Reduce Cell Damage Research Articles

Intravenous gene therapy improves lifespan and clinical outcomes in feline Sandhoff Disease.

Sandhoff Disease (SD), a fatal neurodegenerative disorder, is caused by the absence of ß-hexosaminidase (Hex) and subsequent accumulation of GM2 ganglioside in lysosomes. Previous studies have led to adeno-associated virus (AAV) gene therapy for children with GM2 gangliosidosis in both expanded access and Phase I/II clinical trials via intracranial and/or cerebrospinal fluid-based delivery. The current study investigated intravenous (IV) gene therapy of SD cats, treated at one month of age with a bicistronic AAV vector. While untreated SD cats lived to 4.3±0.2 months, cats treated with low and high doses lived to 8.3±1.2 and 12.4±2.7 months, respectively. In-life assessments revealed clear clinical benefit of AAV treatment, with the most dramatic improvement seen in the reduction of overt full-body tremors. Cerebrospinal fluid levels of aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) were decreased, indicating a reduction of cell damage within the central nervous system. Magnetic resonance imaging (MRI) and spectroscopy (MRS) acquired on a 7 Tesla scanner indicated that structural pathology and metabolite abnormalities are partially normalized by AAV treatment. Dose-dependent reduction of GM2 ganglioside storage and increases in Hex activity were most substantial in the caudal regions of the brain and in the spinal cord. Immunohistochemistry revealed reduction in neuroinflammatory cell populations and partial correction of myelin deficits. These results support the dose-dependent efficacy of AAV delivered IV for significant restoration of clinical metrics and Hex function in a feline model of SD.

Modeling and Evaluation of Penetration Process Based on 3D Mechanical Simulation.

In biological micromanipulation, cell penetration is a typical procedure that precedes cell injection or oocyte enucleation. During this procedure, cells usually undergo significant deformation, which leads to cell damage. In this paper, we focus on modeling and evaluating the cell penetration process to reduce cell deformation and stress, thereby reducing cell damage. Initially, a finite element model (FEM) is established to simulate the cell penetration process. The effectiveness of the model is then verified through visual detection and comparison of cell deformation with experimental data. Next, various mechanical responses are analyzed, considering the influence of parameters, such as the radius and shape of the injection micropipettes, material properties, and size of the cells. Finally, the relationship between the intracellular stress and the cell penetration depth of biological cells is obtained. The evaluation results will be applied to develop optimized operation plans, enhancing the efficiency and safety of the cell penetration process.

PdbCRF5 Overexpression Negatively Regulates Salt Tolerance by Downregulating PdbbZIP61 to Mediate Reactive Oxygen Species Scavenging and ABA Synthesis in Populus davidiana × P. bolleana.

Salt stress is the main factor limiting the large-scale cultivation of Shanxin poplar; therefore, improving its salt tolerance is crucial. In this study, we identified and characterized a CRF gene (PdbCRF5) in Shanxin poplar. Compared with the wild-type poplar, the Shanxin poplar overexpressing PdbCRF5 were more sensitive to salt stress. The PdbCRF5-silenced plants exhibited improved salt tolerance. ChIP‒PCR, EMSA, and Y1H confirmed that PdbCRF5 can regulate the expression of the PdbbZIP61 by binding to ABRE element. Further analysis revealed that the overexpression of PdbbZIP61 can reduce cell damage by increasing ROS scavenging, and on the other hand, overexpression of PdbbZIP61 can improve the salt tolerance of Shanxin poplar by regulating the expression of the PdbNCED genes to increase the ABA content. In addition, we also demonstrated that PdbCRF5 can inhibit the expression of the PdbbZIP61 in combination with PdbCRF6. The overexpression of PdbCRF6 also reduced the salt tolerance of Shanxin poplar. Therefore, we found that PdbCRF5 negatively regulates the salt tolerance of Shanxin poplar by inhibiting the PdbbZIP61, indicating that PdbCRF5 plays an important role in the tolerance of Shanxin poplar to salt stress and is an important candidate gene for gene editing and breeding in forest trees.

Co-Assembled Binary Polyphenol Natural Products for the Prevention and Treatment of Radiation-Induced Skin Injury.

Radiation therapy, a fundamental treatment for tumors, is often accompanied by radiation-induced skin injury (RISI). Excessive production of reactive oxygen species (ROS) and subsequent inflammation are two key factors in RISI development that will cause skin injury and affect radiotherapy. Herein, the co-assembled binary polyphenol natural products inspired the development of a dual-functional cascade microneedle system for prevention and treatment of RISI. Specifically, epigallocatechin gallate (EGCG) and curcumin (CUR) were co-assembled into nanoparticles (CEPG) by intermolecular interactions and then incorporated with catalase (CAT) to achieve a cascade system in the microneedles (this microneedle system was conducive to penetrate into the epidermal keratinocytes where RISI had the greatest impact). When using microneedles, the tip dissolved rapidly and delivered CEPG and CAT into the dermis, where CEPG NPs were able to respond to ROS and decompose into EGCG and CUR. More importantly, EGCG and CAT formed a cascade that converts superoxide anions into water step-by-step, which can reduce cell damage caused by free radicals in the early stages of radiation for prevention; meanwhile, CUR inhibited inflammatory pathways, achieving the treatment of skin inflammation in the post-radiotherapy period. These explorations broaden the strategy for the application of natural products in RISI.

SS-31 modification alleviates ferroptosis induced by superparamagnetic iron oxide nanoparticles in hypoxia/reoxygenation cardiomyocytes

Superparamagnetic iron oxide nanoparticles (SPION) are widely used in cardiovascular applications. However, their potential to induce ferroptosis in myocardial cells post-ischemia-reperfusion hinders clinical adoption. We investigated the mechanisms behind SPION-induced cytotoxicity in myocardial cells and explored whether co-loading SPION with SS-31 (a kind of mitochondrial-targeted antioxidant peptide) could counteract this toxicity.To create SPION@SS-31, SS-31 was physically adsorbed onto SPION. To study the dose- and time-dependent cytotoxic effects and assess the influence of SS-31 on reducing SPION-induced damage, hypoxia/reoxygenation(H/R) H9C2 cells were treated with either SPION or SPION@SS-31. We examined the relationship between SPION and ferroptosis by measuring mitochondrial ROS, mitochondrial membrane potential (MMP), lipid peroxidation products, ATP, GSH, GPX4, mitochondrial structure, nonheme iron content, cellular iron regulation, and typical ferroptosis markers.The findings showed that SPION induced concentration- and time-dependent toxicity, marked by a significant cell viability loss and an increase in LDH levels. In contrast, SPION@SS-31 produced results comparable to the H/R group, implying that SS-31 can notably reduce cell damage induced by SPION. SPION disrupted cellular iron homeostasis, with FtH and FtMt expression increased and reduced levels of FPN1 and ABCB8, which led to the overload of mitochondrial iron. This iron dysregulation damaged mitochondrial function and integrity, causing ATP depletion, MMP loss, and decreased GPX4 and GSH levels, accompanied by a burst of mitochondrial lipid peroxidation, ultimately resulting in ferroptosis in H/R cardiomyocytes. Notably, SS-31 significantly alleviated SPION-induced ferroptosis by decreasing mitochondrial MDA production and maintaining GSH and GPX4 levels, indicating its possibility to reverse SPION-induced cytotoxicity. The viability of H/R cells and cells treated with SPION and Fer-1 did not differ statistically, whereas cells exposed to SPION along with inhibitors like 3-MA, zVAD, or Nec-1 showed a substantial loss in viability, implying that ferroptosis is the primary mechanism behind SPION-induced myocardial toxicity.SPION triggers mitochondrial lipid peroxidation by causing overload of iron, leading to ferroptosis in H/R H9C2 cells. Mitochondria appear to be the primary target of SPION-induced toxic effects. SS-31 demonstrates potential in inhibiting this ferroptosis by acting as a mitochondria-targeted antioxidant, suggesting that the modification of mitochondria-targeted antioxidant peptides represents an innovative and practical approach to attenuate the myocardial toxicity associated with SPION.

Knockdown of IGF2BP3 Down-Regulates PDCD4 Levels to Attenuate Hypoxic-Ischemic Brain Damage

Background: Hypoxic-ischemic brain damage (HIBD) is a prevalent brain injury with high mortality and morbidity. It results from hypoxia and ischemia of the brain due to various perinatal factors. A previous study showed that knockdown of programmed cell death factor 4 (PDCD4) could reduce infarction injury resulting from ischemia/reperfusion injury. However, exact mechanism by which PDCD4 acts in HIBD is not yet understood. Our aim in present investigation was to investigate the function and mechanism of PDCD4 in alleviating HIBD. Methods: An HIBD model was developed using neonatal rats. After 48 h of modeling, short-term neurological function was evaluated and the brain tissue removed for assessment of cerebral infarct volume and brain water content (BWC). A cell model of oxygen glucose deprivation/reoxygenation (OGD/R) was also constructed. Overexpression or knockdown of insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3) or PDCD4 was performed in pretreated cells. Results: The geotaxis reflex time, cerebral infarct volume, and BWC all increased after HIBD in this neonatal rat model. Additionally, the levels of PDCD4 and of the N6-Methyladenosine (m6A) reader protein IGF2BP3 were increased in HIBD rats and OGD/R-stimulated pheochromocytoma (PC12) cells relative to controls. Moreover, OGD/R-stimulated pheochromocytoma PC12 cells showed decreased cell viability, increased apoptosis, and elevated Interleukin 6 (IL-6), Interleukin 1 β (IL-1β), and tumor necrosis factor-α (TNF-α) contents. These features were reversed after knocking down IGF2BP3. The interaction between IGF2BP3 protein and PDCD4 mRNA was confirmed by RNA immunoprecipitation and RNA pull-down assays. Furthermore, knockdown of IGF2BP3 in OGD/R-stimulated PC12 cells reduced cell damage via down-regulation of PDCD4. Finally, the IGF2BP3/PDCD4 axis alleviated OGD/R-induced cell injury in primary cortical neurons (PCNs). Conclusions: PDCD4 and m6A reader protein IGF2BP3 were up-regulated in an HIBD neonatal rat model. Knockdown of IGF2BP3 in OGD/R-stimulated PC12 cells or PCNs alleviated cell damage through reducing PDCD4.

Bacterial Volatile Organic Compounds as a Strategy to Increase Drought Tolerance in Maize (Zea mays L.): Influence on Plant Biochemistry.

Maize is highly susceptible to drought, which affects growth and yield. This study investigated how bacterial volatile organic compounds (BVOCs) affect maize drought tolerance. Drought reduced shoot size but increased root length, an adaptation for accessing deeper soil moisture. BVOCs from strain D12 significantly increased root length and shoot growth under drought conditions. Drought also altered root biochemistry, decreasing enzyme activity, and increased osmolyte levels. BVOCs from strains F11 and FS4-14 further increased osmolyte levels but did not protect membranes from oxidative damage, while BVOCs from strains D12 and D7 strains reduced osmolyte levels and cell damage. In shoots, drought increased the levels of osmolytes and oxidative stress markers. BVOCs from FS4-14 had minimal effects on shoot biochemistry. BVOCs from D12 and F11 partially restored metabolic activity but did not reduce cell damage. BVOCs from D7 reduced metabolic activity and cell damage. These results suggest that BVOCs can modulate the biochemical response of maize to drought, with some strains evidencing the potential to enhance drought tolerance.

Genome-Wide Identification of DREB Transcription Factor Family and Functional Analysis of PaDREB1D Associated with Low-Temperature Stress in Phalaenopsis aphrodite

Low temperatures are the most significant abiotic stressor for the conservation and production of Phalaenopsis in non-tropical areas. CBF/DREB1 transcription factors play an important role in the plant abiotic stress response. In this study, 31 DREB family members were identified in the Phalaenopsis genome. Expression pattern analysis showed that the expression of different PaDREB members varied among tissue sites. PaDREB1D was isolated from Phalaenopsis aphrodite, and multiple sequence alignment showed that PaDREB1D belonged to the A1 subgroup of the DREB family and was localized in the nucleus. PaDREB1D overexpression in protocorm-like bodies of Phalaenopsis reduced cell damage during low-temperature stress, increased antioxidant enzyme activity, and enhanced the low-temperature tolerance of protocorm-like bodies. The results of this study provide a theoretical basis for breeding for cold resistance and investigating the molecular mechanisms related to low-temperature responses in Phalaenopsis.

Enhanced IGF-IIRα Expression Exacerbates Lipopolysaccharide-Induced Cardiac Inflammation, Hypertrophy, and Apoptosis Through Calcineurin Activation.

Cardiovascular disease is one of the leading causes of death worldwide and has a high prevalence. Insulin-like growth factor-II receptor α (IGF-IIRα) acts as a stress-inducible negative regulator. This study focused on the substantial impact of heightened expression of IGF-IIRα in cardiac myoblasts and its association with the exacerbation of cardiac dysfunction. Using lipopolysaccharide (LPS)-induced H9c2 cardiac myoblasts as a model for sepsis, we aimed to elucidate the molecular interactions between IGF-IIRα and LPS in exacerbating cardiac injury. Our findings demonstrated a synergistic induction of cardiac inflammation and hypertrophy by LPS stimulation and IGF-IIRα overexpression, leading to decreased cell survival. Excessive calcineurin activity, triggered by this combined condition, was identified as a key factor exacerbating the negative effects on cell survival. Cellular changes such as cell enlargement, disrupted actin filaments, and upregulation of hypertrophy-related and inflammation-related proteins contributed to the overall hypertrophic and inflammatory responses. Overexpression of IGF-IIRα also exacerbated apoptosis induced by LPS in H9c2 cardiac myoblasts. Inhibiting calcineurin in LPS-treated H9c2 cardiac myoblasts with IGF-IIRα overexpression effectively reversed the detrimental effects, reducing cell damage and mitigating apoptosis-related cardiac mechanisms. Our study suggests that under sepsis-like conditions in the heart with IGF-IIRα overexpression, hyperactivation of calcineurin worsens cardiac damage. Suppressing IGF-IIRα and calcineurin expression could be a potential intervention to alleviate the impact of the illness and improve cardiac function.

Transcriptional dynamic changes in energy metabolism, protein synthesis and cell cycle regulation reveal the biological adaptation mechanisms of juvenile Acrossocheilus wenchowensis under acute temperature changes

In recent years, frequent acute temperature changes have posed a serious threat to the physiology and survival of fish. This study utilized RNA-Seq technology to analyze the transcriptional dynamics in the muscle tissues of Acrossocheilus wenchowensis under various acute temperature conditions (16◦C, 20◦C, 24◦C, 28◦C and 32◦C). Through comprehensive analysis, we identified 11509 differentially expressed genes (DEGs), a gene set (profiles 19) that was significantly up-regulated with increasing temperature, and two weighted gene co-expression network analysis (WGCNA) modules that were significantly correlated with acute temperature changes. Furthermore, we identified 28 transcription factors that are pivotal in oxidative stress and energy metabolism under acute temperature changes. Our results showed that, compared to the control group (24°C), KEGG functional enrichment analysis revealed significant enrichment of DEGs in the cell cycle, DNA replication, and p53 signaling pathway, with an overall trend of suppressed expression. This indicates that maintaining cell stability and reducing cell damage is an effective adaptive mechanism for A. wenchowensis to cope with acute temperature changes. Through STEM analysis and the black WGCNA module associated with high-temperature stress, we identified significant up-regulation of pathways and hub genes related to energy metabolism including oxidative phosphorylation, TCA cycle, purine metabolism, and glutathione metabolism, as well as the central roles of signal transduction pathways such as MAPK signaling pathway and AMPK signaling pathway, which synergistically regulate energy production. Under acute low-temperature stress, the turquoise WGCNA module highlighted significant up-regulation of hub genes associated with Ribosomal and Spliceosomal pathways related to protein synthesis and processing, as well as activation of calcium signaling pathways, which plays an important role in maintaining cellular function during low-temperature adaptation. These findings provide a critical theoretical and molecular basis for the adaptation of eurythermal fish to rapid temperature changes.

Leonurine as a dietary compound: Its role in ferroptosis inhibition through Nrf2 signaling pathway activation

This research explores the potential of leonurine, a component found in motherwort, to inhibit intestinal inflammatory response in patients of inflammatory bowel disease (IBD) through dietary means with a particular emphasis on how it influences the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. Using colon epithelial cell lines, HT29 and Caco-2, we set up models to study the impact of inflammation, oxidative stress, and apoptosis induced by lipopolysaccharide (LPS). In addition, we employed Nrf2 knockout cell lines to understand its function in a better way. The introduction of leonurine is aimed to evaluate its ability to reduce cell damage and inflammatory reactions by activating the Nrf2–heme oxygenase-1 (HO-1) pathway. Results indicated that LPS exposure led to inflammation, oxidative stress, apoptosis, and potential ferroptosis. It was observed that Nrf2 acted as a suppressor in this scenario; its absence increased cell susceptibility to these challenges. Treatment with leonurine notably decreased inflammation, oxidative stress, and apoptosis; however, these protective effects were significantly reduced in cells lacking Nrf2. This confirms that leonurine can inhibit oxidative stress, inflammatory response, apoptosis, and potential ferroptosis mechanism of colon epithelial cells by activating Nrf2. This study not only enhances our understanding of how leonurine regulates IBD but also highlights the importance of Nrf2 by shedding light on IBD development and potential nutritional approaches for its management.

SIRT4 Protects Müller Glial Cells Against Apoptosis by Mediating Mitochondrial Dynamics and Oxidative Stress.

SIRT4 is a member of the sirtuin family, which is related to mitochondrial function and possesses antioxidant and regulatory redox effects. Currently, the roles of SIRT4 in retinal Müller glial cells, oxidative stress, and mitochondrial function are still unclear. We confirmed, by immunofluorescence staining, that SIRT4 is located mainly in the mitochondria of retinal Müller glial cells. Using flow cytometry and Western blotting, we analyzed cell apoptosis, intracellular reactive oxygen species (ROS) levels, apoptotic and proapoptotic proteins, mitochondrial dynamics-related proteins, and mitochondrial morphology and number after the overexpression and downregulation of SIRT4 in rMC-1 cells. Neither the upregulation nor the downregulation of SIRT4 alone affected apoptosis. SIRT4 overexpression reduced intracellular ROS, reduced the BAX/BCL2 protein ratio, and increased the L-OPA/S-OPA1 ratio and the levels of the mitochondrial fusion protein MFN2 and the mitochondrial cleavage protein FIS1, increasing mitochondrial fusion. SIRT4 downregulation had the opposite effect. Mitochondria tend to divide after serum starvation for 24 h, and SIRT4 downregulation increases mitochondrial fragmentation and oxidative stress, leading to aggravated cell damage. The mitochondrial division inhibitor Mdivi-1 reduced oxidative stress levels and thus reduced cell damage caused by serum starvation. The overexpression of SIRT4 in rMC-1 cells reduced mitochondrial fragmentation caused by serum starvation, leading to mitochondrial fusion and reduced expression of cleaved caspase-3, thus alleviating the cellular damage caused by oxidative stress. Thus, we speculate that SIRT4 may protect retinal Müller glial cells against apoptosis by mediating mitochondrial dynamics and oxidative stress.

Mechanism of Lian Hua Qing Wen capsules regulates the inflammatory response caused by M1 macrophage based on cellular experiments and computer simulations

PurposeThe polarization of macrophages with the resulting inflammatory response play a crucial part in tissue and organ damage due to inflammatory. Study has proved Lian Hua Qing Wen capsules (LHQW) can reduce activation of inflammatory response and damage of tissue derived from the inflammatory reactions. However, the mechanism of LHQW regulates the macrophage-induced inflammatory response is unclear. Therefore, we investigated the mechanism of LHQW regulated the inflammatory response of M1 macrophages by cellular experiments and computer simulations. MethodsThis study has analysed the targets and mechanisms of macrophage regulating inflammatory response at gene and protein levels through bioinformatics. The monomeric components of LHQW were analyzed by High Performance Liquid Chromatography (HPLC). We established the in vitro cell model by M1 macrophages (Induction of THP-1 cells into M1 macrophages). RT-qPCR and immunofluorescence were used to detect changes in gene and protein levels of key targets after LHQW treatment. Computer simulations were utilized to verify the binding stability of monomeric components and protein targets. ResultsMacrophages had 140,690 gene targets, inflammatory response had 12,192 gene targets, intersection gene targets were 11,772. Key monomeric components (including: Pinocembrin, Fargesone-A, Nodakenin and Bowdichione) of LHQW were screened by HPLC. The results of cellular experiments indicated that LHQW could significantly reduce the mRNA expression of CCR5, CSF2, IFNG and TNF, thereby alleviating the inflammatory response caused by M1 macrophage. The computer simulations further validated the binding stability and conformation of key monomeric components and key protein targets, and IFNG/Nodakenin was able to form the most stable binding conformation for its action. ConclusionIn this study, the mechanism of LHQW inhibits the polarization of macrophages and the resulting inflammatory response was investigated by computer simulations and cellular experiments. We found that LHQW may not only reduce cell damage and death by acting on TNF and CCR5, but also inhibit the immune recognition process and inflammatory response by regulating CSF2 and IFNG to prevent polarization of macrophages. Therefore, these results suggested that LHQW may act through multiple targets to inhibit the polarization of macrophages and the resulting inflammatory response.

A coupled model between circadian, cell-cycle, and redox rhythms reveals their regulation of oxidative stress

Most organisms possess three biological oscillators, circadian clock, cell cycle, and redox rhythm, which are autonomous but interact each other. However, whether their interactions and autonomy are beneficial for organisms remains unclear. Here, we modeled a coupled oscillator system where each oscillator affected the phase of the other oscillators. We found that multiple types of coupling prevent a high H2O2 level in cells at M phase. Consequently, we hypothesized a high H2O2 sensitivity at the M phase and found that moderate coupling reduced cell damage due to oxidative stress by generating appropriate phase relationships between three rhythms, whereas strong coupling resulted in an elevated cell damage by increasing the average H2O2 level and disrupted the cell cycle. Furthermore, the multicellularity model revealed that phase variations among cells confer flexibility in synchronization with environments at the expense of adaptability to the optimal environment. Thus, both autonomy and synchrony among the oscillators are important for coordinating their phase relationships to minimize oxidative stress, and couplings balance them depending on environments.

Mechanisms of Lanthanum-mediated mitigation of salt stress in soybean (Glycine max L.).

Salinity is considered one of the abiotic stresses that have the greatest impact on soybean production worldwide. Lanthanum (La) is a rare earth element that can reduce adverse conditions on plant growth and productivity. However, the regulatory mechanism of La-mediated plant response to salt stress has been poorly studied, particularly in soybeans. Therefore, our study investigated the mechanisms of La-mediated salt stress alleviation from the perspectives of the antioxidant system, subcellular structure, and metabolomics responses. The results indicated that salt stress altered plant morphology and biomass, resulting in an increase in peroxidation, inhibition of photosynthesis, and damage to leaf structure. Exogenous La application effectively promoted the activity of superoxide dismutase (SOD) and peroxidase (POD), as well as the soluble protein content, while decreasing the Na+ content and Na+/K+ ratio in roots and leaves, and reducing oxidative damage. Moreover, transmission electron microscopy (TEM) demonstrated that La prevented the disintegration of chloroplasts. Fourier-transform infrared spectroscopy (FTIR) analysis further confirmed that La addition mitigated the decline in protein, carbohydrates, and pectin levels in the leaves. Lanthanum decreased the leaf flavonoid content and synthesis by inhibiting the content of key substances in the phenylalanine metabolism pathway during NaCl exposure. Collectively, our research indicates that La reduces cell damage by regulating the antioxidant system and secondary metabolite synthesis, which are important mechanisms for the adaptive response of soybean leaves, thereby improving the salt tolerance of soybeans.

Research Progress of Traditional Chinese Medicine Based on TGF-β/Smad Signal Pathway in Preventing and Treating Myocardial Fibrosis in Heart Failure

Heart failure is the terminal stage of cardiovascular disease, and its pathological mechanism is ventricular remodeling. Therefore, the fundamental of preventing and treating heart failure is to inhibit ventricular remodeling. The important link of ventricular remodeling is myocardial fibrosis. It can prevent and cure heart failure by inhibiting the occurrence of myocardial fibrosis. By querying relevant domestic and foreign literatures in recent years, it was found that TGF-β/Smad signaling pathway plays an important role in the development of myocardial fibrosis, it may reduce cell damage through anti-inflammatory, antioxidant stress, anti-apoptosis, etc., Maintaining extracellular matrix stability, alleviate the degree of myocardial fibrosis, Chinese medicine in the prevention and treatment of fibrosis has high efficacy, multi-target, improve long-term prognosis and other advantages. To explore a more accurate target drug for preventing and treating myocardial fibrosis in heart failure, reduce the rate of readmission of patients with heart failure, and provide a greater possibility for promoting the prevention and treatment of myocardial fibrosis in heart failure by traditional Chinese medicine.

Baicalin reduced injury of and autophagy-related gene expression in RAW264.7 cells infected with H6N6 avian influenza virus

In the present study, we investigated whether baicalin could reduce the damage caused to RAW264.7 cells following infection with H6N6 avian influenza virus. In addition, we studied the expression of autophagy-related genes. The morphological changes in cells were observed by hematoxylin and eosin (H&E) staining, and the inflammatory factors in the cell supernatant were detected by enzyme-linked immunosorbent assay (ELISA). Transmission electron microscopy (TEM) was used to detect the levels of RAW264.7 autophagosomes, and western blotting and immunofluorescence were used to detect the protein expression of autophagy marker LC3. Quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) was used to detect the mRNA transcription levels of autophagy key factors. The results showed that different doses of baicalin significantly reduced the H6N6 virus-induced damage of RAW264.7 cells. The contents of interleukin (IL)-1β, IL-2, IL-6, and tumor necrosis factor (TNF)-α in the cell supernatant significantly decreased. In addition, the protein expression of LC3 and Beclin-1, ATG12, ATG5 the mRNA levels were significantly decreased. This study showed that baicalin can reduce cell damage and affect the H6N6-induced autophagy level of RAW264.7 cells.

Genomic regions, candidate genes, and pleiotropic variants associated with physiological and anatomical indicators of heat stress response in lactating sows

BackgroundHeat stress (HS) poses significant threats to the sustainability of livestock production. Genetically improving heat tolerance could enhance animal welfare and minimize production losses during HS events. Measuring phenotypic indicators of HS response and understanding their genetic background are crucial steps to optimize breeding schemes for improved climatic resilience. The identification of genomic regions and candidate genes influencing the traits of interest, including variants with pleiotropic effects, enables the refinement of genotyping panels used to perform genomic prediction of breeding values and contributes to unraveling the biological mechanisms influencing heat stress response. Therefore, the main objectives of this study were to identify genomic regions, candidate genes, and potential pleiotropic variants significantly associated with indicators of HS response in lactating sows using imputed whole-genome sequence (WGS) data. Phenotypic records for 18 traits and genomic information from 1,645 lactating sows were available for the study. The genotypes from the PorcineSNP50K panel containing 50,703 single nucleotide polymorphisms (SNPs) were imputed to WGS and after quality control, 1,622 animals and 7,065,922 SNPs were included in the analyses.ResultsA total of 1,388 unique SNPs located on sixteen chromosomes were found to be associated with 11 traits. Twenty gene ontology terms and 11 biological pathways were shown to be associated with variability in ear skin temperature, shoulder skin temperature, rump skin temperature, tail skin temperature, respiration rate, panting score, vaginal temperature automatically measured every 10 min, vaginal temperature measured at 0800 h, hair density score, body condition score, and ear area. Seven, five, six, two, seven, 15, and 14 genes with potential pleiotropic effects were identified for indicators of skin temperature, vaginal temperature, animal temperature, respiration rate, thermoregulatory traits, anatomical traits, and all traits, respectively.ConclusionsPhysiological and anatomical indicators of HS response in lactating sows are heritable but highly polygenic. The candidate genes found are associated with important gene ontology terms and biological pathways related to heat shock protein activities, immune response, and cellular oxidative stress. Many of the candidate genes with pleiotropic effects are involved in catalytic activities to reduce cell damage from oxidative stress and cellular mechanisms related to immune response.

Anthocyanin of Black Highland Barley Alleviates H2O2-Induced Cardiomyocyte Injury and Myocardial Infarction via Activating the Phosphatase and Tensin Homolog/Phosphatidylinositol 3-Kinase/Protein Kinase B Pathway.

Cardiovascular disease (CVD) represents a substantial global health challenge, with its impact on mortality and morbidity rates surpassing that of cancer. The present study was designed to explore the cardioprotective properties of anthocyanin (ACN), a compound derived from black barley, against oxidative stress-induced damage in myocardial cells and to uncover the molecular mechanisms at play. Utilizing both in vitro and in vivo experimental models, our findings indicate that ACN notably reduced cell damage caused by oxidative stress and effectively prevented apoptosis. High-throughput RNA sequencing analysis has shed light on the mechanism by which ACN achieves its antioxidative stress effects, implicating the PTEN-Akt signaling pathway. ACN was found to modulate PTEN expression levels, which in turn influences the Akt pathway, leading to a reduction in apoptotic processes. This novel insight lays the groundwork for the potential clinical utilization of ACN in the management of CVD. While this study has shed light on some of the functions of ACN, it is important to recognize that natural compounds often interact with multiple molecular targets and engage in intricate signaling cascades. Future research endeavors will concentrate on further elucidating the regulatory mechanisms by which ACN influences PTEN expression, with the goal of enhancing our comprehension and expanding the therapeutic potential of ACN in the treatment of cardiovascular conditions.

Bacillus tequilensis influences metabolite production in tomato and restores soil microbial diversity during Fusarium oxysporum infection.

This study evaluates cellular damage, metabolite profiling, and defence-related gene expression in tomato plants and soil microflora during Fusarium wilt disease after treatment with B. tequilensis PBE-1. Histochemical analysis showed that PBE-1 was the primary line of defence through lignin deposition and reduced cell damage. GC-MS revealed that PBE-1 treatment ameliorated stress caused by F. oxysporum infection. PBE-1 also improved transpiration, photosynthesis, and stomatal conductance in tomato. qRT-PCR suggested that the defence-related genes FLS2, SERK, NOS, WRKYT, NHO, SAUR, and MYC2, which spread infection, were highly upregulated during F. oxysporum infection, but either downregulated or expressed normally in PBE-1 + P treated plants. This indicates that the plant not only perceives the bio-control agent as a non-pathogen entity but its presence in normal metabolism and gene expression within the host plant is maintained. The study further corroborated findings that application of PBE-1 does not cause ecological disturbances in the rhizosphere. Activity of soil microflora across four treatments, measured by Average Well Colour Development (AWCD), showed continuous increases from weeks 1 to 4 post-pathogen infection, with distinct substrate usage patterns like tannic and fumaric acids impacting microbial energy source utilization and diversity. Principal Component Analysis (PCA) and diversity indices like McIntosh, Shannon, and Simpson further illustrated significant microbial community shifts over the study period. In conclusion, our findings demonstrate that B. tequilensis PBE-1 is an ideal bio-agent for field application during Fusarium wilt disease management in tomato.