SUMMARYUnderstanding how commonly used chemical microbicides affect pathogenic microorganisms is important for formulation of microbicides. This review focuses on the mechanism(s) of action of chemical microbicides commonly used in infection prevention and control. Contrary to the typical site-specific mode of action of antibiotics, microbicides often act via multiple targets, causing rapid and irreversible damage to microbes. In the case of viruses, the envelope or protein capsid is usually the primary structural target, resulting in loss of envelope integrity or denaturation of proteins in the capsid, causing loss of the receptor-binding domain for host cell receptors, and/or breakdown of other viral proteins or nucleic acids. However, for certain virucidal microbicides, the nucleic acid may be a significant site of action. The region of primary damage to the protein or nucleic acid is site-specific and may vary with the virus type. Due to their greater complexity and metabolism, bacteria and fungi offer more targets. The rapid and irreversible damage to microbes may result from solubilization of lipid components and denaturation of enzymes involved in the transport of nutrients. Formulation of microbicidal actives that attack multiple sites on microbes, or control of the pH, addition of preservatives or potentiators, and so on, can increase the spectrum of action against pathogens and reduce both the concentrations and times needed to achieve microbicidal activity against the target pathogens.

In recent years, a growing body of research has confirmed that the gut microbiota plays a major role in the maintenance of human health and disease. A gut microbiota imbalance can lead to the development of many diseases, such as pregnancy complications, adverse pregnancy outcomes, polycystic ovary syndrome, endometriosis, and cancer. Short-chain fatty acids are metabolites of specific intestinal bacteria and are crucial for maintaining intestinal homeostasis and regulating metabolism and immunity. Endometriosis is the result of cell proliferation, escape from immune surveillance, and invasive metastasis. There is a strong correlation between the anti-proliferative and anti-inflammatory effects of short-chain fatty acids produced by gut microbes and the development of endometriosis. Given that the mechanism of action of gut microbiota and Short-chain fatty acids in endometriosis remain unclear, this paper aims to provide a comprehensive review of the complex interactions between intestinal flora, short-chain fatty acids and endometriosis. In addition, we explored potential microbial-based treatment strategies for endometriosis, providing new insights into the future development of diagnostic tests and prevention and treatment methods for endometriosis.

Slow wound healing has been a troublesome problem in clinic. In China, traditional methods such as antibiotics and silver sulfadiazine are used to treat skin wound, but the abuse use has many disadvantages, such as chronic wounds and pathogen resistance. Studies have shown that the microorganisms with symbiotic relationship with organisms have benefits on skin wound. Therefore, the way to develop and utilize probiotics to promote wound healing has become a new research direction. In this paper, we reviewed the studies on the bacteriotherapy in the world, described how the probiotics can play a role in promoting wound healing through local wound and intestine, and introduced some mature probiotics products and clinical trials, aiming to provide foundations for further development of bacteriotherapy and products.
伤口愈合缓慢是目前临床上较为棘手的问题，国内多采用抗生素和磺胺嘧啶银等较为传统的方法来治疗皮肤伤口，但其不恰当的使用存在诸多弊端，如导致伤口的慢性化和病原体的耐药性等。有研究表明，与机体存在共生关系的微生物可对皮肤伤口产生有益影响，因此如何开发并利用益生菌来促进伤口愈合已然成为了一项新的研究方向。本文根据国内外有关益生菌疗法的相关文献，阐述了益生菌是如何通过局部伤口和肠道来发挥其促愈合作用的，并且还提到了部分相对成熟的益生菌产品和临床试验，旨在为国内进一步开展益生菌疗法及其产品研发提供相关依据。.

The understanding of antibiotic resistance, one of the major health threats of our time, is mostly based on dated and incomplete notions, especially in clinical contexts. The \"canonical\" mechanisms of action and pharmacodynamics of antibiotics, as well as the methods used to assess their activity upon bacteria, have not changed in decades; the same applies to the definition, acquisition, selective pressures, and drivers of resistance. As a consequence, the strategies to improve antibiotic usage and overcome resistance have ultimately failed. This review gathers most of the \"non-canonical\" notions on antibiotics and resistance: from the alternative mechanisms of action of antibiotics and the limitations of susceptibility testing to the wide variety of selective pressures, lateral gene transfer mechanisms, ubiquity, and societal factors maintaining resistance. Only by having a \"big picture\" view of the problem can adequate strategies to harness resistance be devised. These strategies must be global, addressing the many aspects that drive the increasing prevalence of resistant bacteria aside from the clinical use of antibiotics.

Antimicrobial peptides (AMPs) are being explored as a potential strategy to combat antibiotic resistance due to their ability to reduce susceptibility to antibiotics. This study explored whether the [R4W4] peptide mode of action is bacteriostatic or bactericidal using modified two-fold serial dilution and evaluating the synergism between gentamicin and [R4W4] against Escherichia coli (E. coli) and methicillin-resistant Staphylococcus aureus (MRSA) by a checkered board assay. [R4W4] exhibited bactericidal activity against bacterial isolates (MBC/MIC ≤ 4), with a synergistic effect with gentamicin against E. coli (FICI = 0.3) but not against MRSA (FICI = 0.75). Moreover, we investigated the mechanism of action of [R4W4] against MRSA by applying biophysical assays to evaluate zeta potential, cytoplasmic membrane depolarization, and lipoteichoic acid (LTA) binding affinity. [R4W4] at a 16 mg/mL concentration stabilized the zeta potential of MRSA -31 ± 0.88 mV to -8.37 mV. Also, [R4W4] at 2 × MIC and 16 × MIC revealed a membrane perturbation process associated with concentration-dependent effects. Lastly, in the presence of BODIPY-TR-cadaverine (BC) fluorescence dyes, [R4W4] exhibited binding affinity to LTA comparable with melittin, the positive control. In addition, the antibacterial activity of [R4W4] against MRSA remained unchanged in the absence and presence of LTA, with an MIC of 8 µg/mL. Therefore, the [R4W4] mechanism of action is deemed bactericidal, involving interaction with bacterial cell membranes, causing concentration-dependent membrane perturbation. Additionally, after 30 serial passages, there was a modest increment of MRSA strains resistant to [R4W4] and a change in antibacterial effectiveness MIC [R4W4] and vancomycin by 8 and 4 folds with a slight change in Levofloxacin MIC 1 to 2 µg/mL. These data suggest that [R4W4] warrants further consideration as a potential AMP.

The riboflavin analogues, roseoflavin and 8-aminoriboflavin, inhibit malaria parasite proliferation by targeting riboflavin utilization. To determine their mechanism of action, we generated roseoflavin-resistant parasites by in vitro evolution. Relative to wild-type, these parasites were 4-fold resistant to roseoflavin and cross-resistant to 8-aminoriboflavin. Whole genome sequencing of the resistant parasites revealed a missense mutation leading to an amino acid change (L672H) in the gene coding for a putative flavokinase (PfFK), the enzyme responsible for converting riboflavin into the cofactor flavin mononucleotide (FMN). To confirm that the L672H mutation is responsible for the phenotype, we generated parasites with the missense mutation incorporated into the PfFK gene. The IC50 values for roseoflavin and 8-aminoriboflavin against the roseoflavin-resistant parasites created through in vitro evolution were indistinguishable from those against parasites in which the missense mutation was introduced into the native PfFK. We also generated two parasite lines episomally expressing GFP-tagged versions of either the wild-type or mutant forms of PfFK. We found that PfFK-GFP localizes to the parasite cytosol and that immunopurified PfFK-GFP phosphorylated riboflavin, roseoflavin, and 8-aminoriboflavin. The L672H mutation increased the KM for roseoflavin, explaining the resistance phenotype. Mutant PfFK is no longer capable of phosphorylating 8-aminoriboflavin, but its antiplasmodial activity against resistant parasites can still be antagonized by increasing the extracellular concentration of riboflavin, consistent with it also inhibiting parasite growth through competitive inhibition of PfFK. Our findings, therefore, are consistent with roseoflavin and 8-aminoriboflavin inhibiting parasite proliferation by inhibiting riboflavin phosphorylation and via the generation of toxic flavin cofactor analogues.

At low medically-relevant concentrations, ozone serves as an oxidant with a wide spectrum of antimicrobial activity and the ability to promote healing and reduce inflammation. Despite providing therapeutic benefits in a range of diseases, certain adverse effects and contraindications of ozone treatment must be considered. These are primarily related to toxicity from inhalation and systemic types of administration and can be avoided by following relevant guidelines and recommendations. Ozone therapy has been implemented in a number of fields of dentistry and the most commonly used formulations for the oral cavity are gaseous ozone, ozonized water and ozonized oil. The biological mechanisms underlying the molecular effects of ozone have been increasingly reported, but currently remain largely unknown. The aim of the present review was to provide an overview of the mechanisms involved in ozone interaction with dental tissues. The present review focused on relevant evidence regarding the effect of ozone on dental tissues, including periodontal structures, dental cells, enamel and dentine, considering in vitro studies in addition to animal and human studies. A variety of biological mechanisms acting through multiple biochemical target pathways were reported to be responsible for the therapeutic effects of ozone. The main beneficial effects of ozone occurred in the following domains: antimicrobial activity, remineralization and microstructural changes of hard dental tissues, immunomodulation and biostimulation of dental and periodontal cells. Additional research could provide further insights into the use of ozone, increase its use for broader clinical applications and assist in the selection of targeted protocols.

Learning and memory impairment (LMI), a common degenerative central nervous system disease. Recently, more and more studies have shown that Ganoderma lucidum (GL) can improve the symptoms of LMI. The active ingredients in GL and their corresponding targets were screened through TCMSP (Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform) and BATMAN-TCM (Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine) databases, and the potential LMI targets were searched for through GeneCard (GeneCards Human Gene Database) and DrugBank. Then, we construct a \"main active ingredient-target\" network and a protein-protein interaction (PPI) network diagram.The GO (Gene Ontology) functional enrichment analysis and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway annotation analysis were performed on the common targets through DAVID (Database for Annotation Visualization and Integrated Discovery) to clarify the potential molecular mechanism of action of active ingredients in GL. The TNF protein was verified by western blot;Twenty one active ingredients in GL and 142 corresponding targets  were screened out, including 59 targets shared with LMI. The 448 biological processes shown by the GO functional annotation results and 55 signal pathways shown by KEGG enrichment analysis were related to the improvement of LMI by GL, among which the correlation of Alzheimer disease pathway is the highest, and TNF was the most important protein; TNF can improve LMI.GL can improve LMI mainly by 10 active ingredients in it, and they may play a role by regulating Alzheimer disease pathway and TNF protein.

Cinnamaldehyde is extracted from Cinnamomum cassia and other species, providing diverse sources for varying chemical properties and therapeutic effects. Besides natural extraction, synthetic production and biotechnological methods like microbial fermentation offer scalable and sustainable alternatives. Cinnamaldehyd demonstrates a broad pharmacological range, impacting various diseases through detailed mechanisms. This review aims to encapsulate the diverse therapeutic effects of cinnamaldehyde, its molecular interactions, and its potential in clinical applications. Drawing on recent scientific studies and databases like Web of Science, PubMed, and ScienceDirect, this review outlines cinnamaldehyde\'s efficacy in treating inflammatory conditions, bacterial infections, cancer, diabetes, and cardiovascular and kidney diseases. It primarily operates by inhibiting the NF-κB pathway and modulating pro-inflammatory mediators, alongside disrupting bacterial cells and inducing apoptosis in cancer cells. The compound enhances metabolic health by improving glucose uptake and insulin sensitivity and offers cardiovascular protection through its anti-inflammatory and lipid-lowering effects. Additionally, it promotes autophagy in kidney disease management. Preclinical and clinical research supports its therapeutic potential, underscoring the need for further investigation into its mechanisms and safety to develop new drugs based on cinnamaldehyde.

Parkinson\'s disease (PD) is the second most common neurodegenerative disorder after Alzheimer\'s disease (AD). Currently, there is no cure for PD, and medications can only control the progression of the disease. Various experimental studies have shown the significant efficacy of TCM in treating PD, and combination with western medicine can enhance the effects and reduce toxicity. Thus, exploring effective anti-PD compounds from TCM has become a popular research fields. This review summarizes commonly used TCM extracts and natural products for the treatment of PD, both domestically and internationally. Furthermore, it delves into various mechanisms of TCM in treating PD, such as anti-oxidative stress, anti-inflammatory, anti-apoptotic, improve mitochondrial dysfunction, inhibits α-synuclein (α-Syn) misfolding and aggregation, regulating neurotransmitters, regulates intestinal flora, enhances immunity, and so on. The results reveal that most TCMs exert their neuroprotective effects through anti-inflammatory and anti-oxidative stress actions, thereby slowing down the progression of the disease. These TCM may hold the key to improving PD therapy and have tremendous potential to be developed as novel anti-PD drugs.