Fingolimod synergizes and reverses K. pneumoniae resistance to colistin.

Klebsiella pneumoniae (K. pneumoniae) infection and the rapid spread of multi-drug resistant (MDR) bacteria pose a serious threat to global healthcare. Polymyxin E (colistin), a group of cationic antimicrobial polypeptides, is currently one of the last resort treatment options against carbapenem-resistant Gram-negative pathogens. The effectiveness of colistin has been compromised due to its intensive use. This study found that fingolimod (FLD), a natural product derivative, exhibited a significant synergistic bactericidal effect on K. pneumoniae when combined with colistin, both in vitro and in vivo. The checkerboard method was employed to assess the in vitro synergistic effect of FLD with colistin. FLD enhanced the susceptibility of bacteria to colistin and lowered effectively minimum inhibitory concentrations (MIC) when compared to colistin MIC, and the fractional inhibitory concentrations (FIC) value was less than 0.3. The time-kill curve demonstrated that the combination treatment of FLD and colistin had significant bactericidal efficacy. The in vitro concurrent administration of colistin and FLD resulted in heightening membrane permeability, compromising cell integrity, diminishing membrane fluidity, and perturbing membrane homeostasis. They also induced alterations in membrane potential, levels of reactive oxygen species, and adenosine triphosphate synthesis, ultimately culminating in bacterial death. Moreover, the combination of FLD with colistin significantly influenced fatty acid metabolism. In the mouse infection model, the survival rate of mice injected with K. pneumoniae was significantly improved to 67% and pathological damage was significantly relieved with combination treatment of FLD and colistin when compared with colistin treatment. This study highlights the potential of FLD in combining with colistin for treating infections caused by MDR isolates of K. pneumoniae.

Metabolism and liver toxicity of cannabidiol.

Increasing public interest has resulted in the widespread use of non-pharmaceutical cannabidiol (CBD) products. The sales of CBD products continue to rise, accompanied by concerns regarding unsubstantiated benefits, lack of product quality control, and potential health risks. Both animal and human studies have revealed a spectrum of toxicological effects linked to the use of CBD. Adverse effects related to exposure of humans to CBD include changes in appetite, gastrointestinal discomfort, fatigue, and elevated liver aminotransferase enzymes. Animal studies reported changes in organ weight, reproduction, liver function, and the immune system. This review centers on human-derived data, including clinical studies and in vitro investigations. Animal studies are also included when human data is not available. The objective is to offer an overview of CBD-related hepatotoxicity, metabolism, and potential CBD-drug interactions, thereby providing insights into the current understanding of CBD's impact on human health. It's important to note that this review does not serve as a risk assessment but seeks to summarize available information to contribute to the broader understanding of potential toxicological effects of CBD on the liver.

Efficacy and safety of intrathecal dexamethasone combined with isoniazid in the treatment of tuberculous meningitis: a meta-analysis.

BACKGROUND: The treatment regimen for tuberculous meningitis (TBM) remains unclear and requires optimization. There are some reports on successful adjunct intrathecal dexamethasone and isoniazid (IDI) treatment strategies for TBM, however, there is equivocal evidence on their efficacy and safety. METHODS: A comprehensive search of English and Chinese databases was conducted from inception to February 2024. A meta-analysis was performed on randomized controlled trials (RCTs) estimating the effects of adjunct IDI on conventional anti-TB (C anti-TB) treatments or C anti-TB alone. Efficacy, adverse reaction rate, cerebrospinal fluid (CSF) leukocytes, and CSF protein were used as primary outcome indicators. CSF glucose, CSF chlorides, CSF pressure, recovery time for laboratory indicators and recovery time for clinical symptoms were used as secondary outcome indicators. RESULTS: A total of 17 studies involving 1360 (IDI group vs. C anti-TB group: 392 vs. 372; higher-dose IDI group vs. lower-dose IDI group: 319 vs. 277) patients were included in our analysis. Efficacy was significantly higher (RR 1.3, 95% CI 1.2-1.4, P < 0.001) and adverse reaction rate was significantly lower in the IDI groups (RR 0.59, 95% CI 0.37-0.92, P = 0.021). Furthermore, CSF leukocytes (WMD - 29.33, 95% CI [- 40.64 to-18.02], P < 0.001) and CSF protein (WMD - 0.79, 95%CI [-0.96 to-0.61], P < 0.001) were significantly lower in the IDI groups. Recovery time indicators were all shorter in the IDI groups, fever (SMD - 2.45, 95% CI [-3.55 to-1.35], P < 0.001), coma (SMD-3.75, 95% CI [-4.33 to-3.17], P < 0.001), and headache (SMD  - 3.06, 95% CI [- 4.05 to-2.07], P < 0.001), respectively. Higher-dose IDI was more effective than lower-dose IDI (RR 1.23, 95% CI 1.14-1.33, P < 0.001), with no significant difference in adverse reaction rate between the two (RR 0.82, 95%CI 0.43-1.56, P = 0.544). CONCLUSION: Adjunct IDI with C anti-TB can enhance therapeutic outcomes and reduce adverse reaction rate in adult TBM patients, with higher-dose IDI showing superior efficacy. These findings highlight the potential of IDI as an adjunctive therapy in TBM management. However, more high-quality RCTs from more regions should be conducted to support our results. TRIAL REGISTRATION: Retrospectively registered in PROSPERO  https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023388860 .

Prognostic Value of CT-Derived Myocardial Biomarkers: Extracellular Volume Fraction and Strain in Patients with Severe Aortic Stenosis Undergoing Transcatheter Aortic Valve Replacement: A Systematic Review and Meta-analysis.

RATIONALE AND OBJECTIVES: This study aimed to investigate the prognostic value of preoperative CT scan-derived myocardial biomarkers in patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR). MATERIALS AND METHODS: In April 2024, three databases (PubMed, Web of Science and Embase) were searched to identify studies. A random-effects model for meta-analysis was conducted to calculate pooled hazard ratios (HR) and 95% confidence intervals (CI) to assess the prognostic value. The I2 statistic was used to assess heterogeneity. Meta-regression analysis was conducted to appraise which variables yielded a significant impact on the HR of included biomarkers. RESULTS: 11 studies were identified, of which six studies involved 678 patients reporting extracellular volume fraction (ECV), one study involved 300 patients reporting ECV and left ventricular global longitudinal strain (LVGLS), three studies involved 868 patients reporting LVGLS and one study involved 376 patients reporting LVGLS and peak left atrial longitudinal strain (PALS). The endpoints included all-cause mortality, major adverse cardiovascular events (MACE) and a composite outcome of the previous two. The meta-analysis revealed that ECV, whether considered as a dichotomous variable (pooled HR: 3.87, 95% CI: 2.63-5.70, I2 = 0%), or as a continuous variable (pooled HR: 1.12, 95% CI: 1.05-1.19, I2 = 66%), and LVGLS, whether considered as a dichotomous variable (pooled HR: 1.70, 95% CI: 1.30-2.22, I2 = 0%) or a continuous variable (pooled HR: 1.07, 95% CI: 1.04-1.10, I2 = 0%) were all significant predictors for outcomes in patients with severe AS after TAVR. Age, sex, follow-up time and mean pressure gradient had a significant impact on the model of ECV (continuous). CONCLUSION: The higher CT-derived ECV and impaired LVGLS are able to predict worse outcomes in patients with severe AS who have undergone TAVR.

Activating Inert Perovskite Oxides for CO2 Electroreduction via Slight Cu2+ Doping in B-Sites.

Perovskite oxides are proven as a striking platform for developing high-performance electrocatalysts. Nonetheless, a significant portion of them show CO2 electroreduction (CO2RR) inertness. Here a simple but effective strategy is reported to activate inert perovskite oxides (e.g., SrTiO3) for CO2RR through slight Cu2+ doping in B-sites. For the proof-of-concept catalysts of SrTi1-xCuxO3 (x = 0.025, 0.05, and 0.1), Cu2+ doping (even in trace amount, e.g., x = 0.025) can not only create active, stable CuO6 octahedra, increase electrochemical active surface area, and accelerate charge transfer, but also significantly regulate the electronic structure (e.g., up-shifted band center) to promote activation/adsorption of reaction intermediates. Benefiting from these merits, the stable SrTi1-xCuxO3 catalysts feature great improvements (at least an order of magnitude) in CO2RR activity and selectivity for high-order products (i.e., CH4 and C2+), compared to the SrTiO3 parent. This work provides a new avenue for the conversion of inert perovskite oxides into high-performance electrocatalysts toward CO2RR.

EGF-like growth factors upregulate pentraxin 3 expression in human granulosa-lutein cells.

The epidermal growth factor (EGF)-like factors, comprising amphiregulin (AREG), betacellulin (BTC), and epiregulin (EREG), play a critical role in regulating the ovulatory process. Pentraxin 3 (PTX3), an essential ovulatory protein, is necessary for maintaining extracellular matrix (ECM) stability during cumulus expansion. The aim of this study was to investigate the impact of EGF-like factors, AREG, BTC, and EREG on the expression and production of PTX3 in human granulosa-lutein (hGL) cells and the molecular mechanisms involved. Our results demonstrated that AREG, BTC, and EREG could regulate follicular function by upregulating the expression and increasing the production of PTX3 in both primary (obtained from 20 consenting patients undergoing IVF treatment) and immortalized hGL cells. The upregulation of PTX3 expression was primarily facilitated by the activation of the extracellular signal-regulated kinase 1 and 2 (ERK1/2) signaling pathway, induced by these EGF-like factors. In addition, we found that the upregulation of PTX3 expression triggered by the EGF-like factors was completely reversed by either pretreatment with the epidermal growth factor receptor (EGFR) inhibitor, AG1478, or knockdown of EGFR, suggesting that EGFR is crucial for activating the ERK1/2 signaling pathway in hGL cells. Overall, our findings indicate that AREG, BTC, and EREG may modulate human cumulus expansion during the periovulatory stage through the upregulation of PTX3.

Phillyrin reduces ROS production to alleviate the progression of intervertebral disc degeneration by inhibiting NF-κB pathway.

BACKGROUND: Intervertebral disc degeneration (IDD) is an increasingly important cause of low back pain (LBP) that results in substantial health and economic burdens. Inflammatory pathway activation and the production of reactive oxygen species (ROS) play vital roles in the progression of IDD. Several studies have suggested that phillyrin has a protective role and inhibits inflammation and the production of ROS. However, the role of phillyrin in IDD has not been confirmed. PURPOSE: The purpose of this study was to investigate the role of phillyrin in IDD and its mechanisms. STUDY DESIGN: To establish IDD models in vivo, ex-vivo, and in vitro to verify the function of phillyrin in IDD. METHOD: The effects of phillyrin on extracellular matrix (ECM) degeneration, inflammation, and oxidation in nucleus pulposus (NP) cells were assessed using immunoblotting and immunofluorescence analysis. Additionally, the impact of phillyrin administration on acupuncture-mediated intervertebral disc degeneration (IDD) in rats was evaluated using various techniques such as MRI, HE staining, S-O staining, and immunohistochemistry (IHC). RESULT: Pretreatment with phillyrin significantly inhibited the IL-1ß-mediated reduction in the degeneration of ECM and apoptosis by alleviating activation of the NF-κB inflammatory pathway and the generation of ROS. In addition, in vivo and ex-vivo experiments verified the protective effect of phillyrin against IDD. CONCLUSION: Phillyrin can attenuate the progression of IDD by reducing ROS production and activating inflammatory pathways.

EpiCarousel: memory- and time-efficient identification of metacells for atlas-level single-cell chromatin accessibility data.

SUMMARY: Recent technical advancements in single-cell chromatin accessibility sequencing (scCAS) have brought new insights to the characterization of epigenetic heterogeneity. As single-cell genomics experiments scale up to hundreds of thousands of cells, the demand for computational resources for downstream analysis grows intractably large and exceeds the capabilities of most researchers. Here, we propose EpiCarousel, a tailored Python package based on lazy loading, parallel processing, and community detection for memory- and time-efficient identification of metacells, i.e. the emergence of homogenous cells, in large-scale scCAS data. Through comprehensive experiments on five datasets of various protocols, sample sizes, dimensions, number of cell types, and degrees of cell-type imbalance, EpiCarousel outperformed baseline methods in systematic evaluation of memory usage, computational time, and multiple downstream analyses including cell type identification. Moreover, EpiCarousel executes preprocessing and downstream cell clustering on the atlas-level dataset with 707 043 cells and 1 154 611 peaks within 2 h consuming <75 GB of RAM and provides superior performance for characterizing cell heterogeneity than state-of-the-art methods. AVAILABILITY AND IMPLEMENTATION: The EpiCarousel software is well-documented and freely available at https://github.com/biox-nku/epicarousel. It can be seamlessly interoperated with extensive scCAS analysis toolkits.

Toxicity of cannabidiol and its metabolites in TM3 mouse Leydig cells: a comparison with primary human Leydig cells.

Cannabidiol (CBD), one of the major components extracted from the plant Cannabis sativa L., has been used as a prescription drug to treat seizures in many countries. CBD-induced male reproductive toxicity has been reported in animal models; however, the underlying mechanisms remain unclear. We previously reported that CBD induced apoptosis in primary human Leydig cells, which constitute the primary steroidogenic cell population in the testicular interstitium. In this study, we investigated the effects of CBD and its metabolites on TM3 mouse Leydig cells. CBD, at concentrations below 30 µM, reduced cell viability, induced G1 cell cycle arrest, and inhibited DNA synthesis. CBD induced apoptosis after exposure to high concentrations (≥ 50 µM) for 24 h or a low concentration (20 µM) for 6 days. 7-Hydroxy-CBD and 7-carboxy-CBD, the main CBD metabolites of CBD, exhibited the similar toxic effects as CBD. In addition, we conducted a time-course mRNA-sequencing analysis in both primary human Leydig cells and TM3 mouse Leydig cells to understand and compare the mechanisms underlying CBD-induced cytotoxicity. mRNA-sequencing analysis of CBD-treated human and mouse Leydig cells over a 5-day time-course indicated similar responses in both cell types. Mitochondria and lysosome dysfunction, oxidative stress, and autophagy were the major enriched pathways in both cell types. Taken together, these findings demonstrate comparable toxic effects and underlying mechanisms in CBD-treated mouse and primary human Leydig cells.

Analysis of chaos and capsizing of a class of nonlinear ship rolling systems under excitation of random waves.

The action of wind and waves has a significant effect on the ship's roll, which can be a source of chaos and even capsize. The influence of random wave excitation is considered in order to investigate complex dynamic behavior by analytical and numerical methods. Chaotic rolling motions are theoretically studied in detail by means of the relevant Melnikov method with or without noise excitation. Numerical simulations are used to verify and analyze the appropriate parameter excitation and noise conditions. The results show that by changing the parameters of the excitation amplitude or the noise intensity, chaos can be induced or suppressed.

Biomimetic Hydrogels Promote Pseudoislet Formation to Improve Glycemic Control in Diabetic Mice.

Islet or ß-cell transplantation is currently considered to be the ideal treatment for diabetes, and three-dimensional (3D) bioprinting of a bionic pancreas with physiological stiffness is considered to be promising for the encapsulation and transplantation of ß-cells. In this study, a 5%GelMA/2%AlgMA hybrid hydrogel with pancreatic physiological stiffness was constructed and used for ß-cell encapsulation, 3D bioprinting, and in vivo transplantation to evaluate glycemic control in diabetic mice. The hybrid hydrogel had good cytocompatibility and could induce insulin-producing cells (IPCs) to form pseudoislet structures and improve insulin secretion. Furthermore, we validated the importance of betacellulin (BTC) in IPCs differentiation and confirmed that IPCs self-regulation was achieved by altering the nuclear and cytoplasmic distributions of BTC expression. In vivo transplantation of diabetic mice quickly restored blood glucose levels. In the future, 3D bioprinting of ß-cells using biomimetic hydrogels will provide a promising platform for clinical islet transplantation for the treatment of diabetes.

Operando Studies of Bismuth Nanoparticles Embedded in N, O-Doped Porous Carbon for High-Performance Potassium-Ion Hybrid Capacitor.

A highly viable alternative to lithium-ion batteries for stationary electrochemical energy-storage systems is the potassium dual-ion hybrid capacitor (PIHC), especially toward fast-charging capability. However, the sluggish reaction kinetics of negative electrode materials seriously impedes their practical implementation. In this paper, a new negative electrode Bi@RPC (Nano-bismuth confined in nitrogen- and oxygen-doped carbon with rationally designed pores, evidenced by advanced characterization) is developed, leading to a remarkable electrochemical performance. PIHCs building with the active carbon YP50F positive electrode result in a high operation voltage (0.1-4 V), and remarkably well-retained energy density at a high-power density (11107 W kg-1 at 98 Wh kg-1 ). After 5000 cycles the proposed PHICs still show a superior capacity retention of 92.6%. Moreover, a reversible mechanism of "absorption-alloying" of the Bi@RPC nanocomposite is revealed by operando synchrotron X-ray diffraction and Raman spectroscopy. With the synergistic potassium ions storage mechanism arising from the presence of well-structured pores and nano-sized bismuth, the Bi@RPC electrode exhibits an astonishingly rapid kinetics and high energy density. The results demonstrate that PIHCs with Bi@RPC-based negative electrode is the promising option for simultaneously high-capacity and fast-charging energy storage devices.

Tangshen formula targets the gut microbiota to treat non-alcoholic fatty liver disease in HFD mice: A 16S rRNA and non-targeted metabolomics analyses.

BACKGROUND: Tangshen formula (TSF) has an ameliorative effect on hepatic lipid metabolism in non-alcoholic fatty liver disease (NAFLD), but the role played by the gut microbiota in this process is unknown. METHOD: We conducted three batches of experiments to explore the role played by the gut microbiota: TSF administration, antibiotic treatment, and fecal microbial transplantation. NAFLD mice were induced with a high-fat diet to investigate the ameliorative effects of TSF on NAFLD features and intestinal barrier function. 16S rRNA sequencing and serum untargeted metabolomics were performed to further investigate the modulatory effects of TSF on the gut microbiota and metabolic dysregulation in the body. RESULTS: TSF ameliorated insulin resistance, hypercholesterolemia, lipid metabolism disorders, inflammation, and impairment of intestinal barrier function. 16S rRNA sequencing analysis revealed that TSF regulated the composition of the gut microbiota and increased the abundance of beneficial bacteria. Antibiotic treatment and fecal microbiota transplantation confirmed the importance of the gut microbiota in the treatment of NAFLD with TSF. Subsequently, untargeted metabolomics identified 172 differential metabolites due to the treatment of TSF. Functional predictions suggest that metabolisms of choline, glycerophospholipid, linoleic acid, alpha-linolenic acid, and arachidonic acid are the key metabolic pathways by which TSF ameliorates NAFLD and this may be influenced by the gut microbiota. CONCLUSION: TSF treats the NAFLD phenotype by remodeling the gut microbiota and improving metabolic profile, suggesting that TSF is a functional gut microbial and metabolic modulator for the treatment of NAFLD.

A novel method for high level production of protein glutaminase by sfGFP tag in Bacillus subtilis.

Protein glutaminase (PG; EC 3.5.1.44) is a novel deamidase that helps to improve functional properties of food proteins. Currently, the highest activated PG enzyme activity was 26 U/mg when recombinantly expressed via the twin-arginine translocation (Tat) pathway in Corynebacterium glutamicum. In this study, superfolder green fluorescent protein (sfGFP) was used to replace traditional signal peptides to facilitate efficient heterologous expression and secretion of Propeptide-Protein glutaminase (PP) in Bacillus subtilis. The fusion protein, sfGFP-PP, was secreted from 12 h of fermentation and reached its highest extracellular expression at 28 h, with a secretion efficiency of about 93 %. Moreover, when fusing sfGFP with PP at the N-terminus, it significantly enhances PG expression up to 26 U/mL by approximately 2.2-fold compared to conventional signal-peptides- guided PP with 11.9 U/mL. Finally, the PG enzyme activity increased from 26 U/mL to 36.9 U/mL after promoter and RBS optimization. This strategy not only provides a new approach to increase PG production as well as extracellular secretion but also offers sfGFP as an effective N-terminal tag for increased secreted production of difficult-to-express proteins.

Evaluation of weak genotoxicity of hydroxychloroquine in human TK6 cells.

Hydroxychloroquine (HCQ), a derivative of chloroquine (CQ), is an antimalarial and antirheumatic drug. Since there is limited data available on the genotoxicity of HCQ, in the current study, we used a battery of in vitro assays to systematically examine the genotoxicity of HCQ in human lymphoblastoid TK6 cells. We first showed that HCQ is not mutagenic in TK6 cells up to 80 µM with or without exogenous metabolic activation. Subsequently, we found that short-term (3-4 h) HCQ treatment did not cause DNA strand breakage as measured by the comet assay and the phosphorylation of histone H2A.X (γH2A.X), and did not induce chromosomal damage as determined by the micronucleus (MN) assay. However, after 24-h treatment, both CQ and HCQ induced comparable and weak DNA damage and MN formation in TK6 cells; upregulated p53 and p53-mediated DNA damage responsive genes; and triggered apoptosis and mitochondrial damage that may partially contribute to the observed MN formation. Using a benchmark dose (BMD) modeling analysis, the lower 95% confidence limit of BMD50 values (BMDL50) for MN induction in TK6 cells were about 19.7 µM for CQ and 16.3 µM for HCQ. These results provide additional information for quantitative genotoxic risk assessment of these drugs.

In Situ Polymerization of Hydrogel Electrolyte on Electrodes Enabling the Flexible All-Hydrogel Supercapacitors with Low-Temperature Adaptability.

All-hydrogel supercapacitors are emerging as promising power sources for next-generation wearable electronics due to their intrinsic mechanical flexibility, eco-friendliness, and enhanced safety. However, the insufficient interfacial adhesion between the electrode and electrolyte and the frozen hydrogel matrices at subzero temperatures largely limit the practical applications of all-hydrogel supercapacitors. Here, an all-hydrogel supercapacitor is reported with robust interfacial contact and anti-freezing property, fabricated by in situ polymerizing hydrogel electrolyte onto hydrogel electrodes. The robust interfacial adhesion is developed by the synergistic effect of a tough hydrogel matrix and topological entanglements. Meanwhile, the incorporation of zinc chloride (ZnCl2) in the hydrogel electrolyte prevents the freezing of water solvents and endows the all-hydrogel supercapacitor with mechanical flexibility and fatigue resistance across a wide temperature range of 20 °C to -60 °C. Such all-hydrogel supercapacitor demonstrates satisfactory low-temperature electrochemical performance, delivering a high energy density of 11 mWh cm-2 and excellent cycling stability with a capacitance retention of 90% over 10000 cycles at -40 °C. Notably, the fabricated all-hydrogel supercapacitor can endure dynamic deformations and operate well under 2000 tension cycles even at -40 °C, without experiencing delamination and electrochemical failure. This work offers a promising strategy for flexible energy storage devices with low-temperature adaptability.

Genetic evidence suggests a genetic association between major depressive disorder and reduced cortical gray matter volume: A Mendelian randomization study and mediation analysis.

BACKGROUND: Several studies have suggested an association between major depressive disorder (MDD) and abnormal brain structure. However, it is unclear whether MDD affects cortical gray matter volume, a common indicator of cognitive function. We aimed to determine whether MDD was associated with decreased cortical gray matter volume (GMV) through a Mendelian randomization (MR) study. METHODS: We obtained summary genetic data from a study conducted by the Psychiatric Genomics Consortium, which recruited a total of 480,359 participants (135,458 cases and 344,901 controls). Genetic tools-single nucleotide polymorphisms (SNPs)-of MDD were extracted from the study and their effects on gray matter volumes of the cortex and total brain were evaluated in a large cohort from the UK Biobank (n = 8427). The effects of the SNPs were pooled using inverse variance weighted (IVW) analysis and further tested in several sensitivity analyses. We tested whether C-reactive protein (CRP) levels and interleukin-6 signaling were the mediators of the effects using a multivariate MR model. RESULTS: Thirty-three SNPs were identified and adopted as genetic tools for predicting MDD. IVW analysis showed that MDD was associated with lower overall GMV (beta value -0.106, 95%CI -0.188 to -0.023, p = 0.011) in the frontal pole (left frontal pole, -0.152, 95%CI -0.177 to -0.127, p = 0.013; right frontal pole, -0.133, 95%CI -0.253 to -0.013, p = 0.028). Multivariate and mediation analysis showed that interleukin-6 was an important mediator of GMV reduction. Reverse causality analysis found no evidence that total GMV affected the risk of MDD, but showed that increased left precuneus cortex volume and left posterior cingulate cortex volume were associated with increased risk of MDD. LIMITATIONS: Potential pleiotropic effects and overestimation of real-world effects. Key assumptions for MR analysis may not be satisfactorily met. CONCLUSION: MDD was associated with a reduced GMV, and interleukin-6 might be a mediator of GMV reduction.

Mechanism of action of anthocyanin on the detoxification of foodborne contaminants-A review of recent literature.

Foodborne contaminants refer to substances that are present in food and threaten food safety. Due to the progress in detection technology and the rising concerns regarding public health, there has been a surge in research focusing on the dangers posed by foodborne contaminants. These studies aim to explore and implement strategies that are both safe and efficient in mitigating the associated risks. Anthocyanins, a class of flavonoids, are abundantly present in various plant species, such as blueberries, grapes, purple sweet potatoes, cherries, mulberries, and others. Numerous epidemiological and nutritional intervention studies have provided evidence indicating that the consumption of anthocyanins through dietary intake offers a range of protective effects against the detrimental impact of foodborne contaminants. The present study aims to differentiate between two distinct subclasses of foodborne contaminants: those that are generated during the processing of food and those that originate from the surrounding environment. Furthermore, the impact of anthocyanins on foodborne contaminants was also summarized based on a review of articles published within the last 10 years. However, further investigation is warranted regarding the mechanism by which anthocyanins target foodborne contaminants, as well as the potential impact of individual variations in response. Additionally, it is important to note that there is currently a dearth of clinical research examining the efficacy of anthocyanins as an intervention for mitigating the effects of foodborne pollutants. Thus, by exploring the detoxification effect and mechanism of anthocyanins on foodborne pollutants, this review thereby provides evidence, supporting the utilization of anthocyanin-rich diets as a means to mitigate the detrimental effects of foodborne contaminants.

The role of endoplasmic reticulum stress, mitochondrial dysfunction and their crosstalk in intervertebral disc degeneration.

Low back pain (LBP) is a pervasive global health issue. Roughly 40% of LBP cases are attributed to intervertebral disc degeneration (IVDD). While the underlying mechanisms of IVDD remain incompletely understood, it has been confirmed that apoptosis and extracellular matrix (ECM) degradation caused by many factors such as inflammation, oxidative stress, calcium (Ca2+) homeostasis imbalance leads to IVDD. Endoplasmic reticulum (ER) stress and mitochondrial dysfunction are involved in these processes. The initiation of ER stress precipitates cell apoptosis, and is also related to inflammation, levels of oxidative stress, and Ca2+ homeostasis. Additionally, mitochondrial dynamics, antioxidative systems, disruption of Ca2+ homeostasis are closely associated with Reactive Oxygen Species (ROS) and inflammation, promoting cell apoptosis. However, numerous crosstalk exists between the ER and mitochondria, where they interact through inflammatory cytokines, signaling pathways, ROS, or key molecules such as CHOP, forming positive and negative feedback loops. Furthermore, the contact sites between the ER and mitochondria, known as mitochondria-associated membranes (MAM), facilitate direct signal transduction such as Ca2+ transfer. However, the current attention towards this issue is insufficient. Therefore, this review summarizes the impacts of ER stress and mitochondrial dysfunction on IVDD, along with the possibly potential crosstalk between them, aiming to unveil novel avenues for IVDD intervention.