Quantitative Proteomics Reveals the Relationship between Protein Changes and Volatile Flavor Formation in Hunan Bacon during Low-Temperature Smoking.

This study aimed to investigate the changes in proteins and volatile flavor compounds that occur in bacon during low-temperature smoking (LTS) and identify potential correlations between these changes. To achieve this, a combination of gas chromatography-mass spectrometry and proteomics was employed. A total of 42 volatile flavor compounds were identified in the bacon samples, and, during LTS, 11 key volatile flavor compounds with variable importance were found at a projection value of >1, including 2',4'-dihydroxyacetophenone, 4-methyl-2H-furan-5-one, Nonanal, etc. In total, 2017 proteins were quantified at different stages of LTS; correlation coefficients and KEGG analyses identified 27 down-regulated flavor-related proteins. Of these, seven were involved in the tricarboxylic acid (TCA) cycle, metabolic pathways, or amino acid metabolism, and they may be associated with the process of flavor formation. Furthermore, correlation coefficient analysis indicated that certain chemical parameters, such as the contents of free amino acids, carbonyl compounds, and TCA cycle components, were closely and positively correlated with the formation of key volatile flavor compounds. Combined with bioinformatic analysis, the results of this study provide insights into the proteins present in bacon at various stages of LTS. This study demonstrates the changes in proteins and the formation of volatile flavor compounds in bacon during LTS, along with their potential correlations, providing a theoretical basis for the development of green processing methods for Hunan bacon.

Comprehensive Review of EGCG Modification: Esterification Methods and Their Impacts on Biological Activities.

Epigallocatechin gallate (EGCG), the key constituent of tea polyphenols, presents challenges in terms of its lipid solubility, stability, and bioavailability because of its polyhydroxy structure. Consequently, structural modifications are imperative to enhance its efficacy. This paper comprehensively reviews the esterification techniques applied to EGCG over the past two decades and their impacts on bioactivities. Both chemical and enzymatic esterification methods involve catalysts, solvents, and hydrophobic groups as critical factors. Although the chemical method is cost-efficient, it poses challenges in purification; on the other hand, the enzymatic approach offers improved selectivity and simplified purification processes. The biological functions of EGCG are inevitably influenced by the structural changes incurred through esterification. The antioxidant capacity of EGCG derivatives can be compromised under certain conditions by reducing hydroxyl groups, while enhancing lipid solubility and stability can strengthen their antiviral, antibacterial, and anticancer properties. Additionally, esterification broadens the utility of EGCG in food applications. This review provides critical insights into developing cost-effective and environmentally sustainable selective esterification methods, as well as emphasizes the elucidation of the bioactive mechanisms of EGCG derivatives to facilitate their widespread adoption in food processing, healthcare products, and pharmaceuticals.

Glycyrrhizic acid treatment ameliorates anxiety-like behaviour via GLT1 and Per1/2-dependent pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: As a traditional Chinese medicinal herb, Glycyrrhiza. URALENSIS: Fisch. (licorice root, chinese name: Gancao) has a variety of medicinal values and is widely used clinically. Its main active ingredient, glycyrrhizic acid (GA), is believed to have a neuroprotective effect. However, the underlying biological mechanisms of GA on stress-induced anxiety disorders are still unclear. AIM OF THE STUDY: To investigate the anti-anxiety effect of GA and its underlying mechanism. METHODS: We selected the anxiety model induced by repeated chronic restraint stress (CRS) for 2 h on each of 7 consecutive days. GA (4, 20, 100 mg/kg) was injected intraperitoneally once daily for 1 week. The potential GA receptors were identified using whole-cell patches and computer-assisted docking of molecules. High-throughput RNA sequencing, adeno-associated virus-mediated gene regulation, Western blotting, and RT-qPCR were used to assess the underlying molecular pathways. RESULTS: GA alleviate depression-like and anxiety-like behaviors in CRS mice. GA decreased synaptic transmission by facilitating glutamate reuptaking in mPFC. Meanwhile, long-term GA treatment increased the expression of clock genes Per1 and Per2. Suppressing both Per1 and Per2 abolished the anxiolytic effects of GA treatment. CONCLUSION: Our study suggests that GA may be developed for the treatment of stress-induced anxiety disorders, and its mechanism is related to GLT1 and Per1/2-dependent pathways. This presents a novel approach to discovering potent therapeutic drugs.

Elucidation of the mechanism of action of ailanthone in the treatment of colorectal cancer: integration of network pharmacology, bioinformatics analysis and experimental validation.

Background: Ailanthone, a small compound derived from the bark of Ailanthus altissima (Mill.) Swingle, has several anti-tumour properties. However, the activity and mechanism of ailanthone in colorectal cancer (CRC) remain to be investigated. This study aims to comprehensively investigate the mechanism of ailanthone in the treatment of CRC by employing a combination of network pharmacology, bioinformatics analysis, and molecular biological technique. Methods: The druggability of ailanthone was examined, and its targets were identified using relevant databases. The RNA sequencing data of individuals with CRC obtained from the Cancer Genome Atlas (TCGA) database were analyzed. Utilizing the R programming language, an in-depth investigation of differentially expressed genes was carried out, and the potential target of ailanthone for anti-CRC was found. Through the integration of protein-protein interaction (PPI) network analysis, GO and KEGG enrichment studies to search for the key pathway of the action of Ailanthone. Then, by employing molecular docking verification, flow cytometry, Transwell assays, and Immunofluorescence to corroborate these discoveries. Results: Data regarding pharmacokinetic parameters and 137 target genes for ailanthone were obtained. Leveraging The Cancer Genome Atlas database, information regarding 2,551 differentially expressed genes was extracted. Subsequent analyses, encompassing protein-protein interaction network analysis, survival analysis, functional enrichment analysis, and molecular docking verification, revealed the PI3K/AKT signaling pathway as pivotal mediators of ailanthone against CRC. Additionally, the in vitro experiments indicated that ailanthone substantially affects the cell cycle, induces apoptosis in CRC cells (HCT116 and SW620 cells), and impedes the migration and invasion capabilities of these cells. Immunofluorescence staining showed that ailanthone significantly inhibited the phosphorylation of AKT protein and suppressed the activation of the PI3K/AKT signaling pathway, thereby inhibiting the proliferation and metastasis of CRC cells. Conclusion: Therefore, our findings indicate that Ailanthone exerts anti-CRC effects primarily by inhibiting the activation of the PI3K/AKT pathway. Additionally, we propose that Ailanthone holds potential as a therapeutic agent for the treatment of human CRC.

Follicle stimulating hormone controls granulosa cell glutamine synthesis to regulate ovulation.

Polycystic ovary syndrome (PCOS) is the leading cause of anovulatory infertility. Inadequate understanding of the ovulation drivers hinders PCOS intervention. Herein, we report that follicle stimulating hormone (FSH) controls follicular fluid (FF) glutamine levels to determine ovulation. Murine ovulation starts from FF-exposing granulosa cell (GC) apoptosis. FF glutamine, which decreases in pre-ovulation porcine FF, elevates in PCOS patients FF. High-glutamine chow to elevate FF glutamine inhibits mouse GC apoptosis and induces hormonal, metabolic, and morphologic PCOS traits. Mechanistically, follicle-development-driving FSH promotes GC glutamine synthesis to elevate FF glutamine, which maintain follicle wall integrity by inhibiting GC apoptosis through inactivating ASK1-JNK apoptotic pathway. FSH and glutamine inhibit the rapture of cultured murine follicles. Glutamine removal or ASK1-JNK pathway activation with metformin or AT-101 reversed PCOS traits in PCOS models that are induced with either glutamine or EsR1-KO. These suggest that glutamine, FSH, and ASK1-JNK pathway are targetable to alleviate PCOS.

Laryngopharyngeal Reflux and Benign Vocal Fold Lesions: A Systematic Review and Meta-analysis.

OBJECTIVE: There is a link between laryngopharyngeal reflux (LPR) and the formation of benign vocal fold lesions (BVFLs). However, previous studies have mainly focused on LPR suggested by symptoms and signs, rather than objectively diagnosed LPR via pharyngeal pH monitoring. We, therefore, conducted a Meta-analysis to evaluate the association between pharyngeal pH monitoring diagnosed LPR and the odds of BVFLs. DATA SOURCES: Relevant observational studies were identified by searching PubMed, Embase, Cochrane Library, and Web of Science. REVIEW METHODS: We evaluated between-study heterogeneity using the Cochrane Q test and estimated the I2 statistic. Random-effects models were used when significant heterogeneity was observed; otherwise, fixed-effects models were used. RESULTS: Thirteen datasets from 9 studies were included. Among them, 493 were diagnosed with LPR and 344 had BVFLs. LPR was related to a higher odds of BVFLs (odds ratio: 3.26, 95% confidence interval: 1.84-5.76, P < .001) with moderate heterogeneity (P for Cochrane Q test = .006, I2 = 57%). Subgroup analyses showed that the association was similar in studies with only pharyngeal pH monitoring (Restech), with double-probe or 3-site pH monitoring, and with 24-hour multichannel intraluminal impedance-pH monitoring (P for subgroup difference = .15). In addition, subgroup analysis showed consistent results in studies from Asia and Europe (P for subgroup analysis = .12), and the association seemed to be consistent for vocal Reinke's edema, nodules, and polyps (P for subgroup difference = .09). CONCLUSION: Pharyngeal pH monitoring diagnosed LPR is associated with the formation of BVFLs.

Age-adjusted D-Dimer Thresholds Combined with the Modified Wells Score as a Predictor of Lower Extremity Deep Venous Thrombosis.

BACKGROUND: Neurosurgical patients are at an increased risk of deep venous thrombosis (DVT), which, if not properly managed, can lead to pulmonary embolism. This study aimed to investigate the accuracy of age-adjusted D-dimer thresholds combined with the modified Wells score as a predictor for lower extremity DVT diagnosis. METHODS: We conducted a study among patients aged >50 years with suspected lower extremity DVT in the neurosurgery intensive care unit between December 2019 and December 2020. Receiver operating characteristic curve analysis was performed to examine the diagnostic capacity of age-adjusted D-dimer combined with the modified Wells score. RESULTS: A total of 233 participants, with an average age of 71.81 ± 12.59 years, were enrolled in the study. The mean D-dimer levels were 0.73 ± 0.39 mg/L. Among the participants, 57 (57.9%, 33 males) were diagnosed with DVT. The age-adjusted D-dimer combined with the modified Wells score had the highest area under the curve for diagnosing lower extremity DVT compared to D-dimer and age-adjusted D-dimer alone, with an AUC of 0.858. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the age-adjusted D-dimer combined with the modified Wells score for DVT diagnosis were 78.95%, 80.68%, 57%, 92.2%, and 80.26%, respectively. When analyzing subgroups, the accuracy was 79.55% for participants with cerebral hemorrhage, 81.69% for those with craniocerebral injury, 74.99% for participants with intracranial infection, and 88.89% for those with craniocerebral tumor. CONCLUSION: The combination of the age-adjusted D-dimer thresholds with the modified Wells score might effectively predict lower extremity DVT.

Effect of edible oil type on the formation of protein-bound Nε-(carboxymethyl)lysine in roasted pork patties.

Protein-bound Nε-(carboxymethyl)lysine (CML), an advanced glycation end product within meat products, poses a potential health risk to humans. The objective of this study was to explore the impact of various edible oils on the formation of protein-bound CML in roasted pork patties. Eleven commercially edible oils including lard oil, corn oil, palm oil, olive oil, flaxseed oil, blended oil, camellia oil, walnut oil, soybean oil, peanut oil, and colza oil were added to pork tenderloin mince, respectively, at a proportion of 4 % to prepare raw pork patties. The protein-bound CML contents in the pork patties were determined by HPLC-MS/MS before and after roasting at 200 °C for 20 min. The results indicated that walnut oil, flaxseed oil, colza oil, olive oil, lard oil, corn oil, blended oil, and palm oil significantly reduced the accumulation of protein-bound CML in pork patties, of which the inhibition rate was in the 24.43 %-37.96 % range. Moreover, the addition of edible oil contributed to a marginal reduction in the loss of lysine. Meanwhile, glyoxal contents in pork patties were reduced by 16.72 %-43.21 % after roasting. Other than blend oil, all the other edible oils restrained protein oxidation in pork patties to varying degrees (between 20.16 % and 61.26 %). In addition, camellia oil, walnut oil, and flaxseed oil increased TBARS values of pork patties by 2.2-8.6 times when compared to the CON group. After analyzing the fatty acid compositions of eleven edible oils, five main fatty acids (palmitic acid, stearic acid, oleic acid, linoleic acid, and linolenic acid) were selected to establish Myofibrillar protein-Glucose-fatty acids systems to simulate the roasting process. The results showed that palmitic acid, oleic acid, linoleic acid, and linolenic acid obviously mitigated the formation of myofibrillar protein-bound CML, exhibiting suppression rates ranging from 10.38 % to 40.32 %. In conclusion, the addition of specific edible oil may curb protein-bound CML production in roasted pork patty by restraining protein or lipid oxidation, reducing lysine loss, and suppressing glyoxal production, which may be attributed to the fatty acid compositions of edible oils. This finding provides valuable guidance for the selection of healthy roasting oils in the thermal processing of meat products.

Optimizing noble gas pressure for enhanced self-compensation in spin-exchange relaxation-free comagnetometers.

The coupling of electron spin and nuclear spin through spin-exchange collisions compensates for external magnetic field interference in the spin-exchange relaxation-free (SERF) comagnetometer. However, the compensation ability for magnetic field interference along the detection axis is limited due to the presence of nuclear spin relaxation. This paper aims to enhance the self-compensation capability of the system by optimizing the pressure of the noble gas during cell filling. Models are established to describe the relationships between the nuclear spin polarization, the polarizing magnetic field of nuclei, the magnetic field suppression factors, and the pressure of the noble gas in the K-Rb-21Ne atomic ensemble. Experiments are conducted using five cells with different pressure. The results indicate that in the positive pressure area, the nuclear spin polarization decreases while the equivalent magnetic field experienced by the noble gas increases with increasing pressure. The magnetic field suppression factor for transverse fields increases as the pressure increases, leading to a decrease in the ability to suppress low-frequency magnetic field interference. Moreover, at the cell temperature of 180°C and a transverse residual field gradient of 4.012 nT/cm, the system exhibits its strongest capability to suppress transverse magnetic field interference when the pressure of 21Ne is around 0.7 atm.

Telmisartan inhibits microglia-induced neurotoxic A1 astrocyte conversion via PPARγ-mediated NF-κB/p65 degradation.

Astrocytes are crucially involved in neuroinflammation. Activated astrocytes exhibit at least two phenotypes, A1 (neurotoxic) and A2 (neuroprotective). The A1 phenotype is the major reactive astrocyte phenotype involved in aging and neurodegenerative diseases. Telmisartan, which is an antihypertensive agent, is a promising neuroprotective agent. This study aimed to investigate the effects of telmisartan on the phenotype of reactive astrocytes. Astrocytes were activated by culturing with the conditioned medium derived from lipopolysaccharide-stimulated microglia. This conditioned medium induced early, transient A2 astrocyte conversion (within 24 h) and late, sustained A1 conversion (beginning at 24 h and lasting up to 7 days), with a concomitant increase in the production of pro-inflammatory cytokines (interleukin [IL]-1ß, tumor necrosis factor [TNF]α, and IL-6) and phosphorylation of nuclear factor-κB (NF-κB)/p65. Telmisartan treatment promoted and inhibited A2 and A1 conversion, respectively. Telmisartan reduced total and phosphorylated p65 protein levels. Losartan, a specific angiotensin II type-1 receptor (AT1R) blocker, did not influence the reactive state of astrocytes. Additionally, AT1R activation by angiotensin II did not induce the expression of pro-inflammatory cytokines and A1/A2 markers, indicating that the AT1R signaling pathway is not involved in the astrocyte-mediated inflammatory response. A peroxisome proliferator-activated receptor γ (PPARγ) antagonist reversed the effects of telmisartan. Moreover, telmisartan-induced p65 downregulation was reversed by the proteasome inhibitor MG132. These results indicate that telmisartan suppresses activated microglia-induced neurotoxic A1 astrocyte conversion through p65 degradation. Our findings contribute towards the elucidation of the anti-inflammatory activity of telmisartan in brain disorders.

Improvements of the Tada formula in estimating the intracerebral hemorrhage volume based on computed tomography.

Background: The Tada formula has been used widely for assessing intracerebral hemorrhage (ICH) volume. However, it is only suitable for calculating regular and small volume hematomas. Therefore, we attempted to improve the formula to increase its accuracy and maintain its efficiency. Methods: Computed tomography (CT) data of 15 balls of different shapes filled with predetermined volumes of water were collected to verify the high accuracy of FireVoxel in measuring the volume. CT data from 329 patients with ICH from two different hospitals grouped by hematoma shape and volume were retrospectively reviewed. The distinctly shaped ICH volumes of 245 patients from one of the hospitals were estimated using FireVoxel and the Tada formula grouped by the hematoma shape and volume. Taking the hematoma volumes measured by FireVoxel as the reference standard, the accuracy and reliability of the Tada formula were evaluated. Polynomial fitting was employed to determine the associations of the values calculated between the Tada formula and FireVoxel. Then, a corrected Tada formula (C-Tada formula) was produced, and the limits of agreement between the C-Tada formula and Tada formula were analyzed with Bland-Altman analysis. The C-Tada formula was validated by the CT data of 84 patients from another hospital. Results: The volume measured by FireVoxel can be set as the reference standard. The ICH volume calculated by the Tada formula was significantly greater than that calculated by FireVoxel for different shapes and volumes. The percentage deviation between the volumes calculated by FireVoxel and the Tada formula was also statistically significant and influenced by ICH shape and volume. The limits of agreement between the C-Tada formula and FireVoxel were tighter than those between the Tada formula and FireVoxel. The percentage deviation of the C-Tada formula calculation from the FireVoxel estimate was greatly reduced relative to that for the Tada formula for each group. Conclusions: The C-Tada formula is more clinically valuable than the Tada formula, given its sufficient efficiency and greater accuracy and reliability in ICH volume calculation.

Rapid recognition and targeted isolation of potential anti-breast cancer xanthones in Hypericum bellum Li by "seed" mass spectra-based molecular networking and in silico MS/MS fragmentation.

INSTRUCTION: Hypericum bellum Li is rich in xanthones with various bioactivities, especially in anti-breast cancer. While the scarcity of mass spectral data of xanthones in Global Natural Products Social Molecular Networking (GNPS) libraries have challenged the rapid recognition of xanthones with similar structures. OBJECTIVE: This study is aimed to enhance the molecular networking (MN)-based dereplication and visualisation ability of potential anti-breast cancer xanthones from H. bellum to overcome the scarcity of xanthones mass spectral data in GNPS libraries. Separating and purifying the MN-screening bioactive xanthones to verify the practicality and accuracy of this rapid recognition strategy. METHODOLOGY: A combined strategy of "seed" mass spectra-based MN, in silico annotation tools, substructure identification tools, reverse molecular docking, ADMET screening, molecular dynamics (MDs) simulation experiments, and an MN-oriented separation procedure was first introduced to facilitate the rapid recognition and targeted isolation of potential anti-breast cancer xanthones in H. bellum. RESULTS: A total of 41 xanthones could only be tentatively identified. Among them, eight xanthones were screened to have potential anti-breast cancer activities, and six xanthones that were initially reported in H. bellum were obtained and verified to have good binding abilities with their paired targets. CONCLUSION: This is a successful case study that validated the application of "seed" mass spectral data could overcome the drawbacks of GNPS libraries with limited mass spectra and enhance the accuracy and visualisation of natural products (NPs) dereplication, and this rapid recognition and targeted isolation strategy can be also applicable for other types of NPs.

GLP-1 receptor agonists for the treatment of obesity: Role as a promising approach.

Obesity is a complex disease characterized by excessive fat accumulation which is caused by genetic, environmental and other factors. In recent years, there has been an increase in the morbidity, disability rate,and mortality due to obesity, making it great threat to people's health and lives, and increasing public health care expenses. Evidence from previous studies show that weight loss can significantly reduce the risk of obesity-related complications and chronic diseases. Diet control, moderate exercise, behavior modification programs, bariatric surgery and prescription drug treatment are the major interventions used to help people lose weight. Among them, anti-obesity drugs have high compliance rates and cause noticeable short-term effects in reducing obese levels. However, given the safety or effectiveness concerns of anti-obesity drugs, many of the currently used drugs have limited clinical use. Glucagon-like peptide-1 receptor (GLP-1R) agonists are a group of drugs that targets incretin hormone action, and its receptors are widely distributed in nerves, islets, heart, lung, skin, and other organs. Several animal experiments and clinical trials have demonstrated that GLP-1R agonists are more effective in treating or preventing obesity. Therefore, GLP-1R agonists are promising agents for the treatment of obese individuals. This review describes evidence from previous research on the effects of GLP-1R agonists on obesity. We anticipate that this review will generate data that will help biomedical researchers or clinical workers develop obesity treatments based on GLP-1R agonists.

Upregulation of Formaldehyde in Parkinson's Disease Found by a Near-Infrared Lysosome-Targeted Fluorescent Probe.

Parkinson's disease (PD) is one of the major neurodegenerative diseases caused by complex pathological processes. As a signal molecule, formaldehyde is closely linked to nervous systems, but the relationship between PD and formaldehyde levels remains largely unclear. We speculated that formaldehyde might be a potential biomarker for PD. To prove it, we constructed the first near-infrared (NIR) lysosome-targeted formaldehyde fluorescent probe (named NIR-Lyso-FA) to explore the relationship between formaldehyde and PD. The novel fluorescent probe achieves formaldehyde detection in vitro and in vivo, thanks to its excellent properties such as NIR emission, large Stokes shift, and fast response to formaldehyde. Crucially, utilizing the novel probe NIR-Lyso-FA, formaldehyde overexpression was discovered for the first time in cellular, zebrafish, and mouse PD models, supporting our guess that formaldehyde can function as a possible biomarker for PD. We anticipate that this finding will offer insightful information for PD pathophysiology, diagnosis, medication development, and treatment.

Omnifarious fruit polyphenols: an omnipotent strategy to prevent and intervene diabetes and related complication?

Diabetes mellitus is a metabolic syndrome which cannot be cured. Recently, considerable interest has been focused on food ingredients to prevent and intervene in complications of diabetes. Polyphenolic compounds are one of the bioactive phytochemical constituents with various biological activities, which have drawn increasing interest in human health. Fruits are part of the polyphenol sources in daily food consumption. Fruit-derived polyphenols possess the anti-diabetic activity that has already been proved either from in vitro studies or in vivo studies. The mechanisms of fruit polyphenols in treating diabetes and related complications are under discussion. This is a comprehensive review on polyphenols from the edible parts of fruits, including those from citrus, berries, apples, cherries, mangoes, mangosteens, pomegranates, and other fruits regarding their potential benefits in preventing and treating diabetes mellitus. The signal pathways of characteristic polyphenols derived from fruits in reducing high blood glucose and intervening hyperglycemia-induced diabetic complications were summarized.

Vancomycin Pretreatment on MPTP-Induced Parkinson's Disease Mice Exerts Neuroprotection by Suppressing Inflammation Both in Brain and Gut.

A growing body of evidence implies that gut microbiota was involved in pathogenesis of Parkinson's disease (PD), but the mechanism is still unclear. The aim of this study is to investigate the effects of antibiotics pretreatment on the 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced PD mice. In this study, vancomycin pretreatment was given by gavage once daily with either vancomycin or distilled water for 14 days to mice, then mice were administered with MPTP (20 mg/kg, i.p) for four times in one day to establish an acute PD model. Results show that vancomycin pretreatment significantly improved motor dysfunction of mice in pole and traction tests. Although vancomycin pretreatment had no effect on dopamine (DA) or the process of DA synthesis, it inhibited the metabolism of DA by suppressing the expression of striatal monoamine oxidase B (MAO-B). Furthermore, vancomycin pretreatment reduced the number of astrocytes and microglial cells in the substantia nigra pars compacta (SNpc) to alleviate neuroinflammation, decreased the expression of TLR4/MyD88/NF-κB/TNF-α signaling pathway in both brain and gut. Meanwhile, vancomycin pretreatment changed gut microbiome composition and the levels of fecal short chain fatty acids (SCFAs). The abundance of Akkermansia and Blautia increased significantly after vancomycin pretreatment, which might be related to inflammation and inhibition of TLR4 signaling pathway. In summary, these results demonstrate that the variation of gut microbiota and its metabolites induced by vancomycin pretreatment might decrease dopamine metabolic rate and relieve inflammation in both gut and brain via the microbiota-gut-brain axis in MPTP-induced PD mice. The neuroprotection of vancomycin pretreatment on MPTP-induced Parkinson's disease mice The alterations of gut microbiota and SCFAs induced by vancomycin pretreatment might not only improve motor dysfunction, but also decrease dopamine metabolism and relieve inflammation in both brain and gut via TLR4/MyD88/NF-κB/TNF-α pathway in MPTP-induced PD mice.

Tripartite motif containing 23 functions as a critical regulator in macrophages to control the pathological feature of diabetic nephropathy.

BACKGROUND: Diabetic nephropathy (DN) is a kidney disease resulting from diabetes. Macrophages and macrophage-mediated inflammation contributed to the development of DN. Tripartite motif containing 23 (TRIM23) is E3 ligase and has been involved in inflammation. Until now, the precise roles of TRIM23 in DN are not described yet. Therefore, we evaluated the functions of TRIM23 in DN. METHODS: We generated mice with TRIM23 deficiency in macrophages. We also established diabetic mice model. The expression of TRIM23 was measured in diabetic animals. The DN symptoms were compared between diabetic wild-type (WT) mice and TRIM23 conditional knock out mice. The cytokine expression, ubiquitination of TAB2, and interactions between TAB2 and IKK were compared in oxidized low-density lipoprotein (oxLDL) or lipopolysaccharides (LPS)-treated WT and TRIM23-deficient macrophages. RESULTS: Upregulation of TRIM23 was observed in diabetic mice and LPS or oxLDL-treated macrophages. Diabetic mice with TRIM23 deficiency in macrophages had attenuated DN symptoms. TRIM23-deficient macrophages had decreased pro-inflammatory cytokines production after oxLDL or LPS stimulation. TRIM23 was predicted to interact with TAB2. The ubiquitination of TAB2 was abolished in oxLDL-treated TRIM23-deficient macrophages, which correlated with decreased activation of IKK. CONCLUSION: TRIM23 regulates inflammation in macrophages and plays important role in DN.

Canonical transient receptor potential channel 1 aggravates myocardial ischemia-and-reperfusion injury by upregulating reactive oxygen species.

The canonical transient receptor potential channel (TRPC) proteins form Ca2+-permeable cation channels that are involved in various heart diseases. However, the roles of specific TRPC proteins in myocardial ischemia/reperfusion (I/R) injury remain poorly understood. We observed that TRPC1 and TRPC6 were highly expressed in the area at risk (AAR) in a coronary artery ligation induced I/R model. Trpc1-/- mice exhibited improved cardiac function, lower serum Troponin T and serum creatine kinase level, smaller infarct volume, less fibrotic scars, and fewer apoptotic cells after myocardial-I/R than wild-type or Trpc6-/- mice. Cardiomyocyte-specific knockdown of Trpc1 using adeno-associated virus 9 mitigated myocardial I/R injury. Furthermore, Trpc1 deficiency protected adult mouse ventricular myocytes (AMVMs) and HL-1 cells from death during hypoxia/reoxygenation (H/R) injury. RNA-sequencing-based transcriptome analysis revealed differential expression of genes related to reactive oxygen species (ROS) generation in Trpc1-/- cardiomyocytes. Among these genes, oxoglutarate dehydrogenase-like (Ogdhl) was markedly downregulated. Moreover, Trpc1 deficiency impaired the calcineurin (CaN)/nuclear factor-kappa B (NF-κB) signaling pathway in AMVMs. Suppression of this pathway inhibited Ogdhl upregulation and ROS generation in HL-1 cells under H/R conditions. Chromatin immunoprecipitation assays confirmed NF-κB binding to the Ogdhl promoter. The cardioprotective effect of Trpc1 deficiency was canceled out by overexpression of NF-κB and Ogdhl in cardiomyocytes. In conclusion, our findings reveal that TRPC1 is upregulated in the AAR following myocardial I/R, leading to increased Ca2+ influx into associated cardiomyocytes. Subsequently, this upregulates Ogdhl expression through the CaN/NF-κB signaling pathway, ultimately exacerbating ROS production and aggravating myocardial I/R injury.

Prognostic Value of Systemic Immune-Inflammation Index (SII) in Patients with Glioblastoma: A Comprehensive Study Based on Meta-Analysis and Retrospective Single-Center Analysis.

Inflammation is related to cancer. The systemic immune-inflammation index (SII) has been linked to the prognosis of many types of cancer. The present study aimed to determine the prognostic value of the SII in glioblastoma (GBM) patients based on meta-analysis and single-center retrospective analysis. Relevant publications published before 1 October 2022 were identified by searching PubMed, EMBASE, Cochrane Library databases, and Web of Science. Moreover, 208 GBM patients from Zhongnan Hospital were incorporated. Kaplan−Meier and Cox regression analyses determined the prognostic significance of inflammatory markers. By combining these indicators, we developed scoring systems. Nomograms were also built by incorporating independent variables. The accuracies of nomograms were evaluated by Harrell's concordance index (c-index) and the calibration curve. According to meta-analysis, an elevated SII predicted the worst overall survival (OS) (Hazard ratio [HR] = 1.87, p < 0.001). Furthermore, a higher SII (>510.8) (HR = 1.782, p = 0.007) also predicted a poorer outcome in a retrospective cohort. The scoring systems of SII-NLR (neutrophil-to-lymphocyte ratio) showed the best predictive power for OS. The nomogram without MGMT (c-index = 0.843) exhibited a similar accuracy to that with MGMT (c-index = 0.848). A pre-treatment SII is independently associated with OS in GBM. A nomogram integrating the SII-NLR score may facilitate a comprehensive survival evaluation independent of molecular tests in GBM.

Association of dietary meat consumption habits with neurodegenerative cognitive impairment: an updated systematic review and dose-response meta-analysis of 24 prospective cohort studies.

The association between dietary meat consumption habits and neurodegenerative cognitive impairment (NCI) has been made but recent studies have reported controversial results. Herein, we have systematically explored associations between meat consumption and NCI risk. PubMed, Embase, and MEDLINE databases were explored for data sources of primary studies. Twenty-four prospective cohort studies that met the selection criteria, involving over 500 000 participants from 11 countries, were included. Relative risks (RRs) were pooled using random-effects model meta-analysis, and a dose-response analysis was conducted using a 2-stage generalized least-squares trend program. The results showed that total meat (RRs 1.14; 95% CI: 1.04-1.24), fish (RRs 0.87; 95% CI: 0.78-0.98), and poultry (RRs 0.88; 95% CI: 0.80-0.98) intake was significantly associated with NCI risk but red meat (RRs 1.03; 95% CI: 0.92-1.16) showed a non-significant association. Subgroup analysis further demonstrated a significant association between total meat consumption and the risk of NCI, especially for total processed meat (RRs 1.67; 95% CI, 1.46-1.92) and processed red meat (RRs 1.22; 95% CI, 1.11-1.34). Each additional 50 g day-1 intake of total meat (RRs 1.03; 95% CI: 1.00-1.05) and processed meat (RRs 1.12; 95% CI: 1.08-1.17) increased the risk of NCI. In contrast, a 50 g day-1 increment of fish (RRs 0.97; 95% CI: 0.94-0.99) and poultry (RRs 0.948; 95% CI: 0.90-0.99) intake was associated with lower NCI risk. This study provided evidence for further understanding the relationship between the type and amount of meat intake and the occurrence of NCI.