deficiency （LPD）. MethodFifty SPF female BN rats were randomly divided into a model group， a dydrogesterone group （0.002 g·kg-1）， and a low （4.5 g·kg-1）， a medium （9 g·kg-1）， and a high-dose （18 g·kg-1） BSZYP groups， with ten rats in each group. The rats were administrated with corresponding drugs by gavage， once a day for three estrus cycle. Western blot was used to detected the protein expression levels of c-Jun NH2 terminal kinase （JNK）， extracellular signal-regulated kinase （ERK）， phosphorylated-ERK （p-ERK）， phosphorylated-JNK （p-JNK）， p38 mitogen-activated protein kinase （p38 MAPK）， phosphorylated-p38 MAPK （p-p38 MAPK ）， B-cell lymphoma （Bcl-2）， and Bcl-2 associated X protein （Bax） in ovary. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression levels of ERK， JNK， p38 MAPK， Bax， and Bcl-2 in ovary. Enzyme-linked immunosorbent assay （ELISA） was used to detect the serum progesterone （P） and estradiol （E2） levels. Hematoxylin-eosin （HE） staining was used to observe the ovarian tissue morphology. ResultCompared with the model group， the recovery of estrus cycle of rats in all BSZYP groups had statistical significance after 1-circle administration （P<0.05）. The ovarian tissue morphology in the low-dose BSZYP group was improved， and that in the medium and high-dose BSZYP groups was significantly improved with clear follicle， less vesicular follicle and atretic follicle， and more granular layers. The number of luteum， especially the fresh luteum， in the medium and high-dose groups was increased with smooth edge and large volume. The mRNA expression level of Bcl-2 was increased in all-dose BSZYP groups， while the mRNA expression level of Bax was significantly decreased in all-dose BSZYP group （P<0.05， P<0.01）. The mRNA expression levels of JNK and p38 MAPK were significantly decreased in the high-dose BSZYP group （P<0.01）， and the mRNA expression levels of ERK were increased in the low and medium-dose BSZYP groups （P<0.05）. The protein expression level of Bcl-2 was significantly increased in the medium and high-dose BSZYP groups （P<0.01）， and the protein expression level of Bax was significantly decreased in the all-dose BSZYP groups （P<0.01）. No significant difference was observed in the protein expressions of JNK， ERK， and p38 MAPK in the BSZYP groups. The protein expression levels of p-ERK in the ovarian tissues of rats were significantly inoreased in the medium and high-dose BSZYP group （P<0.01）， p-JNK， and p-p38 MAPK in the ovarian tissues of rats were significantly decreased in the medium and high-dose BSZYP group （P<0.01）. The level of E2 was increased in all-dose BSZYP groups （P<0.05， P<0.01）， and the level of P in the medium-dose BSZYP group was increased （P<0.05）. ConclusionBSZYP improved the serum sex hormones， restored the estrous cycle， reduced atretic follicle and vesiculation， and maintained luteal morphology and function of BN rats， so as to improve luteal function and treat luteal phase deficiency. The mechanism of BSZYP may be related to reduce the level of ovarian tissue apoptosis in BN rats by regulating MAPKs signaling pathway.

Herb-Induced Liver Injury Related to Reynoutria multiflora (Thunb.) Moldenke: Risk Factors, Molecular and Mechanistic Specifics.

Herbal medicine is widely used in Asia as well as the west. Hepatotoxicity is one of the most severe side effects of herbal medicine which is an increasing concern around the world. Reynoutria multiflora (Thunb.) Moldenke (Polygonum multiflorum Thunb., PM) is the most common herb that can cause herb-induced liver injury (HILI). The recent scientific and technological advancements in clinical and basic research are paving the way for a better understanding of the molecular aspects of PM-related HILI (PM-HILI). This review provides an updated overview of the clinical characteristics, predisposing factors, hepatotoxic components, and molecular mechanisms of PM-HILI. It can also aid in a better understanding of HILI and help in further research on the same.

Application of DNA barcoding and metabarcoding for species identification in salmon products.

Mislabelling is a significant manifestation of food fraud. Traditional Sanger sequencing technology is the gold standard for seafood species identification. However, this method is not suitable for analysing processed samples that may contain more than one species. This study tested the feasibility of next-generation sequencing in identifying mixed salmon products. Salmon samples containing up to eight species were amplified using 16S rRNA mini-barcode primers, and sequenced on an Illumina HiSeq2500 platform. All species were accurately identified, and mixtures as low as 1% (w/w) could be detected. Furthermore, this study conducted a market survey of 32 products labelled as salmon. For pure and mixed fish products, Sanger and next-generation sequencing techniques were respectively used for species identification, and for NGS results, we also used real-time PCR method to cross-validate the mixed products to further verify the accuracy of the DNA metabarcoding technology established in this study. DNA barcoding and metabarcoding of commercial salmon food products revealed the presence of mislabelling in 16 of 32 (50%) samples. The developed DNA barcoding and metabarcoding methods are useful for the identification of salmon species in food and can be used for quality control of various types of salmon products.

Infection deteriorating hepatitis B virus related acute-on-chronic liver failure: a retrospective cohort study.

BACKGROUND: Infection is common in acute-on-chronic liver failure (ACLF), which may worsen the clinical condition and prognosis. However, the characteristics of infection and its influence on prognosis in hepatitis B virus related ACLF (HBV-ACLF) as defined by the European Association for the Study of the Liver (EASL) have not been clarified. We aimed to investigate the characteristics of infection and its influence on mortality in patients with HBV-ACLF defined by EASL in China. METHODS: We performed a retrospective cohort study in patients with HBV-ACLF defined by EASL in a single center from January 2015 to December 2017. These patients were divided into two groups with and without infection. The incidence, sites of infection, isolated strains, and risk factors associated with mortality were evaluated. RESULTS: A total of 289 patients were included, among them 185 (64.0%) were diagnosed with an infection. The most common type of infection was pneumonia (55.7%), followed by spontaneous bacterial peritonitis (47.6%) and others. The gram-negative bacteria were the most frequent (58.3%). Patients with one, two, and three or more infection sites had a gradually increasing incidence of sepsis (P < 0.01), septic shock (P < 0.001), and ACLF-3 (P < 0.05). Also, patients with infection isolated one, two, and three or more strains showed a growing incidence of sepsis (P < 0.01) and septic shock (P < 0.001). Patients with infection showed a significantly higher 28-day mortality than those without (P < 0.01), especially in patients with ACLF-3. Infection was identified as an independent risk factor for 28-day mortality in all HBV-ACLF patients. Pneumonia and sepsis were identified as independent predictors of 28-day mortality for patients with infection. CONCLUSIONS: Infection is associated with severe clinical course and high mortality in HBV-ACLF defined by EASL. The increased number of infection sites or isolated strains was associated with the occurrence of sepsis and septic shock. Pneumonia and sepsis were independent predictors for mortality in HBV-ACLF patients with infection.