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Antibiotic resistance by methicillin-resistant Staphylococcus aureus (MRSA) is an urgent threat to human health. The biofilm and persister cells formation ability of MRSA and Staphylococcus epidermidis often companied with extremely high antimicrobial resistance. Pinaverium bromide (PVB) is an antispasmodic compound mainly used for irritable bowel syndrome. Here we demonstrate that PVB could rapidly kill MRSA and S. epidermidis planktonic cells and persister cells avoiding resistance occurrence. Moreover, by crystal violet staining, viable cells counting and SYTO9/PI staining, PVB exhibited strong biofilm inhibition and eradication activities on the 96-well plates, glass surface or titanium discs. And the synergistic antimicrobial effects were observed between PVB and conventional antibiotics (ampicillin, oxacillin, and cefazolin). Mechanism study demonstrated the antimicrobial and antibiofilm effects by PVB were mainly mediated by proton motive force disrupting as well as reactive oxygen species inducing. Although, relatively poor pharmacokinetics were observed by systemic use, PVB could significantly reduce the viable bacterial cell loads and inflammatory infiltration in abscess in vivo caused by the biofilm forming strain ATCC 43,300. In all, our results indicated that PVB could be an alternative antimicrobial reagent for the treatment of MRSA, S. epidermidis and its biofilm related skin and soft tissue infections., Competing Interests: Declarations. Ethics approval and consent to participate: This article does not contain any studies with human participants performed by any of the authors. This murine-related laboratory procedures were approved by the Ethics Committee of the Third Xiangya Hospital of Central South University (NO. CSU-2022-0599). Consent for publication: Not applicable. Competing interests: The authors declare no competing interest., (© 2024. The Author(s).)

Staphylococcus aureus, a common gram-positive pathogenic bacterium, is a main cause of hospital infection. The prevalence rate of methicillin-resistant S. aureus (MRSA) has made its treatment difficult in recent decades. Moreover, S. aureus in the highly tolerant format of biofilm or persister often renders infections refractory. Thus, developing new active compounds against resistant S. aureus is urgently needed. In this study, by a high-throughput screening assay, we identified a small molecule, L007-0069, that exhibited strong and effective bactericidal activity against S. aureus and its high resistance patterns, such as biofilms and persisters, with a low probability of inducing resistance. By molecular dynamics and fluorescent probe analysis, mechanistic studies revealed that the bactericidal activity of L007-0069 was mainly mediated by membrane disruption and metabolic disorder induction. Furthermore, L007-0069 showed effective anti-MRSA effects in vivo in both a wound infection model and a peritonitis-sepsis model, with no detectable toxicity observed at the therapeutic dosage. In conclusion, L007-0069 has the potential to become an alternative for the treatment of highly resistant S. aureus-related infections., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Enterococci are important pathogens of nosocomial infections and are increasingly difficult to treat due to their intrinsic and acquired resistance to a range of antibiotics. Therefore, there is an urgent need to develop novel antibacterial agents, while drug repurposing is a promising approach to address this issue. Our study aimed to determine the antimicrobial efficacy of halicin against enterococci and found that the minimum inhibitory concentrations (MIC) of halicin against different strains of Enterococcus faecalis and Enterococcus faecium ranged from 4 to 8 μg/ml. In addition, the synergistic antibacterial effect between halicin and doxycycline (DOX) against Enterococcus was observed through the checkerboard method, and it was observed that halicin and DOX could significantly synergistically inhibit biofilm formation and eradicate preformed biofilms at sub-MICs. Moreover, the electron microscope results revealed that halicin could also disrupt the bacterial cell membrane at high concentrations. Furthermore, it is also confirmed that the combination of halicin and DOX has no significant cytotoxic effect on erythrocytes and other human-derived cells. In addition, the mouse subcutaneous model and H&E staining showed that the combination of halicin and DOX could effectively reduce the bacterial load and inflammatory infiltration without obvious side effects. In nutshell, these results demonstrate the potential of halicin in combination with DOX as a novel therapy against infections by Enterococcus., (© The Author(s) 2022. Published by Oxford University Press on behalf of FEMS.)

Purpose: The purpose of this study was to quantify thickness, vessel density (VD) of retina and choroid in young adults (18-24 years old) using OCTA., Methods: This observational, cross-sectional study included 154 eyes from 77 young myopic adults. En-face angiogram OCTA was performed on a 3.00 × 3.00 mm region centered on the macula. Automated thickness calculations and macular maps were measured. Spherical equivalent refraction (SER) and AL were examined to determine associations with thickness, vessel density (VD) of retina and choroid., Results: A total of 148 healthy eyes from 77 young myopic adults (29 males and 48 females) with a mean age of 21.80 ± 1.32 years (range: 18-24 years) were included. The mean SER and AL were - 4.06 ± 2.26D and 25.25 ± 1.28 mm, respectively. The mean retinal thickness (RT, ILM-RPE layer) was 240.91 ± 13.36 μm, the retinal superficial (SVD) and deep vessel density (DVD) in fovea region were 18.35 ± 4.77% and 32.99 ± 6.01%, respectively. The foveal avascular zone (FAZ) area was 0.31 ± 0.10 mm 2 . The mean subfoveal choroidal thickness (SFCT) and choriocapillaris (CC) perfusion area were 232.16 ± 56.65 μm and 2.17 ± 0.10 mm 2 , respectively. By Pearson's correlation analysis, SER was revealed to be negatively correlated with RT (r = -0.180, p = 0.028) and DVD (r = -0.185, p = 0.025) in fovea region. SER was revealed to be positively correlated with RT in nasal (r = 0.224, p = 0.006) and inferior (r = 0.217, p = 0.008) regions. AL was revealed to be positively correlated with RT (r = 0.250, p = 0.002) and DVD (r = 0.284, p < 0.001) in fovea region. SER was revealed to be positively correlated with SFCT (r = 0.486, p < 0.001). AL was revealed to be negatively correlated with FAZ area (r = -0.232, p = 0.005) and SFCT (r = -0.407). RT was revealed to be negatively correlated with FAZ area (r = -0.645, p < 0.001). SER (r = -0.079), AL (r = 0.071) and SFCT (r = 0.089) did not correlate significantly with the CC perfusion area (all p > 0.05)., Conclusion: Myopic eyes present increased RT, DVD and thinned SFCT in fovea, while no significant correlation could be found between SER, AL, SFCT and CC perfusion area. It may indicate that the SFCT thinning may be secondary to ocular elongation, while the CC perfusion area may be a factor independent of AL growth., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Buyanghuanwu Decoction (BYHWD), as a traditional Chinese medicine, has been developed to treat vascular dementia for hundreds of years, but the underlying mechanisms remain unknown. In this research, the protective effects of BYHWD on hippocampal neuron were examined in the rats of ischemia-reperfusion. Ischemia-reperfusion injury was induced by the four-vessel occlusion method and continued for 30 days. BYHWD (per 6.25g/kg/d) was orally given to rats twice each day for 30 days after ischemia-reperfusion, Nimodipine (per 10mg/kg/d) was orally given to rats twice each day for 30 days. In VD+BYHWD group rats, the neuronal injury in the hippocampal CA1 region was significantly less than that of VD group's. BYHWD of intragastric administration also markedly increased the expression of Extracellular signal-regulated kinase 2 (ERK2) and Calcium/calmodulin-dependent protein kinaseII (CaMKIIIy)in the CA1 region. Our results suggested that increased ERK2 and CaMKIIIy due to BYHWD may partially account for its effect of neuroprotection standing against ischemic injury in the hippocampal CA1 region, and participated in the rebuilding of synapse, strengthened the expression of LTP, promoted the ability recover of learning and memory in VD rats., (Copyright © 2013 Elsevier Inc. All rights reserved.)