Rapid Characterization of Undeclared Pharmaceuticals in Herbal Preparations by Ambient Ionization Mass Spectrometry for Emergency Care.

In Asia, some herbal preparations have been found to be adulterated with undeclared synthetic medicines to increase their therapeutic efficiency. Many of these adulterants were found to be toxic when overdosed and have been documented to bring about severe, even life-threatening acute poisoning events. The objective of this study is to develop a rapid and sensitive ambient ionization mass spectrometric platform to characterize the undeclared toxic adulterated ingredients in herbal preparations. Several common adulterants were spiked into different herbal preparations and human sera to simulate the clinical conditions of acute poisoning. They were then sampled with a metallic probe and analyzed by the thermal desorption-electrospray ionization mass spectrometry. The experimental parameters including sensitivity, specificity, accuracy, and turnaround time were prudently optimized in this study. Since tedious and time-consuming pretreatment of the sample is unnecessary, the toxic adulterants could be characterized within 60 s. The results can help emergency physicians to make clinical judgments and prescribe appropriate antidotes or supportive treatment in a time-sensitive manner.

Effect of sheep bone protein hydrolysate on promoting calcium absorption and enhancing bone quality in low-calcium diet fed rats.

Calcium deficiency is prone to fractures, osteoporosis and other symptoms. In this study, sheep bone protein hydrolysates (SBPHs) were obtained by protease hydrolysis. A low-calcium-diet-induced calcium-deficiency rat model was established to investigate the effects of SBPHs on calcium absorption and intestinal flora composition. The results showed that an SBPHs + CaCl2 treatment significantly increased the bone calcium content, bone mineral density, trabecular bone volume, and trabecular thickness, and reduced trabecular separation, and changed the level of bone turnover markers (P < 0.05). Supplementation of SBPHs + CaCl2 can remarkably enhance the bone mechanical strength, and the microstructure of bone was improved, and the trabecular network was more continuous, complete, and thicker. Additionally, SBPHs + CaCl2 dietary increased the abundance of Firmicutes and reduced the abundance of Proteobacteria and Verrucomicrobiota, and promoted the production of short chain fatty acids. This study indicated that SBPHs promoted calcium absorption and could be applied to alleviate osteoporosis.

Unveiling the nitrogen and phosphorus removal potential: Comparative analysis of three coastal wetland plant species in lab-scale constructed wetlands.

It is well accepted that tidal wetland vegetation performs a significant amount of water filtration for wetlands. However, there is currently little information on how various wetland plants remove nitrogen (N) and phosphorus (P) and how they differ in their denitrification processes. This study compared and investigated the denitrification and phosphorus removal effects of three typical wetland plants in the Yangtze River estuary wetland (Phragmites australis, Spartina alterniflora, and Scirpus mariqueter), as well as their relevant mechanisms, using an experimental laboratory-scale horizontal subsurface flow constructed wetland (CW). The results showed that all treatment groups with plants significantly reduced N pollutants as compared to the control group without plants. In comparison to S. mariqueter (77.2-83.2%), S. alterniflora and P. australis had a similar total nitrogen (TN)removal effectiveness of nearly 95%. With a removal effectiveness of over 99% for ammonium nitrogen (NH4+-N), P. australis outperformed S. alterniflora (95.6-96.8%) and S. mariqueter (94.6-96.5%). The removal of nitrite nitrogen (NO2--N)and nitrate nitrogen (NO3--N)from wastewater was significantly enhanced by S. alterniflora compared to the other treatment groups. Across all treatment groups, the removal rate of PO43--P was greater than 95%. P. australis and S. alterniflora considerably enriched more 15N than S. mariqueter, according to the results of the 15N isotope labeling experiment. While the rhizosphere and bulk sediments of S. alterniflora were enriched with more simultaneous desulfurization-denitrification bacterial genera (such as Paracoccus, Sulfurovum, and Sulfurimonas), which have denitrification functions, the rhizosphere and bulk sediments of P. australis were enriched with more ammonia-oxidizing archaea and ammonia-oxidizing bacteria. As a result, compared to the other plants, P. australis and S. alterniflora demonstrate substantially more significant ability to remove NH4+-N and NO2--N/NO3--N from simulated domestic wastewater.

Probiotics Increase Intramuscular Fat and Improve the Composition of Fatty Acids in Sunit Sheep through the Adenosine 5'-Monophosphate-Activated Protein Kinase (AMPK) Signaling Pathway.

This experiment aims to investigate the impact of probiotic feed on growth performance, carcass traits, plasma lipid biochemical parameters, intramuscular fat and triglyceride content, fatty acid composition, mRNA expression levels of genes related to lipid metabolism, and the activity of the enzyme in Sunit sheep. In this experiment, 12 of 96 randomly selected Sunit sheep were assigned to receive the basic diet or the basic diet supplemented with probiotics. The results showed that supplementation with probiotics significantly increased the loin eye area, and decreased plasma triglycerides and free fatty acids, increasing the content of intramuscular fat and triglycerides in the muscle and improving the composition of the fatty acids. The inclusion of probiotics in the diet reduced the expression of adenosine 5'-monophosphate-activated protein kinase alpha 2 (AMPKα2) mRNA and carnitine palmitoyltransferase 1B (CPT1B) mRNA, while increasing the expression of acetyl-CoA carboxylase alpha (ACCα) mRNA, sterol regulatory element-binding protein-1c (SREBP-1c) mRNA, fatty acid synthase mRNA, and stearoyl-CoA desaturase 1 mRNA. The results of this study indicate that supplementation with probiotics can regulate fat deposition and improves the composition of fatty acids in Sunit sheep through the signaling pathways AMPK-ACC-CPT1B and AMPK-SREBP-1c. This regulatory mechanism leads to an increase in intramuscular fat content, a restructuring of muscle composition of the fatty acids, and an enhancement of the nutritional value of meat. These findings contribute to a better understanding of the food science of animal resources and provide valuable references for the production of meat of higher nutritional value.

Screening Serum Biomarkers for Rats Preconditioned with Hyperbaric Oxygen: Potential of Predicting Prognosis for Stroke.

BACKGROUND: Stroke is a major health concern and a leading cause of mortality and morbidity. We and other groups have documented that hyperbaric oxygen preconditioning could significantly alleviate neuronal damage in ischemia‒reperfusion models through various mechanisms. However, we found that some of the subjects did not benefit from preconditioning with hyperbaric oxygen. The preconditioning phenomenon is similar to vaccination, in which the endogenous survival system is activated to fight against further injuries. However, with vaccine inoculations, we could test for specific antibodies against the pathogens to determine if the vaccination was successful. Likewise, this experiment was carried out to explore a biomarker that can reveal the effectiveness of the preconditioning before neuronal injury occurs. METHODS: Middle cerebral artery occlusion (MCAO) was used to induce focal cerebral ischemia-reperfusion injury. 2D-DIGE-MALDI-TOF-MS/MS proteomic technique was employed to screen the differentially expressed proteins in the serum of rats among the control (Con) group (MCAO model without hyperbaric oxygen (HBO) preconditioning), hyperbaric oxygen protective (HBOP) group (in which the infarct volume decreased after HBO preconditioning vs. Con), and hyperbaric oxygen nonprotective (HBOU) group (in which the infarct volume remained the same or even larger after HBO preconditioning vs. Con). Candidate biomarkers were confirmed by western blot and enzyme linked immunosorbent assay (ELISA), and the relationship between the biomarkers and the prognosis of cerebral injury was further validated. RESULTS: Among the 15 differentially expressed protein spots detected in the HBOP group by Two-dimensional fluorescence difference gel electrophoresis (2D-DIGE), 3 spots corresponding to 3 different proteins (haptoglobin, serum albumin, and haemopexin) products were identified by MALDI-TOF-MS/MS. Serum albumin and haemopexin were upregulated, and haptoglobin was downregulated in the HBOP group (p < 0.05 vs. Con and HBOU groups). After the western blot study, only the changes in haemopexin were validated and exhibited similar changes in subjects from the HBOP group in accordance with MALDI-TOF-MS/MS proteomic analysis and enzyme linked immunosorbent assay (ELISA) analysis. The serum level of the hemopexin (HPX) at 2 h after HBO preconditioning was correlated with the infarct volume ratio after MCAO. CONCLUSIONS: Haemopexin may be developed as a predictive biomarker that indicated the effectiveness of a preconditioning strategy against cerebral ischaemic injury.

Effect of dietary arginine supplementation on protein synthesis, meat quality and flavor in growing lambs.

This study aimed to assess the effect of dietary arginine supplementation on protein synthesis, meat quality and flavor in lambs. Eighteen Dorper (♂) × Small Tailed Han sheep (♀) crossed ewe lambs of similar weight (27.29 ± 2.02 kg; aged 3 months) were assigned to two groups, the control group was fed the basal diet (Con group), and the arginine group (Arg group) was supplemented with 1% l-arginine based on the Con group for 90 d. The results suggested that dietary arginine significantly increased final body weight, loin eye muscle area, muscle fiber diameter, cross-sectional area (P < 0.050), and decreased shear force value and cooking loss (P < 0.050), as well as altered the composition and contents of volatile flavor compounds in lambs. Importantly, the total protein (TP) content, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AKP) activities in serum, branched-chain aminotransferase (BCAT), AST, ALT activities and neuronal nitric oxide synthase (nNOS) gene expression and content were elevated (P < 0.050), while content of urea nitrogen (BUN) in serum and 3-methylhistidine (3-MH) were decreased in arginine fed lambs (P < 0.050). In addition, arginine triggered muscle protein synthesis through protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway, while minimized protein degradation by regulating gene expression of myogenin (MyoG), myostatin (MSTN), muscle atrophy F-box (MAFbx) and forkhead box O3 family (FoxO3) (P < 0.050). Taken together, this study suggested that arginine can be used to improve protein deposition and meat quality in lamb production.

Supplemental Clostridium butyricum modulates skeletal muscle development and meat quality by shaping the gut microbiota of lambs.

This study evaluated the contributions of Clostridium butyricum on skeletal muscle development, gastrointestinal flora and meat quality of lambs. Eighteen Dorper (♂) × Small Tailed Han sheep (♀) crossed ewe lambs of similar weight (27.43 ± 1.94 kg; age, 88 ± 5 days) were divided into two dietary treatments. The control group was fed the basal diet (C group), and the probiotic group was supplemented with C. butyricum on the basis of the C group (2.5 × 108 cfu/g, 5 g/day/lamb; P group) for 90 d. The results showed that dietary C. butyricum elevated growth performance, muscle mass, muscle fiber diameter and cross-sectional area, and decreased the shear force value of meat (P < 0.05). Moreover, C. butyricum supplementation accelerated protein synthesis by regulating the gene expression of IGF-1/Akt/mTOR pathway. We identified 54 differentially expressed proteins that regulated skeletal muscle development through different mechanisms by quantitative proteomics. These proteins were associated with ubiquitin-protease, apoptosis, muscle structure, energy metabolism, heat shock, and oxidative stress. The metagenomics sequencing results showed that Petrimonas at the genus level and Prevotella brevis at the species level in the rumen, while Lachnoclostridium, Alloprevotella and Prevotella at the genus level in the feces, were significantly enriched in the P group. Also, butyric acid and valeric acid levels were elevated in both rumen and feces of the P group. Overall, our results support the idea that C. butyricum could change gastrointestinal flora, and affect skeletal muscle development and meat quality of lambs by modulating gut-muscle axis.

The Tian-Men-Dong decoction suppresses the tumour-infiltrating G-MDSCs via IL-1ß-mediated signalling in lung cancer.

ETHNOPHARMACOLOGICAL RELEVANCE: The traditional Chinese medicine (TCM) Tian-Men-Dong decoction (TD) has been able to effectively treat lung cancer in China for thousands of years. TD improves the quality of life in lung cancer patients by promoting nourishment of yin and reducing dryness, clearing the lung and removing toxins. Pharmacological studies show that TD contains active antitumour ingredients, but its underlying mechanism remains unknown. AIM OF THE STUDY: This study aims at exploring potential mechanisms of TD in the treatment of lung cancer by regulating granulocytic-myeloid-derived suppressor cells (G-MDSCs). MATERIALS AND METHODS: An orthotopic lung cancer mouse model was generated by intrapulmonary injection with LLC-luciferase cells in immunocompetent C57BL/6 mice or immunodeficient nude mice. TD/saline was orally administered once to the model mice daily for 4 weeks. Live imaging was conducted to monitor tumour growth. Immune profiles were detected by flow cytometry. H&E and ELISA were applied to test the cytotoxicity of the TD treatment. RT-qPCR and western blotting were performed to detect apoptosis-related proteins in G-MDSCs. A neutralizing antibody (anti-Ly6G) was utilized to exhaust the G-MDSCs via intraperitoneal injection. G-MDSCs were adoptively transferred from wild-type tumour-bearing mice. Immunofluorescence, TUNEL and Annexin V/PI staining were conducted to analyse apoptosis-related markers. A coculture assay of purified MDSCs and T cells labelled with CFSE was performed to test the immunosuppressive activity of MDSCs. The presence of TD/IL-1ß/TD + IL-1ß in purified G-MDSCs cocultured with the LLC system was used for ex vivo experiments to detect IL-1ß-mediated apoptosis of G-MDSCs. RESULTS: TD prolonged the survival of immune competent C57BL/6 mice in an orthotopic lung cancer model, but did not have the same effect in immunodeficient nude mice, indicating that its antitumour properties of TD are exerted by regulating immunity. TD induced G-MDSC apoptosis via the IL-1ß-mediated NF-κB signalling cascade leading to effectively weaken the immunosuppressive activity of G-MDSCs and promote CD8+ T-cell infiltration, which was supported by both the depletion and adoptive transfer of G-MDSCs assays. In addition, TD also showed minimal cytotoxicity both in vivo and in vitro. CONCLUSION: This study reveals for the first time that TD, a classic TCM prescription, is able to regulate G-MDSC activity and trigger its apoptosis via the IL-1ß-mediated NF-κB signalling pathway, reshaping the tumour microenvironment and demonstrating antitumour effects. These findings provide a scientific foundation the clinical treatment of lung cancer with TD.

Detection of multiple types of cancer driver mutations using targeted RNA sequencing in non-small cell lung cancer.

BACKGROUND: DNA-based next-generation sequencing has been widely used in the selection of target therapies for patients with nonsmall cell lung cancer (NSCLC). RNA-based next-generation sequencing has been proven to be valuable in detecting fusion and exon-skipping mutations and is recommended by National Comprehensive Cancer Network guidelines for these mutation types. METHODS: The authors developed an RNA-based hybridization panel targeting actionable driver oncogenes in solid tumors. Experimental and bioinformatics pipelines were optimized for the detection of fusions, single-nucleotide variants (SNVs), and insertion/deletion (indels). In total, 1253 formalin-fixed, paraffin-embedded samples from patients with NSCLC were analyzed by DNA and RNA panel sequencing in parallel to assess the performance of the RNA panel in detecting multiple types of mutations. RESULTS: In analytical validation, the RNA panel achieved a limit of detection of 1.45-3.15 copies per nanogram for SNVs and 0.21-6.48 copies per nanogram for fusions. In 1253 formalin-fixed, paraffin-embedded NSCLC samples, the RNA panel identified a total of 124 fusion events and 26 MET exon 14-skipping events, in which 14 fusions and six MET exon 14-skipping mutations were missed by DNA panel sequencing. By using the DNA panel as the reference, the positive percent agreement and the positive predictive value of the RNA panel were 98.08% and 98.62%, respectively, for detecting targetable SNVs and 98.15% and 99.38%, respectively, for detecting targetable indels. CONCLUSIONS: Parallel DNA and RNA sequencing analyses demonstrated the accuracy and robustness of the RNA sequencing panel in detecting multiple types of clinically actionable mutations. The simplified experimental workflow and low sample consumption will make RNA panel sequencing a potentially effective method in clinical testing.

Directional conjugation of Trop2 antibody to black phosphorus nanosheets for phototherapy in orthotopic gastric carcinoma.

Tumor-associated calcium signal transducer 2 (Trop2) is highly specific expressed in gastric carcinoma (GC). The combination of Trop2 antibody and phototherapy agents could exhibit synergetic antitumor activity. Black phosphorus nanosheets (BP) are covalently modified with Trop2 IgG antibodies via heterobifunctional linker of polyethylene glycol (PEG). Then the Trop2 antibody was directionally conjugated to BP via Schiff base reaction between aldehyde group from oxidized Trop2 antibody and amino group of PEG. The Trop2-functionalzied BP can significantly increase the endocytosis of BP in Trop2-positive GC cells exhibiting a reinforced antitumor activity under near infrared (NIR) irradiation. More importantly, a murine orthotopic GC model demonstrates that Trop2 antibody modification can significantly promote the accumulation of BP at tumor tissues and strengthen antitumoral activity of phototherapy. Directional conjugation of Trop2 antibody to BP facilitates the BP with superior stability, tumor targeting ability and excellent anti-tumor activity under NIR irradiation without systemic toxicity.

Dietary linseed supplementation improves meat quality and flavor of sheep by altering muscle fiber characteristics and antioxidant capacity.

Linseed as a common oil crop that has been implicated in regulating the meat quality of animals. The aim of this investigation was to establish the effects of dietary linseed supplementation on carcass traits, meat quality, muscle fiber characteristics, volatile compounds and antioxidant capacity of sheep. Twenty-four Sunit sheep were distributed into 2 groups with different diet: control (CO) fed a standard diet and linseed (LS, 8% of extruded linseed). The results showed that linseed not only increased M. longissimus thoracis (LT) increased the loin-eye area but also decreased pH24h, L* and shear force. Meanwhile, linseed increased mRNA expression of MyHCI and MyHCIIx and decreased in cross-sectional area (CSA) and muscle fiber diameter. In addition, linseed altered the composition of meat volatile flavor compounds, such as Z-10-Pentadecen-1-ol, pentanal, 2-Octenal, (E)-, decanal, butane, and 2-heptanone. Moreover, linseed increased total antioxidative capacity (T-AOC) activity, the mRNA expression of glutathione peroxidase (GSH-Px) and catalase (CAT), decreased malondialdehyde (MDA) content. Overall, the results suggest that linseed is an effective feed additive in improving meat quality and flavor. The underlying mechanisms for its effectiveness may be partly due to a change in muscle fiber characteristics and antioxidant capacity.

Lipid transformation during postmortem chilled aging in Mongolian sheep using lipidomics.

This present study aimed to investigate the effects of postmortem chilled aging on lipid and molecular transformation mechanisms in Mongolian sheep. UPLC-ESI-MS/MS was used to identify 812 lipids in Mongolian sheep within four days of chilled aging. Using multivariate analysis, 95 significant differential lipids were identified. The levels of phosphatidylcholine, phosphatidylinositol, and certain free fatty acids were observed to rise significantly, while other phospholipids and acylcarnitines showed a downward trend. In addition, levels of most of the lysophospholipids increased significantly in the early postmortem period; however, their levels did not alter significantly after 48 h. The Kyoto encyclopedia of genes and genomes pathway analysis revealed that these differential lipids are primarily involved in glycerophospholipid metabolism, linoleic acid metabolism, arachidonic acid metabolism, and thermogenesis. Our results have important implications in terms of understanding lipid transformation and changes in meat quality during postmortem chilled aging in Mongolian sheep.

Transcriptome analysis reveals the molecular regulatory network of muscle development and meat quality in Sunit lamb supplemented with dietary probiotic.

Supplementing animal feed with probiotic additives can promote muscle production and improve meat quality. The study aimed to explore the effects of dietary probiotics supplementation on the performance, meat quality and muscle transcriptome profile in Sunit lamb. Overall, feeding probiotics significantly increased the body length, LT area, pH24h and intramuscular fat (IMF) content, but decreased cooking loss and meat shear force compared to the control group (P < .05). A total of 651 differentially expressed genes (DEGs) were found in probiotic supplemented lambs. Pathway analysis revealed that DEGs were involved in multiple pathways related to muscle development and fat deposition, such as the ECM-receptor interactions, the MAPK signaling pathway and the FoxO signaling pathway. Therefore, dietary probiotic supplementation can improve muscle development and final meat quality in Sunit lambs by altering gene expression profiles associated with key pathways, providing unique insights into the molecular mechanisms by which dietary probiotics regulate muscle development in the lamb industry.

Isolation, Purification and Structure Identification of a Calcium-Binding Peptide from Sheep Bone Protein Hydrolysate.

To isolate a novel peptide with calcium-binding capacity, sheep bone protein was hydrolyzed sequentially using a dual-enzyme system (alcalase treatment following neutrase treatment) and investigated for its characteristics, separation, purification, and structure. The sheep bone protein hydrolysate (SBPH) was enriched in key amino acids such as Gly, Arg, Pro, Leu, Lys, Glu, Val, and Asp. The fluorescence spectra, circular dichroism spectra, and Fourier-transform infrared spectroscopy results showed that adding calcium ions decreased the α-helix and ß-sheet content but significantly increased the random and ß-turn content (p < 0.05). Carboxyl oxygen and amino nitrogen atoms of SBPH may participate in peptide−calcium binding. Scanning electron microscopy and energy dispersive spectrometry results showed that SBPH had strong calcium-chelating ability and that the peptide−calcium complex (SBPH−Ca) combined with calcium to form a spherical cluster structure. SBPH was separated and purified gradually by ultrafiltration, gel filtration chromatography, and reversed-phase high-performance liquid chromatography. Liquid chromatography-electrospray ionization/mass spectrometry identified the amino acid sequences as GPSGLPGERG (925.46 Da) and GAPGKDGVRG (912.48 Da), with calcium-binding capacities of 89.76 ± 0.19% and 88.26 ± 0.25%, respectively. The results of this study provide a scientific basis for the preparation of a new type of calcium supplement and high-value utilization of sheep bone.

Ginsenoside Rb1 improves brain, lung, and intestinal barrier damage in middle cerebral artery occlusion/reperfusion (MCAO/R) micevia the PPARγ signaling pathway.

Ischemic stroke causes brain inflammation and multi-organ injury, which is closely associated with the peroxisome proliferator-activated receptor-gamma (PPARγ) signaling pathway. Recent studies have indicated that ginsenoside Rb1 (GRb1) can protect the integrity of the blood-brain barrier after stroke. In the current study, a mouse model of middle cerebral artery occlusion/reperfusion (MCAO/R) was established to determine whether GRb1 can ameliorate brain/lung/intestinal barrier damage via the PPARγ signaling pathway. Staining (2,3,5-triphenyltetrazolium chloride, hematoxylin, and eosin) and Doppler ultrasonography were employed to detect pathological changes. Endothelial breakdown was investigated with the leakage of Evans Blue dye and the expression of TJs (tight junctions) and AJs (adherent junctions). Western blot and immunofluorescence were used to determine the levels of cell junction proteins, PPARγ and NF-κB. Results showed that GRb1 significantly mitigated multi-organ injury and increased the expression of cerebral microvascular, pulmonary vascular, and intestinal epithelial connexins. In brain, lung, and intestinal tissues, GRb1 activated PPARγ, decreased the levels of phospho-NF-κB p65, and inhibited the production of proinflammatory cytokines, thereby maintaining barrier permeability. However, co-treatment with GRb1 and the PPARγ antagonist GW9662 reversed the barrier-protective effect of GRb1. These findings indicated that GRb1 can improve stroke-induced brain/lung/intestinal barrier damagevia the PPARγ pathway.

IL-38, a potential therapeutic agent for lupus, inhibits lupus progression.

BACKGROUND: Previous studies reported that IL-38 was abnormally expressed in patients with systemic lupus erythematosus (SLE). However, the involvement of IL-38 in the pathophysiology of SLE remains unknown. METHODS: The therapeutic potential of IL-38 was tested in pristane-treated wild-type (WT) and IL-38-/- mice. Thus, SLE was induced via pristane in WT and IL-38-/- mice. Afterwards, the liver, spleen, and kidney of each mouse were obtained. The flow cytometric analysis of the immune cells, serologic expression of inflammatory cytokines and autoantibodies, renal histopathology, and inflammatory signaling were evaluated. RESULTS: WT mice with pristane-induced lupus exhibited hepatomegaly, splenomegaly, severe kidney damages, increased lymphoproliferation, enhanced lymphoproliferation, and upregulated inflammatory cytokines, such as IL-6, IL-13, IL-17A, MIP-3α, IL-12p70, and IFNγ, and elevated levels of autoantibodies, such as ANA IgG, anti-dsDNA IgG, and total IgG. IL-38-/- mice whose lupus progressed, had elevated cells of CD14+, CD19+, CD3+, and Th1, upregulated inflammatory cytokines and autoantibodies, and severe pathological changes in kidney. Administration of recombinant murine IL-38 to pristane-treated IL-38-/- mice improved their renal histopathology, which depended on ERK1/2, JNK1/2, p38, NF-κB p65, and STAT5 signaling pathways. CONCLUSION: IL-38 regulates SLE pathogenesis. Furthermore, targeting IL-38 is critical in the treatment of SLE.

Selenium as an emerging versatile player in heterocycles and natural products modification.

The diverse pharmacological activities of organoselenium compounds are closely correlated to their ability to scavenge and induce reactive oxygen species (ROS), their intrinsic oxidative properties, and their Se(0) release property. The incorporation of selenium into small molecules, and particularly into heterocycles and natural products, has shown great potential in altering the potency and selectivity of these molecules. Therefore, selenium will play an important role in drug discovery in the near future. We summarize how different organoselenium species affect cellular oxidative stress levels, and try to correlate the structural properties of selenium-containing heterocycles and natural product derivatives to their biological activities and therapeutic applications. We also provide some information to guide the rational design of selenium-containing drugs.

Natural component plumbagin as a potential antibacterial agent against Streptococcus agalactiae infection.

Streptococcus agalactiae, also known as Group B Streptococcus (GBS), can infect humans, terrestrial animals and fish. The emergence of bacterial resistance of S. agalactiae to antibiotics leads to an urgent need of exploration of new antimicrobial agents. In the study, the antibacterial activity of natural component plumbagin (PLB) against S. agalactiae was investigated in vitro and in vivo. The results showed that the minimal inhibitory concentration (MIC) of PLB against S. agalactiae was 8 mg/L. The growth curve assay revealed that PLB could inhibit the growth of S. agalactiae. In addition, the time-killing curve showed that S. agalactiae was killed almost completely by 2-fold MIC of PLB within 12 h. Transmission electron microscopy results showed obvious severe morphological destruction and abnormal cells of S. agalactiae after treated with PLB. The pathogenicity of S. agalactiae to zebrafish was significantly decreased after preincubation with PLB for 2 h in vitro, further indicating the bactericidal activity of PLB. Interestingly, PLB could kill S. agalactiae without inducing resistance development. Furthermore, pretreatment and post-treatment assays suggested that PLB also exhibited the antibacterial activity against S. agalactiae infection in vivo by effectively reducing the bacterial load and improving the survival rate of S. agalactiae-infected zebrafish. In summary, PLB had potent antibacterial activity against S. agalactiae in vitro and in vivo, and it could be an excellent antimicrobial candidate to prevent and control S. agalactiae infection.

Sodium Alginate Hydrogel-Mediated Cancer Immunotherapy for Postoperative In Situ Recurrence and Metastasis.

With the development of technology, adjuvant immunotherapy has become a promising strategy for prevention of postoperative tumor regression and metastasis by stimulating the host immune response. However, the therapeutic effects are still unsatisfactory due to the lack of synergy between different methods. In this study, an efficient synergistic immunotherapy system based on injectable sodium alginate hydrogels was designed to inhibit in situ recurrence and metastasis at the same time. On the one hand, an injectable sodium alginate (SA) hydrogel microsystem loaded with toll-like receptor (TLR) agonists (CpG ODNs) was synthesized for inhibiting in situ recurrence, and then carcinoembryonic antigen (CEA) probe was also added to detect CEA based on fluorescence resonance energy transfer (FRET) technology to monitor the occurrence and development of tumor recurrence. On the other hand, an anti-programmed cell death 1 ligand 1 antibody (anti-PD-L1)-modified SA nanogel loaded with indocyanine green (ICG@SA-anti-PD-L1 nanogel) was prepared for diagnosing and inhibiting lung metastasis by assisting orthotopic tumor therapy. In vitro and in vivo results demonstrated that this SA micro/nanosystem could monitor and inhibit postoperative recurrence and metastasis. We hope that this micro/nano-synergistic system will become an effective strategy for postoperative adjuvant immunotherapy.

Shared and specific patterns of structural and functional thalamo-frontal disturbances in manic and euthymic pediatric bipolar disorder.

Bipolar disorder (BD) is clinically defined by alternating depressive and manic episodes with a separated period of euthymia. Thalamo-frontal loop plays vital role in psychotic symptoms, altered motor control and executive difficulties in BD. It remains unclear that structural and functional alterations of thalamo-frontal loop among the different mood states in BD, especially in pediatric BD(PBD).Twenty manic PBD (mPBD), 20 euthymic PBD (ePBD) and 19 healthy controls (HCs) were included in the study. By analyzing the T1 images and fMRI signals, thalamus volume and frontal grey matter cortical thickness were tested, and functional connectivity (FC) between bilateral thalamus and frontal cortex was calculated. Relationship between clinical indices and thalamo-frontal FC was also evaluated in mPBD and ePBD adolescents.Compared to HCs, the cortical thickness of left middle frontal gyrus (MFG), bilateral superior frontal gyrus (SFG) was significantly decreased in both mPBD and ePBD patients, and volume of left thalamus and cortical thickness of right MFG significantly decreased in mPBD patients. Compared to that of the HCs and ePBD subjects, thalamo-frontal hyperconnectivity with MFG was found in mPBD, and compared with that of HCs, thalamo-frontal hypoconnectivity with precentral gyrus/SFG was found in ePBD. In ePBD patients, episode times positively correlated with FC values between thalamus and precentral gyrus.The findings of the present study demonstrate detailed knowledge regarding shared and specific structural and functional disruption in thalamo-frontal loop in mPBD and ePBD subjects. Thalamo-frontal abnormalities reported in adult BD subjects were also observed in adolescent BD patients, and thalamo-frontal dysfunction may be a crucial treatment target in BD.