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Multi-Drug Resistant (MDR) Pseudomonas aeruginosa is one of the most important bacterial pathogens that causes infection with a high mortality rate due to resistance to different antibiotics. This bacterium prompts extensive tissue damage with varying factors of virulence, and its biofilm production causes chronic and antibiotic-resistant infections. Therefore, due to the non-applicability of antibiotics for the destruction of P. aeruginosa biofilm, alternative approaches have been considered by researchers, and phage therapy is one of these new therapeutic solutions. Bacteriophages can be used to eradicate P. aeruginosa biofilm by destroying the extracellular matrix, increasing the permeability of antibiotics into the inner layer of biofilm, and inhibiting its formation by stopping the quorum-sensing activity. Furthermore, the combined use of bacteriophages and other compounds with anti-biofilm properties such as nanoparticles, enzymes, and natural products can be of more interest because they invade the biofilm by various mechanisms and can be more effective than the one used alone. On the other hand, the use of bacteriophages for biofilm destruction has some limitations such as limited host range, high-density biofilm, sub-populate phage resistance in biofilm, and inhibition of phage infection via quorum sensing in biofilm. Therefore, in this review, we specifically discuss the use of phage therapy for inhibition of P. aeruginosa biofilm in clinical and in vitro studies to identify different aspects of this treatment for broader use.

In patients with hematologic malignancies due to immune system disorders, especially persistent febrile neutropenia, invasive fungal infections (IFI) occur with high mortality. Aspergillosis, candidiasis, fusariosis, mucormycosis, cryptococcosis and trichosporonosis are the most important infections reported in patients with hematologic malignancies that undergo hematopoietic stem cell transplantation. These infections are caused by opportunistic fungal pathogens that do not cause severe issues in healthy individuals, but in patients with hematologic malignancies lead to disseminated infection with different clinical manifestations. Prophylaxis and creating a safe environment with proper filters and air pressure for patients to avoid contact with the pathogens in the surrounding environment can prevent IFI. Furthermore, due to the absence of specific symptoms in IFI, rapid and accurate diagnosis reduces the mortality rate of these infections and using molecular techniques along with standard mycological methods will improve the diagnosis of disseminated fungal infection in patients with hematologic disorders. Amphotericin B products, extended-spectrum azoles, and echinocandins are the essential drugs to control invasive fungal infections in patients with hematologic malignancies, and according to various conditions of patients, different results of treatment with these drugs have been reported in different studies. On the other hand, drug resistance in recent years has led to therapeutic failures and deaths in patients with blood malignancies, which indicates the need for antifungal susceptibility tests to use appropriate therapies. Life-threatening fungal infections have become more prevalent in patients with hematologic malignancies in recent years due to the emergence of new risk factors, new species, and increased drug resistance. Therefore, in this review, we discuss the different dimensions of the most critical invasive fungal infections in patients with hematologic malignancies and present a list of these infections with different clinical manifestations, treatment, and outcomes. Keywords: invasive fungal infection, blood malignancies, aspergillosis, candidiasis, fusariosis, mucormycosis, cryptococcosis, trichosporonosis

Multi-Drug Resistant (MDR) uropathogenic bacteria have increased in number in recent years and the development of new treatment options for the corresponding infections has become a major challenge in the field of medicine. In this respect, recent studies have proposed bacteriophage (phage) therapy as a potential alternative against MDR Urinary Tract Infections (UTI) because the resistance mechanism of phages differs from that of antibiotics and few side effects have been reported for them. Escherichia coli , Klebsiella pneumoniae , and Proteus mirabilis are the most common uropathogenic bacteria against which phage therapy has been used. Phages, in addition to lysing bacterial pathogens, can prevent the formation of biofilms. Besides, by inducing or producing polysaccharide depolymerase, phages can easily penetrate into deeper layers of the biofilm and degrade it. Notably, phage therapy has shown good results in inhibiting multiple-species biofilm and this may be an efficient weapon against catheter-associated UTI. However, the narrow range of hosts limits the use of phage therapy. Therefore, the use of phage cocktail and combination therapy can form a highly attractive strategy. However, despite the positive use of these treatments, various studies have reported phage-resistant strains, indicating that phage–host interactions are more complicated and need further research. Furthermore, these investigations are limited and further clinical trials are required to make this treatment widely available for human use. This review highlights phage therapy in the context of treating UTIs and the specific considerations for this application.

Pseudomonas aeruginosa biofilm is a community of bacteria that adhere to live or non-living surfaces and are encapsulated by an extracellular polymeric substance. Unlike individual planktonic cells, biofilms possess a notable inherent resistance to sanitizers and antibiotics. Overcoming this resistance is a substantial barrier in the medical and food industries. Hence, while antibiotics are ineffective in eradicating P. aeruginosa biofilm, scientists have explored alternate strategies, including the utilization of natural compounds as a novel treatment option. To this end, curcumin, carvacrol, thymol, eugenol, cinnamaldehyde, coumarin, catechin, terpinene-4-ol, linalool, pinene, linoleic acid, saponin, and geraniol are the major natural compounds extensively utilized for the management of the P. aeruginosa biofilm community. Noteworthy, the exact interaction of natural compounds and the biofilm of this bacterium is not elucidated yet; however, the interference with the quorum sensing system and the inhibition of autoinducer production in P. aeruginosa are the main possible mechanisms. Noteworthy, the use of different drug platforms can overcome some drawbacks of natural compounds, such as insolubility in water, limited oral bioavailability, fast metabolism, and degradation. Additionally, drug platforms can deliver different antibiofilm agents simultaneously, which enhances the antibiofilm potential of natural compounds. This article explores many facets of utilizing natural compounds to inhibit and eradicate P. aeruginosa biofilms. It also examines the techniques and protocols employed to enhance the effectiveness of these compounds.

Fusobacterium nucleatum (Fn) has been extensively studied for its connection to colorectal cancer (CRC) and its potential role in chemotherapy resistance. Studies indicate that Fn is commonly found in CRC tissues and is associated with unfavorable prognosis and treatment failure. It has been shown that Fn promotes chemoresistance by affecting autophagy, a cellular process that helps cells survive under stressful conditions. Additionally, Fn targets specific signaling pathways that activate particular microRNAs and modulate the response to chemotherapy. Understanding the current molecular mechanisms and investigating the importance of Fn-inducing chemoresistance could provide valuable insights for developing novel therapies. This review surveys the role of Fn in tumor proliferation, metastasis, and chemoresistance in CRC, focusing on its effects on the tumor microenvironment, gene expression, and resistance to conventional chemotherapy drugs. It also discusses the therapeutic implications of targeting Fn in CRC treatment and highlights the need for further research.

Objective The foodborne pathogen Salmonella enterica serovar Typhimurium causes self-limiting gastroenteritis in humans and is difficult to eliminate due to its ability to adhere to surfaces and form biofilms that exhibit high resistance to antimicrobial agents. To explore alternative strategies for biofilm treatment, it is essential to investigate novel agents that inhibit Salmonella biofilms. Method In this study, we investigated the minimum biofilm inhibitory concentrations (MBICs) and minimum biofilm eradication concentrations (MBECs) of nafcillin and diosmin, both previously identified as Lon protease inhibitors, against biofilms formed by S . Typhimurium. Furthermore, we examined the expression of genes associated with the type II toxin-antitoxin system to enhance our understanding of the impact of these inhibitors. Results The findings indicated a strong antibiofilm effect of nafcillin, with MBIC and MBEC values of 8 µg/mL and 32 µg/mL, respectively. These results were confirmed by field emission scanning electron microscopy (FE-SEM), which showed that biofilm formation was reduced in the presence of nafcillin. Additionally, it revealed morphological changes in the bacteria within the nafcillin-treated biofilms. Furthermore, gene expression analyses demonstrated a significant reduction in the expression of type II TA system genes following treatment with nafcillin and diosmin. Conclusion This study highlights the effectiveness of nafcillin in disrupting the biofilms of S . Typhimurium. These results suggest promising avenues for the development of novel therapeutic strategies targeting biofilms associated with S . Typhimurium.

Salmonella Typhimurium is an invasive intracellular pathogen that employs various factors for its survival within host cells. To mitigate S . Typhimurium survival, it is crucial to identify factors that influence bacterial survival and to develop drugs that inhibit these factors. In this study, we investigated the effects of nafcillin and diosmin, both of which have been identified as inhibitors of Lon protease, on the intracellular survival of S . Typhimurium and its survival under various stress conditions. Additionally, we examined the expression of genes associated with the type II toxin-antitoxin system to enhance our understanding of the impact of these systems on the bacterium’s survival. Our findings indicate that while nafcillin and diosmin did not affect S . Typhimurium attachment, they significantly reduced bacterial intracellular survival, particularly in Hep2 cells after 16 h. These inhibitors were also effective in decreasing bacterial survival under oxidative and acidic stress conditions. Furthermore, gene expression analysis revealed that although there were variations in the expression of TA system genes in S . Typhimurium across different cell lines, the relEB system emerged as the most effective among those studied, exhibiting the highest increase in expression. This study highlights the efficacy of nafcillin and diosmin in reducing the intracellular survival of S . Typhimurium as well as its survival under stress conditions. These findings suggest potential new strategies for developing therapies aimed at preventing S . Typhimurium infections.

Background Hepatic Actinomycosis (HA) is one of the infections that causes disorders in patients when diagnosed untimely and inappropriately. Methods Case reports on HA in patients published between 2000 and April 2020 were gathered by carrying out a structured search through PubMed/Medline. Results Through a survey of the Medline database, 130 studies were identified and then, 64 cases with HA were included in the final analysis. Asia had the largest share of cases with 37.5% (24 reports), followed by Europe and the Americas. Affected patients were predominantly males (64%) and the overall mortality rate was 1% with only one male patient in his 50 s dying. Nearly all patients (92%) were immunocompetent. However, in four patients, the use of immunosuppressive medication led to depression of the immune system. Most of the patients (80%) experienced complications. In terms of the complications, the most frequent ones were previous history of abdominal surgery (32%) and foreign bodies in the abdominopelvic region (20%). Actinomyces israelii was the most common pathogen isolated from patients. Abdominal pain (66%), fever (62%), weight loss (48%), night sweat, malaise, and anorexia (14%) over about 3.1 months were the most frequently reported clinical symptoms. Extension to one or more surrounding organs was evident in 18 patients (28%). Histopathologic examination confirmed infection in 67% of the patients and samples obtained from liver puncture biopsy (32%) were most frequently used in diagnosis. Surgery or puncture drainage + anti-infection was the most common method to treat patients and penicillin, Amoxicillin, Doxycycline, and ampicillin were the most frequently used drugs to control infection. Conclusion HA should be considered in patients with a subacute or chronic inflammatory process of the liver. With accurate and timely diagnosis of infection, extensive surgery can be prevented.

Salmonella Typhimurium, a major foodborne pathogen, forms biofilms that enhance its environmental persistence and resistance to antibiotics, presenting significant public health challenges. The CsgD protein, a key transcriptional regulator, orchestrates biofilm formation by regulating curli fimbriae and cellulose production. This study aimed to identify and evaluate potential CsgD inhibitors to disrupt S. Typhimurium biofilms using a combination of computational and experimental methodologies. Molecular docking was performed to screen 145 FDA‐approved antibiotics from DrugBank against the CsgD protein. Carbenicillin, identified as a top candidate, was further analyzed through 100 ns molecular dynamics simulations to assess the stability of the carbenicillin‐CsgD complex. Experimental evaluations determined the minimum biofilm inhibitory concentration (MBIC), and minimum biofilm eradication concentration (MBEC) of carbenicillin against S. Typhimurium isolates. Biofilm structure and curli production were examined using scanning electron microscopy (SEM) and Congo red agar assays, respectively. Molecular docking revealed carbenicillin's high binding affinity to CsgD. Molecular dynamics simulations confirmed the structural stability of the carbenicillin‐CsgD complex. Experimental assays established MBIC and MBEC at 1 and 4 μg/mL, respectively. SEM analysis showed morphological changes and disrupted biofilm architecture at 0.5–1 μg/mL carbenicillin, while Congo red agar assays demonstrated dose‐dependent suppression of curli production. Carbenicillin exhibits significant potential as a CsgD‐targeted anti‐biofilm agent, providing a foundation for novel therapeutic strategies to combat S. Typhimurium infections and address their public health burden. Salmonella Typhimurium biofilms, driven by the CsgD protein, enhance antibiotic resistance and pose public health concerns. This study employed molecular docking to screen 145 FDA‐approved antibiotics, identifying carbenicillin as a potent CsgD inhibitor. Molecular dynamics simulations confirmed stable carbenicillin‐CsgD binding. Experimental assays revealed a minimum biofilm inhibitory concentration (MBIC) of 1 μg/mL and minimum biofilm eradication concentration (MBEC) of 4 μg/mL. Scanning electron microscopy and Congo red agar assays demonstrated disrupted biofilm architecture and reduced curli production. Carbenicillin's anti‐biofilm efficacy highlights its potential as a novel therapeutic to combat S. Typhimurium infections.

CRS with nasal polyps (CRSwNP) is a multifactorial disease, and various etiological factors like bacterial superantigens are known to develop this disease. Recent studies reported that Staphylococcus aureus nasal colonization was detected in 67% of the patients with CRSwNP. Moreover, it was reported that specific IgE against S. aureus enterotoxins are discovered in almost half of the nasal tissue homogenates from nasal polyps. Thus, investigations have highlighted the role of staphylococcal enterotoxins, especially enterotoxin B (SEB), in pathogenesis of CRSwNP. The destruction of mucosal integrity was reported as a main SEB-related pathogenic mechanisms in CRSwNP. SEB activates Toll Like Receptor 2 and triggers the production of pro-inflammatory cytokines; furthermore, it induces reactive oxygen species and endoplasmic reticulum stress-induced inflammation that may cause epithelial cell integrity disruption and enhance their permeability. SEB-induced Type 2/Th2 pathway results in degranulation of eosinophils, cationic proteins production, and localized eosinophilic inflammation. Furthermore, SEB may be involved in the expression of RORC and HIF-1α in Tregs and by maintaining the inflammation in sinonasal mucosa that could have a main role in the pathogenesis of nasal polyposis. Different in vitro findings were confirmed in animal studies; however, in vivo analysis of SEB-induced nasal polyps and CRS remains unfulfilled due to the lack of appropriate animal models. Finally, after elucidating different aspects of SEB pathogenesis in CRSwNP, therapeutic agents have been tested in recent studies with some encouraging results. The purpose of this article is to summarize the most important findings regarding SEB-induced CRS and nasal polyposis. 6DmwcpuBjtAL6omjhrKSRy Video Abstract