ZNT1 and Zn 2+ control TLR4 and PD-L1 endocytosis in macrophages to improve chemotherapy efficacy against liver tumor.

BACKGROUND AND AIMS: HCC is closely associated with inflammation and immune modulation, and combined chemotherapy with other strategies is under extensive investigation to achieve better efficacy. HCC is accompanied by zinc (Zn) deficiency. This study aims to understand how Zn could affect macrophage function and its application for HCC therapy. APPROACH AND RESULTS: Zn 2+ and the Zn transporter 1 (ZNT1, solute carrier family 30 member 1) were markedly reduced in intrahepatic macrophages from patients with HCC and from mouse liver tumors. Lower ZNT1 expression was associated with higher IL-6 production and shorter survival time in patients with HCC. Critically, ZNT1 regulated endosomal Zn 2+ levels for endocytosis of toll-like receptor 4 and programmed cell death ligand 1, thereby decreasing macrophage-induced inflammation and immunosuppression to protect from liver tumors. Myeloid-specific deletion of ZNT1 in mice increased chronic inflammation, liver fibrosis, tumor numbers, and size. Notably, Zn supplementation could reduce inflammation and surface programmed cell death ligand 1 expression in macrophages with the increased CD8 + T cell cytotoxicity, which synergized the antitumor efficacy of Sorafenib/Lenvatinib. CONCLUSIONS: Our study proposes a new concept that ZNT1 and Zn regulate endosome endocytosis to maintain surface receptors, and Zn supplements might be synergized with chemotherapy to treat inflammation-associated tumors, especially those containing programmed cell death ligand 1 + myeloid cells.

Integrated brain and plasma dual-channel metabolomics to explore the treatment effects of Alpinia oxyphyllaFructus on Alzheimer's disease.

Alpinia oxyphylla Fructus, called Yizhi in Chinese, is the dried fruit of Alpinia oxyphylla Miquel. It has been used in traditional Chinese medicine to treat dementia and memory defects of Alzheimer's disease for many years. However, the underlying mechanism is still unclear. In this study, we used a rat Alzheimer's disease model on intrahippocampal injection of aggregated Aß1-42 to study the effects of Alpinia oxyphylla Fructus. A brain and plasma dual-channel metabolomics approach combined with multivariate statistical analysis was further performed to determine the effects of Alpinia oxyphylla Fructus on Alzheimer's disease animals. As a result, in the Morris water maze test, Alpinia oxyphylla Fructus had a clear ability to ameliorate the impaired learning and memory of Alzheimer's disease rats. 11 differential biomarkers were detected in AD rats' brains. The compounds mainly included amino acids and phospholipids; after Alpinia oxyphylla Fructus administration, 9 regulated biomarkers were detected compared with the AD model group. In the plasma of AD rats, 29 differential biomarkers, primarily amino acids, phospholipids and fatty acids, were identified; After administration, 23 regulated biomarkers were detected. The metabolic pathways of regulated metabolites suggest that Alpinia oxyphylla Fructus ameliorates memory and learning deficits in AD rats principally by regulating amino acid metabolism, lipids metabolism, and energy metabolism. In conclusion, our results confirm and enhance our current understanding of the therapeutic effects of Alpinia oxyphylla Fructus on Alzheimer's disease. Meanwhile, our work provides new insight into the potential intervention mechanism of Alpinia oxyphylla Fructus for Alzheimer's disease treatment.

Network Pharmacology and Molecular Docking to Unveil the Mechanism of Shudihuang against Amyotrophic Lateral Sclerosis.

BACKGROUND: Shudihuang has been clinically proven to be an effective Chinese medicine compatible with the treatment of amyotrophic lateral sclerosis. However, the underlying mechanism of Shudihuang against amyotrophic lateral sclerosis remains unclear. OBJECTIVES: The present study aims to elucidate the possible mechanism of Shudihuang in treating ALS using network pharmacology and molecular docking. METHODS: The primary active components of Shudihuang and their relevant targets were identified by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and the Swiss Target Prediction database, respectively. The ALS-related targets were obtained from the Disgenet and OMIM databases. The shared targets were derived by the intersection of disease-associated and component-associated targets and then introduced into the Cytoscape software to construct a network of drug-component-target. In addition, protein interaction relationships among the shared targets were analyzed by the STRING and Cytoscape software. Furthermore, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) functional enrichment analysis were conducted by the Metascape platform. The binding activities between the hub targets and the active components were assessed with molecular docking. RESULTS: Stigmasterol and sitosterol were identified as the core components of Shudihuang, and the hub targets of ALS are PTGS2, PPARG, ESR1, IGF-1R, and MAPK3, with the highest degrees in the PPI network. The finding that stigmasterol and sitosterol had a good affinity with PTGS2, PPARG, ESR1, IGF-1R, and MAPK3 also supported this. Finally, it was revealed that Shudihuang treatment of ALS predominantly involves estrogen- related pathways such as nuclear receptor activity and steroid binding. CONCLUSION: In summary, this study suggested that the main active components of Shudihuang (stigmasterol and sitosterol) may exert a critical effect in ALS treatment by binding to hub targets (PTGS2, PPARG, ESR1, IGF-1R, and MAPK3) and then modulating estrogen receptor-related pathways to attenuate glutamate excitotoxicity, inhibit oxidative stress and antagonize inflammation.

The Effects of Foliar Supplementation of Silicon on Physiological and Biochemical Responses of Winter Wheat to Drought Stress during Different Growth Stages.

Drought is one of the major environmental stresses, resulting in serious yield reductions in wheat production. Silicon (Si) has been considered beneficial to enhancing wheat resistance to drought stress. However, few studies have explored the mediated effects of foliar supplementation of Si on drought stress imposed at different wheat growth stages. Therefore, a field experiment was carried out to investigate the effects of Si supplementation on the physiological and biochemical responses of wheat to drought stress imposed at the jointing (D-jointing), anthesis (D-anthesis) and filling (D-filling) stages. Our results showed that a moderate water deficit markedly decreased the dry matter accumulation, leaf relative water content (LRWC), photosynthetic rate (Pn), stomatal conductance (Sc), transpiration rate (Tr) and antioxidant activity [peroxidase (POD), superoxide dismutase (SOD) and catalase (CAT)]. On the contrary, it remarkably increased the content of osmolytes (proline, soluble sugar, soluble protein) and lipid peroxidation. The grain yields of D-jointing, D-anthesis and D-filling treatments were 9.59%, 13.9% and 18.9% lower, respectively, compared to the control treatment (CK). However, foliar supplementation of Si at the anthesis and filling stages significantly improved plant growth under drought stress due to the increased Si content. Consequently, the improvement in antioxidant activity and soluble sugar, and the reduction in the content of ROS, increased the LRWC, chlorophyll content, Pn, Sc and Tr, and ultimately boosted wheat yield by 5.71% and 8.9%, respectively, in comparison with the non-Si-treated plants subjected to water stress at the anthesis and filling stages. However, the mitigating effect of Si application was not significant at the jointing stage. It was concluded that foliar supplementation of Si, especially at the reproductive stage, was effective in alleviating drought-induced yield reduction.

Preparation of robust, water-resistant, antibacterial, and antioxidant chitosan-based films by incorporation of cinnamaldehyde-tannin acid-zinc acetate nanoparticles.

Chitosan (CS) films have poor mechanical property, low water-resistance and limited antimicrobial activity, which hinder their application in food preservation industry. Cinnamaldehyde-tannic acid-zinc acetate nanoparticles (CTZA NPs) assembled from edible medicinal plant extracts were successfully incorporated into CS films to solve these issues. The tensile strength and water contact angle of the composite films increased about 5.25-fold and 17.55°. The addition of CTZA NPs reduced the water sensitivity of CS films, which could undergo appreciable stretching in water without breaking. Furthermore, CTZA NPs significantly enhanced the UV adsorption, antibacterial, and antioxidant properties of the films, while reduced their water vapor permeability. Moreover, it was possible to print inks onto the films because the presence of the hydrophobic CTZA NPs facilitated the deposition of carbon powder onto their surfaces. The films with great antibacterial and antioxidant activities can be applied for food packaging application.

ROS mediated pyroptosis-M1 polarization crosstalk participates in inflammation of chicken liver induced by bisphenol A and selenium deficiency.

The earth's natural environmental factors and man-made industrial pollution often lead to the co-occurrence of environmental pathogenic factors and malnutrition. Bisphenol A (BPA) is a serious environmental endocrine disruptor, and its exposure can cause liver tissue damage. Selenium (Se) deficiency is a worldwide problem that afflicts thousands of people, and Se deficiency can cause M1/M2 imbalance. In addition, the crosstalk between hepatocyte and immune cell is closely related to the occurrence of hepatitis. Therefore, this study found for the first time that the combined exposure of BPA and Se deficiency caused liver pyroptosis and M1 polarization through ROS, and the crosstalk between pyroptosis and M1 polarization aggravated liver inflammation in chicken. In this study, the BPA or/and Se deficiency chicken liver, single and co-culture model of LMH and HD11 cells were established. The results displayed that BPA or Se deficiency induced liver inflammation accompanied by pyroptosis and M1 polarization through oxidative stress, and increased expressions of chemokines (CCL4, CCL17, CCL19, and MIF) and inflammatory factors (IL-1ß and TNF-α). The vitro experiments further verified the above changes and showed that LMH pyroptosis promoted M1 polarization of HD11 cells, and vice versa. NAC counteracted pyroptosis and M1 polarization caused by BPA and low-Se, reducing the release of inflammatory factors. In brief, BPA and Se deficiency treatment can exacerbate liver inflammation by increasing oxidative stress to induce pyroptosis and M1 polarization.

Electroacupuncture relieves visceral hypersensitivity through modulation of the endogenous cannabinoid system.

BACKGROUND: Electroacupuncture (EA) can effectively relieve visceral hypersensitivity (VH). However, its mechanisms are still unclear. OBJECTIVE: To investigate the impact of EA on VH caused by ileitis, and whether EA relieves VH by modulating the endogenous cannabinoid system (ECS). METHODS: Thirty male native goats were randomly divided into a saline-treated control group (Saline, n = 9) and three 2,4,6-trinitro-benzenesulfonic acid (TNBS)-treated VH model groups that underwent injection of TNBS into the ileal wall to induce VH and remained untreated (TNBS, n = 9) or received six sessions of EA (for 30 min every 3 days) (TNBS + EA, n = 6) or sham acupuncture (TNBS + Sham, n = 6). The visceromotor response (VMR) to colorectal distention (CRD) was measured after each EA treatment. Three goats in the Saline/TNBS groups were euthanized after 7 days for histopathological examination; the remaining 24 (n = 6/group) underwent sampling of the ileal wall, T11 spinal cord and brain nuclei/areas related to visceral regulation and ascending pain modulation system on day 22. Expression of cannabinoid receptor 1 (CB1R), fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) was detected by immunohistochemistry. RESULTS: VMR to CRD was greater in TNBS-treated goats than in saline-treated goats (p < 0.01) from day 7 to 22. After day 7, EA-treated goats showed a decreased (p < 0.05) VMR compared with untreated TNBS-exposed goats. TNBS treatment decreased CB1R and increased FAAH and MAGL expression in the ileum and related nuclei/areas; this was reversed by EA. CONCLUSION: EA ameliorates VH, probably by regulating the ECS in the intestine and nuclei/areas related to visceral regulation and descending pain modulation systems.

ROS/ER stress contributes to trimethyltin chloride-mediated hepatotoxicity; Tea polyphenols alleviate apoptosis and immunosuppression.

Trimethyltin chloride (TMT) is an organotin-based contaminant present in the water environment that poses a great threat to aquatic organisms and humans. The liver is the detoxification organ of the body and TMT exposure accumulates in the liver. Tea polyphenol (TP) is a natural antioxidant extracted from tea leaves and has been widely used as a food and feed additive. To investigate the mechanism of toxicity caused by TMT exposure on grass carp hepatocytes (L8824 cells) and the mitigating effect of TP, we established a hepatocyte model of TMT toxicity and/or TP treatment. L8824 cells were treated with 0.5 µM of TMT and/or 4 µg/mL of TP for 24 h and assayed for relevant indices. The results showed that TMT exposure caused oxidative stress, resulting in increased intracellular ROS content, resulting in intracellular ROS accumulation and increased MDA content, and inhibiting the activities of T-AOC, SOD, CAT, and GSH. Meanwhile, TMT exposure activated the endoplasmic reticulum apoptotic signaling pathway, resulting in abnormal expression of GRP78, ATF-6, IRE1, PERK, Caspase-3 and Caspase-12. In addition, TMT exposure also led to up-regulation of cytokines IL-1ß, IL-6, TNF-α, and decreased expression of IL-2, IFN-γ, and antimicrobial peptides Hepcidin, ß-defensin, and LEAP2. However, the addition of TP could mitigate the above changes. In conclusion, TP can alleviate TMT exposure-mediated hepatotoxicity by inhibiting ROS/ER stress in L8824 cells. In addition, this trial enriches the cytotoxicity study of TMT and provides a new theoretical basis for the use of TP as a mitigating agent for TMT.

Auditory event-related potentials, neurocognition, and global functioning in drug naïve first-episode schizophrenia and bipolar disorder.

BACKGROUND: Deficits in event-related potential (ERP) including duration mismatch negativity (MMN) and P3a have been demonstrated widely in chronic schizophrenia (SZ) but inconsistent findings were reported in first-episode patients. Psychotropic medications and diagnosis might contribute to different findings on MMN/P3a ERP in first-episode patients. The present study examined MMN and P3a in first episode drug naïve SZ and bipolar disorder (BPD) patients and explored the relationships among ERPs, neurocognition and global functioning. METHODS: Twenty SZ, 24 BPD and 49 age and sex-matched healthy controls were enrolled in this study. Data of clinical symptoms [Positive and Negative Symptoms Scale (PANSS), Young Manic Rating Scale (YMRS), Hamilton Depression Rating Scale (HAMD)], neurocognition [Wechsler Adult Intelligence Scale (WAIS), Cattell's Culture Fair Intelligence Test (CCFT), Delay Matching to Sample (DMS), Rapid Visual Information Processing (RVP)], and functioning [Functioning Assessment Short Test (FAST)] were collected. P3a and MMN were elicited using a passive auditory oddball paradigm. RESULTS: Significant MMN and P3a deficits and impaired neurocognition were found in both SZ and BPD patients. In SZ, MMN was significantly correlated with FAST (r = 0.48) and CCFT (r = -0.31). In BPD, MMN was significantly correlated with DMS (r = -0.54). For P3a, RVP and FAST scores were significant predictors in SZ, whereas RVP, WAIS and FAST were significant predictors in BPD. CONCLUSIONS: The present study found deficits in MMN, P3a, neurocognition in drug naïve SZ and BPD patients. These deficits appeared to link with levels of higher-order cognition and functioning.

Distinct common signatures of gut microbiota associated with damp-heat syndrome in patients with different chronic liver diseases.

Background: Chronic hepatitis B (CHB) and non-alcoholic fatty liver disease (NAFLD) are prevalent in China. According to traditional Chinese medicine (TCM) theory, damp-heat (DH) syndrome is common in chronic liver disease. However, the biological characteristics related to quantitative diagnosis remain to be determined. This study aimed to identify the consistent alterations in the gut microbiota associated with DH syndrome in patients with CHB or NAFLD. Methods: A total of 405 individuals were recruited, of which 146 were participants who met the consistent TCM diagnosis by three senior TCM physicians and were typical syndromes. All participants were required to provide fresh stool and serum samples. The gut microbiota was assessed by fecal 16S rRNA gene sequencing, and the serum metabolite profiles of participants were quantified by an ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) system. DH syndrome-related bacteria taxa were identified based on the 146 individuals with typical syndromes and validated in all 405 volunteers. Results: The results showed that CHB and NAFLD patients with typical TCM DH syndrome had consistently elevated serum total bile acid (TBA) levels. Significant alterations in microbial community were observed according to TCM syndromes identification. A total of 870 microbial operational taxonomic units and 21 serum metabolites showed the same variation trends in both the CHB and NAFLD DH syndrome groups. The functional analysis predicts consistent dysregulation of bile acid metabolism. Five genera (Agathobacter, Dorea, Lachnospiraceae_NC2004_group, Subdoligranulum, and unclassified_c__Clostridia) significantly decreased in abundance in patients with DH syndrome. We utilize these five genera combined with TBA to construct a random forest classifier model to predict TCM diagnosis. The diagnostic receiver-operator characteristic (ROC) areas for DH syndrome were 0.818 and 0.791 in internal tenfold cross-validation and the test set based on all 405 individuals, respectively. Conclusion: There are common signatures of gut microbiota associated with DH syndrome in patients with different chronic liver diseases. Serum TBA combined with DH-related genera provides a good diagnostic potential for DH syndrome in chronic liver disease.

Phytochemical Properties and In Vitro Biological Activities of Phenolic Compounds from Flower of Clitoria ternatea L.

Phenolic compounds from the flower of Clitoria ternatea L. (PCFCTL) were extracted using a high-speed shearing extraction technique and purified by AB-8 macroporous resins, and the phytochemical composition of the purified phenolic compounds from the flower of Clitoria ternatea L. (PPCFCTL) was then analyzed. Subsequently, its bioactivities including antioxidant properties, enzyme inhibitory activities, and antiproliferative activities against several tumor cell lines were evaluated. Results indicated that the contents of total phenolics, flavonoids, flavonols, flavanols, and phenolic acids in PPCFCTL were increased by 3.29, 4.11, 2.74, 2.43, and 2.96-fold, respectively, compared with those before being purified by AB-8 macroporous resins. The results showed PPCFCTL have significant antioxidant ability (measured by reducing power, RP, and ferric reducing antioxidant power method, FRAP) and good DPPH, ABTS+, and superoxide anion radical scavenging activities. They can also significantly inhibit lipase, α-amylase, and α-glucosidase. In addition, morphological changes of HeLa, HepG2, and NCI-H460 tumor cells demonstrated the superior antitumor performance of PPCFCTL. However, the acetylcholinesterase inhibitory activity was relatively weak. These findings suggest that PPCFCTL have important potential as natural antioxidant, antilipidemic, anti-glycemic and antineoplastic agents in health-promoting foods.

Phosphatidylserine, inflammation, and central nervous system diseases.

Phosphatidylserine (PS) is an anionic phospholipid in the eukaryotic membrane and is abundant in the brain. Accumulated studies have revealed that PS is involved in the multiple functions of the brain, such as activation of membrane signaling pathways, neuroinflammation, neurotransmission, and synaptic refinement. Those functions of PS are related to central nervous system (CNS) diseases. In this review, we discuss the metabolism of PS, the anti-inflammation function of PS in the brain; the alterations of PS in different CNS diseases, and the possibility of PS to serve as a therapeutic agent for diseases. Clinical studies have showed that PS has no side effects and is well tolerated. Therefore, PS and PS liposome could be a promising supplementation for these neurodegenerative and neurodevelopmental diseases.

Influence of biocurrent self-generated by indigenous microorganisms on soil quality.

The redox process driven by anaerobic respiration is a link between matter conversion and energy exchange in soil biogeochemistry. Microbial extracellular electron transfer forming biocurrents is a force in element cycling and community living in soil. However, the effect of indigenous microorganisms generating biocurrents on soil quality is unclear. We found that soil biocurrent showed little adverse influence on soil pH, cation exchange capacity, and available nitrogen, phosphorus and potassium and deblocked sequestered organic matter (29%). In addition, the bioelectric field derived from biocurrent obviously forced the migration of mineral elements, which was a supplement to the theory of water-salt transport, providing a new perspective on element transport. Moreover, the soil biocurrent directly regulated the availability of Ca and Fe (increase of 7-fold), indicating that electron transfer plays an important role in weathering and mineralization and thus pedogenesis. From a microbial ecology point of view, the soil bacterial richness and diversity were perfectly restored to their original state when the biocurrent stopped; including bacterial functions; although a temporary enrichment of certain species was observed. The above results provide new insights into the interactions between electron transfer and soil quality and confirm the safety of soil bioelectrochemical technology.

A review of nanostructured delivery systems for the encapsulation, protection, and delivery of silymarin: An emerging nutraceutical.

Silymarin exhibits biological activities that may promote human health and wellbeing, including antioxidant, antimicrobial, anti-inflammatory, and anti-cancer activities. Consequently, it has potential for application as a nutraceutical ingredient in functional foods and supplements. But its application for this purpose is currently limited by its poor water solubility, chemical stability, and bioavailability. The potential of nano-delivery systems to improve the functional performance of silymarin was reviewed in this manuscript. The formation, attributes, and applications of biopolymer-based, lipid-based, surfactant-based, and miscellaneous nanocarriers are discussed. In particular, the impact of the different delivery systems such as biopolymer-based, lipid-based delivery systems on the gastrointestinal fate of silymarin is summarized. The encapsulation in edible nanocarriers can improve the bioavailability of silymarin by enhancing its water-dispersibility, inhibiting its degradation, and increasing its absorption.These nanocarriers may therefore be utilized to incorporate this nutraceutical into functional foods and supplements in a bioavailable form.

Tanshinone IIA Has a Potential Therapeutic Effect on Kawasaki Disease and Suppresses Megakaryocytes in Rabbits With Immune Vasculitis.

Background and Objective: It is urgent to find out an alternative therapy for Kawasaki disease (KD) since around 20% patients are resistant to intravenous immunoglobulin (IVIG) or aspirin. Tanshinone IIA is the active component of the traditional Chinese medicine Danshen (Salvia miltiorrhiza), which has anti-inflammatory and anti-platelet properties; however, whether or not tanshinone IIA has a therapeutic effect on KD remains unclear. Therefore, the present study aimed to examine the effect of tanshinone IIA on KD patients and rabbits with immune vasculitis, and to identify the potential mechanisms with special emphasis on megakaryopoiesis and megakaryocytic apoptosis. Methods: Kawasaki disease patients were recruited and prescribed with tanshinone IIA in the absence or presence of aspirin and IVIG, and the inflammatory responses and platelet functions were determined. Megakaryocytes (MKs) isolated from rabbits with immune vasculitis and human megakaryocytic CHRF-288-11 cells were treated with tanshinone IIA to examine the colony forming unit (CFU) and apoptosis, respectively. Microarray assay was conducted to identify potential targets of tanshinone IIA-induced apoptosis. Results: Tanshinone IIA reduced the serum levels of C-reactive protein (CRP), interleukin (IL)-1ß, IL-6, and P-selectin in KD patients; such inhibitory effect was more significant compared to aspirin and IVIG. It also dose-dependently lowered the levels of tumor necrosis factor (TNF)-α and IL-8 in peripheral blood mononuclear cells isolated from KD patients. In rabbits with immune vasculitis, tanshinone IIA significantly reduced the serum levels of proinflammatory cytokines and platelet functions. In addition, tanshinone IIA significantly decreased the number of bone marrow MKs and inhibited the Colony Forming Unit-Megakaryocyte (CFU-MK) formation. In human megakaryocytic CHRF-288-11 cells, tanshinone IIA induced caspase-dependent apoptosis, probably through up-regulating TNF receptor superfamily member 9 (TNFRSF9) and the receptor (TNFRSF)-interacting serine/threonine-protein kinase 1 (RIPK1), which may contribute to its anti-platelet and anti-inflammatory properties. Conclusion: Tanshinone IIA exerts better anti-inflammatory and anti-platelet effects in treating KD patients than aspirin and IVIG. It attenuates immune vasculitis likely by inhibiting IL-mediated megakaryopoiesis and inducing TNFRSF9/RIPK1/caspase-dependent megakaryocytic apoptosis. The findings therefore suggest that tanshinone IIA may be a promising alternative therapy for the treatment of KD.

Tea polyphenols alleviates acetochlor-induced apoptosis and necroptosis via ROS/MAPK/NF-κB signaling in Ctenopharyngodon idellus kidney cells.

Overuse of acetochlor pollutes soil and rivers, causing threats to the ecosystem. Studies found that acetochlor exposure could damage multiple organs and tissues in fish and mammal. Tea polyphenols (TP), a natural antioxidant that extracted from tea, has been widely used in food and feed additions. However, the mechanism by which acetochlor causes tissue damage is unclear, and its mitigating agent has yet to be developed. Therefore, we established acetochlor exposure and TP mitigation models by treating Ctenopharyngodon idellus kidney (CIK) cells with 20 µM acetochlor and/or 2.5 µg/mL TP for 24 h, and detected the programmed cell death and its related pathways. The results showed that acetochlor exposure modified antioxidant enzyme activities, induced oxidative stress, resulted in the decline of MMP and ATP levels, enhanced glycolysis and lactate accumulation, and triggered apoptosis and necroptosis in CIK cells. However, TP could inhibit CYP450s expression, activate Nrf2 pathway, enhance antioxidant capacity, further effectively alleviate acetochlor-induced CIK cell death. Overall, the present study proved that acetochlor exposure triggered mitochondrial damage and lactate accumulation-mediated apoptosis and necroptosis through CYP450s/ROS/MAPK/NF-κB pathway. Furthermore, TP could alleviate effectively cell death through relieving oxidative stress and lightening Warburg-like effect.

Schisandrol A, the main active ingredient of Schisandrae Chinensis Fructus, inhibits pulmonary fibrosis through suppression of the TGF-ß signaling pathway as revealed by UPLC-Q-TOF/MS, network pharmacology and experimental verification.

ETHNOPHARMACOLOGICAL RELEVANCE: Schisandra chinensis decoction derived from the book of Waitai Miyao (Tao Wang, Tang dynasty) is often used in the treatment of idiopathic pulmonary fibrosis (IPF), which is included in the Grand Ceremony of Chinese formulae (Huairen Peng, 1994). Schisandrae Chinensis Fructus (Sch) is one of the most important herbs in this formula. According to the "Shennong's Herbal Classicherbal" of the Han Dynasty, Sch has sour taste, warm nature, which has the effect of tonifying qi and curing cough. In addition, according to the "Compendium of Materia Medica" of the Ming Dynasty, Sch is used to treat cough and asthma, which has the effect of moistening the lung and tonifying the kidney. However, the active ingredients of Sch absorption into the plasma and its pharmacological mechanism of treatment for IPF still remained unclear. AIM OF THE STUDY: Our research aimed at identifying the absorbed active ingredients and metabolized of Sch in rat plasma and the mechanism of anti-IPF based on serum pharmacochemistry. MATERIALS AND METHODS: First, the rats were divided into control group and Sch group. Sch sample was orally administrated to the rats for seven days. The blood samples were drawn into an Eppendorf tube after the last dosing. The ultrahigh performance liquid chromatography coupled with quadrupole-time of flight mass spectrometry (UPLC-Q-TOF/MS) was applied to identify the absorption components and metabolites of Sch in rat plasma. Second, the network pharmacology combined with molecular docking analysis was further investigated to illuminate its potential mechanism of treatment for IPF by the biological targets regulating related pathways. Finally, the mechanism of action was verified by experimental in vitro and in vivo. RESULTS: A total of 78 compounds, consist of 13 prototype lignans and 65 metabolites (including isomers) were identified. Network pharmacology study and molecular docking analysis indicated that schisandrol A (L1) play an anti-fibrosis role by regulating the TGF-ß signaling pathway. Experimental in vitro and in vivo verified that the schisandrol A could inhibiting pulmonary fibrosis through TGF-ß signaling pathway. The effect and mechanism of schisandrol A inhibiting pulmonary fibrosis were reported for the first time. CONCLUSIONS: In this study, the absorption active ingredients of Sch in rat plasma were combined with the network pharmacology investigation and experimental in vitro and in vivo to elucidate its biological mechanism of treatment for IPF. The results provided a theoretical support for understanding the bioactive compounds and the pharmacological mechanism of Sch.

Insight into the effect of fatty acid composition on the texture of French fries.

BACKGROUND: Several researchers have reported that the texture of fries is affected by the fatty acid composition of oil, although the mechanism of this effect is not clear. In this regard, fries were fried in refined rapeseed oil and fully hydrogenated rapeseed oil with diverse proportions (0%, 20%, 40%, 60%, 80% and 100%) and were analyzed based on the content of moisture and oil, texture, thermal properties, crystalline properties and microstructure. RESULTS: The outcomes presented that fries fried in fully hydrogenated oil had less oil absorption and moisture loss than those fried in refined oil. The results from the texture analyzer, differential scanning calorimetry and X-ray diffraction showed that hardness, enthalpy and relative crystallinity increased with an increase in the proportion of fully hydrogenated oil. However, the peaks of starch-lipid complexes were hardly observed during frying. Furthermore, scanning electron microscopy results displayed that some physically trapped fat was observed in fries fried in mixed hydrogenated oil. Stereomicroscope images showed that the crust thickness of the fries increased slightly with an increase in the proportion of fully hydrogenated oil. CONCLUSION: Overall, the upsurge in crust thickness and oil crystals was responsible for an increase in the hardness of the fries. This indicated that the texture of fries can be manipulated by altering the fatty acid composition of the oil. © 2021 Society of Chemical Industry.

Alterations in CRY2 and PER3 gene expression associated with thalamic-limbic community structural abnormalities in patients with bipolar depression or unipolar depression.

Objectives The current study aimed to identify shared and distinct brain structure abnormalities and their relationships with the expression of circadian genes in patients with bipolar or unipolar depression. Method A total of 93 subjects participated in this study, including 32 patients with bipolar depression (BDP), 26 patients with unipolar depression (UDP) and 35 age- and sex-matched healthy controls. Brain structural magnetic resonance imaging scans were obtained, and optimized voxel-based morphometry was used to explore group differences in regional gray matter volume (GMV). The mRNA expression levels of circadian genes in peripheral blood were measured using reverse transcription quantitative real-time polymerase chain reaction. Results Our results showed that the GMV in brain regions in the thalamus-limbic pathways had significantly increased in the BDP patients compared to controls, while the increased GMV in UDP patients compared to controls was limited to the thalamus. The mRNA expression levels of circadian-related genes decreased significantly in patients with BDP, but increased in patients with UDP, compared to controls. In addition, the GMV in the right thalamus in the patients with UDP was positively associated with mRNA levels of CRY2, while the GMV in the right hippocampus in the patients with BDP was negatively associated with mRNA levels of PER3. Conclusion Our study suggested that patients with BDP or MDD shared GMV abnormalities in the right thalamus. The PER3 and CRY2 genes might be critical to right hippocampal dysfunction in BDP and right thalamic dysfunction in UDP, respectively. The result provided potentially important molecular targets for the treatment of mood disorders.

Selenium Deficiency Induces Apoptosis and Necroptosis Through ROS/MAPK Signal in Human Uterine Smooth Muscle Cells.

Selenium (Se) is one of the essential trace elements; its deficiency induces ROS production and cell death in cardiomyocytes, skeletal muscle cells, and vascular smooth muscle cells, but it is still not clear the impact of Se deficiency on human uterine smooth muscle cells (HUSMCs). To investigate the effect of low Se on the mRNA expression of selenoproteins, the mRNA and protein expression of apoptosis and necroptosis of HUSMCs and their mechanism, Se deficient HUSMCs mode was established through culturing with 1% FBS containing 0 ng/mL, 0.7 ng/mL, and 7 ng/mL Se, and 10% FBS was as the control group. Then, the apoptosis and necroptosis rates, intracellular ROS content and the expression levels of selenoproteins, apoptosis, necroptosis, MAPK pathway-related genes were examined under different Se concentrations. The results showed that Se deficiency led to the augment of cell apoptosis and necroptosis in HUSMCs (p < 0.05), downregulated (p < 0.05) 19 selenoproteins (GPX1, GPX2, GPX3, GPX4, GPX6, Dio3, Txnrd2, Txnrd3, SEPHS2, SEL15, SELH, SELI, SELM, SELN, SELO, SELS, SELT, SELV, and SELW), while Dio2, SELK, Txnrd1, and MSRB1 were not affected by Se deficiency (p ≥ 0.05). In addition, Se deficiency led to increased intracellular ROS content, p-P38 and p-JNK gene expression levels (p < 0.05), the mitochondrial apoptosis pathway Bax, Casp9 and Cle-Casp3 protein expression levels (p < 0.05), and decreased Bcl2 protein expression level (p < 0.05), simultaneously, increased necroptosis marker genes RIP1, RIP3, and MLKL protein expression levels (p < 0.05) with a dose-dependent pattern. The above results indicate that Se deficiency induces HUSMCs apoptosis and necroptosis through the ROS/MAPK pathway and is closely related to selenoproteins.