The prognostic value of separate lymphatic invasion and vascular invasion in oesophageal squamous cell carcinoma: a meta-analysis and systematic review.

BACKGROUND: Lymphovascular invasion (LVI) is a factor correlated with a poor prognosis in oesophageal squamous cell carcinoma (ESCC). Lymphatic invasion (LI) and vascular invasion (VI) should be reported separately because they may indicate a difference in prognosis. The prognostic role of LI and VI in ESCC patients remains controversial. A meta-analysis was conducted to resolve this question. METHODS: We searched the PubMed, EMBASE, Web of Science, Scopus and Cochrane Library databases for studies on the association between LI and VI and the prognosis of patients with ESCC. The PICOs (Participant, Intervention, Comparison, Outcome) strategy were selected for the systematic review and meta-analysis. The effect size (ES) was the hazard ratio (HR) or relative ratio (RR) with 95% confidence intervals (CI) for overall survival (OS) and recurrence-free survival (RFS). RESULTS: A total of 27 studies with 5740 patients were included. We calculated the pooled results from univariate and multivariate analysis using the Cox proportional hazards method. The heterogeneity was acceptable in OS and RFS. According to the pooled results of multivariate analysis, both LI and VI were correlated with a worse OS. VI was a negative indicator for RFS, while the p value of VI was greater than 0.05. The prognostic role was weakened in subgroup analysis with studies using haematoxylin-eosin staining method. CONCLUSIONS: Both LI and VI were indicators of a worse OS outcome. LI was a more significant indicator in predicting a worse RFS. More larger sample studies with immunohistochemical staining and good designs are required to detect the prognostic value of separate LI and VI in ESCC.

Autophagy involvement in T lymphocyte signalling induced by nickel with quantitative phosphoproteomic analysis.

Nickel-induced allergic contact dermatitis (ACD) is a common skin disease. The mechanism by which nickel causes ACD is not clear. There is no treatment for it, only symptomatic therapy. However, due to the lifetime sensitization characteristics, the recurrence rate in patients is high. T lymphocytes play a key role in nickel-induced ACD. Elucidating the potential mechanism underlying nickel-induced T lymphocyte signalling might make it possible to achieve targeted treatment of nickel-induced ACD. In our study, a phosphoproteomic approach based on tandem mass tag (TMT) labelling and LCMS/MS analyses was employed. An animal model of nickel allergy was established. Splenic T lymphocytes were purified for quantitative phosphoproteomic analysis. The numbers of phosphoproteins, phosphopeptides and phosphosites identified in this study were 3072, 7977 and 10,200, respectively. Comprehensive gene ontology (GO) analysis combined with Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed that nickel can significantly affect the phosphorylation of the mTOR signalling pathway in T lymphocytes. Western blotting analysis was used to detect changes in the expression of autophagy-related proteins (Beclin 1, LC3II, and p62). Nickel allergy changed autophagy-related protein expression (p < 0.05). It has been demonstrated that nickel causes autophagy of T lymphocytes in the spleen. Using autophagy inhibitors to intervene, it was found that Th1 differentiation was inhibited, and the expression of Th1-related inflammatory factors was downregulated. Overall, the identification of relevant signalling pathways yielded new insights into the molecular mechanisms underlying nickel allergy and might help in the discovery and development of mechanism-based drugs.

Hydroquinones Inhibit Biofilm Formation and Virulence Factor Production in Staphylococcus aureus.

Staphylococcus aureus is one of the major pathogens responsible for antimicrobial resistance-associated death. S. aureus can secrete various exotoxins, and staphylococcal biofilms play critical roles in antibiotic tolerance and the persistence of chronic infections. Here, we investigated the inhibitory effects of 18 hydroquinones on biofilm formation and virulence factor production by S. aureus. It was found that 2,5-bis(1,1,3,3-tetramethylbutyl) hydroquinone (TBHQ) at 1 µg/mL efficiently inhibits biofilm formation by two methicillin-sensitive and two methicillin-resistant S. aureus strains with MICs of 5 µg/mL, whereas the backbone compound hydroquinone did not (MIC > 400 µg/mL). In addition, 2,3-dimethylhydroquinone and tert-butylhydroquinone at 50 µg/mL also exhibited antibiofilm activity. TBHQ at 1 µg/mL significantly decreased the hemolytic effect and lipase production by S. aureus, and at 5−50 µg/mL was non-toxic to the nematode Caenorhabditis elegans and did not adversely affect Brassica rapa seed germination or growth. Transcriptional analyses showed that TBHQ suppressed the expression of RNAIII (effector of quorum sensing). These results suggest that hydroquinones, particularly TBHQ, are potentially useful for inhibiting S. aureus biofilm formation and virulence.

Electromagnetic field exposure-induced depression features could be alleviated by heat acclimation based on remodeling the gut microbiota.

BACKGROUND: Electromagnetic pollution cannot be ignored. Long-term low-dose electromagnetic field (EMF) exposure can cause central nervous system dysfunction without effective prevention. MATERIALS/METHODS: Male C57BL/6J mice (6-8 weeks, 17-20 g) were used in this study. Depression-like and anxiety-like behaviors detected by behavioral experiments were compared among different treatments. 16S rRNA gene sequencing and non-targeted liquid chromatography-mass spectrometry (LC-MS) metabolomics were used to explore the relationship between EMF exposure and heat acclimation (HA) effects on gut microbes and serum metabolites. RESULTS: Both EMF and HA regulated the proportions of p_Firmicutes and p_Bacteroidota. EMF exposure caused the proportions of 6 kinds of bacteria, such as g_Butyricicoccus and g_Anaerotruncus, to change significantly (p < 0.05). HA restored the balance of gut microbes that was affected by EMF exposure and the proportion of probiotics (g_Lactobacillus) increased significantly (p < 0.01). Serum metabolite analysis suggested that HA alleviated the disturbance of serum metabolites (such as cholesterol and D-mannose) induced by EMF exposure. Both the metabolic KEGG pathways and PICRUSt functional analysis demonstrated that tryptophan metabolism, pyrimidine metabolism and amino acid biosynthesis were involved. CONCLUSIONS: EMF exposure not only led to depression-like neurobehavioral disorders, but also to gut microbiota imbalance. HA alleviated the depression features caused by EMF exposure. Based on the analysis of gut microbiota associated with serum metabolites, we speculated that gut microbiota might play a vital role in the cross-tolerance provided by HA.

Relationship of lymphovascular invasion with lymph node metastasis and prognosis in superficial esophageal carcinoma: systematic review and meta-analysis.

BACKGROUND: The development of tumor cells inside the lymphatics or blood vessels is known as lymphovascular invasion (LVI). The correlation between LVI, lymph node metastasis (LNM), and the diagnosis of superficial esophageal carcinoma (SEC) remains unclear. METHODS: We searched Embase, PubMed, Web of Science, and Cochrane Library databases for prospective articles to better understand the relationship between LVI, LNM, and SEC diagnosis. RESULTS: We included 23 articles containing data for 4749 patients (range: 54-598) in our meta-analysis. The hazard ratio between LVI and overall survival (OS) was 1.85 with 95% confidence interval (CI) (1.10-3.11, P = 0.02). LNM rate was higher in SEC patients with LVI than SEC patients without LVI (univariate: OR = 4.94, 95% CI: 3.74-6.53, P < 0.0001; multivariate: OR = 5.72, 95%CI: 4.38-7.4, P < 0.0001). No obvious publication was found. CONCLUSIONS: The results indicate that LVI plays a dominant role in the prognosis of LNM in SEC and in the prognostic prediction for SEC.

NCBP1 promotes the development of lung adenocarcinoma through up-regulation of CUL4B.

Lung cancer is the most frequent cancer type and is the leading cause of tumour-associated deaths worldwide. Nuclear cap-binding protein 1 (NCBP1) is necessary for capped RNA processing and intracellular localization. It has been reported that silencing of NCBP1 resulted in cell growth reduction in HeLa cells. Nevertheless, its clinical significance and underlying molecular mechanisms in non-small-cell lung cancer remain unclear. In this study, we found that NCBP1 was significantly overexpressed in lung cancer tissues and several lung cancer cell lines. Through knockdown and overexpression experiments, we showed that NCBP1 promoted lung cancer cell growth, wound healing ability, migration and epithelial-mesenchymal transition. Mechanistically, we found that cullin 4B (CUL4B) was a downstream target gene of NCBP1 in NSCLC. NCBP1 up-regulated CUL4B expression via interaction with nuclear cap-binding protein 3 (NCBP3). CUL4B silencing significantly reversed NCBP1-induced tumorigenesis in vitro. Based on these findings, we propose a model involving the NCBP1-NCBP3-CUL4B oncoprotein axis, providing novel insight into how CUL4B is activated and contributes to LUAD progression.

Evaluation of culture conditions for mixed biofilm formation with clinically isolated non-albicans Candida species and Staphylococcus epidermidis on silicone.

Silicone is frequently used in clinical and medical fields for medical devices. Mixed biofilms composed of Candida and bacterial species causes frequently failure of medical silicone devices, In this in vitro study, we analyzed mixed biofilm formation of clinically isolated non-albicans Candida species and Staphylococcus epidermidis, including Candida tropicalis, Candida krusei and Candida parapsilosis under the influence of different growth media (RPMI 1640, BHI and TSB) and several culture variables (incubation period, feeding conditions and FBS). Our results showed that culture conditions strongly influence mixed biofilm formation. TSB and BHI resulted in larger amount of biofilm formations with stronger metabolic activity of biofilms. Growth conditions may also influence the biofilm formation, which was enhanced by longer incubation period, using a fed-batch system and FBS. Therefore, the potential influences of external environmental factors are very important for mixed biofilm formation with clinically isolated non-albicans Candida species and S. epidermidis, which should be considered when designing or studying the mixed biofilm under in vitro conditions.

Dispersal of single and mixed non-albicans Candida species biofilms by ß-1,3-glucanase in vitro.

ß-1,3-glucan plays a role in non-albicans Candida species biofilm formation and survival of biofilm Candida to stresses. In this study, we evaluated the antibiofilm activity of ß-1,3-glucanase, which can degrade poly-ß(1 â†’ 3)-glucose of non-albicans Candida species biofilms, on single and mixed species biofilm of non-albicans Candida species, including Candida tropicalis, Candida parapsilosis and Candida krusei. Biofilm by all tested species in microplate were dispersed more than 60%. ß-1,3-glucanase also detached mixed species biofilm in microplate and on medical material surface. ß-1,3-glucanase had no effect on Candida planktonic growth as well as adhesion. However, further biofilm formation was inhibited with ß-1,3-glucanase added at 24 h after biofilm initiation. ß-1,3-glucanase markedly enhanced the antifungal susceptibility of amphotericin B. The examination using confocal laser scanning microscopy and scanning electron microscope confirmed the antibiofilm activity of ß-1,3-glucanase. Our findings demonstrate that ß-1,3-glucanase may be useful as an antibiofilm agent.

Inhibition activity of Lactobacilli supernatant against fungal-bacterial multispecies biofilms on silicone.

Fungal-bacterial multispecies biofilms play a major role in failure of medical silicone devices, such as voice prostheses in laryngectomiy. In this study, we determined the effect of Lactobacilli supernatant (cell free) on mixed biofilm formation of fungi and bacteria on silicone in vitro. Lactobacilli supernatant inhibited the adhesion (90 min) of mixed fungi and bacteria species with an efficiency of >90%. Mixed biofilm formation and the metabolic activity of the biofilms were inhibited by 72.23% and 58.36% by Lactobacilli supernatant. The examination using confocal laser scanning microscopy and scanning electron microscopy confirmed that Lactobacilli supernatant inhibited the growth of mixed biofilm and damaged the cells. Moreover, Lactobacilli supernatant also inhibited Candida yeast-to-hyphal transition. Therefore, Lactobacilli supernatant may serve as a possible antibiofilm agent to limit biofilm formation on voice prostheses.

Systemic C3 modulates CD8+ T cell contraction after Listeria monocytogenes infection.

Ag-specific CD8(+) T cell contraction (contraction), which occurs after the resolution of infection, is critical for homeostasis of the immune system. Although complement components regulate the primary CD8(+) T cell response, there is insufficient evidence supporting their role in regulating contraction and memory. In this study, we show that C3-deficient (C3(-/-)) mice exhibited significantly less CD8(+) T cell contraction than did wild-type mice postinfection with recombinant Listeria monocytogenes expressing OVA. Kinetic analyses also revealed decreased contraction in mice treated with cobra venom factor to deplete C3, which was consistent with the results in C3(-/-) recipient mice transplanted with bone marrow cells from the same donors as wild-type recipient mice. The phenotypes of memory cells generated by C3(-/-) mice were not altered compared with those of wild-type mice. Further, C5aR signaling downstream of C3 was not involved in the regulation of contraction. Moreover, the regulation of contraction by C3 may be independent of the duration of antigenic stimulation or the functional avidity of effector CD8(+) T cells. However, reduced contraction in C3(-/-) mice was accompanied by a decrease in the proportion of KLRG-1(hi) (killer-cell lectin-like receptor G1) CD127(lo) short-lived effector cells at the peak of the response and correlated with a reduction in the levels of inflammatory cytokines, such as IL-12 and IFN-γ, produced early postinfection. These results provide new insights into the role of systemic C3 in regulating contraction following intracellular bacterial infection and may help to develop vaccines that are more effective.

C5aR, TNF-α, and FGL2 contribute to coagulation and complement activation in virus-induced fulminant hepatitis.

BACKGROUND & AIMS: Viral fulminant hepatitis (FH) is a disease with a high mortality rate. Activation of the complement system correlates with the development of FH. However, the key factors mediating complement activation in FH remain elusive. METHODS: Liver tissues were isolated from FH patients infected by hepatitis B virus (HBV) and from mice infected with murine hepatitis virus strain 3 (MHV-3). Wild type mice were treated with or without antagonists of C5aR or TNF-α, and mice deficient for C5aR (C5aR(-/-)), Fgl2 (Fgl2(-/-)), and Tnfα (Tnfα(-/-)) mice were not treated with the antagonists. C5b-9, C5aR, FGL2, CD31, CD11b, fibrin, TNF-α, and complement C3 cleavage products were detected by immunohistochemistry, immunofluorescence, or ELISA. Sorted liver sinusoidal endothelial cells (LSECs) or myeloid-derived (CD11b(+)) cells were stimulated with C5a, TNF-α or MHV-3 in vitro. The mRNA expressions levels of Fgl2 and Tnfα were determined by qRT-PCR analyses. RESULTS: We observed that complement activation, coagulation and pro-inflammatory cytokine production were upregulated in the HBV(+) patients with FH. Similar observations were made in the murine FH models. Complement activation and coagulation were significantly reduced in MHV-3 infected mice in the absence of C5aR, Tnfα or Fgl2. The MHV-3 infected C5aR(-/-) mice exhibited reduced numbers of infiltrated inflammatory CD11b(+) cells and a reduced expression of TNF-α and FGL2. Moreover, C5a administration stimulated TNF-α production by CD11b(+) cells, which in turn promoted the expression of FGL2 in CD31(+) LSEC-like cells in vitro. Administration of antagonists against C5aR or TNF-α ameliorated MHV-3-induced FH. CONCLUSIONS: Our results demonstrate that C5aR, TNF-α, and FGL2 form an integral network that contributes to coagulation and complement activation, and suggest that those are potential therapeutic targets in viral FH intervention.

Fungal ß-1,3-glucan increases ofloxacin tolerance of Escherichia coli in a polymicrobial E. coli/Candida albicans biofilm.

In the past, biofilm-related research has focused mainly on axenic biofilms. However, in nature, biofilms are often composed of multiple species, and the resulting polymicrobial interactions influence industrially and clinically relevant outcomes such as performance and drug resistance. In this study, we show that Escherichia coli does not affect Candida albicans tolerance to amphotericin or caspofungin in an E. coli/C. albicans biofilm. In contrast, ofloxacin tolerance of E. coli is significantly increased in a polymicrobial E. coli/C. albicans biofilm compared to its tolerance in an axenic E. coli biofilm. The increased ofloxacin tolerance of E. coli is mainly biofilm specific, as ofloxacin tolerance of E. coli is less pronounced in polymicrobial E. coli/C. albicans planktonic cultures. Moreover, we found that ofloxacin tolerance of E. coli decreased significantly when E. coli/C. albicans biofilms were treated with matrix-degrading enzymes such as the ß-1,3-glucan-degrading enzyme lyticase. In line with a role for ß-1,3-glucan in mediating ofloxacin tolerance of E. coli in a biofilm, we found that ofloxacin tolerance of E. coli increased even more in E. coli/C. albicans biofilms consisting of a high-ß-1,3-glucan-producing C. albicans mutant. In addition, exogenous addition of laminarin, a polysaccharide composed mainly of poly-ß-1,3-glucan, to an E. coli biofilm also resulted in increased ofloxacin tolerance. All these data indicate that ß-1,3-glucan from C. albicans increases ofloxacin tolerance of E. coli in an E. coli/C. albicans biofilm.

Structural characterization of the glucan from Gastrodia elata Blume and its ameliorative effect on DSS-induced colitis in mice.

The polysaccharide glucan was extracted from Gastrodia elata Blume, and its structural characterizations and beneficial effects against acute dextran sulfate sodium (DSS)-induced ulcerative colitis were investigated. The results showed that a polysaccharide GP with a molecular weight of 811.0 kDa was isolated from G. elata Blume. It had a backbone of α-D-1,4-linked glucan with branches of α-d-glucose linked to the C-6 position. GP exhibited protective effects against DSS-induced ulcerative colitis, and reflected in ameliorating weight loss and pathological damages in mice, increasing colon length, inhibiting the expression of inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß), decreasing the levels of inflammatory related proteins NLRP3 and ASC, and elevating the anti-inflammatory cytokine interleukin-10 (IL-10) level in mouse colon tissues. GP supplementation also reinforced the intestinal barrier by promoting the expression of ZO-1, Occludin, and MUC2 of colon tissues, and positively regulated intestinal microbiota. Thus, GP treatment possessed a significant improvement in ulcerative colitis in mice, and it was expected to be developed as a functional food.

Synergistic and antibiofilm activity of DNase I and glucose oxidase loaded chitosan nanoparticles against dual-species biofilms of Listeria monocytogenes and Salmonella.

Salmonella and Listeria monocytogenes are two of the most common foodborne pathogens in the food industry. They form dual-species biofilms, which have a higher sensitivity to antimicrobial treatment and a greater microbial adhesion. In this experiment, we loaded DNase I and glucose oxidase (GOX) on chitosan nanoparticles (CSNPs) to explore their inhibitory effects on and disruption of dual-species biofilms of Salmonella enterica and L. monocytogenes. Transmission electron microscopy (TEM) showed that CSNP-DNase-GOX and CSNPs were spherical in shape. CSNP-DNase-GOX was shifted and altered compared to the infrared peaks of CSNPs. CSNPs loaded with DNase I and GOX showed an increase in the particle size and an alteration in the polydispersity index (PDI) and the zeta potential. Compared to free DNase I or GOX, DNase I and GOX loaded on CSNPs had higher stability at different temperatures. CSNP-DNase-GOX was more effective in inhibiting dual-species biofilms than CSNP-GOX. Scanning electron microscopy (SEM) and fluorescence microscopy were used to observe the structure of the biofilm, which further illustrated that CSNP-DNase-GOX disrupted the dual-species biofilms of S. enterica and L. monocytogenes.

Cloning, expression and characterization of a new ι-carrageenase from marine bacterium, Cellulophaga sp.

PURPOSE OF WORK: The purpose of this study is to report a ι-carrageenase which degrades ι-carrageenan yielding neo-ι-carratetraose as the main product in the absence of NaCl. The gene for a new ι-carrageenase, CgiB_Ce, from Cellulophaga sp. QY3 was cloned and sequenced. It comprised an ORF of 1,386 bp encoding for a protein of 461 amino acid residues. From its sequence analysis, CgiB_Ce is a new member of GH family 82 and shared the highest identity of 32% in amino acids with ι-carrageenase CgiA2 from Zobellia galactanovorans indicating that it is a hitherto uncharacterized protein. The recombinant CgiB_Ce had maximum specific activity (1,870 U/mg) at 45 °C and pH 6.5. It was stable between pH 6.0-9.6 and below 40 °C. Although its activity was enhanced by NaCl, the enzyme was active in the absence of NaCl. CgiB_Ce is an endo-type ι-carrageenase that hydrolyzes ß-1,4-linkages of ι-carrageenan, yielding neo-ι-carratetraose as the main product (more than 80% of the total product).

Dissection of a circulating and intrahepatic CD4(+)Foxp3(+) T-cell subpopulation in chronic hepatitis B virus (HBV) infection: a highly informative strategy for distinguishing chronic HBV infection states.

BACKGROUND: The definition of CD4(+)Foxp3(+) regulatory T cells (Tregs) is challenging as it relates to chronic hepatitis B virus (HBV) infection. Recently, the heterogeneity of human CD4(+)Foxp3(+) T cells has been confirmed. METHODS: Three circulating CD4(+)Foxp3(+) T-cell subpopulations in chronic HBV patients were identified, and their frequencies associated with clinical parameters were analyzed. Antigen specificity of Tregs was further studied. RESULTS: We found that circulating and intrahepatic CD4(+)CD45RA(-)Foxp3(hi)-activated Tregs (aTregs) were selectively increased in patients with chronic active hepatitis B and acute-on-chronic liver failure (ACLF) but not in asymptomatic carriers. The aTreg frequency was strongly correlated with HBV DNA load but not liver damage. In both peripheral blood mononuclear cells and livers, ACLF patients showed a dramatically elevated frequency of interleukin 17A-secreting CD45RA(-)Foxp3(lo) nonsuppressive T cells (non-Tregs), which were shown to be associated with severe liver damage. Interestingly, an HBV core antigen (HBcAg)-derived peptide could preferentially expand CD4(+)CD25(+)Foxp3(+) T cells and aTregs in HLA-DR9(+) chronic active hepatitis B patients, and these Tregs required ligand-specific reactivation for suppressor function. CONCLUSIONS: The delineation of a CD4(+)Foxp3(+) T-cell subpopulation is a highly informative strategy for distinguishing different chronic HBV infection states. HBcAg-derived peptides may be responsible for activation of Tregs that, in turn, specifically inhibit anti-HBV immune response but not liver inflammation.

Antimicrobial and antibiofilm activities of formylchromones against Vibrio parahaemolyticus and Vibrio harveyi.

Gram-negative Vibrio species are major foodborne pathogens often associated with seafood intake that causes gastroenteritis. On food surfaces, biofilm formation by Vibrio species enhances the resistance of bacteria to disinfectants and antimicrobial agents. Hence, an efficient antibacterial and antibiofilm approach is urgently required. This study examined the antibacterial and antivirulence effects of chromones and their 26 derivatives against V. parahaemolyticus and V. harveyi. 6-Bromo-3-formylchromone (6B3FC) and 6-chloro-3-formylchromone (6C3FC) were active antibacterial and antibiofilm compounds. Both 6B3FC and 6C3FC exhibited minimum inhibitory concentrations (MICs) of 20 µg/mL for planktonic cell growth and dose-dependently inhibited biofilm formation. Additionally, they decreased swimming motility, protease activity, fimbrial agglutination, hydrophobicity, and indole production at 20 µg/mL which impaired the growth of the bacteria. Furthermore, the active compounds could completely inhibit the slimy substances and microbial cells on the surface of the squid and shrimp. The most active compound 6B3FC inhibited the gene expression associated in quorum sensing and biofilm formation (luxS, opaR), pathogenicity (tdh), and membrane integrity (vmrA) in V. parahaemolyticus. However, toxicity profiling using seed germination and Caenorhabditis elegans models suggests that 6C3FC may have moderate effect at 50 µg/mL while 6B3FC was toxic to the nematodes 20-100 µg/mL. These findings suggest chromone analogs, particularly two halogenated formylchromones (6B3FC and 6C3FC), were effective antimicrobial and antibiofilm agents against V. parahaemolyticus in the food and pharmaceutical sectors.

Antivirulence activities of retinoic acids against Staphylococcus aureus.

Multidrug-resistant bacteria such as Staphylococcus aureus constitute a global health problem. Gram-positive S. aureus secretes various toxins associated with its pathogenesis, and its biofilm formation plays an important role in antibiotic tolerance and virulence. Hence, we investigated if the metabolites of vitamin A1 might diminish S. aureus biofilm formation and toxin production. Of the three retinoic acids examined, 13-cis-retinoic acid at 10 µg/mL significantly decreased S. aureus biofilm formation without affecting its planktonic cell growth (MIC >400 µg/mL) and also inhibited biofilm formation by Staphylococcus epidermidis (MIC >400 µg/mL), but less affected biofilm formation by a uropathogenic Escherichia coli strain, a Vibrio strain, or a fungal Candida strain. Notably, 13-cis-retinoic acid and all-trans-retinoic acid significantly inhibited the hemolytic activity and staphyloxanthin production by S. aureus. Furthermore, transcriptional analysis disclosed that 13-cis-retinoic acid repressed the expressions of virulence- and biofilm-related genes, such as the two-component arlRS system, α-hemolysin hla, nuclease (nuc1 and nuc2), and psmα (phenol soluble modulins α) in S. aureus. In addition, plant and nematode toxicity assays showed that 13-cis-retinoic acid was only mildly toxic at concentrations many folds higher than its effective antibiofilm concentrations. These findings suggest that metabolites of vitamin A1, particularly 13-cis-retinoic acid, might be useful for suppressing biofilm formation and the virulence characteristics of S. aureus.

Transcriptome sequencing reveals neurotoxicity in embryonic neural stem/progenitor cells under heat stress.

Neural tube malformation is a common kind of human birth defect. High temperature is one of the most common physical teratogenic factors. Several studies have suggested that heat stress may cause neurotoxicity during brain development, but more studies are warranted to reveal the mechanism and draw consistent conclusions. The current study used a cell model of primary mouse embryonic neural stem/progenitor cells (NSPCs) subjected to heat stress of 43 °C for 20 min. Our study investigated the changes in the NSPCs transcriptome under heat stress using high-throughput mRNA-seq. The NSPCs showed remarkably altered genes associated with cell growth, proliferation, cell cycle, and survival when exposed to heat stress. Heat stress reduced cell viability, proliferation, and neurosphere formation and caused cell cycle arrest and apoptosis in cultured NSPCs. PCR arrays confirmed that the TNF receptor family plays an important role in the apoptosis of NSPCs during heat stress. The results of real-time PCR confirmed that heat stress affects the expression of critical genes. We provide transcriptomic insight into heat stress-induced developmental neurotoxic effects and the underlying mechanisms.

New Insights in Molecular Mechanisms in Antimicrobial Resistance and Strategies in Anti-Biofilms.

This topical collection, entitled "Antimicrobial resistance and anti-biofilms", was first launched in the journal Antibiotics in November of 2020 [...].