Phytochemicals are effective and are gaining attention in fighting against drug-resistant bacterial strains. In the present study, rutin and quercetin were tested for antibacterial, antibiofilm, and wound healing activities on excision wounds infected with MDR-P. aeruginosa in diabetic mice. Antibacterial and antibiofilm activities were studied in vitro using broth dilution assay and crystal violet assay, respectively. These phytochemicals were tested alone for wound-healing activities at different concentrations (0.5% and 1% in ointment base) and in combination with gentamicin to evaluate any additive effects. Rutin and quercetin demonstrated effectiveness against MDR-P. aeruginosa at higher concentrations. Both phytochemicals inhibited biofilm formation in vitro and contributed to the healing of diabetic wounds by eradicating biofilm in the wounded tissue. Rutin at a low concentration (0.5%) had a lesser effect on reducing the epithelization period and regeneration of the epithelial layer compared to quercetin. When combined with gentamicin, quercetin (1%) displayed the maximum effect on epithelium regeneration, followed by rutin (1%) in combination with gentamicin. Both phytochemicals were found to be more effective in controlling biofilm and wound-healing activities when used as an additive with gentamicin. The study supports the traditional use of phytochemicals with antibacterial, antibiofilm, and wound-healing activities in managing diabetic infections.

Background: CCAAT/enhancer‐binding protein β (C/EBPβ) is a transcription factor whose high expression in human cancers is associated with tumour aggressiveness and poor outcomes. Most advanced cancer patients will develop cachexia, characterized by loss of skeletal muscle mass. In response to secreted factors from cachexia‐inducing tumours, C/EBPβ is stimulated in muscle, leading to both myofibre atrophy and the inhibition of muscle regeneration. Involved in the regulation of immune responses, C/EBPβ induces the expression of many secreted factors, including cytokines. Because tumour‐secreted factors drive cachexia and aggressive tumours have higher expression of C/EBPβ, we examined a potential role for C/EBPβ in the expression of tumour‐derived cachexia‐inducing factors.Methods: We used gain‐of‐function and loss‐of‐function approaches in vitro and in vivo to evaluate the role of tumour C/EBPβ expression on the secretion of cachexia‐inducing factors.Results: We report that C/EBPβ overexpression up‐regulates the expression of 260 secreted protein genes, resulting in a secretome that inhibits myogenic differentiation (−31%, P < 0.05) and myotube maturation [−38% (fusion index) and −25% (myotube diameter), P < 0.05]. We find that knockdown of C/EBPβ in cachexia‐inducing Lewis lung carcinoma cells restores myogenic differentiation (+25%, P < 0.0001) and myotube diameter (+90%, P < 0.0001) in conditioned medium experiments and, in vivo, prevents muscle wasting (−51% for small myofibres vs. controls, P < 0.01; +140% for large myofibres, P < 0.01). Conversely, overexpression of C/EBPβ in non‐cachectic tumours converts their secretome into a cachexia‐inducing one, resulting in reduced myotube diameter (−41%, P < 0.0001, EL4 model) and inhibition of differentiation in culture (−26%, P < 0.01, EL4 model) and muscle wasting in vivo (+98% small fibres, P < 0.001; −76% large fibres, P < 0.001). Comparison of the differently expressed transcripts coding for secreted proteins in C/EBPβ‐overexpressing myoblasts with the secretome from 27 different types of human cancers revealed ~18% similarity between C/EBPβ‐regulated secreted proteins and those secreted by highly cachectic tumours (brain, pancreatic, and stomach cancers). At the protein level, we identified 16 novel secreted factors that are present in human cancer secretomes and are up‐regulated by C/EBPβ. Of these, we tested the effect of three factors (SERPINF1, TNFRSF11B, and CD93) on myotubes and found that all had atrophic potential (−33 to −36% for myotube diameter, P < 0.01).Conclusions: We find that C/EBPβ is necessary and sufficient to induce the secretion of cachexia‐inducing factors by cancer cells and loss of C/EBPβ in tumours attenuates muscle atrophy in an animal model of cancer cachexia. Our findings establish C/EBPβ as a central regulator of cancer cachexia and an important therapeutic target.

Antimicrobial resistance (AMR) is a present, pressing global public health crisis associated with rising morbidity and mortality rates due to previously curable infectious disease. Targeted drug delivery is an important approach to address AMR due to its ability to improve the therapeutic performance of antibiotics without leading to any adverse effects or organ toxicities. In this review we explore molecular mechanisms of AMR and drawbacks of conventional antibiotic therapies and discuss unique drug delivery approaches to compensate these. Nanoparticulate carrier systems, stimuli-responsive systems, antibody–drug conjugates, and CRISPR-Cas systems are some of the carrier method designs that are promising for tackling hard to treat infections related to pathogenic strains and biofilms due to their features. Many of these are among the most significant advances in the field. However, there are many challenges to be overcome, with biological limitations, scaling and regulatory challenges, etc., before they can be employed in commercial applications. Materials are being developed, and an approach standardized and applicable to future work is in development to improve the efficiency of targeted delivery systems. Controlled drug delivery, which could be the answer to an increasing AMR problem, will not only help in alerting awareness among individuals but will also help in prolonging the activity of antibiotics by providing synergistic interdisciplinary solutions. This review emphasizes the complementary role of targeted drug delivery in transitioning from laboratory investigations to clinical therapy. It addresses underrepresented aspects, including new materials, scalability, regulatory considerations, and ethical implications, while offering a roadmap for translating innovations into next-generation antimicrobials.

Achillea fragrantissima, a desert plant commonly known as yarrow, is traditionally used as an antimicrobial agent in folklore medicine in Saudi Arabia. The current study was undertaken to determine its antibiofilm activity against methicillin-resistant Staphylococcus aureus (MRSA) and multi-drug-resistant Pseudomonas aeruginosa (MDR-P. aeruginosa) using in vitro and in vivo studies. A biofilm model induced through an excision wound in diabetic mice was used to evaluate its effect in vivo. The skin irritation and cytotoxic effects of the extract were determined using mice and HaCaT cell lines, respectively. The Achillea fragrantissima methanolic extract was analyzed with LC-MS to detect different phytoconstituents, which revealed the presence of 47 different phytoconstituents. The extract inhibited the growth of both tested pathogens in vitro. It also increased the healing of biofilm-formed excision wounds, demonstrating its antibiofilm, antimicrobial, and wound-healing action in vivo. The effect of the extract was concentration-dependent, and its activity was stronger against MRSA than MDR-P. aeruginosa. The extract formulation was devoid of a skin irritation effect in vivo and cytotoxic effect on HaCaT cell lines in vitro.

The study developed a simple and inexpensive method to induce biofilm formation in-vivo for the evaluation of the antibiofilm activity of pharmacological agents using Swiss albino mice. Animals were made diabetic using streptozocin and nicotinamide. A cover slip containing preformed biofilm along with MRSA culture was introduced into the excision wound in these animals. The method was effective in developing biofilm on the coverslip after 24 h incubation in MRSA broth which was confirmed by microscopic examination and a crystal violet assay. Application of preformed biofilm along with microbial culture induced a profound infection with biofilm formation on excision wounds in 72 h. This was confirmed by macroscopic, histological, and bacterial load determination. Mupirocin, a known antibacterial agent effective against MRSA was used to demonstrate antibiofilm activity. Mupirocin was able to completely heal the excised wounds in 19 to 21 days while in the base-treated group, healing took place between 30 and 35 days. The method described is robust and can be reproduced easily without the use of transgenic animals and sophisticated methods such as confocal microscopy.

Background: Obesity is a growing global health concern, often accompanied by dyslipidemia, contributing to cardiovascular risk. Understanding the patterns of dyslipidemia in different glycemic states is crucial for targeted interventions. This study compares dyslipidemia patterns in normoglycemic and prediabetic obesity to improve clinical management strategies. Methods: The study analyzed the complete lipid profiles of 138 subjects, comparing the medians, prevalence, diagnostic performance, and risk assessment of each lipid parameter across 54 non-obese (NO), 44 normoglycemic obese (NG-OB), and 40 pre-diabetic obese (PreDM-OB) groups. Results: Elevated total cholesterol (TC) and low-density lipoprotein (LDL) were the most prevalent forms of dyslipidemia observed in obesity (45.35% and 43.53%, respectively). Stratification by glycemic status revealed that triglyceride (TG) levels were elevated in both the NG-OB and PreDM-OB groups, with a more marked increase in the latter group (73.07 mg/dL vs. 97.87 mg/dL vs. 121.8 mg/dL, respectively). Elevated LDL showed better diagnostic performance and higher odds ratios (OR) in the NG-OB group (AUC = 0.660, p = 0.006; OR = 2.78, p = 0.022). Conversely, low high-density lipoprotein (HDL) was more common and exhibited significant diagnostic performance, with higher OR values in the PreDM-OB group (AUC = 0.687, p = 0.002; OR = 3.69, p = 0.018). Importantly, all lipid ratios were elevated in obesity, with TC/HDL showing the highest predictive ability for prediabetes (AUC = 0.7491, p < 0.001). Conclusions: These findings revealed unique and common lipid abnormalities in normoglycemic and prediabetic obesity. Future research should explore the effects of targeted lipid management on obesity-associated complications.