Corrigendum: TAT-HSP27 peptide improves neurologic deficits via reducing apoptosis after experimental subarachnoid hemorrhage.

[This corrects the article DOI: 10.3389/fncel.2022.878673.].

Identification of NOX4 as a New Biomarker in Hepatocellular Carcinoma and Its Effect on Sorafenib Therapy.

To improve the survival of patients with hepatocellular carcinoma (HCC), new biomarkers and therapeutic targets are urgently needed. In this study, the GEO and TCGA dataset were used to explore the differential co-expressed genes and their prognostic correlation between HCC and normal samples. The mRNA levels of these genes were validated by qRT-PCR in 20 paired fresh HCC samples. The results demonstrated that the eight-gene model was effective in predicting the prognosis of HCC patients in the validation cohorts. Based on qRT-PCR results, NOX4 was selected to further explore biological functions within the model and 150 cases of paraffin-embedded HCC tissues were scored for NOX4 immunohistochemical staining. We found that the NOX4 expression was significantly upregulated in HCC and was associated with poor survival. In terms of function, the knockdown of NOX4 markedly inhibited the progression of HCC in vivo and in vitro. Mechanistic studies suggested that NOX4 promotes HCC progression through the activation of the epithelial-mesenchymal transition. In addition, the sensitivity of HCC cells to sorafenib treatment was obviously decreased after NOX4 overexpression. Taken together, this study reveals NOX4 as a potential therapeutic target for HCC and a biomarker for predicting the sorafenib treatment response.

Characterization and Antioxidant Evaluation of Four Kinds of Marine Oils in vitro.

The objective of this study was to characterize the lipid class and fatty acid composition of four kinds of marine oils including Phaeodactylum tricornutum oil (PO), Laminaria japonica oil (LO), krill oil (KO) and fish oil (FO), and evaluate their antioxidant capacities in vitro. The results indicated that compared to other three oils, PO showed the highest contents of total lipids and fucoxanthin (194.70 and 7.48 mg/g dry weight, respectively), the relatively higher content of long-chain polyunsaturated fatty acids including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (30.94 % in total fatty acids), and total phenolic content (675.88 mg gallic acid equivalent /100 g lipids), thereby contribute to great advantages in scavenging free radicals such as 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2-azino-bis (3-ethylbenzthiazoline)-6-sulfonic acid (ABTS), peroxyl radical, as well as reducing FRAP value. In conclusion, PO should be considered as a potential ingredient for dietary supplement with antioxidant capacity.

TAT-HSP27 Peptide Improves Neurologic Deficits via Reducing Apoptosis After Experimental Subarachnoid Hemorrhage.

Cell apoptosis plays an important role in early brain injury (EBI) after subarachnoid hemorrhage (SAH). Heat shock protein 27 (HSP27), a member of the small heat shock protein (HSP) family, is induced by various stress factors and exerts protective role on cells. However, the role of HSP27 in brain injury after SAH needs to be further clarified. Here, we reported that HSP27 level of cerebrospinal fluid (CSF) is increased obviously at day 1 in patients with aneurysmal SAH (aSAH) and related to the grades of Hunt and Hess (HH), World Federation of Neurological Surgeons (WFNS), and Fisher score. In rat SAH model, HSP27 of CSF is first increased and then obviously declined; overexpression of HSP27, not knockdown of HSP27, attenuates SAH-induced neurological deficit and cell apoptosis in the basal cortex; and overexpression of HSP27 effectively suppresses SAH-elevated activation of mitogen-activated protein Kinase Kinase 4 (MKK4), the c-Jun N-terminal kinase (JNK), c-Jun, and caspase-3. In an in vitro hemolysate-damaged cortical neuron model, HSP2765-90 peptide effectively inhibits hemolysate-induced neuron death. Furthermore, TAT-HSP2765-90 peptide, a fusion peptide consisting of trans-activating regulatory protein (TAT) of HIV and HSP2765-90 peptide, effectively attenuates SAH-induced neurological deficit and cell apoptosis in the basal cortex of rats. Altogether, our results suggest that TAT-HSP27 peptide improves neurologic deficits via reducing apoptosis.

Therapeutic Effect of Darkling Beetle (Zophobas morio) Hemolymph on Skin Thermal Injury in Mice Infected by Staphylococcus haemolyticus.

Staphylococci are the most common pathogens isolated from skin infections in livestock or companion animals. Antibiotic therapy is the best treatment for infections, but local or systemic use of antimicrobials increases the risk of bacterial resistance. Insects are rich in antimicrobial peptides, which can reduce bacterial resistance and can be used to treat bacterial infections after skin burns. We propose that the use of the darkling beetle (Z. morio) hemolymph to treat skin infections in mice by Staphylococcus haemolyticus is one of the alternatives. Z. morio hemolymph alleviated the increase in wound area temperature in mice with a skin infection, reduced the bacterial load of the wound, and accelerated the wound healing speed significantly. Pathological sections showed that Z. morio hemolymph can significantly reduce inflammatory cell infiltration, and promote skin tissue repair. Real-time fluorescent quantitative polymerase chain reaction (PCR) revealed that the Z. morio hemolymph can significantly reduce the levels of pro-inflammatory cytokines, including interleukin-1 beta (IL-1ß), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and chemokine interleukin-8 (IL-8). Our findings suggest that Z. morio antibacterial hemolymph can promote wound contraction, relieve local inflammatory responses and promote wound healing in mice infected with a heat injury, which has a positive therapeutic effect and enormous potential for skin thermal injury.

Metformin Attenuates Silica-Induced Pulmonary Fibrosis by Activating Autophagy via the AMPK-mTOR Signaling Pathway.

Long-term exposure to crystalline silica particles leads to silicosis characterized by persistent inflammation and progressive fibrosis in the lung. So far, there is no specific treatment to cure the disease other than supportive care. In this study, we examined the effects of metformin, a prescribed drug for type || diabetes on silicosis and explored the possible mechanisms in an established rat silicosis model in vivo, and an in vitro co-cultured model containing human macrophages cells (THP-1) and human bronchial epithelial cells (HBEC). Our results showed that metformin significantly alleviated the inflammation and fibrosis of lung tissues of rats exposed to silica particles. Metformin significantly reduced silica particle-induced inflammatory cytokines including transforming growth factor-ß1 (TGF-ß1), tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) in rat lung tissue and HBEC culture supernatant. The protein levels of Vimentin and α-smooth muscle actin (α-SMA) were significantly decreased by metfomin while expression level of E-cadherin (E-Cad) increased. Besides, metformin increased the expression levels of phosphorylated adenosine 5'-monophosphate (AMP)-activated protein kinase (p-AMPK), microtubule-associated protein (MAP) light chain 3B (LC3B) and Beclin1 proteins, and reduced levels of phosphorylated mammalian target of rapamycin (p-mTOR) and p62 proteins in vivo and in vitro. These results suggest that metformin could inhibit silica-induced pulmonary fibrosis by activating autophagy through the AMPK-mTOR pathway.

Preparation of organic acid lignin submicrometer particle as a natural broad-spectrum photo-protection agent.

Valorization of lignin by-product is an urgent issue in the context of biorefinery. Lignin is a natural anti-UV active ingredient with great potential applications. In this study, a natural broad-spectrum photo-protection agent was prepared using lignin from organic acid extraction process. The submicrometer particles were prepared by dialysis lignin recovered from the pretreatments with organic acid extraction processes (formic acid, formic acid/hydrogen peroxide, and acetic acid/hydrogen peroxide/HCl) and they served as active ingredients in sunblock formulation. The structures of the lignin submicrometer particles were characterized by multiple spectroscopies. The submicrometer particles from organic acid lignin showed high capacities to enhance the sun protection factor values of lotion by 2.80-3.53 at the dosage of 5%, and the lotions containing lignin submicrometer particles had good UV-blocking properties. In addition, the UVA/UVB values (i.e., the ratio of absorbance at UVA to that at UVB) were in the range of 0.69-0.72 for the organic acid lignin submicrometer particles, indicating that they exhibited superior properties. The results indicated that the lignin submicrometer-based lotions with excellent antioxidant and UV protection capacities offered a natural source for sunblock cosmetics.

Polyaspartic acid (PASP)-urea and optimised nitrogen management increase the grain nitrogen concentration of rice.

Increase in grain nitrogen concentration (GNC), which is directly affected by nitrogen (N) application, can help overcome the issues of malnutrition. Here, the effects of urea type (polyaspartic acid (PASP) urea and conventional urea) and N management method (two splits and four splits) on GNC and N concentration of head rice were investigated in field experiments conducted in Sichuan, China, in 2014 and 2015. N concentration of grain and head rice were significantly (P < 0.05) increased by N redistribution from the leaf lamina, activities of glutamine synthetase (GS), and glutamate synthase (GOGAT) at the heading stage, and N concentration and GOGAT activity in the leaf lamina at the maturity stage. Compared to conventional urea, PASP-urea significantly improved N concentration of grain and head rice by improving the activities of GS and GOGAT, thereby increasing N distribution in the leaf lamina. The four splits method, unlike the two splits method, enhanced N concentration and activities of key N metabolism enzymes of leaf lamina, leading to increased GNC and N concentration in head rice too. Overall, four splits is a feasible method for using PASP-urea and improving GNC.

Conversion of poplar into bio-oil via subcritical hydrothermal liquefaction: Structure and antioxidant capacity.

Subcritical hydrothermal liquefaction of poplar was performed at 220-280 °C, and the liquid phase produced was extracted by ethyl acetate to obtain light oil (LO), which contained LO1 (water-soluble) and LO2 (ethyl acetate-soluble). The residue was further extracted with acetone to produce heavy oil (HO) and solid residue (SR). The highest bio-oil yield of 19.88% was obtained at 260 °C. The HO produced at 260 °C had the highest content of C (69.13%) and the higher heating value was 27.97 MJ/kg. The O/C and H/C ratios of LO were higher than those of HO due to less aromatics in LO. Oxidative inhibition rates of bio-oils, measured in DPPH-ethanol solution at a concentration of 0.1 mg/mL, reached 60.76% for LO1 while 90.29% and 90.85% for LO2 and HO, respectively. The bio-oil with good antioxidant activity can be utilized as an additive in bio-diesel to improve oxidation stability.

Torrefaction of corncob to produce charcoal under nitrogen and carbon dioxide atmospheres.

Corncob was torrefied under nitrogen and carbon dioxide atmospheres at 220-300 °C, obtaining solid products with mass yields of 69.38-95.03% and 67.20-94.99% and higher heating values of 16.58-24.77 MJ/kg and 16.68-24.10 MJ/kg, respectively. The changes of physicochemical properties of the charcoal was evaluated by many spectroscopies, contact angle determination, and combustion test. Hemicelluloses were not detected for the torrefaction under the hard conditions. As the severity increased, C concentration raised while H and O concentrations reduced. Combustion test showed that the burnout temperature of charcoal declined with the elevation of reaction temperature, and torrefaction at a high temperature shortened the time for the whole combustion process. Base on the data, torrefaction at 260 °C under carbon dioxide was recommended for the torrefaction of corncob.

Biphasic 2-methyltetrahydrofuran/oxalic acid/water pretreatment to enhance cellulose enzymatic hydrolysis and lignin valorization.

A biphasic pretreatment was adopted to disturb the recalcitrant structure of bamboo for further enzymatic hydrolysis and to obtain easily valorized lignin by-product. The biphasic system consisted of biomass-derived chemicals-2-methyltetrahydrofuran and oxalic acid as well as water, and the reactions were conducted at 120-180°C for 20min. The treatment resulted in notable removal of hemicelluloses and lignin. After the pretreatment, the cellulose conversion rate during enzymatic hydrolysis was enhanced by 6.7-fold as compared to the unpretreated raw material. Comprehensive analysis of the lignin product indicated that it exhibited representative structure (such as ß-O-4, ß-ß linkages) as compared to native lignin, contained a very low amount of contaminated sugars (0.67-2.39%), and had a relatively medium molecular weight (Mw 2240-3730g/mol) and good solubility in many organic solvents. This indicated that the lignin showed great potential application in conversion into materials and liquid fuels.

Valorization of bamboo by γ-valerolactone/acid/water to produce digestible cellulose, degraded sugars and lignin.

A novel pretreatment process was developed to achieve valorization of bamboo components into digestible cellulose, degraded sugars and lignin. In this case, bamboo was pretreated with 60% γ-valerolactone (GVL)/40% water containing 0.05mol/L H2SO4, yielding solid fraction rich in cellulose. The resulting liquor was further treated with the addition of NaCl and ultrasound, resulting in water phase rich in degraded sugars and GVL phase containing lignin, which was easy to recover. Results showed that the enzymatic hydrolysis was enhanced by 6.7-fold after treatment as compared to the control. The degraded sugars released in water phase contained monosaccharides (70.72-160.47g/kg) together with oligo- and polysaccharides (46.4-181.85g/kg). The lignin obtained had high purity, low molecular weight (1820-2970gmol-1) and low polydispersity (1.93-1.98). The present study creates a novel pretreatment process for the conversion of Gramineae biomass into useful feedstocks with potential applications in the fields of fuels, chemicals and polymers.

Localization of neonatal Fc receptor for IgG in aggregated lymphoid nodules area in abomasum of Bactrian camels (Camelus bactrianus) of different ages.

BACKGROUND: The neonatal Fc receptor (FcRn) plays a crucial role in transporting IgG and associated antigens across polarized epithelial barriers in mucosal immunity. However, it was not clear that FcRn expression in aggregated lymphoid nodules area (ALNA) in abomasum, a unique and important mucosal immune structure discovered only in Bactrian camels. In the present study, 27 Alashan Bactrian camels were divided into the following five age groups: fetus (10-13 months of gestation), young (1-2 years), pubertal (3-5 years), middle-aged (6-16 years) and old (17-20 years). The FcRn expressions were observed and analyzed in detail with histology, immunohistochemistry, micro-image analysis and statistical methods. RESULTS: The results showed that the FcRn was expressed in mucosal epithelial cells of ALNA from the fetus to the old group, although the expression level rapidly declined in old group; moreover, after the ALNA maturated, the FcRn expression level in the non-follicle-associated epithelium (non-FAE) was significantly higher than that in FAE (P < 0.05). In addition, the FcRn was also expressed in the vessel endothelium, smooth muscle tissue, and macrophages and dendritic cells (DCs) of secondary lymphoid follicles (sLFs). CONCLUSIONS: It was demonstrated that FcRn was mainly expressed in non-FAE, the effector sites, although which was expressed in FAE, the inductive sites for mucosal immunity. And it was also expressed in DCs and macrophages in sLFs of all ages of Bactrian camels. The results provided a powerful evidence that IgG (including HCAb) could participate in mucosal immune response and tolerance in ALNA of Bactrian camels through FcRn transmembrane transport.

Friend or foe: differential responses of rice to invasion by mutualistic or pathogenic fungi revealed by RNAseq and metabolite profiling.

The rice endophyte Harpophora oryzae shares a common pathogenic ancestor with the rice blast fungus Magnaporthe oryzae. Direct comparison of the interactions between a single plant species and two closely-related (1) pathogenic and (2) mutualistic fungi species can improve our understanding of the evolution of the interactions between plants and fungi that lead to either mutualistic or pathogenic interactions. Differences in the metabolome and transcriptome of rice in response to challenge by H. or M. oryzae were investigated with GC-MS, RNA-seq, and qRT-PCR. Levels of metabolites of the shikimate and lignin biosynthesis pathways increased continuously in the M. oryzae-challenged rice roots (Mo-roots); these pathways were initially induced, but then suppressed, in the H. oryzae-challenged rice roots (Ho-roots). Compared to control samples, concentrations of sucrose and maltose were reduced in the Ho-roots and Mo-roots. The expression of most genes encoding enzymes involved in glycolysis and the TCA cycle were suppressed in the Ho-roots, but enhanced in the Mo-roots. The suppressed glycolysis in Ho-roots would result in the accumulation of glucose and fructose which was not detected in the Mo-roots. A novel co-evolution pattern of fungi-host interaction is proposed which highlights the importance of plant host in the evolution of fungal symbioses.

[Relationship between bronchoalveolar lavage mycoplasma load and clinical characteristics in children with Mycoplasma pneumoniae pneumonia].

OBJECTIVE: Mycoplasma pneumoniae (MP) is an important pathogen for community-acquired pneumonia in children. MP infection was considered to be self-limited, but many severe refractory MP pneumonia cases have been reported in recent years. The reason for variation in severity of MP pneumonia remains unclear. MP virulence including drug-resistance and host immunologic function are important influencing factors. The present study aimed to clarify relationship between local MP load and severity of MP pneumonia. METHOD: MP DNA was quantitatively detected by fluorescent real-time PCR in bronchoalveolar lavage fluid (BALF) from 77 children with MP pneumonia. They were classified into groups of low MP load ( < 10(3)/ml, n = 14) , moderate MP load (10(3)-10(6)/ml, n = 22) and high MP load ( > 10(6)/ml, n = 41) . Clinical symptoms, main laboratory and imaging results of children among the three groups were compared. RESULT: When compared with low load group and moderate load group, high load group had longer fever duration (7 d, 10 d vs. 12 d) , longer time to normalization of temperature with macrolide administration (4 d, 8 d vs. 10 d) , more patients with high fever (50.0%, 68.2% vs. 87.8%) and longer duration of fever than 10 d (35.7%, 50.0% vs. 73.2%).Statistically significant difference existed in CRP among the three groups (1.0 mg/L, 11.5 mg/L, 34 mg/L). Large field of consolidation or atelectasis were found in 58.5% of high load patients, much higher than 22.7% in moderate load and 14.3% in low load patients. Bilateral or massive pleural effusion was not found in low load group, while in moderate load and high load group, they were 13.6% and 24.4%. However, no significant difference was found in symptoms and main laboratory and imaging results among different age groups in high load patients. CONCLUSION: There is a close relationship between MP load in BALF and clinical characteristics in children with MP pneumonia. Those with high MP load have a more severe process.

Investigation into the anti-thrombosis effect and contents of total saponins and flavonoids in the bioactive fraction of Naodesheng prescription.

ETHNOPHARMACOLOGICAL RELEVANCE: Naodesheng prescription is a widely used traditional Chinese medicine (TCM), and mainly applied in clinics to treat cerebral arteriosclerosis, ischemic stroke, sequelae of cerebral hemorrhage etc. AIM OF THE STUDY: The present study was designed to investigate the anti-thrombosis effects of this prescription, and to search its bioactive fraction. MATERIALS AND METHODS: We evaluated the anti-thrombotic effects by measuring platelet aggregation in rats, and the clotting time and protection rate in mice. The contents of total saponins and flavonoids in the bioactive fraction were determined by UV-vis spectrophotometry. RESULTS: The results showed that Naodesheng has significant anti-thrombotic and anticoagulation effects. The contents of total saponins and flavonoids in the bioactive fraction were 7.885% and 8.434%, respectively. CONCLUSIONS: Such study will contribute to further exploration of Naodesheng in the therapy of thrombosis diseases and to its re-development based on the bioactive fraction and ingredients.

[Mixed infections in children with Mycoplasma pneumoniae pneumonia].

OBJECTIVE: To investigate the incidence and clinical features of mixed infections in children with Mycoplasma pneumoniae (MP) pneumonia. METHOD: A total of 201 cases diagnosed as MP pneumonia were investigated for mixed infections by sputum bacterial culture, respiratory virus antigen detection and serum Chlamydia pneumoniae antibody test. For those with the indications for bronchoscopy, we also did bronchoalveolar lavage and lavage bacterial culture. RESULT: A high incidence (103/201, 51.2%) of mixed infections in children with MP pneumonia was revealed. The most frequent co-infected pathogen was Chlamydia pneumoniae (52, 25.9%), followed by viruses (29, 14.4%), and bacteria (22, 10.9%). Among viruses, respiratory syncytial virus was the most common (17, 8.5%), followed by adenovirus (6, 3.0%), parainfluenza virus type III (4, 2.0%) and influenza virus type B (2, 1.0%). Sputum bacterial culture was positive in 14/201 (7.0%) cases, Streptococcus pneumonia being most common (6, 3.0%). BALF culture yielded positive results in 11.6% (8/69), Streptococcus pneumonia was also common (5, 7.3%). Among 29 cases with MP and virus coinfection, 26 were younger than 3 years (89.7%), while for MP and Chlamydia pneumoniae coinfection, most of them were older than 3 years (40/52, 76.9%). Compared with non-mixed infections, those with mixed infections had longer fever duration (24.5% and 40.8% longer than 10 d), more frequently developed pleural effusion (11.2%, 23.3%) and large area of shadow in chest imaging (35.7%, 51.5%). White blood cell [(14.28 ± 4.99) × 10(9)/L], C-reactive protein (CRP) [69(32.5 - 99.5) mg/L] and neutrophil ratio in BALF [0.86 (0.63 - 0.91)] were much higher in children with mixed bacterial infections than that in non-mixed infections [(9.06 ± 3.47) × 10(9)/L, 3 (0 - 31.0) mg/L, 0.44 (0.03 - 0.88)]. But no significant difference was found in peripheral blood neutrophil proportion between mixed bacterial infections (0.38 ± 0.25) and non-mixed infections (0.51 ± 0.19). CONCLUSION: More than half of cases with MP pneumonia had mixed infections, most commonly caused by Chlamydia pneumonia followed by viruses. The incidence of mixed infections with bacteria was low. Mixed infections with virus were more common in young children, while mixed infection with Chlamydia pneumoniae was more common in older ones. Bacterial infections should be paid more attention, especially those caused by Streptococcus pneumoniae, for those with high peripheral white blood cell counts, high CRP levels and high proportion of neutrophils in BALF.

Multiple information contents derived from the chromatograms and their application to the modeling of quantitative profile-efficacy relationship.

Herbal medicine has been successfully applied in clinical therapeutics throughout the world. In this paper, various information contents in addition to a best-first search strategy are proposed for improving prediction quality of quantitative profile-efficacy relationship (QPER). As a demonstration, a QPER model was constructed to predict the blood-clotting time increasing effect of Naodesheng prescription, a widely used herbal medicine in China. Evaluated by both the self-consistency test and the rigorous jackknife test, the predictive accuracy was increased by feeding the model with the merged information contents compared to only with the common chromatographic peak areas. The confirmation experiment exhibited that the predicted blood-clotting time were well consistent with the observed values. Furthermore, it has not escaped from our notice that the important potential application of the current QPER model is to be extended to help search active fractions, which has attracted more and more attention in the re-developments of herbal medicines based on the active compounds.

[Simulation study of antithrombotic active fraction of Naodesheng by support vector machine].

OBJECTIVE: To screen the antithrombotic active fraction of Naodesheng. METHODS: The collagen and adrenaline-induced thrombosis by tail intravenous injection in mice was used. Based on orthogonal design, the support vector machine model was established for pharmacodynamics prediction of TCM prescriptions. RESULTS: The model established in this study could predict the drug actions of different combinations. CONCLUSION: The pharmacodynamic actions of several formulas are superior to that of the original formula and CD has the best effect.