Predicting Antibiotic Tolerance in hvKP and cKP Respiratory Infections Through Biofilm Formation Analysis and Its Resistance Implications.

Introduction: Respiratory infections are a major global health concern, with Klebsiella pneumoniae standing out due to its evolving antibiotic resistance. This study compares the resistance profiles of hypervirulent Klebsiella pneumoniae (hvKP) and classical Klebsiella pneumoniae (cKP), aiming to shed light on their clinical implications. Methods: We analyzed 86 cases, comprising 42 hvKP and 44 cKP strains, using comprehensive antimicrobial susceptibility testing and clinical data evaluation to assess antibiotic tolerance and resistance mechanisms. Results: Our findings reveal distinct resistance patterns between hvKP and cKP, highlighting the role of chromosomal mutations and plasmid-mediated gene transfer in conferring antibiotic resistance. Notably, hvKP strains exhibited unique resistance trends, including the production of extended-spectrum ß-lactamases (ESBLs) and carbapenemases, differing from those of cKP. Discussion: This research underscores the importance of continuous surveillance and the development of targeted therapies against antibiotic-resistant Klebsiella pneumoniae. It emphasizes the critical need for judicious antibiotic use and novel therapeutic approaches to combat respiratory infections caused by these increasingly resistant pathogens.

Development and validation of a nomogram model for accurately predicting severe fatigue in maintenance hemodialysis patients: A multicenter cross-sectional study in China.

INTRODUCTION: This study aims to analyze the risk factors for severe fatigue in maintenance hemodialysis (MHD) patients and develop a clinical prediction model to help doctors and patients prevent severe fatigue. METHODS: Multicentre MHD patients were included in this study. The objective was to investigate the risk factors for severe fatigue in MHD patients and develop a prediction model. RESULTS: A total of 243 MHD patients were included in the study, and the incidence of severe fatigue was found to be 20.99%. Using age, body mass index, total cholesterol, and albumin levels, a predictive nomogram for fatigue was constructed. In the training set, the nomogram had an area under the curve of 0.851, sensitivity of 82.86%, specificity of 81.76%, and c-index of 0.851. The nomogram was accurate in calibration and proved to be clinically useful. CONCLUSION: The nomogram developed in this study is a practical and reliable tool for quickly identifying severe fatigue in MHD patients.

Modeling greenhouse gas emissions from biological wastewater treatment process with experimental verification: A case study of paper mill.

Wastewater treatment plants (WWTPs) have been regarded as the main sources of greenhouse gas (GHG) emissions. This study compares the influent characteristics of industrial wastewater represented by the WWTP of paper mill and that of domestic sewage represented by the Benchmark Simulation Model No. 1 (BSM1) under stormy weather. The various sources of GHG emissions from the two processes are calculated, and the contribution of each source to the total GHG emissions is assessed. Firstly, based on the mass balance analysis and the recognized emission factors, a GHG emission calculation model was established for the on-site and off-site GHG emission sources from the WWTP of paper mill. Simultaneously, a GHG emission experimental model was established by determining the dissolved concentrations of carbon dioxide (CO2) and nitrous oxide (N2O) in the papermaking wastewater, to verify the accuracy of the developed GHG calculation model. Subsequently, an optimum aeration rate for the paper mill was investigated to comply with the discharging norms. Under the optimum aeration rate of 10 h-1, the obtained calculation accuracies of CO2 and N2O emissions were 94.6 % and 91.1 %, respectively. The mean total GHG emission in the WWTP of paper mill was 550 kg CO2-eq·h-1, of which 44.6 % came from the on-site emission sources and 55.4 % from the off-site emission sources. It was also uncovered that the electrical consumption for aeration was the largest contributor to the total GHG emissions with a proportion of 25.2 %, revealing that the control strategy of the aeration rate is highly significant in reducing GHG emissions in WWTP of paper mills.

[Study on the management of granulation during surgery for congenital preauricular fistula infection stage].

Objective:To investigate the management of granulation tissue during surgery for infected congenital preauricular fistula and to assess the surgical outcomes. Methods:To summarize the surgical methods and the treatment of granulation methods in 140 cases of congenital preauricular fistula during the period of infection treated in our department from January 2018 to September 2022. The study divided patients into an observation group （79 patients） undergoing fistulectomy without granulation treatment, and a control group （61 patients） where fistulectomy and granulation resection were performed concurrently.. After six months of follow-up, the wound healing, recurrence rates, and the aesthetic assessment of granulation healing were evaluated using the Stony Brook Scar Evaluation Scale（SBSES）. Results:The two surgical approaches were applied to a total of 140 patients with infected congenital preauricular fistula. There was no statistical difference in wound healing and recurrence rates between the observation group and the control group. However, the observation group exhibited smaller scars. Conclusion:In cases of infected congenital preauricular fistula, surgical removal without excising granulation tissue is feasible, leading to effective healing and lesser scar formation.

GRP78 improves the therapeutic effect of mesenchymal stem cells on hemorrhagic shock-induced liver injury: Involvement of the NF-кB and HO-1/Nrf-2 pathways.

Mesenchymal stem cells (MSCs) are a popular cell source for repairing the liver. Improving the survival rate and colonization time of MSCs may significantly improve the therapeutic outcomes of MSCs. Studies showed that 78-kDa glucose-regulated protein (GRP78) expression improves cell viability and migration. This study aims to examine whether GRP78 overexpression improves the efficacy of rat bone marrow-derived MSCs (rBMSCs) in HS-induced liver damage. Bone marrow was isolated from the femurs and tibias of rats. rBMSCs were transfected with a GFP-labeled GRP78 expression vector. Flow cytometry, transwell invasion assay, scratch assay immunoblotting, TUNEL assay, MTT assay, and ELISA were carried out. The results showed that GRP78 overexpression enhanced the migration and invasion of rBMSCs. Moreover, GRP78-overexpressing rBMSCs relieved liver damage, repressed liver oxidative stress, and inhibited apoptosis. We found that overexpression of GRP78 in rBMSCs inhibited activation of the NLRP3 inflammasome, significantly decreased the levels of inflammatory factors, and decreased the expression of CD68. Notably, GRP78 overexpression activated the Nrf-2/HO-1 pathway and inhibited the NF-κB pathway. High expression of GRP78 efficiently enhanced the effect of rBMSC therapy. GRP78 may be a potential target to improve the therapeutic efficacy of BMSCs.

Mesenchymal stem cells overexpressing PBX1 alleviates haemorrhagic shock-induced kidney damage by inhibiting NF-κB activation.

Mesenchymal stem cells (MSCs) have favourable outcomes in the treatment of kidney diseases. Pre-B-cell leukaemia transcription factor 1 (PBX1) has been reported to be a regulator of self-renewal of stem cells. Whether PBX1 is beneficial to MSCs in the treatment of haemorrhagic shock (HS)-induced kidney damage is unknown. We overexpressed PBX1 in rat bone marrow-derived mesenchymal stem cells (rBMSCs) and human bone marrow-derived mesenchymal stem cells (hBMSCs) to treat rats with HS and hypoxia-treated human proximal tubule epithelial cells (HK-2), respectively. The results indicated that PBX1 enhanced the homing capacity of rBMSCs to kidney tissues and that treatment with rBMSCs overexpressing PBX1 improved the indicators of kidney function, alleviated structural damage to kidney tissues. Furthermore, administration with rBMSCs overexpressing PBX1 inhibited HS-induced NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome activation and the release of proinflammatory cytokines, and further attenuated apoptosis. We then determined whether NF-κB, an important factor in NLRP3 activation and the regulation of inflammation, participates in HS-induced kidney damage, and we found that rBMSCs overexpressing PBX1 inhibited NF-κB activation by decreasing the p-IκBα/IκBα and p-p65/p65 ratios and inhibiting the nuclear translocation and decreasing the DNA-binding capacity of NF-κB. hBMSCs overexpressing PBX1 also exhibited protective effects on HK-2 cells exposed to hypoxia, as shown by the increase in cell viability, the mitigation of apoptosis, the decrease in inflammation, and the inhibition of NF-κB and NLRP3 inflammasome activation. Our study demonstrates that MSCs overexpressing PBX1 ameliorates HS-induced kidney damage by inhibiting NF-κB pathway-mediated NLRP3 inflammasome activation and the inflammatory response.

Suppresses of LIM kinase 2 promotes radiosensitivity in radioresistant non-small cell lung cancer cells.

Radiation resistance has always been one of the main obstacles to tumor radiotherapy. Therefore, understanding the mechanisms underlying radiotherapy resistance is a focus of research. In this study, we induced two radiation-resistant cell lines to mimic the radiation resistance of NSCLC and investigated the mechanisms of radiotherapy resistance. Cell radiosensitivity was analyzed by single-cell gel electrophoresis, colony formation and tumor sphere formation assays. A wound healing assay was used to analyze cell migration. Western blotting and siRNA were used to identify the potential mechanism. In animal model experiments, xenograft tumors were used to verify the difference between radiotherapy-resistant and nonresistant NSCLC models after radiotherapy. Our results showed that NSCLC radiation-resistant cells exhibited more radioresistance and migratory abilities under low-dose irradiation. The expression of LIMK2 and p-CFL1 were upregulated in NSCLC radiation-resistant cells. Knockdown of LIMK2 significantly enhanced the radiosensitivity of NSCLC-resistant cells. In vivo, low-dose radiotherapy suppressed tumor growth, induced apoptosis and upregulated the expression of LIMK2 in xenograft tumors. However, radiotherapy had little effect on the NSCLC radiation resistance model. In conclusion, NSCLC radiation-resistant cells exhibit more radioresistance and migratory ability under low-dose irradiation. Strikingly, knockdown of LIMK2 enhanced the radiosensitivity of NSCLC-resistant cells.

Effect and Mode of Different Concentrations of Citrus Peel Extract Treatment on Browning of Fresh-Cut Sweetpotato.

Browning is one of the main phenomena limiting the production of fresh-cut sweetpotatoes. This study investigated the anti-browning effect of citrus peel extracts and the key components and modes of action associated with browning in fresh-cut sweetpotatoes. Five different concentrations of citrus peel extract (1, 1.5, 2, 2.5 and 3 g/L) were selected to ensure storage quality; and the physical and chemical properties of fresh-cut sweetpotato slices were analysed. A concentration of 2 g/L of citrus peel extract significantly inhibited the browning of fresh-cut sweetpotatoes. The results showed that the browning index and textural characteristics of fresh-cut sweetpotatoes improved significantly after treatment with citrus peel extract; all the citrus peel extract solutions inhibited browning to some extent compared to the control. In addition; LC-IMS-QTOFMS analysis revealed a total of 1366 components in citrus peel extract; the evaluation of citrus peel extract monomeric components that prevent browning in fresh-cut sweetpotato indicated that the components with better anti-browning effects were citrulloside, hesperidin, sage secondary glycosides, isorhamnetin and quercetin. The molecular docking results suggest that citrullosides play a key role in the browning of fresh-cut sweetpotatoes. In this study, the optimum amount of citrus peel extract concentration was found to be 2 g/L.

Combination effects of baicalin with linezolid against Staphylococcus aureus biofilm-related infections: in vivo animal model.

Staphylococcus aureus is a gram-positive bacterium that can produce biofilm, and biofilm-associated infections are difficult to control. Biofilm prevents antibiotics from penetrating and killing the bacteria. Combined use of antimicrobials is a common strategy to treat S. aureus biofilm-related infections. In this in vivo study, the clinically isolated strain of S. aureus 17546 (t037) was selected to establish a biofilm-associated infection rat model, and baicalin and linezolid were used to treat the infection. CFU counting was used to determine the bacteria within the biofilm, the biofilm structure was viewed using scanning electron microscopy (SEM), histopathology was performed, and inflammatory factors were analyzed by ELISA. Baicalin was efficient in destroying the biofilm and exerted a synergistic bactericidal effect when combined with linezolid. Based on these findings, baicalin combined with linezolid may be efficacious in controlling S. aureus biofilm-related infections.

HSF1 enhances the attenuation of exosomes from mesenchymal stem cells to hemorrhagic shock induced lung injury by altering the protein profile of exosomes.

Severe hemorrhagic shock (HS) leads to lung injury, resulting in respiratory insufficiency. Mesenchymal stem cell (MSC)-derived exosomes have therapeutic effects on the organ injury. HSF1 has been reported to protect the lung against injury. In this study, the role of exosomes from HSF1-overexpressed MSCs (HSF1-EVs) in HS-induced lung injury was investigated. We constructed a mouse model of lung injury by induction with HS and pre-treated it with HSF1-EVs. It was clarified that HSF1-EVs manifested better protective effects on HS-induced lung injury compared with the exosomes derived from control MSCs. Inhalation of HSF1-EVs declined the ratio of wet to dry and total protein concentration in bronchoalveolar lavage fluids. Besides, HSF1-EVs greatly inhibited the production of inflammatory cytokines (IL-1ß, IL-6, MCP-1 and HMGB1), and constrained the pulmonary neutrophilic infiltration induced by HS. A reduction of oxidative stress was observed in HSF1-EV-treated mice. HSF1-EVs suppressed the HS-induced apoptosis of lung cell and downregulated Bcl-2 expression, while promoting Bax expression. The key proteins of pulmonary epithelial barrier, E-cadherin, ZO-1 and Occludin, were all upregulated in HS-treated mice after HSF1-EV inhalation, suggesting that HSF1-EVs played a protective role in the epithelial barrier of lung. Additionally, the results of proteomics showed that HSF1 overexpression altered the protein profile of MSC-derived exosomes, which might explain the more significant relief effect of HSF1-EVs on lung injury compared with that of Plasmid-EVs. These new findings demonstrated that the exosomes secreted by HSF1-overexpressed MSCs can be an effective precautionary measure for lung injury induced by HS.

Cryptotanshinone ameliorates hemorrhagic shock-induced liver injury via activating the Nrf2 signaling pathway.

INTRODUCTION: Hemorrhagic shock (HS) is an important cause of high mortality in traumatized patients. Cryptotanshinone (CTS) is a bioactive compound extracted from Salvia miltiorrhiza Bunge (Danshen). The current study aimed to explore the effect and underlying mechanism of CTS on the liver injury induced by HS. MATERIAL AND METHODS: Male Sprague-Dawley rats were used to establish the HS model by hemorrhaging and monitoring mean arterial pressure (MAP). CTS was intravenously administered at concentration of 3.5 mg/kg, 7 mg/kg, or 14 mg/kg 30 minutes before resuscitation. Twenty-four hours after resuscitation, the liver tissue and serum samples were collected for the following examinations. Hematoxylin and eosin (H&E) staining was used to evaluate hepatic morphology changes. The myeloperoxidase (MPO) activity in liver tissue and the serum activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were examined to reveal the extent of liver injury. The protein expression of Bax and Bcl-2 in liver tissue was detected by western blot. The TUNEL assay determined the apoptosis of hepatocytes. Oxidative stress of liver tissue was assessed by the examination of reactive oxygen species (ROS) generation. The content of malondialdehyde (MDA), glutathione (GSH), and adenosine triphosphate (ATP), the activity of superoxide dismutase (SOD) and oxidative chain complexes (complex I, II, III, IV), as well as cytochrome c expression in cytoplasm and mitochondria, were also used to determine the extent of oxidative injury in the liver. Immunofluorescence (IF) was employed to estimate nuclear factor E2-related factor 2 (Nrf2) expression. The mRNA and protein levels of heme oxygenase 1 (HO-1), NAD(P)H: quinone oxidoreductases 1 (NQO1), cyclooxygenase-2 (COX-2), and nitric oxide synthase (iNOS) were assessed by real-time qPCR, western blot to investigate the mechanism of CTS regulating HS-induced liver injury. RESULTS: H&E staining and a histological score of rat liver suggested that HS induced liver injury. The activity of ALT, AST, and MPO was significantly increased by HS treatment. After CTS administration the ALT, AST, and MPO activities were suppressed, which indicates the liver injury was alleviated by CTS. The HS-induced upregulation of the TUNEL-positive cell rate was suppressed by various doses of CTS. HS-induced ROS production was decreased and the protein expression of Bax and Bcl-2 in the HS-induced rat liver was reversed by CTS administration. In the liver of HS-induced rats, the upregulation of MDA content and the downregulation of GSH content and SOD activitywere suppressed by CTS. Additionally, CTS increases ATP content and mitochondrial oxidative complexes activities and suppressed the release of cytochrome c from mitochondria to the cytoplasm. Moreover, IF and western blot demonstrated that the activation of Nrf2 blocked by HS was recovered by different doses of CTS in liver tissue. The expression of downstream enzymes of the Nrf2 pathway, including HO-1, NQO1, COX-2, and iNOS, was reversed by CTS in the HS rat model. CONCLUSIONS: The current study for the first time revealed the protective effect of CTS in HS-induced liver injury. CTS effectively recovered hepatocyte apoptosis, oxidative stress, and mitochondria damage induced by HS in the rat liver partly via regulating the Nrf2 signaling pathway.

Enhanced enzyme thermostability of a family I.3 lipase LipSR1 by T118A mutation at the calcium-binding site.

OBJECTIVES: The lipase gene lipSR1 isolated from oil-contaminated soil exhibits high hydrolytic activity for short-chain fatty acid substrates. A single calcium ion is required to anchor the lid of LipSR1 in an open conformation by coordination with two aspartate residues and three other residues in the lid. The lid of LipSR1 is anchored by Ca2+, which is coordinated by side-chain carboxyl oxygens of Asp153 and Asp157, carbonyl oxygens of Thr118 and Ser144, and the side chain of Gln120. RESULTS: D157A, D153R, Q120A, S144A, and T118A mutants were produced by site-directed mutagenesis in this study. Analyses of hydrolytic activity and thermostability showed that the properties of D157A, D153R, Q120A, and S144A were almost lost, suggesting that Asp157, Asp153, Gln120, and Ser144 are important residues for LipSR1. However, the catalytic performance of T118A was clearly maintained. Moreover, the thermostability of mutant T118A was higher than that of wild-type LipSR1. CONCLUSIONS: These results indicated that mutation of threonine at position 118 improved the stability of the enzyme at high temperature.

Carboxymethylated Alginate-Resiquimod Micelles Reverse the Immunosuppressive Tumor Microenvironment and Synergistically Enhance the Chemotherapy and Immunotherapy for Gastric Cancer.

Due to the intrinsic weak immunogenicity of tumor cells and the quantitatively and functionally different populations of immune cells, immunosuppression has become the major obstacle for cancer immunotherapy. In this study, the biocompatible alginate was chemically modified with the carboxyethyl linker to facilitate the esterification reaction of the resultant carboxymethylated alginate (CMA) and resiquimod (R848), the agonist of Toll-like receptor 7/8 (TLR7/8a). In aqueous solution, the hydrophilic CMA and the hydrophobic R848 formed stable nanomicelles (CMA-R848) by self-assembling. After combined administration of CMA-R848 and cisplatin (Cis) in a gastric cancer (GC) model, the long-circulating CMA-R848 micelle reached the mild acidic tumor microenvironment (TME); the ester bonds were quickly cleaved by the ubiquitous esterase and released the single molecule of R848. In vitro and in vivo results demonstrated that the released R848 efficiently promoted co-stimulatory molecules' expression of dendritic cells (DCs), enhanced the antigen uptake and cross-presentation, and primed the cytotoxic T lymphocytes' (CTLs) infiltration and killing effects, thereby reprogramming the "cold tumor" into the "hot tumor". In addition, the ex vivo tumor sections revealed that the released R848 effectively repolarized the M2-like tumor-associated macrophages (TAMs) into M1-like macrophages, exerted synergistic antitumor activity, reduced the tumor burden, and prolonged the overall survival duration of the GC animal model. Our study provided a targeting therapeutic strategy overcoming the limitations of R848 in vivo, and enhanced the efficacy of GC chemotherapy and immunotherapy by TME modulation.

Artificial Proteins Designed from G3LEA Contribute to Enhancement of Oxidation Tolerance in E. coli in a Chaperone-like Manner.

G3LEA is a family of proteins that exhibit chaperone-like activity when under distinct stress. In previous research, DosH was identified as a G3LEA protein from model extremophile-Deinococcus radiodurans R1 with a crucial core HD domain consisting of eight 11-mer motifs. However, the roles of motifs participating in the process of resistance to stress and their underlying mechanisms remain unclear. Here, eight different proteins with tandem repeats of the same motif were synthesized, named Motif1-8, respectively, whose function and structure were discussed. In this way, the role of each motif in the HD domain can be comprehensively analyzed, which can help in finding possibly crucial amino acid sites. Circular dichroism results showed that all proteins were intrinsically ordered in phosphate buffer, and changed into more α-helical ordered structures with the addition of trifluoroethanol and glycerol. Transformants expressing artificial proteins had significantly higher stress resistance to oxidation, desiccation, salinity and freezing compared with the control group; E. coli with Motif1 and Motif8 had more outstanding performance in particular. Moreover, enzymes and membrane protein protection viability suggested that Motif1 and Motif8 had more positive influences on various molecules, demonstrating a protective role in a chaperone-like manner. Based on these results, the artificial proteins synthesized according to the rule of 11-mer motifs have a similar function to wildtype protein. Regarding the sequence in all motifs, there are more amino acids to produce H bonds and α-helices, and more amino acids to promote interaction between proteins in Motif1 and Motif8; in addition, considering linkers, there are possibly more amino acids forming α-helix and binding substrates in these two proteins, which potentially provides some ideas for us to design potential ideal stress-response elements for synthetic biology. Therefore, the amino acid composition of the 11-mer motif and linker is likely responsible for its biological function.

High-intensity ultrasound modified the functional properties of Neosalanx taihuensis myofibrillar protein and improved its emulsion stability.

This study aimed to investigate the effects of high-intensity ultrasound treatment on the functional properties and emulsion stability of Neosalanx taihuensis myofibrillar protein (MP). The results showed that the carbonyl groups, emulsification properties, intrinsic fluorescence intensity, and surface hydrophobicity of the ultrasound treated MP solution were increased compared to the MP without ultrasound treatment. The results of secondary structure showed that the ultrasound treatment could cause a huge increase of ß-sheet and a decline of α-helix of MP, indicating that ultrasound induced molecular unfolding and stretching. Moreover, ultrasound reduced the content of total sulfhydryl and led to a certain degree of MP cross-linking. The microscopic morphology of MP emulsion indicated that the emulsion droplet decreased with the increase of ultrasound power. In addition, ultrasound could also increase the storage modulus of the MP emulsion. The results for the lipid oxidation products indicated that ultrasound significantly improved the oxidative stability of N. taihuensis MP emulsions. This study offers an important reference theoretically for the ultrasound modification of aquatic proteins and the future development of N. taihuensis deep-processed products represented by surimi.

Epicatechin Inhibited Lipid Oxidation and Protein Lipoxidation in a Fish Oil-Fortified Dairy Mimicking System.

In this study, a typical tea polyphenol epicatechin (EC) was investigated for its impact on the oxidative stability of whey protein isolate (WPI) in a fish oil-fortified emulsion. The oil-in-water emulsion system consisted of fish oil (1%, w/w), WPI (6 mg/mL), and EC (0.1, 1, and 2 mM), and the oxidation reaction was catalyzed by Fenton's reagent at 25 °C for 24 h. The results showed EC exhibited a dose-dependent activity in the reduction of lipid oxidation (TBARS) and protein carbonylation. A Western blot analysis demonstrated that protein lipoxidation was inhibited by EC via interrupting the covalent binding of lipid secondary oxidation products, MDA, onto proteins. In addition, protein lipoxidation induced a loss of tryptophan fluorescence, and protein hydrolysis was partially recovered by EC. The findings of this study provide an in-depth understanding of the performance of phenolic antioxidants in relieving lipid oxidation and subsequent protein lipoxidation in oil-containing dairy products.

Baicalin Ameliorates Lung Injury in Rats by Inhibiting NLRP3 Inflammasome Activation via NF-[Formula: see text]B Signaling Pathway.

Hemorrhagic shock (HS) is defined as a reduction in tissue oxygenation and organ dysfunction due to severe blood loss. Lung injury is a frequent complication of HS. Baicalin, isolated from Radix Scutellariae, has been reported to profile the antitumor, anti-oxidative, anti-inflammatory, and antibacterial roles in various pathological processes. Nevertheless, the effects of baicalin on HS-induced lung injury are unclear. This study aims to examine the therapeutic effects of baicalin on lung injury. We first established the lung injury rat models by withdrawing blood in the femoral artery followed by resuscitation. A pathological analysis showed that HS-administrated rats presented severe capillary leakage and pulmonary edema, while baicalin therapy alleviated the symptoms. Baicalin therapy reduced the number of macrophages and neutrophils in bronchoalveolar lavage fluid and decreased the expression and activity of myeloperoxidase (neutrophile infiltration marker) in the lung tissues of HS rats, indicating that baicalin alleviated HS-induced infiltration of inflammatory cells. The secretion of inflammatory cytokines, including interleukin (IL)-1[Formula: see text], IL-6, IL-18, and tumor necrosis factor [Formula: see text] (TNF-[Formula: see text]), as well as the activation of the nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing-3 (NLRP3) inflammasome, were inhibited by baicalin administration. Furthermore, we found that the NF-[Formula: see text]B pathway, a canonical pro-inflammatory pathway, was also blocked after treatment with baicalin in HS-evoked rats, as indicated by the decreased expression of p65 and p65 phosphorylation in the lung tissues. In summary, we infer that baicalin may exert a protective role in HS-induced lung injury by suppressing the activation of NLRP3 inflammasome via the NF-[Formula: see text]B pathway.

Synergistic Effects of Baicalin and Levofloxacin Against Hypervirulent Klebsiella pneumoniae Biofilm In Vitro.

Hypervirulent Klebsiella pneumoniae (hvKp) strains that form biofilms have recently emerged worldwide; however, the mechanisms underlying biofilm formation and disruption remain elusive. In this study, we established a hvKp biofilm model, investigated its in vitro formation pattern, and determined the mechanism of biofilm destruction by baicalin (BA) and levofloxacin (LEV). Our results revealed that hvKp exhibited a strong biofilm-forming ability, forming early and mature biofilms after 3 and 5 d, respectively. Early biofilm and bacterial burden were significantly reduced by BA + LEV and EM + LEV treatments, which destroyed the 3D structure of early biofilms. Conversely, these treatments were less effective against mature biofilm. The expression of both AcrA and wbbM was significantly downregulated in the BA + LEV group. These findings indicated that BA + LEV might inhibit the formation of hvKp biofilm by altering the expression of genes regulating efflux pumps and lipopolysaccharide biosynthesis.

KDM4A, involved in the inflammatory and oxidative stress caused by traumatic brain injury-hemorrhagic shock, partly through the regulation of the microglia M1 polarization.

BACKGROUND: Microglial polarization and the subsequent neuroinflammatory response and oxidative stress are contributing factors for traumatic brain injury (TBI) plus hemorrhagic shock (HS) induced brain injury. In the present work, we have explored whether Lysine (K)-specific demethylase 4 A (KDM4A) modulates microglia M1 polarization in the TBI and HS mice. RESULTS: Male C57BL/6J mice were used to investigate the microglia polarization in the TBI + HS model in vivo. Lipopolysaccharide (LPS)-induced BV2 cells were used to examine the mechanism of KDM4A in regulating microglia polarization in vitro. We found that TBI + HS resulted in neuronal loss and microglia M1 polarization in vivo, reflected by the increased level of Iba1, tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, malondialdehyde (MDA) and the decreased level of reduced glutathione (GSH). Additionally, KDM4A was upregulated in response to TBI + HS and microglia were among the cell types showing the increased level of KDM4A. Similar to the results in vivo, KDM4A also highly expressed in LPS-induced BV2 cells. LPS-induced BV2 cells exhibited enhanced microglia M1 polarization, and enhanced level of pro-inflammatory cytokines, oxidative stress and reactive oxygen species (ROS), while this enhancement was abolished by the suppression of KDM4A. CONCLUSION: Accordingly, our findings indicated that KDM4A was upregulated in response to TBI + HS and microglia were among the cell types showing the increased level of KDM4A. The important role of KDM4A in TBI + HS-induced inflammatory response and oxidative stress was at least partially realized through regulating microglia M1 polarization.

Sirtuin3 confers protection against acute pulmonary embolism through anti-inflammation, and anti-oxidative stress, and anti-apoptosis properties: participation of the AMP-activated protein kinase/mammalian target of rapamycin pathway.

An increasing number of studies have suggested that oxidative stress and inflammation play momentous roles in acute pulmonary embolism (APE). Honokiol, a bioactive biphenolic phytochemical substance, is known for its strong anti-oxidative and anti-inflammatory effects, and it served as an activator of sirtuin3 (SIRT3) in the present study. The purposes of the study were to explore the effects of honokiol on APE rats and investigate whether the function of honokiol is mediated by SIRT3 activation. In the study, the rats received a right femoral vein injection of dextran gel G-50 particles (12 mg/kg) to establish the APE model and were subsequently administered honokiol and/or a selective SIRT3 inhibitor 3-(1H-1,2,3-triazol-4-yl)pyridine (3-TYP; 5 mg/kg) intraperitoneally. The results showed that SIRT3 activation by honokiol attenuated the loss in lung function, ameliorated the inflammatory response and oxidative damage, and inhibited apoptosis in lung tissues of the rats with APE but that this was reversed by 3-TYP. In addition, we found that the AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway might be activated by honokiol but restrained by 3-TYP. These results indicated that honokiol was capable of suppressing the adverse effects of APE and that this was diminished by SIRT3 suppression, implying that activation of SIRT3 might serve as a therapeutic method for APE.