Julieta Luna-Herrera’s research while affiliated with National Polytechnic Institute and other places

Mycobacteria, including nontuberculous mycobacteria (NTM) and Mycobacterium tuberculosis complex (MTB), are global pathogens of major concern due to their intrinsic drug resistance and their capacity to cause a wide range of severe infections. The treatment of mycobacterial infections is particularly challenging because of the multidrug resistance. Efflux pumps are involved in drug resistance by actively expelling antibiotics. A promising strategy to decrease drug resistance is the inhibition of efflux pump activity by efflux pump inhibitors. In this chapter, we will review the current knowledge on efflux pumps and their impact on clinical drug resistance, as well as the potential of efflux pump inhibitors to mitigate resistance. The search for novel compounds as efflux pump inhibitors or the inclusion of existing inhibitors in the current drug therapy for mycobacterial infections has become a major goal in the treatment of these diseases.

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains one of the leading infectious causes of death globally, with drug resistance presenting a significant challenge to control efforts. The interplay between type 2 diabetes mellitus (T2DM) and TB introduces additional complexity, as T2DM triples the risk of active TB and exacerbates drug resistance development. This review explores how T2DM-induced metabolic and immune dysregulation fosters the survival of Mtb, promoting persistence and the emergence of multidrug-resistant strains. Mechanisms such as efflux pump activation and the subtherapeutic levels of isoniazid and rifampicin in T2DM patients are highlighted as key contributors to resistance. We discuss the dual syndemics of T2DM–TB, emphasizing the role of glycemic control and innovative therapeutic strategies, including efflux pump inhibitors and host-directed therapies like metformin. This review underscores the need for integrated diagnostic, treatment, and management approaches to address the global impact of T2DM–TB comorbidity and drug resistance.

Mycetoma is currently considered as a neglected tropical disease. The incidence of mycetoma is unknown but most of the worldwide cases are present in the “mycetoma belt” including countries like Mexico, India, Senegal, and others. The treatment of mycetoma depends on the etiological agent responsible for the case. Treatment success reaches 60 to 90%; however, common treatment has been reported to be ineffective in some cases, due in part to resistance to the prescribed antibiotics. Therefore, it is necessary to develop new therapeutic options. In the past two decades, quinoxaline derivatives have shown relevance as antibacterial agents. Therefore, in this work, esters of quinoxaline 1,4-di-N-oxide derivatives were evaluated in vitro against the reference strain CECT-3052 from N. brasiliensis, six clinical isolates, and macrophages J774A.1 to determine their cytotoxicity and security index. Additionally, nine reference drugs were evaluated as controls. The results show that nine esters of quinoxaline 1,4-di-N-oxide derivatives had a minimum inhibitory concentration (MIC) < 1 µg/mL against the reference strain and four of them (N-05, N-09, N-11, and N-13) had an MIC < 1 µg/mL against the clinical isolates. Therefore, the scaffold quinoxaline 1,4-di-N-oxide could be used to develop new and more potent antinocardial agents.

Asthma is a chronic immunological disease related to oxidative stress and chronic inflammation; both processes promote airway remodeling with collagen deposition and matrix thickening, causing pulmonary damage and lost function. This study investigates the immunomodulation of C-phycocyanin (CPC), a natural blue pigment purified from cyanobacteria, as a potential alternative treatment to prevent the remodeling process against asthma. We conducted experiments using ovalbumin (OVA) to induce asthma in Sprague Dawley rats. Animals were divided into five groups: (1) sham + vehicle, (2) sham + CPC, (3) asthma + vehicle, (4) asthma + CPC, and (5) asthma + methylprednisolone (MP). Our findings reveal that asthma promotes hypoxemia, leukocytosis, and pulmonary myeloperoxidase (MPO) activity by increasing lipid peroxidation, reactive oxygen and nitrogen species, inflammation associated with Th2 response, and airway remodeling in the lungs. CPC and MP treatment partially prevented these physiological processes with similar action on the biomarkers evaluated. In conclusion, CPC treatment enhanced the antioxidant defense system, thereby preventing oxidative stress and reducing airway inflammation by regulating pro-inflammatory and anti-inflammatory cytokines, consequently avoiding asthma-induced airway remodeling.

Currently, in developing countries, parasitic and bacterial diseases as amebiasis, giardiasis, trichonomiasis, leishmaniasis, trypanosomiasis, tuberculosis, and nocardiasis are a public health problem. The pharmacological treatment for these diseases is not completely effective and causes several side effects in patients. Therefore, the searchfor new compounds with biological activity is very important to develop new drugs safely and more efficiently. In this study, different organic extracts obtained from thirty-seven species of the Salvadoran flora were evaluated in several in vitromodels to determine their potential activity against five protozoa (Entamoeba histolytica, Giardia lamblia, Trichomonas vaginalis, Leishmania mexicana, and Trypanosoma cruzi) and three bacteria (Acinetobacter baumanni, Mycobacterium tuberculosis, and Nocardia brasiliensis). The results showed the activity of eight extracts with IC50values of less than 100 μg/mL against L. mexicanaand five extracts with MICs values less than <50 μg/mL against M. tuberculosis. Besides, seven plant species showed MICs ≤3.125 μg/mL against N. brasiliensis. Additionally, secondary metabolites (flavonoids and monoterpene oxygenate) previously reported as active were fingerprint by UPLC-MS to establish a potential correlation with the biological activity showed.

The indiscriminate use of antibiotics has generated super bacteria resistant to many conventional drugs. Tuberculosis is caused by the bacterium Mycobacterium tuberculosis, the use of conventional treatments for this disease generates significant damage to the liver and kidney functions of patients, which is why treatments are required that allow early diagnosis and selectivity for Pathogenic bacteria. In this work, a drug currently used for the treatment of tuberculosis (rifampicin) and silver nanoparticles as luminescent biomarkers are being encapsulated, and estimated by means of UV–VIS, FTIR, and DLS techniques for the design of theragnostic liposomes. The results show that this type of liposomes have important characteristics to be used as elements of early diagnosis in addition to its possible therapeutic use.Graphical abstract

Background Mexico has the largest number of the genus salvia plant species, whose main chemical compounds of this genus are diterpenes, these chemical compounds have shown important biological activities such as: antimicrobial, anti-inflammatory and immunomodulatory. Objective This study aimed to evaluate the immunomodulatory activity of three diterpenes: 1) icetexone, 2) anastomosine and 3) 7,20-dihydroanastomosine, isolated from Salvia ballotiflora, over innate immunity and cytokine production in a human alveolar epithelial cell line infected with Mycobacterium tuberculosis. Methods The immunomodulatory activity of diterpenes over innate immunity included reactive oxygen and nitrogen species (ROS and RNS) induction in response to infection; cytokine production included TNF-α and TGF-β induction in response to infection. Results The diterpenes anastomosine and 7,20-dihydroanastomosine showed a statically significant (p < 0.01) increase of RNS after 36 h of infection and treatment of 2.0 µg/mL. Then, the ROS induction in response to infection showed a consistent statically significant (p < 0.01) increase after 12 h of diterpenes treatments. The cell cultures showed an anti-inflammatory effect, in the case of TGF-β induction, in response to infection when treated with the diterpenes. On the other hand, there was not any significant effect on TNF-α release. Conclusion The diterpenes anastomosine and 7,20-dihydroanastomosine increased the production of RNS after 36 h of infection and treatment. Besides, the three diterpenes increased the production of ROS after 12 h. This RNS and ROS modulation can be considered as an in vitro correlation of innate immunity in response to Mycobacterium tuberculosis infection; and an indicator of the damage of epithelial lung tissue. This study also showed an anti-inflammatory immune response by means of TGF-β modulation when compared with control group.

Sporotrichosis is a subacute, or chronic mycosis caused by traumatic inoculation of material contaminated with the fungus Sporothrix schenckii which is part of the Sporothrix spp. complex. The infection is limited to the skin, although its progression to more severe systemic or disseminated forms remains possible. Skin is the tissue that comes into contact with Sporothrix first, and the role of various cell lines has been described with regard to infection control. However, there is little information on the response of keratinocytes. In this study, we used the human keratinocyte cell line (HaCaT) and evaluated different aspects of infection from modifications in the cytoskeleton to the expression of molecules of the innate response during infection with conidia and yeast cells of Sporothrix schenckii. We found that during infection with both phases of the fungus, alterations of the actin cytoskeleton, formation of membrane protuberances, and loss of stress fibers were induced. We also observed an overexpression of the surface receptors MR, TLR6, CR3 and TLR2. Cytokine analysis showed that both phases of the fungus induced the production of elevated levels of the chemokines MCP-1 and IL-8, and proinflammatory cytokines IFN-α, IFN-γ and IL-6. In contrast, TNF-α production was significant only with conidial infection. In late post-infection, cytokine production was observed with immunoregulatory activity, IL-10, and growth factors, G-CSF and GM-CSF. In conclusion, infection of keratinocytes with conidia and yeast cells of Sporothrix schenckii induces an inflammatory response and rearrangements of the cytoskeleton.

Probiotics are considered living microorganisms that help preserve the health of the host who uses them. Bacillus are a genus of Gram-positive bacteria used as probiotics for animal and human consumption. They are currently distributed in various commercial forms. Two of the species used as probiotics are B. licheniformis and B. subtilis. Macrophages are central cells in the immune response, being fundamental in the elimination of microbial pathogens, for which they use various mechanisms, including the formation of extracellular traps (METs). There have been very few studies carried out on the participation of macrophages in response to the interaction of probiotics of the genus Bacillus with the host. In this work, we used macrophages from the J774A mouse cell line.1, and we found that they are susceptible to infection by the two Bacillus species. However, both species were eliminated as the infection progressed. Using confocal microscopy, we identified the formation of METs from the first hours of infection, which were characterized by the presence of myeloperoxidase (MPO) and citrullinated histone (Hit3Cit). Quantitative data on extracellular DNA release were also obtained; release was observed starting in the first hour of infection. The induction of METs by B. licheniformis caused a significant decrease in the colony-forming units (CFU) of Staphylococcus aureus. The induction of METS by bacteria of the Bacillus genus is a mechanism that participates in controlling the probiotic and potentially pathogenic bacteria such as S. aureus. The induction of METs to control pathogens may be a novel mechanism that could explain the beneficial effects of probiotics of the genus Bacillus.

Cleoserrata serrata is used in Mexican-south traditional medicine to treat chicleros ulcer. The phytochemical profile and the anti-inflammatory effect from four extracts obtained by maceration proccess and of the primary fractions from two extracts are described. In addition, the antioxidant, leishmanicidal and antimycobaterial activities and LD50 from active extracts are reported. Anti-inflammatory activity was evaluated in TPA and carrageenan assays. Ethyl palmitate and ?-sitosterol were detected in Hexanic and CH2Cl2 extracts. Same compounds and stigmasta-3,5-dien-7-one, palmitic acid, phytol acetate and phytol were detected in primary fractions from CH2Cl2:EtOH extract. In this and in MeOH extracts a polyphenolmixture was obtained. The MeOH extract was subjected to acid hydrolysis, and kaempferol, quercetin and scopoletin were detected in organic-phase. Polyphenol-mixture and organic-phase (IC50=3730 and 2338 μg/mL) showed moderate antioxidant activity; meanwhile MeOH extract exhibited scarce activity. In carrageenan model, Hexanic extract and polyphenol-mixture showed ED50=131.46 and 64.89 mg/ kg, respectively. Three extracts were active but not-dose-dependent. In TPA-model, CH2Cl2 extract and polyphenol-mixture showed ED50 <0.79 mg/ear, and three extracts were active, however the effect was not-dose-dependent. CH2Cl2:EtOH showed antimycobacterial and leishmanicidal activities. The LD50 was >2 g/kg for all extracts.