Submicron-textured surfaces have been a promising approach to mitigate biofilm development and control microbial infection. However, the use of the single surface texturing approach is still far from ideal for achieving complete control of microbial infections on implanted biomedical devices. The use of a surface topographic modification that might improve the utility of standard antibiotic therapy could alleviate the complications of biofilms on devices. In this study, we characterized the biofilms of Staphylococcus aureus and Pseudomonas aeruginosa on smooth and submicron-textured polyurethane surfaces after 1, 2, 3, and 7 days, and measured the efficacy of common antibiotics against these biofilms. Results show that the submicron-textured surfaces significantly reduced biofilm formation and growth, and that the efficacy of antibiotics against biofilms grown on textured surfaces was improved compared with smooth surfaces. The antibiotic efficacy appears to be related to the degree of biofilm development. At early time points in biofilm formation, antibiotic treatment reveals reasonably good antibiotic efficacy against biofilms on both smooth and textured surfaces, but as biofilms mature, the efficacy of antibiotics drops dramatically on smooth surfaces, with lesser decreases seen for the textured surfaces. The results demonstrate that surface texturing with submicron patterns is able to improve the use of standard antibiotic therapy to treat device-centered biofilms by slowing the development of the biofilm, thereby offering less resistance to antibiotic delivery to the bacteria within the biofilm community.

Broad-spectrum antibacterial drugs often lack specificity, leading to indiscriminate bactericidal activity, which can disrupt the normal microbial balance of the host flora and cause unnecessary cytotoxicity during systemic administration. In this study, we constructed a specifically targeted antimicrobial peptide against Staphylococcus aureus by introducing a phage-displayed peptide onto a broad-spectrum antimicrobial peptide and explored its structure-function relationship through one-factor modification. SFK2 obtained by screening based on the selectivity index and the targeting index showed specific killing ability against S. aureus. Moreover, SFK2 showed excellent biocompatibility in mice and piglet, and demonstrated significant therapeutic efficacy against S. aureus infection. In conclusion, our screening of phage-derived heptapeptides effectively enhances the specific bactericidal ability of the antimicrobial peptides against S. aureus, providing a theoretical basis for developing targeted antimicrobial peptides.

Human health is now inextricably linked to lifestyle choices, which can either protect or predispose people to serious illnesses. The Mediterranean diet, characterized by the consumption of various medicinal plants and their byproducts, plays a significant role in protecting against ailments such as oxidative stress, cancer, and diabetes. To uncover the secrets of this natural treasure, this review seeks to consolidate diverse data concerning the pharmacology, toxicology, phytochemistry, and botany of Olea europaea L. (O. europaea). Its aim is to explore the potential therapeutic applications and propose avenues for future research. Through web literature searches (using Google Scholar, PubMed, Web of Science, and Scopus), all information currently available on O. europaea was acquired. Worldwide, ethnomedical usage of O. europaea has been reported, indicating its effectiveness in treating a range of illnesses. Phytochemical studies have identified a range of compounds, including flavanones, iridoids, secoiridoids, flavonoids, triterpenes, biophenols, benzoic acid derivatives, among others. These components exhibit diverse pharmacological activities both in vitro and in vivo, such as antidiabetic, antibacterial, antifungal, antioxidant, anticancer, and wound-healing properties. O. europaea serves as a valuable source of conventional medicine for treating various conditions. The findings from pharmacological and phytochemical investigations presented in this review enhance our understanding of its therapeutic potential and support its potential future use in modern medicine.

Infectious diseases are among the factors that account for a significant proportion of disease-related deaths worldwide. The primary treatment approach to combat microbial infections is the use of antibiotics. However, the widespread use of these drugs over the past two decades has led to the emergence of resistant microbial species, making the control of microbial infections a serious challenge. One of the most important solutions in the field of combating infectious diseases is the regulation of the host\'s defense system. Toll-like receptors (TLRs) play a crucial role in the first primary defense against pathogens by identifying harmful endogenous molecules released from dying cells and damaged tissues as well as invading microbial agents. Therefore, they play an important role in communicating and regulating innate and adaptive immunity. Of course, excessive activation of TLRs can lead to disruption of immune homeostasis and increase the risk of inflammatory reactions. Targeting TLR signaling pathways has emerged as a new therapeutic approach for infectious diseases based on host-directed therapy (HDT). In recent years, stem cell-derived exosomes have received significant attention as factors regulating the immune system. The regulation effects of exosomes on the immune system are based on the HDT strategy, which is due to their cargoes. In general, the mechanism of action of stem cell-derived exosomes in HDT is by regulating and modulating immunity, promoting tissue regeneration, and reducing host toxicity. One of their most important cargoes is microRNAs, which have been shown to play a significant role in regulating immunity through TLRs. This review investigates the therapeutic properties of stem cell-derived exosomes in combating infections through the interaction between exosomal microRNAs and Toll-like receptors.

Peroxiredoxins are antioxidant proteins that detoxify peroxynitrite, hydrogen peroxide, and organic hydroperoxides, impacting various physiological processes such as immune responses, apoptosis, cellular homeostasis, and so on. In the present study, we identified and characterized peroxiredoxin 1 from Antheraea pernyi (thereafter designated as ApPrx-1) that encodes a predicted 195 amino acid residue protein with a 21.8 kDa molecular weight. Quantitative real-time PCR analysis revealed that the mRNA level of ApPrx-1 was highest in the hemocyte, fat body, and midgut. Immune-challenged larval fat bodies and hemocytes showed increased ApPrx-1 transcript. Moreover, ApPrx-1 expression was induced in hemocytes and the whole body of A. pernyi following exogenous H2O2 administration. A DNA cleavage assay performed using recombinant ApPrx-1 protein showed that rApPrx-1 protein manifests the ability to protect supercoiled DNA damage from oxidative stress. To test the rApPrx-1 protein antioxidant activity, the ability of the rApPrx-1 protein to remove H2O2 was assessed in vitro using rApPrx-1 protein and DTT, while BSA + DDT served as a control group. The results revealed that ApPrx-1 can efficiently remove H2O2 in vitro. In the loss of function analysis, we found that ApPrx-1 significantly increased the levels of H2O2 in ApPrx-1-depleted larvae compared to the control group. We also found a significantly lower survival rate in the larvae in which ApPrx-1 was knocked down. Interestingly, the antibacterial activity was significantly higher in the ApPrx-1 depleted larvae, compared to the control. Collectively, evidence strongly suggests that ApPrx-1 may regulate physiological activities and provides a reference for further studies to validate the utility of the key genes involved in reliving oxidative stress conditions and regulating the immune responses of insects.

Age-associated B cells (ABCs) are a stable subset of memory B lymphocytes that develop during microbial infections and in autoimmune diseases. Despite growing appreciation of their phenotypic and functional characteristics, the transcriptional networks involved in ABC fate commitment and maintenance have remained elusive. In their recent publication, Dai et al. tackle this problem, leveraging both mouse models and human diseases to reveal zinc finger E-box-binding homeobox 2 (ZEB2) as a key transcriptional regulator of ABC lineage specification. In aggregate, their results show that ZEB2, a member of the zinc finger E homeobox binding family, promotes ABC differentiation by repressing alternative differentiative fates and targeting genes important for ABC character and function. Moreover, their results strengthen the case for causal links between ABC fate and function in autoimmune pathologies.

Increasing antimicrobial drug resistance represents a global existential threat. Infection is a particular problem in immunocompromised individuals, such as patients undergoing cancer chemotherapy, due to the targeting of rapidly dividing cells by antineoplastic agents. We recently developed a strategy that targets bacterial nucleotide excision DNA repair (NER) to identify compounds that act as antimicrobial sensitizers specific for patients undergoing cancer chemotherapy. Building on this, we performed a virtual drug screening of a ~120,000 compound library against the key NER protein UvrA. From this, numerous target compounds were identified and of those a candidate compound, Bemcentinib (R428), showed a strong affinity toward UvrA. This NER protein possesses four ATPase sites in its dimeric state, and we found that Bemcentinib could inhibit UvrA\'s ATPase activity by ~90% and also impair its ability to bind DNA. As a result, Bemcentinib strongly diminishes NER\'s ability to repair DNA in vitro. To provide a measure of in vivo activity we discovered that the growth of Escherichia coli MG1655 was significantly inhibited when Bemcentinib was combined with the DNA damaging agent 4-NQO, which is analogous to UV. Using the clinically relevant DNA-damaging antineoplastic cisplatin in combination with Bemcentinib against the urological sepsis-causing E. coli strain EC958 caused complete growth inhibition. This study offers a novel approach for the potential development of new compounds for use as adjuvants in antineoplastic therapy.

Lipocalin 2 (LCN2) plays a pivotal role in iron metabolism, particularly in the context of microbial infection resistance (e.g., viruses, bacteria, parasites, etc.). LCN2 combats microbial infection by directly assisting the body in competing with microorganisms for iron, inducing immune cells to secrete various cytokines to enhance systemic immune responses, or recruiting neutrophils to infectious sites. The liver serves as the primary organ for LCN2 secretion during microbial infections. This review encapsulates recent advances in dynamic changes, clinical values, and the effects of LCN2 in infectious liver diseases caused by various microbial microorganisms.

The worsening problem of antimicrobial drug resistance requires a nuanced approach. Since the conventional drug pipeline is unlikely to be sufficient to avoid massive increases in mortality by the mid-twenty-first century, other methods of antisepsis will be required. These might be used either in place of (allowing conservation) or together with conventional agents. Of such approaches, locally applied protocols involving photo-antimicrobials suggest themselves, particularly as early intervention, e.g. in bacterial tonsillitis, would be curative without recourse to conventional drugs, and would thus prevent the development of more serious diseases such as pneumonia or meningitis. However, given the pharmaceutical industry\'s lack of investment in such approaches, support would be required from other areas of bioscience, such as the biomed or biotech sectors.

BACKGROUND: Considering the limited number of current effective treatments, Multidrug- Resistant (MDR) illnesses have grown to be a serious concern to public health. It has become necessary to look for new antimicrobial drugs because of the emergence of resistance to numerous kinds of antibiotics. The use of flavonoids is one phytotherapeutic strategy that has been researched as a potential remedy for this issue. Secondary plant compounds called flavonoids have been found to have an antibacterial effect against resistant microorganisms.
OBJECTIVE: This review seeks to give readers a glimpse into contemporary studies on flavonoids\' potential to fight MDR infections.
METHODS: A systematic search was conducted on electronic databases (PubMed, Scopus, and Google Scholar) using relevant keywords such as flavonoids, MDR infections, antimicrobial activity, and resistance microbes. Studies that investigated the antimicrobial activity of flavonoids against resistant microbes were included in this review.
RESULTS: Most research found that flavonoids have antibacterial efficacy against resistant microorganisms, and some also showed that they have synergistic benefits with traditional antibiotics. The flavonoids quercetin, kaempferol, apigenin, and luteolin were the most often investigated ones. According to research, flavonoids affect microbial gene expression, inhibit microbial enzymes, and disrupt the integrity of microbial cell membranes. Additionally, a few studies have noted the flavonoids\' low toxicity and safety.
CONCLUSIONS: For the treatment of infections that are resistant to many drugs, flavonoids constitute a promising class of phytotherapeutic agents. To develop flavonoid-based treatment methods for treating MDR illnesses and assess the potential of flavonoids as adjuvants to conventional antimicrobial drugs, more study is required.