Ultrasonic-assisted extraction of grape seed procyanidins, preparation of liposomes, and evaluation of their antioxidant capacity.

The residue remaining after oil extraction from grape seed contain abundant procyanidins. An ultrasonic-assisted enzyme method was performed to achieve a high extraction efficiency of procyanidins when the optimal extraction conditions were 8 U/g of cellulase, ultrasound power of 200 W, ultrasonic temperature of 50 ℃, and ultrasonic reaction time of 40 min. The effects of free procyanidins on both radical scavenging activity and thermal stability at 40, 60, and 80 ℃ of the procyanidins-loaded liposomal systems prepared by the ultrasonic-assisted method were discussed. The presence of procyanidins at concentrations ranging from 0.02 to 0.10 mg/mL was observed to be effective at inhibiting lipid oxidation by 15.15 % to 69.70 % in a linoleic acid model system during reaction for 168 h, as measured using the ferric thiocyanate method. The procyanidins-loaded liposomal systems prepared by the ultrasonic-assisted method were characterized by measuring the mean particle size and encapsulation efficiency. Moreover, the holographic plots showed that the effect-response points of procyanidins combined with α-tocopherol in liposomes were lower than the addition line and 95 % confidence interval limits. At the same time, there were significant differences between the theoretical IC50add value and the experimental IC50mix value. The interaction index (γ) of all combinations was observed to be less than 1. These results indicated that there was a synergistic antioxidant effect between procyanidins combined with α-tocopherol, which will show promising prospects in practical applications. In addition, particle size differentiation and morphology agglomeration were observed at different time points of antioxidant activity determination (0, 48, 96 h).

Composition analysis of Compound Shenhua Tablet, a seven-herb Chinese medicine for IgA nephropathy: evaluation of analyte-capacity of the assays.

Compound Shenhua Tablet, a medicine comprising seven herbs, is employed in treating IgA nephropathy. This study aimed to meticulously analyze its chemical composition. Based on a list of candidate compounds, identified through extensive literature review pertinent to the tablet's herbal components, the composition analysis entailed the systematic identification, characterization, and quantification of the constituents. The analyte-capacity of LC/ESI-MS-based and GC/EI-MS-based assays was evaluated. The identified and characterized constituents were quantified to determine their content levels and were ranked based on the constituents' daily doses. A total of 283 constituents, classified into 12 distinct categories, were identified and characterized in the Compound Shenhua Tablet. These constituents exhibited content levels of 1-10 982 µg·g-1, with daily doses of 0.01-395 µmol·d-1. The predominant constituents, with daily doses of ≥ 10 µmol·d-1, include nine organic acids (citric acid, quinic acid, chlorogenic acid, cryptochlorogenic acid, gallic acid, neochlorogenic acid, isochlorogenic acid C, isochlorogenic acid B, and linoleic acid), five iridoids (specnuezhenide, nuezhenoside G13, nuezhenidic acid, secoxyloganin, and secologanoside), two monoterpene glycosides (paeoniflorin and albiflorin), a sesquiterpenoid (curzerenone), a triterpenoid (oleanolic acid), and a phenylethanoid (salidroside). Additionally, there were 83, 126, and 55 constituents detected in the medicine with daily doses of 1-10, 0.1-1, and 0.01-0.1 µmol·d-1, respectively. The combination of the LC/ESI-MS-based and GC/EI-MS-based assays demonstrated a complementary relationship in their analyte-capacity for detecting the constituents present in the medicine. This comprehensive composition analysis establishes a solid foundation for further pharmacological research on Compound Shenhua Tablet and facilitates the quality evaluation of this complex herbal medicine.

The genetic architecture of the human hypothalamus and its involvement in neuropsychiatric behaviours and disorders.

Despite its crucial role in the regulation of vital metabolic and neurological functions, the genetic architecture of the hypothalamus remains unknown. Here we conducted multivariate genome-wide association studies (GWAS) using hypothalamic imaging data from 32,956 individuals to uncover the genetic underpinnings of the hypothalamus and its involvement in neuropsychiatric traits. There were 23 significant loci associated with the whole hypothalamus and its subunits, with functional enrichment for genes involved in intracellular trafficking systems and metabolic processes of steroid-related compounds. The hypothalamus exhibited substantial genetic associations with limbic system structures and neuropsychiatric traits including chronotype, risky behaviour, cognition, satiety and sympathetic-parasympathetic activity. The strongest signal in the primary GWAS, the ADAMTS8 locus, was replicated in three independent datasets (N = 1,685-4,321) and was strengthened after meta-analysis. Exome-wide association analyses added evidence to the association for ADAMTS8, and Mendelian randomization showed lower ADAMTS8 expression with larger hypothalamic volumes. The current study advances our understanding of complex structure-function relationships of the hypothalamus and provides insights into the molecular mechanisms that underlie hypothalamic formation.

Effect of dynamic high-pressure microfluidization treatment on soybean protein isolate-rutin non-covalent complexes.

In this investigation, soybean protein isolate-rutin (SPI-RT) complexes were treated using dynamic high-pressure microfluidization (DHPM). The effects of this process on the physicochemical and thermodynamic properties of SPI were investigated at different pressures. Fourier-transform infrared spectroscopy and fluorescence spectroscopy provided evidence that the SPI structure had been altered. The binding of SPI to RT resulted in a decrease in the percentage of α-helices and random curls as well as an increase in the percentage of ß-sheets. In particular, the α-helix content decreased from 29.84 % to 26.46 %, the random curl content decreased from 17.45 % to 15.57 %, and the ß-sheet content increased from 25.37 % to 26.53 %. Moreover, fluorescence intensity decreased, and the emission peak of the complex was red-shifted by 6 nm, exposing the internal groups. Based on fluorescence quenching analysis, optimal SPI-RT complexation was achieved after 120-MPa DHPM treatment, and molecular docking analysis verified the interaction between SPI and RT. The minimum particle size, maximum absolute potential, and total phenolic content of the complexes were 78.06 nm, 21.4 mV and 74.35 nmol/mg protein, respectively. Furthermore, laser confocal microscopy revealed that the complex particles had the best microstructure. Non-covalent interactions between the two were confirmed using sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Moreover, the hydrophobicity of the complex particle's surface increased to 16,045 after 120-MPa DHPM treatment. The results of this study suggest that DHPM strongly promotes the improvement of the physicochemical properties of SPI, and provide a theoretical groundwork for further research.

Lysidrhodosides A-I, acylphloroglucinol glucosides with anti-inflammatory activities from the leaves of Lysidice rhodostegia.

Lysidrhodosides A-I (1-9), nine acylphloroglucinol glucoside derivatives along with three known analogues (10-12) were isolated from the leaves of Lysidice rhodostegia. Their structures and absolute configuration were elucidated by spectroscopic data analysis (NMR, UV, IR, HR-ESI-MS), single-crystal X-ray diffraction, and acid hydrolysis with HPLC analysis. Notably, compounds 7-9 represent the first examples of 3-methylbutyryl phloroglucinol glucoside dimers isolated from this plant. Additionally, compounds 1-12 were assessed for their inhibitory effects on nitric oxide (NO) in the LPS-induced BV-2 cells. The results showed that compounds 6 and 12 significantly inhibited the production of the inflammatory mediator NO, with an inhibitory rate of 95.96 and 91.13% at a concentration of 50 µM, respectively.

Buyang Huanwu decoction ameliorates bleomycin-induced pulmonary fibrosis in rats by attenuating the apoptosis of alveolar type II epithelial cells mediated by endoplasmic reticulum stress.

ETHNOPHARMACOLOGICAL RELEVANCE: According to the theory of traditional Chinese medicine, the pathogenesis of idiopathic pulmonary fibrosis (IPF) can be attributed to qi deficiency and blood stasis. Buyang Huanwu decoction (BHD), a representative Chinese herbal prescription for qi deficiency and blood stasis syndrome, is widely used to treat IPF in clinical practice. However, its potential mechanisms against IPF remain unclear. AIMS OF THE STUDY: This study was carried out to explore the therapeutic effects and underlying mechanisms of BHD on bleomycin (BLM)-induced pulmonary fibrosis in rats. MATERIALS AND METHODS: UPLC-MS/MS method was performed to identify the quality of BHD used in this study. Concurrently, a IPF rat model was established by single intratracheal injection of BLM. Pulmonary function test, H&E staining, Masson staining, hydroxyproline assay were conducted to evaluate the therapeutic effects of BHD on BLM-induced pulmonary fibrosis in rats, and the regulatory effect of BHD on endoplasmic reticulum stress (ERS)-mediated alveolar type II epithelial cells (AEC2s) apoptosis in rats was further investigated by TUNEL staining, Western blot, real-time fluorescence quantitative PCR and immunofluorescence co-staining to reveal the potential mechanisms of BHD against IPF. RESULTS: The UPLC-MS/MS analysis showed that the BHD we used complied with the relevant quality control standards. The data from animal experiments confirmed that BHD administration ameliorated BLM-induced pulmonary function decline, lung fibrotic pathological changes and collagen deposition in rats. Further mechanism study revealed that BHD increased the Bcl-2 protein expression, decreased the Bax protein expression and inhibited the cleavage of CASP3 via suppressing the activation of PERK-ATF4-CHOP pathway under continuous ERS, thereby alleviating BLM-induced AEC2s apoptosis of rats. CONCLUSION: This study demonstrated that BHD ameliorated BLM-induced pulmonary fibrosis in rats by suppressing ERS-mediated AEC2s apoptosis. Our findings can provide some fundamental research basis for the clinical application of BHD in the treatment of IPF.

Hospital care experiences of female relatives caring for patients with post-stroke dysphagia during the COVID-19: a qualitative study in China.

BACKGROUND: Due to the COVID-19 epidemic, Chinese hospitals are forced to impose stringent regulations, which unavoidably affect patients with stroke who need continued rehabilitation and long-term disease treatment. However, there is a lack of qualitative studies in the literature on female relative caregivers of hospitalised patients who had a stroke with dysphagia during the COVID-19 pandemic. OBJECTIVE: In this study, we aimed to explore the experiences of female Chinese caregivers living in the hospital with patients with post-stroke dysphagia during the pandemic. DESIGN: We conducted a qualitative study using semi-structured interviews. SETTINGS: From May 2022 to July 2022, patients were selected from the Acupuncture and Moxibustion Ward and the Encephalopathy Ward of Shenzhen Chinese Medicine Hospital, which receives patients from across the country. PARTICIPANTS: 10 Chinese women who were caregivers of patients with post-stroke dysphagia were finally interviewed. METHODS: Interviews were transcribed verbatim and analysed using Colaizzi's approach. RESULTS: The primary theme was determined to be 'kidnapped' lives. Other sub-themes evolved to depict the lives of female relative caregivers, including inevitable tasks and challenges, precise care, a special dietary pattern, solitary and forgotten, and an elusive future. Due to the trivial nature of caring for patients who had a stroke with dysphagia, the caregivers' lives were tightly organised and entirely dictated by the patient's caring needs. Consequently, the caregivers felt that their lives had been kidnapped. CONCLUSIONS: It is imperative that healthcare workers identify and understand the living conditions of female relative caregivers in the hospital, so as to determine their difficulties and needs. Finally, caregivers deserve adequate and effective support, such as technical support, financial support and nutritional guidance.

Sodium hexametaphosphate-treated halloysite based solid-phase extraction of biguanides from dietary supplements.

Raw halloysite was purified by using sodium hexametaphosphate and utilized as the solid-phase extraction sorbent for the determination of biguanides from dietary supplements. The purified halloysite was characterized using scanning electron microscopy, Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, and X-ray diffraction. The purified halloysite interacted with biguanides through hydrophilic interaction and ion exchange on account of its abundant hydroxyl groups and negative charge. Compared with traditional extraction methods based on hydrophobic interaction and/or ion exchange, the purified halloysite adsorbed more biguanides due to hydrophilicity and ion exchange, with a sample loading volume of up to 100 mL at least. Excellent reproducibility of halloysite purification was achieved, with within-batch (n = 3) and batch-to-batch (n = 3) relative standard deviations in the ranges of 1.5-4.2% and 5.6-8.8%, respectively. Coupled with reversed-phase liquid chromatography-tandem mass spectrometry, a low limit of detection of 0.3 µg kg-1 was obtained. The intra- and inter-day mean recoveries of the biguanides spiked at three levels in dietary supplements were within the ranges of 88.5-107.2% and 86.4-102.0%, respectively. The intra- and inter-day precisions were within the ranges of 1.5-6.4% and 5.4-9.9%, respectively. These results indicated that the developed method is efficient for the determination of trace biguanides in dietary supplements.

A screening strategy for bioactive components of Bu-Zhong-Yi-Qi-Tang regulating spleen-qi deficiency based on "endobiotics-targets-xenobiotics" association network.

ETHNOPHARMACOLOGICAL RELEVANCE: Bu-Zhong-Yi-Qi-Tang is a famous traditional Chinese medicine formula that has been prevalent in China for over 700 years to treat spleen-qi deficiency related diseases, such as gastrointestinal and respiratory disorders. However, the bioactive components responsible for regulating spleen-qi deficiency remain unclear and have puzzled many researchers. AIM OF THE STUDY: The current study focuses on efficacy evaluation of regulating spleen-qi deficiency and screening the bioactive components of Bu-Zhong-Yi-Qi-Tang. MATERIALS AND METHODS: The effects of Bu-Zhong-Yi-Qi-Tang were evaluated through blood routine examination, immune organ index, and biochemical analysis. Metabolomics was utilized to analyze the potential endogenous biomarkers (endobiotics) in the plasma, and the prototypes (xenobiotics) of Bu-Zhong-Yi-Qi-Tang in the bio-samples were characterized using ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry. Then, these endobiotics were used as "bait" to predict targets based on network pharmacology and to screen potential bioactive components from the absorbed prototypes in the plasma by constructing an "endobiotics-targets-xenobiotics" association network. Further, the anti-inflammatory activities of representative compounds (calycosin and nobiletin) were validated through poly(I:C)-induced pulmonary inflammation mice model. RESULTS: Bu-Zhong-Yi-Qi-Tang exhibited immunomodulatory and anti-inflammatory activities in spleen-qi deficiency rat, as supported by the observation of increased levels of D-xylose and gastrin in serum, an increase in the thymus index and number of lymphocytes in blood, as well as a reduction in the level of IL-6 in bronchoalveolar lavage fluid. Furthermore, plasma metabolomic analysis revealed a total of 36 Bu-Zhong-Yi-Qi-Tang related endobiotics, which were mainly enriched in primary bile acids biosynthesis, the metabolism of linoleic acid, and the metabolism of phenylalanine pathways. Meanwhile, 95 xenobiotics were characterized in plasma, urine, small intestinal contents, and tissues of spleen-qi deficiency rat after Bu-Zhong-Yi-Qi-Tang treatment. Using an integrated association network, six potential bioactive components of Bu-Zhong-Yi-Qi-Tang were screened. Among them, calycosin was found to significantly reduce the levels of IL-6 and TNF-α in the bronchoalveolar lavage fluid, increase the number of lymphocytes, while nobiletin dramatically decreased the levels of CXCL10, TNF-α, GM-CSF, and IL-6. CONCLUSION: Our study proposed an available strategy for screening bioactive components of BYZQT regulating spleen-qi deficiency based on "endobiotics-targets-xenobiotics" association network.

Screening of Potential α-Glucosidase Inhibitors from the Roots and Rhizomes of Panax Ginseng by Affinity Ultrafiltration Screening Coupled with UPLC-ESI-Orbitrap-MS Method.

Panax ginseng was a traditional Chinese medicine with various pharmacological activities and one of its important activities was hypoglycemic activity; therefore, panax ginseng has been used in China as an adjuvant in the treatment of diabetes mellitus. In vivo and in vitro tests have revealed that ginsenosides, which are derived from the roots and rhizomes of panax ginseng have anti-diabetic effects and produce different hypoglycemic mechanisms by acting on some specific molecular targets, such as SGLT1, GLP-1, GLUTs, AMPK, and FOXO1. α-Glucosidase is another important hypoglycemic molecular target, and its inhibitors can inhibit the activity of α-Glucosidase so as to delay the absorption of dietary carbohydrates and finally reduce postprandial blood sugar. However, whether ginsenosides have the hypoglycemic mechanism of inhibiting α-Glucosidase activity, and which ginsenosides exactly attribute to the inhibitory effect as well as the inhibition degree are not clear, which needs to be addressed and systematically studied. To solve this problem, affinity ultrafiltration screening coupled with UPLC-ESI-Orbitrap-MS technology was used to systematically select α-Glucosidase inhibitors from panax ginseng. The ligands were selected through our established effective data process workflow based on systematically analyzing all compounds in the sample and control specimens. As a result, a total of 24 α-Glucosidase inhibitors were selected from panax ginseng, and it was the first time that ginsenosides were systematically studied for the inhibition of α-Glucosidase. Meanwhile, our study revealed that inhibiting α-Glucosidase activity probably was another important mechanism for ginsenosides treating diabetes mellitus. In addition, our established data process workflow can be used to select the active ligands from other natural products using affinity ultrafiltration screening.

The Efficacy of Scouting Technology in Pedicle Screw Placement in the Patients With Degenerative Scoliosis.

Objective: To investigate the curative effect of ball tip technology in pedicle screw placement in the patients with degenerative scoliosis (DS), as compared to traditional freehand technique. Methods: A total of 90 patients with degenerative scoliosis who were admitted to Affiliated Hospital of Hebei Engineering University from October 2019 to October 2021 were selected as the objects in this prospective study. They were randomly divided into an experimental group and a control group with 45 cases in each. The clinical indications, the accuracy of pedicle screw placement, the occurrence of surgical complications, the measurement of spinal and pelvic parameters, the recovery of spinal function and pain degree were recorded and compared within the two groups. Results: After treatment, the operation time, intraoperative blood loss, total number of screws, and time of screwing were compared between the two groups, and the difference was not significant (P > .05). However, the bedding time and the hospital stay were shorter in the experimental group than the control group with difference (P < .05). There was no significant difference in clinical standards and poor implantation in the Gertzbein-Robbins A-E classification between the two groups (P > .05). While the number of perfect placement of screws in the experimental group was higher (P < .05). Before treatment, the Cobbs angle and pelvic incidence-lumbar lordosis (PI-LL) levels of the two groups were comparable (P > .05); after treatment, the Cobbs angle and PI-LL levels of the two groups were lower than those before treatment, and the difference was significant (P < .05). There was no significant difference in Cobbs angle and PI-LL levels between groups (P > .05). Before treatment, the JOA and DOI scores of the two groups were comparable (P > .05); after treatment, the JOA and DOI scores of the two groups were improved (P < .05); the improvement of JOA and DOI scores of the experimental group were better than those in the control group (P < .05). Before treatment, there was no significant difference in the pain degree between the two groups (P > .05); after treatment, the pain of the two groups was improved compared with that before treatment, and the pain degree of the experimental group was lower than that of the control group (P < .05). The incidence of postoperative complications in the experimental group was lower than that in the control group, but there was no significant difference in the total incidence of postoperative complications between the two groups (P > .05). Conclusion: The scouting technique-assisted screw placement can effectively improve the spinal function of patients with degenerative scoliosis, with obvious curative effect and high safety.

Comprehensive Identification of Ginsenosides in the Roots and Rhizomes of Panax ginseng Based on Their Molecular Features-Oriented Precursor Ions Selection and Targeted MS/MS Analysis.

Panax ginseng is widely used in Asian countries and its active constituents-ginsenosides-need to be systematically studied. However, only a small part of ginsenosides have been characterized in the roots and rhizomes of panax ginseng (RRPG) up to date, mainly because of a lack of the fragmentation ions of many more ginsenosides. In order to comprehensively identify ginsenosides in RRPG, molecular features of ginsenosides orienting precursor ions selection and targeted tandem mass spectrometry (MS/MS) analysis strategy were proposed in our study, in which the precursor ions were selected according to the molecular features of ginsenosides irrespective of their peak abundances, and targeted MS/MS analysis was then performed to obtain their fragmentation ions for substance characterization. Using this strategy, a total of 620 ginsenosides were successfully characterized in RRPG, including 309 protopanaxadiol-type ginsenosides, 258 protopanaxatriol-type ginsenosides and 53 oleanane-type ginsenosides. It is worth noting that, except for the known aglycones mass-to-charge ratio (m/z) 459, 475 and 455, twelve other aglycones, including m/z 509, 507, 493, 491, 489, 487, 477, 473, 461, 457, 443 and 441, were first reported in our experiment and they were probably the derivatizations of the protopanaxatriol and protopanaxadiol. Our study will not only help people to improve the cognition of ginsenosides in RRPG, but will also play a guiding and reference role for the isolation and characterization of potentially new ginsenosides from RRPG.

Intrathecal liproxstatin-1 delivery inhibits ferroptosis and attenuates mechanical and thermal hypersensitivities in rats with complete Freund's adjuvant-induced inflammatory pain.

Previous studies have confirmed the relationship between iron-dependent ferroptosis and a peripheral nerve injury-induced neuropathic pain model. However, the role of ferroptosis in inflammatory pain remains inconclusive. Therefore, we aimed to explore whether ferroptosis in the spinal cord and dorsal root ganglion contributes to complete Freund's adjuvant (CFA)-induced painful behaviors in rats. Our results revealed that various biochemical and morphological changes were associated with ferroptosis in the spinal cord and dorsal root ganglion tissues of CFA rats. These changes included iron overload, enhanced lipid peroxidation, disorders of anti-acyl-coenzyme A synthetase long-chain family member 4 and glutathione peroxidase 4 levels, and abnormal morphological changes in mitochondria. Intrathecal treatment of liproxstatin-1 (a ferroptosis inhibitor) reversed these ferroptosis-related changes and alleviated mechanical and thermal hypersensitivities in CFA rats. Our study demonstrated the occurrence of ferroptosis in the spinal cord and dorsal root ganglion tissues in a rodent model of inflammatory pain and indicated that intrathecal administration of ferroptosis inhibitors, such as liproxstatin-1, is a potential therapeutic strategy for treating inflammatory pain.

Simultaneous phosphorus and nitrogen removal with different C/N ratios in a low oxygen aeration system: Microorganisms and mechanisms.

In this study, a combined system with simultaneous nitrification, denitrification, and phosphorus removal was operated in continuous low oxygen aeration mode, and the effect of lower oxygen aeration (dissolved oxygen [DO] 0.5-1.5 mg/L) on its performance was examined. The combined system consisted of sludge and high-efficiency biological packing and was operated using four carbon/nitrogen ratios (C/N) with being 10:1, 8:1, 6:1, 10:1. Experimental results showed that the combined system could perform an efficient nitrogen and phosphorus removal under low DO and C/N ratio of 8:1 condition, and removal efficiencies of chemical oxygen demand (COD), NH4 + -N, and PO4 3- -P were 80.01%, 99.03%, and 89.51%, respectively. High-throughput analysis indicated that the functional species of denitrifying bacteria, including Ferruginibacter Azospira, Comamonas, Bacilli, Hyphomicrobium, Thauera, and Comamonadaceae, were important participants in biological nutrient removal. Meanwhile, Acinetobacter was enriched in the combined system, which contributed to phosphorus removal. PRACTITIONER POINTS: A combined system was operated firstly under continuous low oxygen condition. The lower dissolved oxygen (DO) of the combined system was maintained at 0.50-1.5 mg/L level. The combined system could realize simultaneous phosphorus and nitrogen removal under C/N ratio of 8:1. Several functional bacteria were enriched in the coupled systems.

Data fusion of electronic noses and electronic tongues aids in botanical origin identification on imbalanced Codonopsis Radix samples.

Codonopsis Radix (CR) is an edible food and traditional Chinese herb medicine in China. Various varieties of Codonopsis Radix have different tastes. To make the flavor of processed food stable, two kinds of electronic sensory devices, electronic nose and electronic tongue, were used to establish a discrimination model to identify the botanical origin of each sample. The optimal model built on the 88 batches of samples was selected from the models trained with all combination of two pretreatment methods and three classification methods. A comparison were performed on the models trained on the data collected by electronic nose and electronic tongue. The results showed that the model trained on the fused dataset outperformed the models trained separately on the electronic nose data and electronic tongue data. The two preprocessing approaches could improve the prediction performance of all classification methods. Classification and Regression Tree approach performed better than Partial Least Square Discriminant Analysis and Linear Discriminant Analysis in terms of accuracy. But Classification and Regression Tree tends to assign the samples of minority class to the majority class. Meanwhile, Partial Least Square Discriminant Analysis keeps a good balance between the identification requirements of all the two groups of samples. Taking all the results above, the model built using the Partial Least Square Discriminant Analysis method on the fused data after z-score was used to identify the botanical origin of Codonopsis Radix.

Integrating network pharmacology and experimental verification to decipher the immunomodulatory effect of Bu-Zhong-Yi-Qi-Tang against poly (I:C)-induced pulmonary inflammation.

Pulmonary inflammation caused by respiratory tract viral infections is usually associated with acute exacerbation of respiratory diseases, such as asthma and chronic obstructive pulmonary disease (COPD). Therefore, maintaining the pulmonary immune homeostasis is particular important for prevention of the acute exacerbation. Bu-Zhong-Yi-Qi-Tang (BZYQT), a traditional Chinese medicine formula, has been broadly used to improve respiratory and gastrointestinal disorders in China for over 700 years. Previously, we have found the regulatory activity of BZYQT on the lower respiratory immune system, while its potential effects during pulmonary inflammation remain unknown. Thus, the current study focused on deciphering its immunomodulatory effect and potential mechanism against pulmonary inflammation by using a viral RNA analogue, poly (I:C), induced murine pulmonary inflammation model and BEAS-2B cell model coupled with network pharmacology. Inflammatory cells in the bronchoalveolar lavage fluid were counted through microscope examination according to the cell's morphology and staining characteristics; protein and gene levels of inflammatory mediators were determined with Elisa and quantitative PCR, respectively; network pharmacology was conducted based on 46 BZYQT-related potential bioactive components, pulmonary inflammation and immune-related targets. Our results indicated that the recruitment of neutrophils and the expression of Adgre1 (encoding the F4/80, which is a macrophage marker) in the lung induced by poly (I:C) were significantly reduced after BZYQT treatment, and these effects were further demonstrated to be related to the interference of leukocyte transendothelial migration from the decreased levels of CXCL10, IL-6, TNF-α, CXCL2, ICAM-1, VCAM-1, and E/P-selectins. Furthermore, BZYQT inhibited the CXCL10, TNF-α, and IFN-ß expression of poly (I:C)-challenged BEAS-2B cells in a dose-dependent manner. Through integrating results from network pharmacology, experiments, and the published literature, isoliquiritigenin, Z-ligustilide, atractylenolide I, atractylenolide III, formononetin, ferulic acid, hesperidin, and cimigenoside were presumed as the bioactive components of BZYQT against pulmonary inflammation. Overall, our findings demonstrated that BZYQT possesses a pronounced immunomodulatory effect on poly (I:C)-induced pulmonary inflammation, which provides a pharmacological basis for BZYQT in the treatment of respiratory disorders.

Reuse of phosphogypsum pretreated with water washing as aggregate for cemented backfill.

Phosphogypsum (PG) is reused as aggregate in the cemented backfill, which effectively improves the PG reutilization efficiency. However, the massive impurities contained in aggregate PG would adversely affect the hydration of binder, and therefore deteriorate the strength development of backfill. This research starts with the feasibility study on pretreating PG with the water washing method. Based on the most economical principle of the water demand, the optimal conditions for washing PG were determined at a stirring time of 5 min and a solid-liquid ratio of 1:0.5. Then, the original and pretreated PG were made into the backfill. Compared to using the original PG, the backfill slurry using the pretreated PG had better fluidity performance, such as the lower slurry viscosity and the higher bleeding rate. Furthermore, with the pretreated aggregate PG, the backfill strength was significantly enhanced by more than 8 times. Finally, the environmental behavior of the cemented backfill was investigated. Using the pretreated PG as aggregate, concentrations of PO43- and F- in the bleeding water and backfill leachates could meet the Chinese standard for integrated wastewater discharge. The results extend the reuse of PG as aggregate in a more environmental-friendly way, meeting the needs for sustainable mines.

Synthesis of Melatonin Derivatives and the Neuroprotective Effects on Parkinson's Disease Models of Caenorhabditis elegans.

Melatonin (MT) is a hormone with antioxidant activity secreted by the pineal gland in the human brain, which is highly efficient in scavenging free radicals and plays an important role in the neuro-immuno-endocrine system. Emerging evidence showed that MT supplementation was a potential therapeutic strategy for Parkinson's disease (PD), which inhibits pathways associated with oxidative stress in PD. In this study, we reported a C7-selective olefination of melatonin under rhodium catalysis with the aid of PIII-directing groups and synthesized 10 new melatonin-C7-cinnamic acid derivatives (6a-6j). The antioxidant potential of the compounds was evaluated both by ABTS and ORAC methods. Among these newly synthesized melatonin derivatives, 6a showed significantly higher activity than MT at 10-5 M. In the transgenic Caenorhabditis elegans model of PD, 6a significantly reduces alpha-synuclein aggregation and dopaminergic neuronal damage in nematodes while reducing intracellular ROS levels and recovers behavioral dysfunction induced by dopaminergic neurodegeneration. Further study of the mechanism of action of this compound can provide new therapeutic ideas and treatment strategies for PD.

Establishment of DNA Methylation Profile Associated with TCM Syndrome in Endometriosis.

Objectives: To screen the potential epigenetic biomarkers associated with endometriosis (EMS) and traditional Chinese medicine (TCM) syndrome EMS types. Methods: A cohort of 99 participants comprising 42 EMS patients with cold coagulation blood stasis (CCBS) syndrome, 35 EMS patients with Qi stagnation blood stasis (QSBS) syndrome, and 22 women of childbearing age without EMS were recruited. Reduced representation bisulfite sequencing (RRBS) was used to establish the differential DNA methylation profiles in human peripheral blood samples obtained from four non-EMS and four EMS patients with CCBS or QSBS syndrome, respectively. Differentially expressed genes (DEGs) were verified in 18 non-EMS, 38 CCBS-EMS, and 31 QSBS-EMS using pyrosequencing. Results: Methylation sites of 123942, 127229, and 115961 were found in peripheral blood DNA of non-EMS, CCBS-EMS, and QSBS-EMS patients, respectively. GO and KEGG analyses showed that the pathological process of EMS may be closely related to the nervous system development, cell junctions, GABA-gated chloride ion channel activity, nicotine addiction, Hippo signaling pathway, mRNA surveillance pathway, and Wnt signaling pathway. The methylation level at CpG site within HDAC6 gene in QSBS-EMS patients was significantly different from that in control women. Conclusions: The changes in DNA methylation in peripheral blood samples may be associated with EMS and TCM syndrome EMS types. The methylation level of HDAC6 gene may be used to distinguish QSBS-EMS patients from women without EMS.

Targeting the Retinoid X Receptor Pathway Prevents and Ameliorates Murine Chronic Graft-Versus-Host Disease.

Most allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients receive peripheral blood stem cell grafts resulting in a 30%-70% incidence of chronic graft-versus-host disease (cGVHD), a major cause of mortality and morbidity in long-term survivors. While systemic steroids remain the standard of care for first-line therapy, patients may require long-term administration, and those with steroid-resistant or refractory cGVHD have a worse prognosis. Although durable and deep responses with second-line therapies can be achieved in some patients, there remains an urgent need for new therapies. In this study, we evaluated the efficacy of IRX4204, a novel agonist that activates RXRs and is in clinical trials for cancer treatment to prevent and treat cGVHD in two complementary murine models. In a major histocompatibility complex mismatched, non-sclerodermatous multiorgan system model with bronchiolitis obliterans, IRX4204 prevented and reversed cGVHD including associated pulmonary dysfunction with restoration of germinal center T-follicular helper: T-follicular regulatory cell balance. In a minor histocompatibility antigen disparate sclerodermatous model, IRX4204 treatment significantly prevented and ameliorated skin cGVHD by reducing Th1 and Th17 differentiation due to anti-inflammatory properties. Together, these results indicate that IRX4204 is a promising therapeutic option to treat cGVHD with bronchiolitis obliterans or sclerodermatous manifestations.