USP13 promotes acute myeloid leukemia cell proliferation and autophagy by promoting ATG5.

OBJECTIVE: To elucidate the role of USP13 in acute myeloid leukemia (AML) by investigating its effects on cell growth, apoptosis and autophagy, and to explore the underlying mechanisms. METHODS: The expression of USP13 in AML cells was assessed using quantitative PCR (qPCR) and immunoblotting. Cell Counting Kit-8 (CCK-8) and Edu staining were employed to evaluate the impact of USP13 on AML cell growth. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and immunostaining assays were conducted to examine the effects of USP13 on apoptosis and autophagy in AML cells, and immunoblot assays were performed to determine the potential underlying mechanistic pathway. RESULTS: USP13 expression was significantly elevated in AML cells, correlating with enhanced cell proliferation and resistance to apoptosis. Moreover, USP13 promoted autophagy in AML cells. Mechanistically, USP13 was found to be associated with upregulating ATG5 expression, which promoted AML progression. CONCLUSION: USP13 promotes AML cell growth and autophagy by upregulating ATG5.

Characterization of Probiotic Properties and Whole-Genome Analysis of Lactobacillus johnsonii N5 and N7 Isolated from Swine.

In our previous microbiome profiling analysis, Lactobacillus (L.) johnsonii was suggested to contribute to resistance against chronic heat stress-induced diarrhea in weaned piglets. Forty-nine L. johnsonii strains were isolated from these heat stress-resistant piglets, and their probiotic properties were assessed. Strains N5 and N7 exhibited a high survival rate in acidic and bile environments, along with an antagonistic effect against Salmonella. To identify genes potentially involved in these observed probiotic properties, the complete genome sequences of N5 and N7 were determined using a combination of Illumina and nanopore sequencing. The genomes of strains N5 and N7 were found to be highly conserved, with two N5-specific and four N7-specific genes identified. Multiple genes involved in gastrointestinal environment adaptation and probiotic properties, including acidic and bile stress tolerance, anti-inflammation, CAZymes, and utilization and biosynthesis of carbohydrate compounds, were identified in both genomes. Comparative genome analysis of the two genomes and 17 available complete L. johnsonii genomes revealed 101 genes specifically harbored by strains N5 and N7, several of which were implicated in potential probiotic properties. Overall, this study provides novel insights into the genetic basis of niche adaptation and probiotic properties, as well as the genome diversity of L. johnsonii.

Nasal drip of dexmedetomidine for optimal sedation during PICC insertion in pediatric burn care.

BACKGROUND: For peripherally inserted central catheter (PICC) inserting, tranquil cooperation of children for an extended period is often required. Therefore, sedation is routinely induced clinically prior to PICC inserting. Chloral hydrate is a commonly used sedative for children. However, its clinical acceptance has remained low. And the sedation effect is non-satisfactory. Previous studies have confirmed the safety and effectiveness of intravenous/oral dosing or nasal dripping for sedation during the examinations of electrocardiography and computed tomography. Yet few studies have assessed the sedating efficacy of dexmedetomidine nasal drops for PICC inserting. METHODS: From a cohort of 40 hospitalized patients scheduled for PICC inserting, 15 children employing a novel sedative mode of dexmedetomidine nasal drops at a dose of 2 ug/kg were assigned into group A while group B included another 25 children sedated routinely via an enema of 10% chloral hydrate at a dose of 0.5 mL/kg. The Ramsay's scoring criteria were utilized for assessing the status of sedation. Two groups were observed with regards to success rate of sedation, onset time of sedation and occurrences of adverse reactions. RESULTS: Statistical inter-group differences existed in success rate and onset time of sedation. The success rate of group A was higher than that of group B (93.3% vs 64.0%, X2 = 4.302, P = .038 < 0.05). Group A had a faster onset of sedation than group B (14.86 ± 2.57 vs 19.06 ± 3.40 minutes, t = 3.781, P = .001 < 0.05). No inter-group difference of statistical significance existed in occurrence of adverse reactions (P = 1.000 > 0.05). Logistic regression analysis showed that the success rate of sedation in group A was higher than that in group B, and the difference was statistically significant (P = .036 < 0.05). CONCLUSIONS: For sedating burn children, nasal dripping of dexmedetomidine is both safe and effective during PICC inserting. Without any obvious adverse reaction, it may relieve sufferings and enhance acceptance.

Identifying patterns of kinesiophobia trajectories among COPD patients: A longitudinal study.

AIM: To determine differences in kinesiophobia levels among COPD patients at different time points 6 months after discharge；To identify potential subgroups of COPD patients who perceived different levels of kinesiophobia over time；and to evaluate differences in identified subgroups based on demographic and disease-related characteristics DESIGN: An observational longitudinal study. METHODS: OPD patients hospitalized in respiratory department of a grade A hospital in Huzhou city from October 2021 to May 2022 were selected as the research objects. TSK scale was used to evaluate the level of kinesiophobia at discharge (T1), 1 month after discharge (T2), 4 months after discharge (T3) and 6 months after discharge (T4). The kinesiophobia level scores at different time points were compared using latent class growth modelling. ANOVA and Fisher's exact tests were used to test differences in demographic characteristics，and univariate analysis and multinomial logistic regression analysis were used to explore the influencing factors. RESULTS: During the first 6 months after discharge, kinesiophobia levels decreased significantly in the entire sample of COPD patients. The best-fitting group-based trajectory model described three distinctive trajectories: Low kinesiophobia group (31.4% of sample); Medium kinesiophobia group (43.4% of sample)；and High kinesiophobia group (25.2% of sample). Logistic regression results showed that sex, age, course of disease, pulmonary function, education level, BMI, the level of pain, MCFS and mMRC were influencing factors of kinesiophobia trajectory in COPD patients (p < 0.05).

Roles of mitochondrial unfolded protein response in mammalian stem cells.

The mitochondrial unfolded protein response (UPRmt) is an evolutionarily conserved adaptive mechanism for improving cell survival under mitochondrial stress. Under physiological and pathological conditions, the UPRmt is the key to maintaining intracellular homeostasis and proteostasis. Important roles of the UPRmt have been demonstrated in a variety of cell types and in cell development, metabolism, and immune processes. UPRmt dysfunction leads to a variety of pathologies, including cancer, inflammation, neurodegenerative disease, metabolic disease, and immune disease. Stem cells have a special ability to self-renew and differentiate into a variety of somatic cells and have been shown to exist in a variety of tissues. These cells are involved in development, tissue renewal, and some disease processes. Although the roles and regulatory mechanisms of the UPRmt in somatic cells have been widely reported, the roles of the UPRmt in stem cells are not fully understood. The roles and functions of the UPRmt depend on stem cell type. Therefore, this paper summarizes the potential significance of the UPRmt in embryonic stem cells, tissue stem cells, tumor stem cells, and induced pluripotent stem cells. The purpose of this review is to provide new insights into stem cell differentiation and tumor pathogenesis.

New insights into mitophagy and stem cells.

Mitophagy is a specific autophagic phenomenon in which damaged or redundant mitochondria are selectively cleared by autophagic lysosomes. A decrease in mitophagy can accelerate the aging process. Mitophagy is related to health and longevity and is the key to protecting stem cells from metabolic stress damage. Mitophagy decreases the metabolic level of stem cells by clearing active mitochondria, so mitophagy is becoming increasingly necessary to maintain the regenerative capacity of old stem cells. Stem cell senescence is the core problem of tissue aging, and tissue aging occurs not only in stem cells but also in transport amplifying cell chambers and the stem cell environment. The loss of the autophagic ability of stem cells can cause the accumulation of mitochondria and the activation of the metabolic state as well as damage the self-renewal ability and regeneration potential of stem cells. However, the claim remains controversial. Mitophagy is an important survival strategy against nutrient deficiency and starvation, and mitochondrial function and integrity may affect the viability, proliferation and differentiation potential, and longevity of normal stem cells. Mitophagy can affect the health and longevity of the human body, so the number of studies in this field has increased, but the mechanism by which mitophagy participates in stem cell development is still not fully understood. This review describes the potential significance of mitophagy in stem cell developmental processes, such as self-renewal, differentiation and aging. Through this work, we discovered the role and mechanism of mitophagy in different types of stem cells, identified novel targets for killing cancer stem cells and curing cancer, and provided new insights for future research in this field.

The Immp2l Mutation Causes Ovarian Aging Through ROS-Wnt/ß-Catenin-Estrogen Pathway: Preventive Effect of Melatonin.

Mitochondria play important roles in ovarian follicle development. Mitochondrial dysfunction, including mitochondrial gene deficiency, impairs ovarian development. Here, we explored the role and mechanism of mitochondrial inner membrane gene Immp2l in ovarian follicle growth and development. Our results revealed that female Immp2l-/- mice were infertile, whereas Immp2l+/- mice were normal. Body and ovarian weights were reduced in the female Immp2l-/- mice, ovarian follicle growth and development were stunted in the secondary follicle stage. Although a few ovarian follicles were ovulated, the oocytes were not fertilized because of mitochondrial dysfunction. Increased oxidative stress, decreased estrogen levels, and altered genes expression of Wnt/ß-catenin and steroid hormone synthesis pathways were observed in 28-day-old Immp2l-/- mice. The Immp2l mutation accelerated ovarian aging process, as no ovarian follicles were detected by age 5 months in Immp2l-/- mice. All the aforementioned changes in the Immp2l-/- mice were reversed by administration of antioxidant melatonin to the Immp2l-/- mice. Furthermore, our in vitro study using Immp2l knockdown granulosa cells confirmed that the Immp2l downregulation induced granulosa cell aging by enhancing reactive oxygen species (ROS) levels, suppressing Wnt16, increasing ß-catenin, and decreasing steroid hormone synthesis gene cyp19a1 and estrogen levels, accompanied by an increase in the aging phenotype of granulosa cells. Melatonin treatment delayed granulosa cell aging progression. Taken together, Immp2l causes ovarian aging through the ROS-Wnt/ß-catenin-estrogen (cyp19a1) pathway, which can be reversed by melatonin treatment.