Seyed Soheil Aghaei

The present document highlights the significance of microbial lipids as new generation anticancer, antitumor, and antioxidant compounds. It focuses on the diverse nature of the action of these lipids in cancer treatment, especially polyunsaturated fatty acids (PUFAs). These mechanisms include membrane disruption, apoptosis/necrosis, DNA damage modifying histone and gene expression, angiogenesis inhibition, cell proliferation/cycle regulation, migration, invasion, metastasis, differentiation, reversal of drug resistance, and immune system modulation. The text also discusses the economical biosynthesis of these lipids via microbial fermentation, chemosynthesis, and other synthesis techniques. The versatility of PUFAs is described in detail in the following areas of study including signal transduction and inflammation. While microbial lipids offer potential cost‐effectiveness due to scalable fermentation processes, it is important to note that specific clinical dosage regimens and comprehensive pharmacoeconomic comparisons with standard chemotherapeutic agents are still under investigation. Current estimates suggest lower long‐term costs if optimized dosing is achieved, but further clinical trials are required to validate these economic benefits.

Microbial lipids—including polyunsaturated fatty acids (PUFAs), lipopolysaccharides (LPS), lipopeptides, and phospholipids—exhibit notable antimicrobial and antibiofilm activities. Among them, PUFAs, especially omega-3 and omega-6 fatty acids produced by oleaginous yeasts and microalgae, have emerged as particularly effective due to their ability to disrupt bacterial membranes and enhance permeability, ultimately causing cell death. This mechanism is especially valuable against antibiotic-resistant and biofilm-forming pathogens. While other microbial lipids such as modified LPS, amphiphilic lipopeptides (e.g., daptomycin), and phospholipids also contribute antimicrobial effects, PUFAs demonstrate superior efficacy and dual functionality as both health-promoting nutrients and antimicrobial agents. Current strategies, including liposomal delivery systems and EPS-degrading enzyme co-administration, aim to enhance the bioavailability and targeted action of these compounds. Future research should focus on exploring PUFA combinations with conventional antimicrobials to exploit potential synergistic effects. Harnessing the structural and functional diversity of microbial lipids, particularly PUFAs, could lead to innovative therapeutic solutions for combating antibiotic resistance and biofilm-related infections.

Antibiotics represent one of the most significant medical breakthroughs of the twentieth century, playing a critical role in combating bacterial infections. However, the rapid emergence of antibiotic resistance has become a major global health crisis, significantly complicating treatment protocols. This paper provides a narrative review of the current state of antibiotic resistance, synthesizing findings from primary research and comprehensive review articles to examine the various mechanisms bacteria employ to counteract antibiotics. One of the primary sources of antibiotic resistance is the improper use of antibiotics in the livestock industry. The emergence of drug-resistant microorganisms from human activities and industrial livestock production has presented significant environmental and public health concerns. Today, resistant nosocomial infections occur following long-term hospitalization of patients, causing the death of many people, so there is an urgent need for alternative treatments. In response to this crisis, non-antibiotic therapeutic strategies have been proposed, including bacteriophages, probiotics, postbiotics, synbiotics, fecal microbiota transplantation (FMT), nanoparticles (NPs), antimicrobial peptides (AMPs), antibodies, traditional medicines, and the toxin-antitoxin (TA) system. While these approaches offer innovative solutions for addressing bacterial infections and preserving the efficacy of antimicrobial therapies, challenges such as safety, cost-effectiveness, regulatory hurdles, and large-scale implementation remain. This review examines the potential and limitations of these strategies, offering a balanced perspective on their role in managing bacterial infections and mitigating the broader impact of antibiotic resistance.

Globally, people widely recognize cancer as one of the most lethal diseases due to its high mortality rates and lack of effective treatment options. Ongoing research into cancer therapies remains a critical area of inquiry, holding significant social relevance. Currently used treatment, such as chemotherapy, radiation, or surgery, often suffers from other problems like damaging side effects, inaccuracy, and the lack of ability to clear tumors. Conventional cancer therapies are usually imprecise and ineffective and usually develop resistance to treatments and cancer recurs. Cancer patients need fresh and innovative treatment that can reduce side effects while maximizing effectiveness. In recent decades several breakthroughs in these, and other areas of medical research, have paved the way for new avenues of fighting cancer including more focused and more effective alternatives. This study reviews exciting possibilities for mesenchymal stem cells (MSCs), nanomaterials, and microbial agents in the modern realm of cancer treatment. Nanoparticles (NPs) have demonstrated surprisingly high potential. They improve drug delivery systems (DDS) significantly, enhance imaging techniques remarkably, and target cancer cells selectively while protecting healthy tissues. MSCs play a double role in tissue repair and are a vehicle for novel cancer treatments such as gene treatments or NPs loaded with therapeutic agents. Additionally, therapies utilizing microbial agents, particularly those involving bacteria, offer an inventive approach to cancer treatment. This review investigates the potential of nanomaterials, MSCs, and microbial agents in addressing the shortcomings of conventional cancer therapies. We will also discuss the challenges and limitations of using these therapeutic approaches. Graphical Abstract

Background: The antibiotic resistance of microorganisms is escalating rapidly. Infections caused by opportunistic pathogens in immunocompromised individuals have prompted researchers to seek for potent and safe antibacterial agents. The purpose of this investigation was to explore the suppression of virulence gene expression, specifically the pga operon genes responsible in biofilm formation in Acinetobacter baumannii, through the utilization of metabolites obtained from probiotic bacteria. Methods: To assess the antimicrobial properties, standard strains of five probiotic bacteria were tested against a standard strain of multidrug-resistant (MDR) A. baumannii employing the agar gel diffusion technique. Following the identification of the most potent probiotic strain (Bacillus licheniformis), the existence of its LanA and LanM genes was confirmed using the polymerase chain reaction (PCR) test. High-performance liquid chromatography (HPLC) and fourier-transform infrared spectroscopy (FTIR) techniques were employed to identify the intended metabolite, which was found to be a lipopeptide nature. The minimum inhibitory concentration (MIC) values and anti-biofilm activity of the targeted metabolite were determined using a dilution method in 96-well microplates and field emission scanning electron microscopy (FE-SEM). Real-time PCR (qPCR) was utilized for comparing the expression of pga operon genes, including pgaABCD, in A. baumannii pre- and post-exposure to the derived lipopeptide. Results: The MIC results indicated that the probiotic product inhibited the growth of A. baumannii at concentrations lower than those needed for conventional antibiotics. Furthermore, it was observed that the desired genes’ expression decreased due to the effect of this substance. Conclusions: This research concludes that the B. licheniformis probiotic product could be a viable alternative for combating drug resistance in A. baumannii.

Background: In the biological method, using nonpathogenic and extremophile bacteria systems are not only safe and highly efficient but also a trump card for synthesizing nanoparticles. Halomonas elongata QW6 IBRC-M 10,214 (He10214) and Salinicoccus iranensis IBRC-M 10,198 (Si10198), indigenous halophilic bacteria, can be used for synthesizing selenium nanoparticles (SeNPs). Methods: SeNP biosynthesis was optimized in two halophilic bacteria and characterized by UV–Vis, Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), field emission scanning electron microscopy (FESEM), X-ray powder diffraction (XRD), zeta potential, and energy dispersive X-ray (EDX). Results: Optimized conditions for synthesizing SeNPs was at 300 °C at 150 rpm for 72 h and 6 mM or 8 mM concentration of Na₂SeO₃. UV–Vis indicated a sharp absorption peak at 294 nm. Spherical-shaped nanoparticles by a diameter of 30–100 nm were observed in FESEM and TEM microscopy images. The produced SeNPs were identified by a peak in FTIR spectra. In XRD analysis, the highest peak diffraction had a relationship with SeNPs. The zeta potential analysis showed SeNP production, and elemental selenium was confirmed by EDX. Conclusions: Halophilic bacteria, owing to easy manipulation to create optimization conditions and high resistance, could serve as appropriate organisms for the bioproduction of nanoparticles. The biological method, due to effectiveness, flexibility, biocompatibility, and low cost, could be used for the synthesis of reproducible and stable nanoparticles.

Biofilm formation and resistance to antibiotics in pathogenic bacteria are important concerns in the treatment of infectious diseases. A new rapid, eco-friendly and cost-effective strategy to overcome these problems is the use of microbial exopolysaccharides (EPS) for green synthesis of various metal nanoparticles (NPs). This study used EPS from a native probiotic Lactobacillus isolate to synthesize silver nanoparticles (AgNPs) with effective antimicrobial, antibiofilm and antioxidant properties. AgNPs were synthesized by 10 mg of EPS of Lactobacillus paracasei (L. paracasei MN₈₀₉₅₂₈) isolated from a local yogurt. The characteristics of EPS AgNPs were confirmed using UV–VIS, FT-IR, DLS, XRD, EDX, FE-SEM, and zeta potential. Antimicrobial, antibiofilm and antioxidant activities of EPS AgNPs were evaluated by the agar well diffusion, microtiter dilution, SEM electron microscopy, and DPPH radical absorption methods, respectively. Spectroscopy data indicated the presence of a 466-nm peak as a feature of AgNPs. FT-IR confirmed the presence of biological agents in the synthesis of AgNPs. FE-SEM results showed that the synthesized AgNPs had a spherical shape with the size of 33–38 nm. Synthesized AgNPs at a concentration of 100 mg/ml demonstrated a significant inhibitory activity compared to chemically synthesized AgNPs. These NPs, exhibited the greatest effect of inhibiting the Escherichia coli and Pseudomonas aeruginosa biofilm formation at sub-MIC concentration, and the best effect of DPPH radical as antioxidant activity was determined at 50-μg/ml concentration. Our findings reveal that EPS AgNPs synthesized by the native isolate of L. paracasei (MN₈₀₉₅₂₈) is an inexpensive and environment-friendly candidate for application in pharmaceuticals fields.

Actinomycetes are filamentous bacteria and the residents of the soil, prone to produce bioactive metabolites. This research aimed to isolate, classify, and investigate the anticancer properties of Actinomycetes secondary metabolites from various saline soils of Qom province. Actinomycetes isolates were molecularly recognized by 16SrRNA gene sequencing after the PCR procedure. The A549 cell line was then exposed to bacterial metabolites to find their cytotoxicity by MTT assay and their capacity to cause apoptosis by Flow cytometry. The expression levels of the bax and bcl-2 genes were determined using Real-time PCR. Bacterial metabolites were distinct by HPLC and GC–MS assays. Sequencing identified three novel Actinomycetes strains, Streptomyces griseoflavus, Streptomyces calvus, and Kitasatospora phosalacineus. The IC₅₀ doses of bacterial metabolites were discovered equal to 1337, 2619, and 4874 µg/ml, respectively. Flow cytometric assay revealed that their secondary metabolites were capable of inducing apoptosis in A549 cells by 25%, 14.5%, and 7.58%, respectively. Real-time PCR findings displayed that the bax gene expression in A549 cells treated with S. griseoflavus and S. calvus, comparatively increased (P < 0.0008, P < 0.00056). The expression of the bcl-2 gene was significantly reduced in cells treated with S. griseoflavus and K. phosalacineus (P < 0.0006, P < 0.0004). The findings of this analysis showed the presence of new isolates in a soil sample from Qom province which can produce new anticancer agents and can be considered appropriate candidates for further research to employ as anticancer drugs.