Association between uric acid and referable diabetic retinopathy in patients with type 2 diabetes.

Plasmatic uric acid (UA) has been inconsistently associated with diabetic retinopathy (DR). Specific sight-threatening stages of DR have not been studied for their association with UA. Cross-sectional, comparative study. Between 2014 and 2018 we recruited 210 Mexican individuals > 18 years-old with type 2 diabetes (T2D). Clinical, ophthalmological and biochemical assessment was performed with standardized funduscopic examination. Certified readers classified DR stages. The association between DR and UA was assessed by multiple logistic regression analysis, calculating odds ratios (OR) and 95% CI, after adjustment for covariates. Two hundred and ten patients were included, 41 (19.5%) had referable DR. Subjects with referable (severe or worse) DR had longer diabetes duration, 22 (15-28) vs 15 (8-20) years (P < 0.01); higher levels of UA, 6.5 (5.8-8.1) vs 5.4 (4.5-6.6) mg/dL (P < 0.01); higher systolic blood pressure, 130 (120-140) vs 120 (110-130) mmHg (P < 0.01); higher diastolic blood pressure, 78.4 ± 9.7 vs 75.4 ± 9.2 mmHg (P = 0.03); and lower glomerular filtration rate , 54.1 (41.5-69.6) vs 87.3 (66.8-108.3) mL/min/1.73m2 (P < 0.01) compared with those without referable DR. With multiple logistic regression, after adjustment, per each unit of change (mg/dL) in UA the probability of having referable DR increased 45% (OR = 1.45, 95% CI 1.12-1.87, P < 0.01). When UA was evaluated as dichotomous variable, those with levels ≥ 7.8 mg/dL had almost two times (OR = 2.81, 95% CI 1.00-7.9., P = 0.049) the probability of having referable DR compared with those with levels < 7.8 mg/dL. UA may contribute to the microvascular damage in retinal vessels and therefore hyperuricemia could be a therapeutic target to prevent DR progression.

Baroreflex and chemoreflex interaction in high-altitude exposure: possible role on exercise performance.

The hypoxic chemoreflex and the arterial baroreflex are implicated in the ventilatory response to exercise. It is well known that long-term exercise training increases parasympathetic and decreases sympathetic tone, both processes influenced by the arterial baroreflex and hypoxic chemoreflex function. Hypobaric hypoxia (i.e., high altitude [HA]) markedly reduces exercise capacity associated with autonomic reflexes. Indeed, a reduced exercise capacity has been found, paralleled by a baroreflex-related parasympathetic withdrawal and a pronounced chemoreflex potentiation. Additionally, it is well known that the baroreflex and chemoreflex interact, and during activation by hypoxia, the chemoreflex is predominant over the baroreflex. Thus, the baroreflex function impairment may likely facilitate the exercise deterioration through the reduction of parasympathetic tone following acute HA exposure, secondary to the chemoreflex activation. Therefore, the main goal of this review is to describe the main physiological mechanisms controlling baro- and chemoreflex function and their role in exercise capacity during HA exposure.

Dentate nucleus: a review and implications for dentatotomy.

PURPOSE: The dentate nucleus (DN) is the largest, most lateral, and phylogenetically most recent of the deep cerebellar nuclei. Its pivotal role encompasses the planning, initiation, and modification of voluntary movement but also spans non-motor functions like executive functioning, visuospatial processing, and linguistic abilities. This review aims to offer a comprehensive description of the DN, detailing its embryology, anatomy, physiology, and clinical relevance, alongside an analysis of dentatotomy. METHODS AND RESULTS: We delve into the history, embryology, anatomy, vascular supply, imaging characteristics, and clinical significance of the DN. Furthermore, we thoroughly review the dentatotomy, emphasizing its role in treating spasticity. CONCLUSIONS: Understanding the intricacies of the anatomy, physiology, vasculature, and projections of the DN has taken on increased importance in current neurosurgical practice. Advances in technology have unveiled previously unknown functions of the deep cerebellar nuclei, predominantly related to non-motor domains. Such discoveries are revitalizing older techniques, like dentatotomy, and applying them to newer, more localized targets.

Leveraging pooled medical examiner records to surveil complex and emerging patterns of polysubstance use in the United States.

BACKGROUND: The United States (US) is an extreme global outlier for drug-related death rates. However, data describing drug-related deaths are generally available only on an 8-13-month lag. Furthermore, granular details about substance-involvement are often not available, which particularly stymies efforts to track fatal polysubstance and novel psychoactive substance use. Detailed medical examiner records provide a powerful source of information for drug-related death surveillance, but have been underutilized. METHODS: We pooled medical examiner data from five US states and 14 counties that together comprise 18% of the US population to examine demographic, geographic, and drug-specific trends in polysubstance drug-related deaths. We employed mixed effects logistic regression to identify demographic factors associated with polysubstance rather than single substance drug-related deaths. We assessed the correlations between drug classes and described geographic variation in the prevalence of specific drugs and the presence of novel and emerging psychoactive substances. RESULTS: Our sample included 73,077 drug-related deaths from 2012 through early 2022. Nearly two-thirds of drug-related deaths were polysubstance-involved, with the number and percentage growing annually. High percentages of polysubstance drug-related deaths were observed in both urban and rural jurisdictions. After adjusting for year and jurisdiction, female, American Indian and Alaska Native, and White individuals had the most elevated odds of polysubstance drug-related deaths. Drug-related deaths involving benzodiazepines or opioids, whether pharmaceutical or illicit, and other pharmaceutical drugs were most likely to have polysubstance involvement, while methamphetamine-involved deaths were least likely to involve multiple substances. Strong correlations were observed between prescription opioids and prescription benzodiazepines, fentanyl and xylazine, and designer benzodiazepines and novel synthetic opioids. CONCLUSIONS: Analysis of detailed medical examiner records reveals the breadth and complexity of polysubstance drug-related deaths in the US. Future efforts to use this unique resource can improve population-based surveillance of drug-related deaths to better tailor interventions and solutions to this critical health crisis.

Stem Cell Markers in Neoplasms and their Relationship with Progression-free and Overall Survival in Patients with Recurrence.

BACKGROUND: Gliomas account for 30% of primary brain tumors in adults, and despite the scientific progress in the field, recurrence is prevalent. Glioma Stem Cells (GSCs) can generate tumor cells in vivo and in vitro and they are associated with treatment resistance, tumor progression, and recurrence. Furthermore, the expression of SOX transcription factors (SOX1, SOX2, SOX9) in these cells is responsible for maintaining an oncogenic genotype and is associated with an aggressive tumor phenotype. The relationship between SOX transcription factors and their prognostic role in recurrent gliomas has not been described in detail. Therefore, we set out to describe the relationship between SOX expression and Progression-free Survival (PFS) and Overall Survival (OS) in patients with recurrent gliomas. METHODS: In this observational study, we have retrospectively analyzed 69 patients, of which 20 met the inclusion criteria. The clinical, radiological, and histopathological findings have been described, and survival analysis has been performed according to SOX expression for PFS and OS. RESULTS: We found SOX1, SOX2, and SOX9 to show a non-statistically significant trend with increasing histopathological grade, co-expressed with Ki67, a cell proliferation factor. CONCLUSION: There has been found an inversely proportional correlation between the degree of immunopositivity of SOX1 and OS. A higher SOX1 immunopositivity could predict a worse clinical prognosis. There has also been found an interaction between a pluripotent genotype (GSC) and cell proliferation.

COL1A1 proximal promoter topology regulates its transcriptional response to transforming growth factor ß.

OBJECTIVE: The COL1A1 proximal promoter contains two GC-rich regions and two inverted CCAAT boxes. The transcription factors Sp1 and CBF bind to the GC sequence at -122 to -115 bp and the inverted CCAAT box at -101 to -96 bp, respectively, and stimulate COL1A1 transcriptional activity. METHODS: To further define the regulatory mechanisms controlling COL1A1 expression by Sp1 and CBF, we introduced 2, 4, 6, or 8 thymidine nucleotides (T-tracts) at position -111 bp of the COL1A1 gene promoter to increase the physical distance between these two binding sites and examined in vitro the transcriptional activities of the resulting constructs and their response to TGF-ß1.`. RESULTS: Insertion of 2 or 4 nucleotides decreased COL1A1 promoter activity by up to 70%. Furthermore, the expected increase in COL1A1 transcription in response to TGF-ß1 was abolished. Computer modeling of the modified DNA structure indicated that increasing the physical distance between the Sp1 and CBF binding sites introduces a rotational change in the DNA topology that disrupts the alignment of Sp1 and CBF binding sites and likely alters protein-protein interactions among these transcription factors or their associated co-activators. CONCLUSION: The topology of the COL1A1 proximal promoter is crucial in determining the transcriptional activity of the gene and its response to the stimulatory effects of TGF-ß1.

Radiation therapy for optic nerve sheath meningiomas: Local control and treatment related visual changes.

Objective: Our primary objective is to evaluate the local control of optic nerve sheath meningiomas (ONSMs) treated with ionizing radiation and related visual changes after treatment. Our secondary objective is to describe the clinical characteristics and perform an analysis of the treatment impact on the functional status of this group of patients. Methods: We present our series of 19 patients treated with ionizing radiation therapy at our radio-neurosurgery unit between 2016 and 2022. The setting, ophthalmological follow-up, morbidity, and survival are analyzed and discussed. Results: Patients were followed up, and the impact of treatment on local disease control, visual alterations of the affected eye, and functional status of the patient were analyzed. The progression-free survival (PFS) median was 60 months (95% CI 50.3-69.6 months). The estimated PFS rates at 48 and 66 months were 100% and 66%, respectively. At diagnosis, nine (47.3%) eyes were in amaurosis and ten (52.6%) with vision. Of the ten patients without amaurosis at the time of diagnosis, three (30%) maintained unchanged visual acuity, and seven (70%) had decreased visual acuity; three of them developed amaurosis during the first year after treatment (p = 0.018). Conclusions: Using ionizing radiation therapy is a successful treatment for the local control of ONSMs. This therapeutic modality can compromise the visual acuity of the affected eye and improve dyschromatopsia and campimetry defects. The life prognosis is good for these patients, with a zero mortality rate, but their vision prognosis is poor.

Coping and risk perception during the COVID-19 pandemic in type 2 diabetes: Does it influence metabolic control?

Diabetes and poor glycemic control are significant predictors of severity and death in the COVID-19 disease. The perception of this risk in individuals with type 2 diabetes (T2D) could modify coping styles, leading to behaviors associated with better self-care and metabolic control. Theoretically, active coping is associated with better glycemic control in patients with T2D. Nonetheless, information during extreme risk like the COVID-19 pandemic is still limited. Our objective was to evaluate the association between coping styles and risk perception in the COVID-19 pandemic and the change in metabolic parameters. This is a prospective study that included individuals with T2D treated in a tertiary care center during the COVID-19 outbreak who returned to follow-up one year later. We assessed coping styles and risk perception with the Extreme Risk Coping Scale and the risk perception questionnaire. Clinical characteristics and metabolic parameters were registered in both visits. Groups were compared using Kruskal Wallis tests, and changes in metabolic parameters were assessed with Wilcoxon rank sum tests. Our sample included 177 participants at baseline, and 118 concluded the study. Passive coping was more frequent in women. Low-risk perception was associated with higher age, lower psychiatric comorbidities, and lower frequency of psychiatric treatment compared with other risk perception groups. Patients with active coping plus high-risk perception did not have a change in metabolic parameters at follow-up, whereas patients with other coping styles and lower risk perception had an increase in total cholesterol, LDL-cholesterol, and triglycerides. There were no differences by coping group or by risk perception in glycemic control.

Risk Factors Associated with Diabetic Retinopathy with and without Macular Edema in Recently Diagnosed Patients with Type 2 Diabetes.

Purpose: To evaluate the risk factors associated with diabetic macular edema (DME) in patients with a recent type 2 diabetes mellitus (T2DM) diagnosis. Patients and Methods: We conducted a case-control study at a third-level hospital in Mexico City. We enrolled patients ≥18 years old, with T2DM less than five years of diagnosis, without disabling complications, and non-smokers. The control group was patients with diabetic retinopathy and without macular edema (DR-DME). Cases were patients with DR+DME. We measured fasting glucose, creatinine, lipid profile, urinary albumin/creatinine ratio (ACR), and HbA1c. An ophthalmological examination consisted of visual acuity measurement, digital three-field fundus photography with an automatic non-mydriatic camera, slit lamp, and Optical coherence tomography (OCT) examination. Results: 183 and 61 patients with DR-DME and DR+DME, respectively, were included in the analysis. The prevalence of mild DR was higher in the DR-DME group, but the frequencies of moderate and severe retinopathy were higher in the DR+DME group. Patients in the DR-DME group had better vision than those in the DR+DME group. Logistic regression analysis revealed that age (OR, 1.07), HbA1c (OR, 1.19), and Albumin-to-Creatinine Ratio (ACR) > 30 mg/g (OR, 3.37) were associated with an increased possibility of DME compared to DR-DME. Conclusion: Our study provides insights into the association between risk factors and DME. We found a statistically strong association between HbA1c levels, age, and ACR. Patients with poor metabolic control should undergo an extensive medical examination to screen for DME, which may be related to the chronicity of DM and renal damage.

Early Atf4 activity drives airway club and goblet cell differentiation.

Activating transcription factor 4 (Atf4), which is modulated by the protein kinase RNA-like ER kinase (PERK), is a stress-induced transcription factor responsible for controlling the expression of a wide range of adaptive genes, enabling cells to withstand stressful conditions. However, the impact of the Atf4 signaling pathway on airway regeneration remains poorly understood. In this study, we used mouse airway epithelial cell culture models to investigate the role of PERK/Atf4 in respiratory tract differentiation. Through pharmacological inhibition and silencing of ATF4, we uncovered the crucial involvement of PERK/Atf4 in the differentiation of basal stem cells, leading to a reduction in the number of secretory cells. ChIP-seq analysis revealed direct binding of ATF4 to regulatory elements of genes associated with osteoblast differentiation and secretory cell function. Our findings provide valuable insights into the role of ATF4 in airway epithelial differentiation and its potential involvement in innate immune responses and cellular adaptation to stress.

De-escalating treatment indications for patients who achieve metabolic goals.

INTRODUCTION: Robust evidence exists regarding initiation, intensification or modification of treatments. Recommendations to de-escalate therapy are lacking, specifically in diabetes. A successful treatment de-intensification reduces overtreatment, polypharmacy, and risk of adverse effects. OBJECTIVE: To encompass current recommendations for deprescribing common drugs and create a consensus among health professionals. METHODS: We reviewed four databases for deprescribing approaches published between 2010 and 2022. Articles were divided into different groups of drugs (for uric-acid, hypoglycemic, lipid-lowering, and psychotropic drugs). RESULTS: Hypoglycemic agents: strategies were limited to newer agents and insulin regimens for elderly individuals. Reducing insulin was associated with 1.1% reduction of A1c over time. SGLT2i and GLP-1RAs dose reduction depends on adverse events. Lipid-lowering agents: studies show that patients with very low cholesterol have fewer cardiovascular events without associated increased risk. Antihypertensive agents: Younger patients, lower systolic blood pressure, and few comorbidities are ideal characteristics for discontinuation. Uric acid therapy: we found no recommendation for dose de-escalation. Poor treatment adherence is associated with episodes of gout and deforming arthritis in the long term. CONCLUSION: Deprescribing hypoglycemic, statins, antihypertensives, and urate-lowering agents may be feasible in selected patients, but periodic surveillance is important. More evidence is necessary to support this decision entirely.

Comparison of Metabolic, Lifestyle and Mental Health Parameters in People with Diabetes and Relatives with and without Family Support.

Purpose: To analyze and compare metabolic, lifestyle and mental health parameters in relatives and people-with-T2DM (PDM) with and without support. Patients and Methods: We included 160 patients with <5 years of diagnosis of T2DM, without disabling complications, and non-smokers, attending a multidisciplinary program for diabetes control, and their accompanying relatives. If the patients or relatives abandoned the program, we contacted them and asked to take laboratory tests and answer surveys regarding anxiety, depression, and perception of their family support. Variables distribution was assessed with the Kolmogorov-Smirnov test. We used ANOVA or Kruskal Wallis Tests, according to variable distribution. Frequencies and percentages are used for categorical values and analyzed with a chi-square test. We separated the participants in four groups: relatives with and without support and PDM with and without support. Results: We included 160 participants, age 51±10, and 54.3% women. Total cholesterol (188±36 vs 204±43 vs 170±34 vs 181±35 mg/dL, p=0.001), LDL-cholesterol (113±35 vs 125±27 vs 101 ±30 vs 109±29, p=0.008), and non-HDL cholesterol (143±32 vs 154 ±30 vs 129±33 vs 135±35 mg/dL, p=0.010) were higher in the group without support. Although patients without family support had lower values, they did not achieve metabolic goals. Weight (75±17 vs 77±19 vs 74.2±10.5 vs 90.2±17.3 kg) and body mass index (28.9±4.8 vs 30.1±4.7 vs 27.4±3.3 vs 33±4.3 kg/m2) were higher in PDM without family support (p<0.001 for both). Conclusion: Support in PDM and their families is important in metabolic control. However, raising awareness among family members to screen for diabetes and changes in lifestyle are points to improve. Including the evaluation of social and family support will allow a more complete assessment to identify barriers to achieving goals.

Comparison of microvascular decompression, percutaneous radiofrequency rhizotomy, and stereotactic radiosurgery in the treatment of trigeminal neuralgia: A long term quasi-experimental study.

BACKGROUND: Microvascular decompression (MVD), radiofrequency rhizotomy (RFR), and stereotactic radiosurgery (SRS) are surgical techniques frequently used in the treatment of idiopathic trigeminal neuralgia (TN), although the results reported for each of these are diverse. OBJECTIVE: This study aimed to compare long-term pain control obtained by MVD, SRS, and RFR in patients with idiopathic TN. METHODS: To compare the results obtained by MVD, SRS, and RFR we chose a quasi-experimental, ambispective design with control groups but no pretest. A total of 52 participants (MVD n = 33, RFR n = 10, SRS n = 9) were included. Using standardized outcome measures, pain intensity, pain relief, quality of life, and satisfaction with treatment were assessed by an independent investigator. The TREND statement for reporting non-randomized evaluations was applied. Clinical outcomes were evaluated at the initial postoperative period and at 6 months, 1, 2, 3, 4, and 5 years postoperatively. RESULTS: MVD has shown better results in pain scales compared to ablative procedures. Significant differences between groups were found regarding pain intensity and pain relief at the initial postoperative period (p < 0.001) and 6 months (p = 0.022), 1 year (p < 0.001), 2 years (p = 0.002), and 3 years (p = 0.004) after the intervention. Those differences exceeded the thresholds of the minimal clinically important difference. A higher percentage of patients free of pain was observed in the group of patients treated by MVD, with significant differences at the initial postoperative period (p < 0.001) and 6 months (p = 0.02), 1 year (p = 0.001), and 2 years (p = 0.04) after the procedure. Also, a higher risk of pain recurrence was observed in the RFR and SRS groups (HR 3.15, 95% CI 1.33-7.46; p = 0.009; and HR 4.26, 95% CI 1.77-10.2; p = 0.001, respectively) compared to the MVD group. No significant differences were found in terms of quality of life and satisfaction with treatment. A higher incidence of complications was observed in the MVD group. CONCLUSION: Concerning pain control and risk of pain recurrence, MVD is superior to RFR and SRS, but not in terms of quality of life, satisfaction with treatment, and safety profile.

Cellular Transdifferentiation: A Crucial Mechanism of Fibrosis in Systemic Sclerosis.

Systemic Sclerosis (SSc) is a systemic autoimmune disease of unknown etiology with a highly complex pathogenesis that despite extensive investigation is not completely understood. The clinical and pathologic manifestations of the disease result from three distinct processes: 1) Severe and frequently progressive tissue fibrosis causing exaggerated and deleterious accumulation of interstitial collagens and other extracellular matrix molecules in the skin and various internal organs; 2) extensive fibroproliferative vascular lesions affecting small arteries and arterioles causing tissue ischemic alterations; and 3) cellular and humoral immunity abnormalities with the production of numerous autoantibodies, some with very high specificity for SSc. The fibrotic process in SSc is one of the main causes of disability and high mortality of the disease. Owing to its essentially universal presence and the severity of its clinical effects, the mechanisms involved in the development and progression of tissue fibrosis have been extensively investigated, however, despite intensive investigation, the precise molecular mechanisms have not been fully elucidated. Several recent studies have suggested that cellular transdifferentiation resulting in the phenotypic conversion of various cell types into activated myofibroblasts may be one important mechanism. Here, we review the potential role that cellular transdifferentiation may play in the development of severe and often progressive tissue fibrosis in SSc.

Walk Locomotion Kinematic Changes in a Model of Penetrating Hippocampal Injury in Male/Female Mice and Rats.

Traumatic brain injury has been the leading cause of mortality and morbidity in human beings. One of the most susceptible structures to this damage is the hippocampus due to cellular and synaptic loss and impaired hippocampal connectivity to the brain, brain stem, and spinal cord. Thus, hippocampal damage in rodents using a stereotaxic device could be an adequate method to study a precise lesion from CA1 to the dentate gyrus structures. We studied male and female rats and mice, analyzing hindlimb locomotion kinematics changes to compare the locomotion kinematics using the same methodology in rodents. We measure (1) the vertical hindlimb metatarsus, ankle, and knee joint vertical displacements (VD) and (2) the factor of dissimilarity (DF). The VD in intact rats in metatarsus, ankle, and knee joints differs from that in intact mice in similar joints. In rats, the vertical displacement through the step cycle changed in the left and right metatarsus, ankle, and knee joints compared to the intact group versus the lesioned group. More subtle changes were also observed in mice. DF demonstrates contrasting results when studying locomotion kinematics of mice or rats and sex-dependent differences. Thus, a precise lesion in a rodent's hippocampal structure discloses some hindlimb locomotion changes related to species and sex. Thus, we only have a qualitative comparison between murine species. In order to make a comparison with other species, we should standardize the model.

Non-functional Pituitary Adenomas: Analysis of Delayed Diagnosis in Mexico.

BACKGROUND:  Although tumors of the central nervous system (CNS) are rare, they can cause significant morbidity and mortality. The clinical presentation of patients with non-functional pituitary adenomas (NFPA) ranges from being completely asymptomatic to causing pituitary, hypothalamic, or visual dysfunction due to their large size. Patients usually arrive with large tumors at the time of diagnosis.  Objectives: Try to describe the characteristics of NFPA and explain the causes of delayed diagnosis.  Methods: We carried out a retrospective study including 58 patients with NFPA and analyzed the tumor volume at the time of diagnosis and its relationship with sociodemographic and health sector variables.  Results: Low socioeconomic status (SES) was associated with high tumor volume (SES 1-2 of 17.4 cm3 vs 3-6 of 11.7 cm3, p=0.018), and the time between first consultation and diagnosis was longer in the public sector than in the private sector (13.5 months vs 5.1 months). The time between the first symptom and the first consultation was shorter when they had visual impairment than when they did not (4.1 vs 18.4 months, p=0.006). CONCLUSIONS: On the one hand, citizens should be made aware that a visual deficit should make them go to a medical check-up, and on the other hand, strengthen the health system so that they have the NFPA as a differential diagnosis in patients with some visual alteration. Socioeconomic inequality in our country undoubtedly puts the underprivileged at greater risk.

Lhermitte-Duclos Disease: A Case Series.

Lhermitte-Duclos disease (LDD), or dysplastic cerebellar gangliocytoma, is a rare benign tumor characterized by unilateral hemispheric cerebellar expansion. It is linked to mutations in the phosphatase and tensin homolog (PTEN) gene, which inhibit the phosphatidylinositol-3'-kinase pathway, leading to increased cell division and defective neuronal migration. This study aims to compare the clinical, radiological, histopathological, surgical resolution, and follow-up characteristics of reported cases of this rare condition. An in-depth search of LDD patients' clinical records at our institute between 2003 and 2023 was conducted, in addition to a systematic literature review on PubMed. Three patients with a diagnosis of LDD were found. Cerebellar abnormalities, varying headaches, and visual impairment were all present clinically. On T2 in the posterior fossa, all three MRI scans displayed the typical hyperintense parallel streak appearance. The histopathological report showed that large ganglion cells had replaced the granular layer, Purkinje cells had degenerated, the molecular layer had become hyper-myelinated, and synaptophysin and chromogranin were positive. Partial tumor resection and avoiding intracranial hypertension were the main goals of treatment. Genetic follow-up was conducted for all three patients. Neurosurgeons must be aware of LDD to provide close genetic monitoring despite the benign nature of the tumor because of its link to Cowden syndrome and elevated risk of cancer in other organs.

Immunomodulatory effects of inactivated Ligilactobacillus salivarius CECT 9609 on respiratory epithelial cells.

The microbiota in humans and animals play crucial roles in defense against pathogens and offer a promising natural source for immunomodulatory products. However, the development of physiologically relevant model systems and protocols for testing such products remains challenging. In this study, we present an experimental condition where various natural products derived from the registered lactic acid bacteria Ligilactobacillus salivarius CECT 9609, known for their immunomodulatory activity, were tested. These products included live and inactivated bacteria, as well as fermentation products at different concentrations and culture times. Using our established model system, we observed no morphological changes in the airway epithelium upon exposure to Pasteurella multocida, a common respiratory pathogen. However, early molecular changes associated with the innate immune response were detected through transcript analysis. By employing diverse methodologies ranging from microscopy to next-generation sequencing (NGS), we characterized the interaction of these natural products with the airway epithelium and their potential beneficial effects in the presence of P. multocida infection. In particular, our discovery highlights that among all Ligilactobacillus salivarius CECT 9609 products tested, only inactivated cells preserve the conformation and morphology of respiratory epithelial cells, while also reversing or altering the natural immune responses triggered by Pasteurella multocida. These findings lay the groundwork for further exploration into the protective role of these bacteria and their derivatives.