Evidence on the benefits of probiotics for preterm infants.

This article reviews the evidence for the use of different strains of probiotics in the prevention of prevalent pathologies in premature neonates. A systematic review was conducted of the use of probiotics in neonates with less than 37 weeks of gestational age, based on a search for systematic reviews and observational and experimental studies performed during the period from January 2014 to February 2021. For this purpose, the PubMed, MEDLINE and Cochrane Library databases were consulted. The aim of this article was to review the existing data on the relationship between the administration of probiotics (with different strains and doses) and the risk of necrotising enterocolitis, mortality, late sepsis and other disease parameters in premature infants. The literature search obtained 240 articles, of which we selected 16, representing a total sample of over 200,000 premature infants. Analysis of the data obtained reveals statistical evidence that the combined administration of probiotics (especially of Lactobacillus and Bifidobacterium strains) reduces the incidence of grade II or higher necrotising enterocolitis, all-cause mortality, late sepsis, length of hospital stay and time until complete enteral nutrition is achieved. However, no benefits were apparent with respect to alleviating bronchopulmonary dysplasia, retinopathy of prematurity or intraventricular haemorrhage. Further research is needed to determine the most appropriate strains, doses and treatment duration for preterm infants to achieve the health benefits identified.

Selective degradation of ribosomes during oncogene-induced senescence: molecular insights and biological perspectives.

Ribosomes are conserved macromolecular machines that are responsible for protein synthesis in all cells. While our knowledge of ribosome biogenesis and function has increased significantly in recent years, little is known about how ribosomes are degraded under specific cellular conditions. We recently uncovered that ribosomes are efficiently turned over by selective macroautophagy/autophagy during oncogene-induced senescence (OIS). By profiling the ribosome interactome in human fibroblasts undergoing OIS, we discovered a key role for the de-ubiquitinating enzyme USP10 in guiding this process. Release of USP10 from ribosomes during senescence leads to their enhanced ubiquitination and selective sequestering by autophagy through the SQSTM1/p62 receptor protein. This process is important for sustaining senescence-associated metabolome and secretome alterations.

Late Neonatal Sepsis in Very-low-birth-weight Premature Newborns Is Associated With Alterations in Neurodevelopment at Twenty-five Months of Age.

AIM: To evaluate the impact of late-onset sepsis (LOS) on the neurodevelopment of very-low-birth-weight (VLBW) premature infants. METHODS: This is a retrospective cohort study of VLBW premature infants. The Mental Development Index (MDI) was determined for a population of 546 VLBW infants, at 14 and 25 months of age, and evaluated using the Bayley test. A history of meningitis or early neonatal sepsis was considered an exclusion criterion. The study parameters analyzed included perinatal variables, the development of neonatal comorbidities and a history of LOS. Multivariate linear regression and multinomial logistic regression analyses were performed. RESULTS: LOS was observed in 115 newborns, among whom microbiological testing showed that 65.0% presented Gram-positive bacteria, with Staphylococcus epidermidis being responsible for 55.4%. There was a significant association between the 25-month MDI and a history of LOS. This represents a decrease of 7.9 points in the MDI evaluation of newborns with a history of LOS. The latter history is also associated with the following neurodevelopmental alternations: mild motor disorders [odds ratio (OR): 2.75; 95% confidence intervals (CI): 1.07-7.05], moderate cognitive delay (OR: 3.07; 95% CI: 1.17-8.00) and cerebral palsy (OR: 2.41; 95% CI: 1.09-5.35). CONCLUSIONS: In our study cohort, LOS was associated with alterations in neurodevelopment, including reduced MDI, together with motor and cognitive disorders and cerebral palsy. To improve neurodevelopmental outcomes in this group of newborns, neonatal intensive care unit personnel should focus attention on preventing hospital-acquired infections.

Breast-feeding as protective factor against bronchopulmonary dysplasia in preterm infants.

Breast-feeding is associated with fewer comorbidities in very-low-birth-weight (VLBW) preterm infants. Bronchopulmonary dysplasia (BPD) of VLBW infants is a multifactorial pathology in which nutritional aspects may be of special importance. The aim of this study is to determine, in a cohort of VLBW infants, whether breast milk nutrition is associated with a reduced prevalence and severity of BPD. A retrospective study was conducted to record the intake of mother's own milk (MOM), pasteurised donor human milk or preterm formula milk in the first 2 weeks of postnatal life of 566 VLBW newborns at our hospital during the period January 2008-December 2021. After applying the relevant exclusion criteria, data for 489 VLBW infants were analysed; 195 developed some degree of BPD. Moderate or severe BPD is associated with less weight gain. Moreover, the preferential ingestion of breast milk in the first and second postnatal weeks had effects associated with lower OR for BPD, which were statistically demonstrable for mild (OR 0·16; 95 % CI 0·03, 0·71) and severe (OR 0·08; 95 % CI 0·009, 0·91) BPD. Breast-feeding during the first weeks of postnatal life is associated with a reduced prevalence of BPD, which is frequently associated with less weight gain as a result of greater respiratory effort with greater energy expenditure.

Plasma levels of intestinal fatty-acid binding protein (I-FABP), abdominal distension and hydrogen concentration after lactitol small intestinal bacterial overgrowth (SIBO) test / Niveles plasmáticos de intestino proteína fijadora de ácidos grasos (I-FABP), distensión abdominal y concentración de hidrógeno después del lactitol intestino delgado prueba de sobrecrecimiento bacteriano (SIBO)

Breath tests with glucose, lactulose or lactitol are useful for diagnosis of small intestinal bacterial overgrowth (SIBO). Nevertheless, they have suboptimal sensitivity and specificity and, indeed, are positive in a considerable number of patients with irritable bowel syndrome (IBS). The complexity in the management of patients with functional intestinal disorders and the availability of these tests are leading to frequent diagnoses of SIBO. Intestinal Fatty-Acid Binding protein (I-FABP) is a protein present in the cytosol of intestinal epithelial cells. Its plasmatic levels have been related to different enteropathies and, therefore, could be a marker of early intestinal damage with unconfirmed clinical utility. Hence, we have studied the plasmatic I-FABP level of patients who are requested a lactitol test to confirm SIBO and related it to clinical and laboratory characteristics and SIBO test results.(AU)

Autophagy-mediated control of ribosome homeostasis in oncogene-induced senescence.

Oncogene-induced senescence (OIS) is a persistent anti-proliferative response that acts as a barrier against malignant transformation. During OIS, cells undergo dynamic remodeling, which involves alterations in protein and organelle homeostasis through autophagy. Here, we show that ribosomes are selectively targeted for degradation by autophagy during OIS. By characterizing senescence-dependent alterations in the ribosomal interactome, we find that the deubiquitinase USP10 dissociates from the ribosome during the transition to OIS. This release of USP10 leads to an enhanced ribosome ubiquitination, particularly of small subunit proteins, including lysine 275 on RPS2. Both reinforcement of the USP10-ribosome interaction and mutation of RPS2 K275 abrogate ribosomal delivery to lysosomes without affecting bulk autophagy. We show that the selective recruitment of ubiquitinated ribosomes to autophagosomes is mediated by the p62 receptor. While ribophagy is not required for the establishment of senescence per se, it contributes to senescence-related metabolome alterations and facilitates the senescence-associated secretory phenotype.

Real-world evidence of sorafenib for the treatment of hepatocellular carcinoma: A single-center study.

Context: Hepatocellular carcinoma is the third leading cause of cancer death. Currently, sorafenib is the treatment of choice in advanced hepatocarcinoma. Aims: Assessing the effectiveness and toxicity of sorafenib in real-word clinical practice in patients with hepatocarcinoma. Settings and Design: Single-centered observational retrospective study. Methods and Material: We included patients with hepatocarcinoma who began treatment with sorafenib between 2008 and 2018. We evaluated overall survival, time to progression, and response using RECIST (Response Evaluation Criteria in Solid Tumors) criteria. Toxicity was assessed according to the Common Terminology Criteria for Adverse Events version 5. 2020. Statistical Analysis Used: Kaplan-Meier curves and the log-rank test were used to determine the survival time and estimate factors associated with these events. Data were analyzed with SPSS 19.0 software. Results: We included 36 patients (88.9% male) with an average age of 64 ± 3.4 years. The tumor stage was advanced (C) in 21 patients (61.8%). We obtained a median overall survival of 8.5 months (IQR 3.14-18.9) and a time to progression of 4.5 months (IQR 2.4-8.8). The main degree of response was progression in 19 patients (36.1%), followed by stable disease in 13 (52.8%). The most commonly reported adverse reactions were: constitutional (83.3%), gastrointestinal (55%) and dermatological symptoms (50.0%). The development of grades 3 or 4 toxicity was not associated with increased overall survival (P = 0.719). Conclusions: The findings of the survival analysis obtained in real practice are similar to those obtained in pivotal clinical trials. Adverse reactions were different from those expected.

Extrauterine growth restriction and low energy intake during the early neonatal period of very low birth weight infants are associated with decreased lung function in childhood.

Premature birth, bronchopulmonary dysplasia or restrictive nutrition in the first weeks of postnatal life may have repercussions on lung development and affect long-term lung function outcomes. This prospective observational study is based on a cohort of 313 very low birth weight (VLBW) neonates, born between 1 January 2008 and 1 December 2016. The daily intake of calories, protein, fat and carbohydrates during the first week of life and evidence of inadequate weight gain (Δwt) until week 36 of gestational age (GA) were recorded. FEV1, FEF25-75 %, forced vital capacity (FVC) and the FEV1/FVC ratio were determined. The relations between these parameters were determined by regression analysis. Spirometric parameters were obtained for 141 children with a mean age of 9 years (95 % CI 7, 11); 69 of them (48·9 %) had presented wheezing episodes on more than three occasions. In addition, 60 (42·5 %) had a history of bronchopulmonary dysplasia. Of these, n 40 (66·6 %) had a history of wheezing. Significant association between protein/energy intake in the first week of life and the lung function parameters analysed was observed. Poor Δwt to GA week 36 was significantly associated with decreased mean pulmonary flow. Inadequate protein/energy intake in the first week of life of VLBW newborns and poor Δwt to week 36 of GA is associated with a significant worsening of lung function parameters.

Plasma levels of intestinal fatty-acid binding protein (I-FABP), abdominal distension and hydrogen concentration after lactitol small intestinal bacterial overgrowth (SIBO) test.

Breath tests with glucose, lactulose or lactitol are useful for diagnosis of small intestinal bacterial overgrowth (SIBO). Nevertheless, they have suboptimal sensitivity and specificity and, indeed, are positive in a considerable number of patients with irritable bowel syndrome (IBS). The complexity in the management of patients with functional intestinal disorders and the availability of these tests are leading to frequent diagnoses of SIBO. Intestinal Fatty-Acid Binding protein (I-FABP) is a protein present in the cytosol of intestinal epithelial cells. Its plasmatic levels have been related to different enteropathies and, therefore, could be a marker of early intestinal damage with unconfirmed clinical utility. Hence, we have studied the plasmatic I-FABP level of patients who are requested a lactitol test to confirm SIBO and related it to clinical and laboratory characteristics and SIBO test results.

Blood products transfusion and retinopathy of prematurity: A cohort study.

AIM: The aim of the study was to assess the influence of blood product transfusions on the development and severity of retinopathy of prematurity (ROP). METHODS: A retrospective cohort study was conducted of very low birth weight (VLBW) newborns with less than 32 weeks gestational age (GA) admitted to the neonatal unit of a tertiary care hospital during the period from 1 January 2008 to 31 December 2021. Data on the degree of ROP and the transfusions received were obtained and analysed. Both univariate and multivariate analyses were performed, by logistic regression. RESULTS: A total of 565 VLBW newborns were recruited, of whom 263 received a red blood cell transfusion prior to 36 weeks corrected GA. The newborns with ROP received significantly more red blood cell transfusions than those not presenting this condition. After adjusting for oxygen therapy and GA, the risk of ROP was found to be 2.77 times higher (95% CI 1.31-5.88) after receiving three or more transfusions, with a 3.95 times higher risk (95% CI 1.40-11.1) of developing severe ROP. Having received the first red blood cell transfusion before 32 weeks corrected GA is associated with an increased risk of ROP (OR 2.18; 95% CI: 1.09-4.36). CONCLUSION: In VLBW neonates, the number of red blood cell transfusions and their administration before 32 weeks corrected GA are important risk factors for ROP.

Regorafenib and trifluridine/tipiracil in real clinical practice.

Background: Colorectal cancer is the ninth leading cause of death in Spain. The latest therapeutic developments in the advanced stages of this disease are the oral drugs trifluridine/tipiracil and regorafenib. Objective: Results of clinical trials (CTs) are not in real conditions and therefore, we want to study the effectiveness and the safety profile in the usual clinical practice and compare it with the bibliography. Materials and Methods: A retrospective and unicentric study was carried out in a health area of 500,000 inhabitants. Patients who started treatment with regorafenib and/or trifluridine/tipiracil were included from the date of marketing until June 2019. Patient-related variables, pathology, effectiveness, and treatment toxicity were collected. The statistical analysis was carried out with the PSPP program. Results: Fifty-four patients were analyzed. Men accounted for 59.3% of patients. Regorafenib was the treatment for 22.2% of patients and 77.8% received trifluridine/tipiracil. The reason for the drug's suspension was the disease progression in 85.2% of patients. No patient had a full response and 3.2% achieved partial response. The median progression-free survival time in treatments with regorafenib was 2.5 months (95% confidence interval [CI]: 0.0-5.4) and the overall survival time was 3.1 months (95% CI: 0.0-6.7), while in treatments with trifluridine/tipiracil, these data were, respectively, 2.8 (95% CI: 2.5-3.2) and 5.7 months (95% CI: 3.8-7.6). Side effects occurred in 91.7% of patients treated with regorafenib and in 100% of treated with trifluridine/tipiracil. Hematological adverse reactions were, on average, 0.4 ± 0.5/patient with regorafenib and 1.5 ± 0.9 with trifluridine/tipiracil. General (77.8%) and gastrointestinal disorders (50%) were common with both drugs. Conclusions: The effectiveness results of standard clinical practice are lower than those described in CTs and in the literature. The toxicity profile does reproduce what is described in the bibliography.

Sensitivity and Specificity of the Newborn Infant Parasympathetic Evaluation Index in Pain Assessment of Very Low Birth Weight Infants.

OBJECTIVE: This article describes the results of a study investigating the sensitivity and specificity of the Newborn Infant Parasympathetic Evaluation (NIPE) index for detecting the physiological changes resulting from nociception in painful procedures in very low birth weight (VLBW) infants. STUDY DESIGN: A prospective observational study was carried on of 44 newborns at 23 to 32 weeks' gestational age. The sensitivity and specificity of the NIPE index are analyzed using a receiver operating characteristic curve. Most of the painful procedures performed were skin-lancing and venipunctures. Nonpainful procedures consist of no intervention, with an interval of at least 1 hour with painful procedures in each newborn. RESULTS: The accuracy of the NIPE index to diagnose mild nociceptive stimulation in VLBW newborns is 73.2%. CONCLUSION: The NIPE index is a useful technique for assessing nociceptive stimulation in newborns, presenting less observer-dependent variability than other pain assessment scales. KEY POINTS: · The NIPE index offers an objective assessment of pain.. · Moderate-high sensitivity of the NIPE index in the evaluation of pain in premature newborns.. · Painful procedures in VLBW newborns are reflected as a decrease in the NIPE score..

Evaluación del sistema parasimpático durante procedimientos dolorosos en neonatología / Parasympathetic evaluation for procedural pain assessment in neonatology

Introducción: El monitor NIPE (Newborn Infant Parasympathetic Evaluation) es una herramienta rápida, continua y objetiva de evaluación del disconfort neonatal. Los objetivos fueron describir los cambios del NIPE tras una extracción sanguínea y los factores implicados en su variación. Material y métodos: Estudio observacional analítico con recogida de datos prospectiva. Se incluyeron los recién nacidos ingresados en cuidados intensivos entre junio y diciembre de 2021 a quienes se les realizó extracción sanguínea. Se recogieron variables demográficas, las relacionadas con la realización del procedimiento, la puntuación NIPE, la frecuencia cardiaca previa y en los minutos 1, 2, 3, 4, 5, 10 y 15 posteriores. Resultados: Se incluyeron 86 registros de 49 pacientes. Durante los primeros cuatro minutos tras el procedimiento hubo un descenso significativo en la puntuación NIPE, siendo el descenso máximo de un 22,8% respecto al valor basal, produciéndose el nadir a los 2,79 minutos. El mayor descenso del NIPE ocurrió en pacientes prematuros, varones, con menor Apgar a los cinco minutos, en procedimientos ya realizados previamente, tras cesárea y en horario matutino. No hubo diferencias con la realización en canguro. La correlación entre NIPE y frecuencia cardíaca fue débil. Conclusiones:Tras un procedimiento doloroso, como una extracción sanguínea, el monitor NIPE mostró un descenso significativo los primeros cuatro minutos, agudizándose el descenso con la prematuridad, la reiteración de procedimientos o el nacimiento tras cesárea. El monitor NIPE puede ayudar a identificar eficazmente a aquellos neonatos que sufren dolor agudo tras un procedimiento, complementándose con las escalas de valoración clínica. (AU)

Introduction: The Newborn Infant Parasympathetic Evaluation (NIPE) index is an instrument that enables continuous, fast and objective assessment of neonatal discomfort. The aim of the study was to analyse changes in NIPE values after performance of blood draws and the factors involved in this variation. Material and methods: We conducted a prospective observational study. We included infants admitted to the neonatal intensive care unit between June and December 2021 who underwent blood draws. We recorded demographic data, aspects related to the procedure, the NIPE index and the heart rate at baseline and 1, 2, 3, 4, 5, 10 and 15min after the procedure. Results: The study included 86 records for 49 patients. In the first 4min after the procedure, there was a significant decrease in the NIPE index, with a maximum decrease of 22.8% relative to baseline and the nadir at 2.79min. The decrease in NIPE values was greater in infants born preterm, male, with lower 5-min Apgar scores and following procedures that had been performed previously, after caesarean section or in the morning. There were no differences when the blood draw was obtained during kangaroo care. The correlation between the NIPE index and the heart rate was weak. Conclusions: After a painful procedure, such as a blood draw, the NIPE monitor showed a significant decrease in the first 4min, which was more pronounced in preterm infants, in repeated procedures or after caesarean delivery. The NIPE index could help identify infants experiencing acute procedural pain, complementing clinical rating scales. (AU)

Ribosome stalling is a signal for metabolic regulation by the ribotoxic stress response.

Impairment of translation can lead to collisions of ribosomes, which constitute an activation platform for several ribosomal stress-surveillance pathways. Among these is the ribotoxic stress response (RSR), where ribosomal sensing by the MAP3K ZAKα leads to activation of p38 and JNK kinases. Despite these insights, the physiological ramifications of ribosomal impairment and downstream RSR signaling remain elusive. Here, we show that stalling of ribosomes is sufficient to activate ZAKα. In response to amino acid deprivation and full nutrient starvation, RSR impacts on the ensuing metabolic responses in cells, nematodes, and mice. The RSR-regulated responses in these model systems include regulation of AMPK and mTOR signaling, survival under starvation conditions, stress hormone production, and regulation of blood sugar control. In addition, ZAK-/- male mice present a lean phenotype. Our work highlights impaired ribosomes as metabolic signals and demonstrates a role for RSR signaling in metabolic regulation.

Parasympathetic evaluation for procedural pain assessment in neonatology.

INTRODUCTION: The Newborn Infant Parasympathetic Evaluation (NIPE) index is an instrument that enables continuous, fast and objective assessment of neonatal discomfort. The aim of the study was to analyse changes in NIPE values after performance of blood draws and the factors involved in this variation. MATERIAL AND METHODS: We conducted a prospective observational study. We included infants admitted to the neonatal intensive care unit between June and December 2021 who underwent blood draws. We recorded demographic data, aspects related to the procedure, the NIPE index and the heart rate at baseline and 1, 2, 3, 4, 5, 10 and 15 min after the procedure. RESULTS: The study included 86 records for 49 patients. In the first 4 min after the procedure, there was a significant decrease in the NIPE index, with a maximum decrease of 22.8% relative to baseline and the nadir at 2.79 min. The decrease in NIPE values was greater in infants born preterm, male, with lower 5-min Apgar scores and following procedures that had been performed previously, after caesarean section or in the morning. There were no differences when the blood draw was obtained during kangaroo care. The correlation between the NIPE index and the heart rate was weak. CONCLUSIONS: After a painful procedure, such as a blood draw, the NIPE monitor showed a significant decrease in the first 4 min, which was more pronounced in preterm infants, in repeated procedures or after caesarean delivery. The NIPE index could help identify infants experiencing acute procedural pain, complementing clinical rating scales.

Altered Surface Expression of Insulin-Degrading Enzyme on Monocytes and Lymphocytes from COVID-19 Patients Both at Diagnosis and after Hospital Discharge.

Although the COVID-19 disease has developed into a worldwide pandemic, its pathophysiology remains to be fully understood. Insulin-degrading enzyme (IDE), a zinc-metalloprotease with a high affinity for insulin, has been found in the interactomes of multiple SARS-CoV-2 proteins. However, the relevance of IDE in the innate and adaptative immune responses elicited by circulating peripheral blood mononuclear cells is unknown. Here, we show that IDE is highly expressed on the surface of circulating monocytes, T-cells (both CD4+ and CD4-), and, to a lower extent, in B-cells from healthy controls. Notably, IDE's surface expression was upregulated on monocytes from COVID-19 patients at diagnosis, and it was increased in more severe patients. However, IDE's surface expression was downregulated (relative to healthy controls) 3 months after hospital discharge in all the studied immune subsets, with this effect being more pronounced in males than in females, and thus it was sex-dependent. Additionally, IDE levels in monocytes, CD4+ T-cells, and CD4- T-cells were inversely correlated with circulating insulin levels in COVID-19 patients (both at diagnosis and after hospital discharge). Of note, high glucose and insulin levels downregulated IDE surface expression by ~30% in the monocytes isolated from healthy donors, without affecting its expression in CD4+ T-cells and CD4- T-cells. In conclusion, our studies reveal the sex- and metabolism-dependent regulation of IDE in monocytes, suggesting that its regulation might be important for the recruitment of immune cells to the site of infection, as well as for glucometabolic control, in COVID-19 patients.

Emerging Blood-Based Biomarkers for Predicting Immunotherapy Response in NSCLC.

Immunotherapy with Immune Checkpoint Inhibitors (ICIs) has demonstrated a profitable performance for Non-Small Cell Lung Cancer (NSCLC) cancer treatment in some patients; however, there is still a percentage of patients in whom immunotherapy does not provide the desired results regarding beneficial outcomes. Therefore, obtaining predictive biomarkers for ICI response will improve the treatment management in clinical practice. In this sense, liquid biopsy appears as a promising method to obtain samples in a minimally invasive and non-biased way. In spite of its evident potential, the use of these circulating biomarkers is still very limited in the real clinical practice, mainly due to the huge heterogeneity among the techniques, the lack of consensus, and the limited number of patients included in these previous studies. In this work, we review the pros and cons of the different proposed biomarkers, such as soluble PD-L1, circulating non-coding RNA, circulating immune cells, peripheral blood cytokines, and ctDNA, obtained from liquid biopsy to predict response to ICI treatment at baseline and to monitor changes in tumor and tumor microenvironment during the course of the treatment in NSCLC patients.

Real-World Evidence for Treat-and-Extend Regimen of Ranibizumab Therapy for Macular Oedema Secondary to Branch Retinal Vein Occlusion.

The aim of this study was to evaluate the efficacy of a treat-and-extend (T&E) regimen of ranibizumab as the first-choice treatment in macular oedema (MO) secondary to branch retinal vein occlusion (BRVO). We conducted a retrospective study of 20 patients who developed MO due to BRVO treated with intravitreal ranibizumab in a T&E regimen between 2016 and 2017 with a minimum follow-up of two years. Patients were classified as complete responders if treated with ranibizumab alone or incomplete responders if salvage treatment with other medications or laser was needed. Data on best corrected visual acuity (BCVA) and central macular thickness (CMT) every 6 months were recorded. The mean BCVA (logMAR) improved from 0.60 ± 0.36 to 0.29 ± 0.44 and the CMT decreased from 559.85 ± 198.61 to 305.85 ± 11.78 µm. We found statistically significant differences between complete and incomplete responders on the average number of injections during the second year (2.46 ± 2.18 compared to 5.43 ± 1.27; p = 0.007) and change of the BCVA and CMT between both groups (p < 0.001) at 6, 12, 18 and 24 months. T&E seems to be effective in MO secondary to BRVO, improving visual function and decreasing CMT, with less need for injections.

Tauroursodeoxycholic acid (TUDCA) is neuroprotective in a chronic mouse model of Parkinson's disease.

OBJECTIVE: Parkinson's disease (PD) is a progressive motor disease of unknown etiology. Although neuroprotective ability of endogenous bile acid, tauroursodeoxycholic acid (TUDCA), shown in various diseases, including an acute model of PD,the potential therapeutic role of TUDCA in progressive models of PD that exhibit all aspects of PD has not been elucidated. In the present study, mice were assigned to one of four treatment groups: (1) Probenecid (PROB); (2) TUDCA, (3) MPTP + PROB (MPTPp); and (3) TUDCA + MPTPp. Methods: Markers for dopaminergic function, neuroinflammation, oxidative stress and autophagy were assessed using high performance liquid chromatography (HPLC), immunohistochemistry (IHC) and western blot (WB) methods. Locomotion was measured before and after treatments. Results: MPTPp decreased the expression of dopamine transporters (DAT) and tyrosine hydroxylase (TH), indicating dopaminergic damage, and induced microglial and astroglial activation as demonstrated by IHC analysis. MPTPp also decreased DA and its metabolites as demonstrated by HPLC analysis. Further, MPTPp-induced protein oxidation; increased LAMP-1 expression indicated autophagy and the promotion of alpha-synuclein (α-SYN) aggregation. Discussion: Pretreatment with TUDCA protected against dopaminergic neuronal damage, prevented the microglial and astroglial activation, as well as the DA and DOPAC reductions caused by MPTPp. TUDCA by itself did not produce any significant change, with data similar to the negative control group. Pretreatment with TUDCA prevented protein oxidation and autophagy, in addition to inhibiting α-SYN aggregation. Although TUDCA pretreatment did not significantly affect locomotion, only acute treatment effects were measured, indicating more extensive assessments may be necessary to reveal potential therapeutic effects on behavior. Together, these results suggest that autophagy may be involved in the progression of PD and that TUDCA may attenuate these effects. The efficacy of TUDCA as a novel therapy in patients with PD clearly warrants further study.