Rational design of multifunctional hydrogels targeting the microenvironment of diabetic periodontitis.

Periodontitis is a chronic inflammatory disease and is the primary contributor to adult tooth loss. Diabetes exacerbates periodontitis, accelerates periodontal bone resorption. Thus, effectively managing periodontitis in individuals with diabetes is a long-standing challenge. This review introduces the etiology and pathogenesis of periodontitis, and analyzes the bidirectional relationship between diabetes and periodontitis. In this review, we comprehensively summarize the four pathological microenvironments influenced by diabetic periodontitis: high glucose microenvironment, bacterial infection microenvironment, inflammatory microenvironment, and bone loss microenvironment. The hydrogel design strategies and latest research development tailored to the four microenvironments of diabetic periodontitis are mainly focused on. Finally, the challenges and potential solutions in the treatment of diabetic periodontitis are discussed. We believe this review will be helpful for researchers seeking novel avenues in the treatment of diabetic periodontitis.

Inflammation assessment and therapeutic monitoring based on highly sensitive and multi-level electrochemical detection of PGE2.

Prostaglandin E2 (PGE2), an eicosane, regulates the physiological activity of inflammatory cells and represents a potential therapeutic target for facilitating tissue repair in vivo. In our work, an electrochemical immunosensor employing Ketjen black-Au nanoparticles (KB-Au) and poly tannic acid nanospheres conjugated with anti-PGE2 polyclonal antibody (PTAN-Ab) was designed to ultra-sensitively analyze PGE2 levels secreted by living cells and tissues. Antibody assembly strategies were explored to achieve signal amplification. Moreover, we studied the therapy effects of docosahexaenoic acid (DHA), arachidonic acid (AA), hyaluronic acid (HA), and small molecule 15-hydroxyprostaglandin dehydrogenase inhibitor (SW033291) on inflammation and evaluated the protective functions of HA and SW033291 in a murine model subjected to colitis induced by dextran sulfate sodium (DSS) using the developed sensor. The sensor exhibited a linear range of 10-5-106 fg/mL and a detection limit (LOD) of 10-5 fg/mL. Fetal bovine serum (FBS) samples were used to achieve high recovery of target analytes. This study not only presents an effective strategy for ultra-sensitively monitoring PGE2 but also provides valuable insights into assessing the degree of inflammation and the therapeutic effect of related drugs. Research on human health monitoring and regenerative medicine could greatly benefit from the findings.

Adrenalectomy for primary aldosteronism and its related surgical characteristics.

Primary aldosteronism (PA) is a common cause of secondary hypertension. Adrenalectomy is an effective treatment for unilateral PA, particularly aldosterone-producing adenoma (APA), resulting in improvements in biochemical parameters and blood pressure in the vast majority of patients. The article provides a comprehensive overview of PA, focusing on the outcomes of adrenalectomy for PA and the factors that may suggest prognostic implications. Analysis of the outcome of different PA patients undergoing adrenalectomy in terms of preoperative factors, vascular and adipose conditions, type of pathology, and somatic variants. In addition, it is recommended to use the histopathology of primary aldosteronism (HISTALDO) consensus to classify the patient's pathological type, with classical and nonclassical pathological types showing a different prognosis and possibly being associated with an unresected contralateral adrenal gland. The primary aldosteronism surgical outcome (PASO) consensus sets uniform standards for postoperative outcomes in unilateral PA, but its setting of thresholds remains controversial. Partial adrenalectomy shows similar surgical results and fewer postoperative complications than total adrenalectomy, but there is a risk of missing the true source of abnormal aldosterone secretion. Steroid profiling and functional imaging techniques offer alternative options to adrenal vein sampling (AVS) for unilateral and bilateral judgments in patients with PA. A combination of factors is needed to predict the prognosis of PA patients undergoing adrenalectomy in order to manage patient expectations of the outcome of the procedure and to closely monitor blood pressure and biochemical parameters in patients who suggest a poorer prognosis.

Clinical and cytological characteristics of serous effusions in 69 cases of lymphoma patients.

BACKGROUND: To explore the value of cell morphology, immunophenotype, and gene alterations of serosal effusion in the diagnosis of lymphoma. METHODS: Serosal effusion of 69 cases of lymphoma patients were collected, including 36 cases with malignant effusion and 33 cases with nonmalignant effusion. Ordinary cytology, liquid-based cytology, cellblock, and immunocytochemical staining were performed in each case, some cases were detected by fluorescence in situ hybridization for C-MYC, BCL2, and BCL6 gene translocations. T/B cell ratio in malignant and nonmalignant serosal effusions was analyzed and compared by flow cytometry (FCM) and immunohistochemical (IHC), respectively. The prognostic value of serous effusion in diffuse large B-cell lymphoma (DLBCL) was investigated and another 20 DLBCL cases without effusion were successively selected as control. RESULTS: The number of naive lymphocytes, apoptotic bodies, and mitotic figures were more common in malignant effusions compared with nonmalignant effusions (p < .01). The top three lymphomas in malignant effusion were DLBCL (19/36, 52.8%), mantle cell lymphoma (MCL) (4/36, 11.1%, 3 blastoid variant) and high-grade B-cell lymphoma (HGBL) (4/36, 11.1%). T/B cell ratio by FCM analysis ranged from 0.00 to 0.55 (mean 0.084) in malignant effusion, and 2.58 to 984.00 (mean 249.9) in nonmalignant effusion. The difference was significant (p = .017). The T/B cell ratio by IHC analysis ranged from 0.02 to 3.00 (mean 0.200) in malignant effusion, and 2.00-100.00 (mean 34.10) in nonmalignant effusion. The difference was significant (p = .017). In the effusions involving DLBCL, most effusions were present at the time of diagnosis (57.9%); single pleural effusions were more common (36.8%). The median overall survival times of patients with malignant effusion, nonmalignant effusion and DLBCL without serous effusion were 11, 17, and 23 months respectively (p = .04). Three patients of HGBL died, and the overall survival times were 5, 8, and 9 months, respectively. CONCLUSIONS: The cytomorphological characteristics combined with immunophenotype, FCM, gene rearrangement, and other tests can diagnose and classify patients with effusion as the first symptom. The T/B cell ratio is less than 1 by FCM or IHC suggesting a malignant serosal effusion. The presence of malignant effusion in DLBCL patients is an important clue for poor prognosis.

Diagnostic value of contrast-enhanced ultrasound and shear-wave elastography for small breast nodules.

Background: The study aims to evaluate the diagnostic efficacy of contrast-enhanced ultrasound (CEUS) and shear-wave elastography (SWE) in detecting small malignant breast nodules in an effort to inform further refinements of the Breast Imaging Reporting and Data System (BI-RADS) classification system. Methods: This study retrospectively analyzed patients with breast nodules who underwent conventional ultrasound, CEUS, and SWE at Gongli Hospital from November 2015 to December 2019. The inclusion criteria were nodules ≤ 2 cm in diameter with pathological outcomes determined by biopsy, no prior treatments, and solid or predominantly solid nodules. The exclusion criteria included pregnancy or lactation and low-quality images. Imaging features were detailed and classified per BI-RADS. Diagnostic accuracy was assessed using receiver operating characteristic curves. Results: The study included 302 patients with 305 breast nodules, 113 of which were malignant. The diagnostic accuracy was significantly improved by combining the BI-RADS classification with CEUS and SWE. The combined approach yielded a sensitivity of 88.5%, specificity of 87.0%, positive predictive value of 80.0%, negative predictive value of 92.8%, and accuracy of 87.5% with an area under the curve of 0.877. Notably, 55.8% of BI-RADS 4A nodules were downgraded to BI-RADS 3 and confirmed as benign after pathological examination, suggesting the potential to avoid unnecessary biopsies. Conclusion: The integrated use of the BI-RADS classification, CEUS, and SWE enhances the accuracy of differentiating benign and malignant small breast nodule, potentially reducing the need for unnecessary biopsies.

Differential gene expression and gut microbiota composition in low-altitude and high-altitude goats.

Previous studies have presented evidence suggesting that altitude exerts detrimental effects on reproductive processes, yet the underlying mechanism remains elusive. Our study employed two distinct goat breeds inhabiting low and high altitudes, and conducted a comparative analysis of mRNA profiles in testis tissues and the composition of gut microbiota. The results revealed a reduced testis size in high-altitude goats. RNA-seq analysis identified the presence of 214 differentially expressed genes (DEGs) in the testis. These DEGs resulted in a weakened immunosuppressive effect, ultimately impairing spermatogenesis in high-altitude goats. Additionally, 16S rDNA amplicon sequencing recognized statistically significant variations in the abundance of the genera Treponema, unidentified_Oscillospiraceae, Desulfovibrio, Butyricicoccus, Dorea, Parabacteroides between the two groups. The collective evidence demonstrated the gut and testis played a synergistic role in causing decreased fertility at high altitudes. Our research provides a theoretical basis for future investigations into the reproductive fitness of male goats.

Drug-coated balloon angioplasty with provisional stenting versus primary stenting for the treatment of de novo coronary artery lesions: REC-CAGEFREE I trial rationale and design.

BACKGROUND: Percutaneous coronary intervention (PCI) with primary stenting, which stands for stent implantation regardless of obtaining satisfactory results with balloon angioplasty, has superseded conventional plain old balloon angioplasty with provisional stenting. With drug-coated balloon (DCB), primary DCB angioplasty with provisional stenting has shown non-inferiority to primary stenting for de novo coronary small vessel disease. However, the long-term efficacy and safety of such a strategy to the primary stenting on clinical endpoints in de novo lesions without vessel diameter restrictions remain uncertain. STUDY DESIGN: The REC-CAGEFREE I is an investigator-initiated, multicenter, randomized, open-label trial aimed to enroll 2270 patients with acute or chronic coronary syndrome from 43 interventional cardiology centers in China to evaluate the non-inferiority of primary paclitaxel-coated balloons angioplasty to primary stenting for the treatment of de novo, non-complex lesions without vessel diameter restrictions. Patients who fulfill all the inclusion and exclusion criteria and have achieved a successful lesion pre-dilatation will be randomly assigned to the two arms in a 1:1 ratio. Protocol-guided DCB angioplasty and bailout stenting after unsatisfactory angioplasty are mandatory in the primary DCB angioplasty group. The second-generation sirolimus-eluting stent will be used as a bailout stent in the primary DCB angioplasty group and the treatment device in the primary stenting group. The primary endpoint is the incidence of Device-oriented Composite Endpoint (DoCE) within 24 months after randomization, including cardiac death, target vessel myocardial infarction, and clinically and physiologically indicated target lesion revascularization. DISCUSSION: The ongoing REC-CAGEFREE I trial is the first randomized trial with a clinical endpoint to assess the efficacy and safety of primary DCB angioplasty for the treatment of de novo, non-complex lesions without vessel diameter restrictions. If non-inferiority is shown, PCI with primary DCB angioplasty could be an alternative treatment option to primary stenting. TRIAL REGISTRATION: Registered on clinicaltrial.gov (NCT04561739).

Biointerface-Engineered Hybrid Nanovesicles for Targeted Reprogramming of Tumor Microenvironment.

The tumor microenvironment (TME) of typical tumor types such as triple-negative breast cancer is featured by hypoxia and immunosuppression with abundant tumor-associated macrophages (TAMs), which also emerge as potential therapeutic targets for antitumor therapy. M1-like macrophage-derived exosomes (M1-Exos) have emerged as a promising tumor therapeutic candidate for their tumor-targeting and macrophage-polarization capabilities. However, the limited drug-loading efficiency and stability of M1-Exos have hindered their effectiveness in antitumor applications. Here, a hybrid nanovesicle is developed by integrating M1-Exos with AS1411 aptamer-conjugated liposomes (AApt-Lips), termed M1E/AALs. The obtained M1E/AALs are loaded with perfluorotributylamine (PFTBA) and IR780, as P-I, to construct P-I@M1E/AALs for reprogramming TME by alleviating tumor hypoxia and engineering TAMs. P-I@M1E/AAL-mediated tumor therapy enhances the in situ generation of reactive oxygen species, repolarizes TAMs toward an antitumor phenotype, and promotes the infiltration of T lymphocytes. The synergistic antitumor therapy based on P-I@M1E/AALs significantly suppresses tumor growth and prolongs the survival of 4T1-tumor-bearing mice. By integrating multiple treatment modalities, P-I@M1E/AAL nanoplatform demonstrates a promising therapeutic approach for overcoming hypoxic and immunosuppressive TME by targeted TAM reprogramming and enhanced tumor photodynamic immunotherapy. This study highlights an innovative TAM-engineering hybrid nanovesicle platform for the treatment of tumors characterized by hypoxic and immunosuppressive TME.

Subcutaneous implantation after endoscopic and traditional thyroid surgery: a retrospective case report.

Subcutaneous implantation is an unexpected complication of thyroid surgery. Our study aimed to analyze the clinical features and outcomes of implantation after thyroid surgery. We retrospectively searched for the patients with implants of thyroid tumor after surgery from our database prior to August 2023. The clinical and pathological data were reviewed. Six female patients with a mean age of 33.6 ± 13.3 years were enrolled in this study. There was a rare case with mucinous adenocarcinoma, three follicular thyroid carcinoma, and two papillary thyroid carcinoma. The case with primary enteric adenocarcinoma of thyroid with subcutaneous implantation was first reported. The patient with mucinous adenocarcinoma received six courses of TP regimen chemotherapy. Five cases received radioactive iodine therapy. After a mean of 69.5 months of follow-up, one case recurred in the lateral region, and no metastasis or recurrence happened in the other five cases. Although the implantation after thyroid surgery is uncommon, the cases serve as a reminder to take greater care to avoid implantation.

Shootin1 Regulates Retinal Ganglion Cell Neurite Development: Insights From an RGC Direct Somatic Cell Reprogramming Model.

Purpose: Retinal ganglion cells (RGCs) connect the retina to the brain. Proper development of the axons and dendrites of RGCs is the basis for these cells to function as projection neurons to deliver visual information to the brain. The purpose of this study was to investigate the function of Shtn1 (which encodes shootin1) in RGC neurite development. Methods: Immunofluorescence (IF) was used to characterize the expression pattern of marker genes. An in vitro direct somatic cell reprogramming system was used to generate RGC-like neurons (iRGCs), which was subsequently used to study the function of Shtn1. Short-hairpin RNAs (shRNAs) were used to knock down Shtn1, and the coding sequence (CDS) of Shtn1 was used to overexpress the gene. Lentiviruses were used to deliver shRNAs or CDSs into iRGCs. The patch clamp technique was used to measure the electrophysiological properties of the iRGCs. RNA sequencing (RNA-seq) was used to examine transcriptome expression. Results: Using IF, we demonstrated that shootin1 is distinctively expressed in RGCs during the period in which RGCs actively develop and adjust the connections of their neurites with upstream and downstream neurons. Using the iRGC system, we demonstrated that Shtn1 promotes the growth and complexity of neurites and thus the electrophysiological maturation, of iRGCs. RNA-seq analyses showed that Shtn1 may also regulate gene expression and neurogenesis in iRGCs. Conclusions: Shtn1 promotes RGC neurite development. These findings improve our understanding of the molecular machinery governing RGC neurite development and may help to optimize future RGC regeneration methods.

Self-Assembly of Strain-Adaptable Surface-Enhanced Raman Scattering Substrate on Polydimethylsiloxane Nanowrinkles.

Flexible surface-enhanced Raman scattering (SERS) substrates adaptable to strains enable effective sampling from irregular surfaces, but the preparation of highly stable and sensitive flexible SERS substrates is still challenging. This paper reports a method to fabricate a high-performance strain-adaptable SERS substrate by self-assembly of Au nanoparticles (AuNPs) on polydimethylsiloxane (PDMS) nanowrinkles. Nanowrinkles are created on prestrained PDMS slabs by plasma-induced oxidation followed by the release of the prestrain, and self-assembled AuNPs are transferred onto the nanowrinkles to construct the high-performance SERS substrate. The results show that the nanowrinkled structure can improve the surface roughness and enhance the SERS signals by ∼4 times compared to that of the SERS substrate prepared on flat PDMS substrates. The proposed SERS substrate also shows good adaptability to dynamic bending up to ∼|0.4| 1/cm with excellent testing reproducibility. Phenolic pollutants, including aniline and catechol, were quantitatively tested by the SERS substrate. The self-assembled flexible SERS substrate proposed here provides a powerful tool for chemical analysis in the fields of environmental monitoring and food safety inspection.

Effects of myricetin and its derivatives on nonenzymatic glycation: A mechanism study based on proteomic modification and fluorescence spectroscopy analysis.

Myricetin and its derivatives, myricitrin and dihydromyricetin, are flavonoids widely presented in foods and phytomedicine that possess tremendous health potential. In this study, we compared the antiglycation activity of myricetin and its derivatives, then investigated the underlying mechanism using proteomic modification and fluorescence spectroscopy analysis. All three compounds exhibited thorough inhibition on nonenzymatic glycation process, with the inhibitory effects on AGEs reaching 85% at 40 µmol/L. They effectively protected bovine serum albumin (BSA) structure by inhibiting protein oxidation, preventing the conversion from α-helix to ß-sheet, and reducing amyloid-like cross-ß structure formation. Among the three compounds, myricetin showed a predominant antiglycation activity. Proteomic analysis identified the early glycated sites that were protected by myricetin, including lysine K235, 256, 336, 421, 420, 489, etc. Additionally, fluorescence spectroscopy revealed spontaneous interactions between BSA and myricetin. Overall, myricetin holds promise as an antiglycation agent in both the food and drug industries.

Environmental monobutyl phthalate exposure promotes liver cancer via reprogrammed cholesterol metabolism and activation of the IRE1α-XBP1s pathway.

Humans are widely exposed to phthalates, a major chemical plasticizer that accumulates in the liver. However, little is known about the impact of chronic phthalate exposure on liver cancer development. In this study, we applied a long-term cell culture model by treating the liver cancer cell HepG2 and normal hepatocyte L02 to environmental dosage of monobutyl phthalate (MBP), the main metabolite of phthalates. Interestingly, we found that long-term MBP exposure significantly accelerated the growth of HepG2 cells in vitro and in vivo, but barely altered the function of L02 cells. MBP exposure triggered reprogramming of lipid metabolism in HepG2 cells, where cholesterol accumulation subsequently activated the IRE1α-XBP1s axis of the unfolded protein response. As a result, the XBP1s-regulated gene sets and pathways contributed to the increased aggressiveness of HepG2 cells. In addition, we also showed that MBP-induced cholesterol accumulation fostered an immunosuppressive microenvironment by promoting tumor-associated macrophage polarization toward the M2 type. Together, these results suggest that environmental phthalates exposure may facilitate liver cancer progression, and alerts phthalates exposure to patients who already harbor liver tumors.

Patent Foramen Ovale in Children: A Review of Recent Progress.

The support has been provided by clinical trials and guidelines for managing patent foramen ovale (PFO) in adults; however, the optimal approach is still unclear for treating PFO in pediatric patients. PFO and its associated clinical syndromes, imaging diagnosis, and management in pediatric patients were analyzed by a comprehensive analysis. Extensive research was performed using electronic databases, including PubMed, Cochrane, Web of Science, and EMBASE. This review includes the studies published until February 1st, 2024. A total of 583 articles were obtained, of which 54 were included in the comprehensive review. Numerous evidences have indicated that a right-to-left shunt through a PFO may be involved in cryptogenic stroke in children, although the connection between migraine and aura has not been substantiated by robust evidence. Children with sickle cell disease and a PFO were at higher risks of paradoxical embolization, rare syndromes caused by PFO could also occur in children such as platypnea-orthodeoxia syndrome, myocardial infarction, and decompression sickness. Contrast transthoracic echocardiography was deemed the most appropriate examination for children due to its favorable transthoracic windows, eliminating the need for anesthesia. This review suggested that the additional treatment was not needed as no evidence was provided for potential future complications linked to isolated PFO in children. For children facing unique circumstances related to PFO, a customized interdisciplinary consultation is essential prior to considering medical interventions.

Identification of a ferroptosis-related prognostic signature and validation of ITGA6-AS1 in enhancing cell proliferation, migration and invasion in glioma.

Glioma is the most common malignant tumor of the adult central nervous system. In this study, we aimed to identify a novel model for predicting glioma prognosis and a potential therapeutic target. Here, lncRNAs related to prognosis and ferroptosis were analyzed and screened through R software and online websites. A nomogram model was established and evaluated with calibration curve, receiver operating characteristic curve and decision curve analysis. Further, an enrichment analysis and immune infiltration analysis were performed. In addition, the expression level and biological function of ITGA6-AS1 were verified in vitro. We obtained a ferroptosis-related 7-lncRNA signature, and constructed a nomogram prognostic model with good predictability for 1-, 3- and 5-year overall survival of glioma patients. The enrichment analysis indicated potential involvement of certain pathways and suggested a correlation between the high-risk group and infiltration of M2 macrophages and MDSCs. Furthermore, the expression level of ITGA6-AS1 in the U118, U87, and LN229 cells was upregulated compared to the H1800 cell. Interestingly, knockdown of ITGA6-AS1 may inhibit U118 cells' proliferation, migration and invasion in vitro. while overexpression of ITGA6-AS1 in LN229 cells plays a promoting role. This study implies that the 7-lncRNA signature may contribute to the stratification of glioma prognosis, and the immune suppressive microenvironment may be associated with macrophage-ferroptosis crosstalk. Furthermore, ITGA6-AS1 may be a potential therapeutic target for patients with glioma.

Association between circulatory complement activation and hypertensive renal damage: a case-control study.

OBJECTIVE: The aim of this study was to investigate the potential importance of complement system activation, with particular emphasis on the complement alternative pathway (AP), in the pathogenesis of hypertensive renal damage. METHODS: Serum complement C3, complement Factor H (CFH) and AP activation were assessed in 66 participants with established essential hypertension with renal damage (RD). Fifty-nine patients with age- and sex-matched essential hypertension without renal damage (NRD) and 58 healthy participants (normal) were selected. RESULTS: Our study revealed that C3 and AP50 continuously increased from normal to NRD to RD (p < 0.05, respectively), while CFH was significantly lower than that in NRD and healthy participants (p < 0.05, respectively). After multifactorial logistic regression analysis corrected for confounders, elevated serum C3 (p = 0.001) and decreased CFH (p < 0.001) were found to be independent risk factors for hypertension in healthy participants; elevated serum C3 (p = 0.034), elevated AP50 (p < 0.001), decreased CFH (p < 0.001), increased age (p = 0.011) and increased BMI (p = 0.013) were found to be independent risk factors for the progression of hypertension to hypertensive renal damage; elevated serum C3 (p = 0.017), elevated AP50 (p = 0.023), decreased CFH (p = 0.005) and increased age (p = 0.041) were found to be independent risk factors for the development of hypertensive renal damage in healthy participants. CONCLUSION: Abnormal activation of complement, particularly complement AP, may be a risk factor for the development and progression of hypertensive renal damage.

The effect of environmental calcium on gene expression, biofilm formation and virulence of Vibrio parahaemolyticus.

Calcium (Ca2+) can regulate the swarming motility and virulence of Vibrio parahaemolyticus BB22. However, the effects of Ca2+ on the physiology of V. parahaemolyticus RIMD2210633, whose genomic composition is quite different with that of BB22, have not been investigated. In this study, the results of phenotypic assays showed that the biofilm formation, c-di-GMP production, swimming motility, zebrafish survival rate, cytoxicity against HeLa cells, and adherence activity to HeLa cells of V. parahaemolyticus RIMD2210633 were significantly enhanced by Ca2+. However, Ca2+ had no effect on the growth, swarming motility, capsular polysaccharide (CPS) phase variation and hemolytic activity. The RNA sequencing (RNA-seq) assay disclosed 459 significantly differentially expressed genes (DEGs) in response to Ca2+, including biofilm formation-associated genes and those encode virulence factors and putative regulators. DEGs involved in polar flagellum and T3SS1 were upregulated, whereas majority of those involved in regulatory functions and c-di-GMP metabolism were downregulated. The work helps us understand how Ca2+ affects the behavior and gene expression of V. parahaemolyticus RIMD2210633.

Feasibility exploration of GSH in the treatment of acute hepatic encephalopathy from the aspects of pharmacokinetics, pharmacodynamics, and mechanism.

Our previous study highlighted the therapeutic potential of glutathione (GSH), an intracellular thiol tripeptide ubiquitous in mammalian tissues, in mitigating hepatic and cerebral damage. Building on this premise, we posited the hypothesis that GSH could be a promising candidate for treating acute hepatic encephalopathy (AHE). To verify this conjecture, we systematically investigated the feasibility of GSH as a therapeutic agent for AHE through comprehensive pharmacokinetic, pharmacodynamic, and mechanistic studies using a thioacetamide-induced AHE rat model. Our pharmacodynamic data demonstrated that oral GSH could significantly improve behavioral scores and reduce hepatic damage of AHE rats by regulating intrahepatic ALT, AST, inflammatory factors, and homeostasis of amino acids. Additionally, oral GSH demonstrated neuroprotective effects by alleviating the accumulation of intracerebral glutamine, down-regulating glutamine synthetase, and reducing taurine exposure. Pharmacokinetic studies suggested that AHE modeling led to significant decrease in hepatic and cerebral exposure of GSH and cysteine. However, oral GSH greatly enhanced the intrahepatic and intracortical GSH and CYS in AHE rats. Given the pivotal roles of CYS and GSH in maintaining redox homeostasis, we investigated the interplay between oxidative stress and pathogenesis/treatment of AHE. Our data revealed that GSH administration significantly relieved oxidative stress levels caused by AHE modeling via down-regulating the expression of NADPH oxidase 4 (NOX4) and NF-κB P65. Importantly, our findings further suggested that GSH administration significantly regulated the excessive endoplasmic reticulum (ER) stress caused by AHE modeling through the iNOS/ATF4/Ddit3 pathway. In summary, our study uncovered that exogenous GSH could stabilize intracerebral GSH and CYS levels to act on brain oxidative and ER stress, which have great significance for revealing the therapeutic effect of GSH on AHE and promoting its further development and clinical application.

L-shaped association of systemic immune-inflammation index (SII) with serum soluble α-Klotho in the prospective cohort study from the NHANES database.

The systemic immune-inflammation index (SII), an integrated and ground-breaking inflammatory measure, has been widely used in various fields. We aimed to assess the association between the systemic immune-inflammation index (SII) and α-Klotho (a new anti-aging biomarker). In this cross-sectional investigation, people with complete information on SII and α-Klotho from the National Health and Nutrition Examination Survey (NHANES) between 2007 and 2016 were the study's subject population. SII was calculated by platelet count × neutrophil count/lymphocyte count. The association between SII and α-Klotho was investigated using multivariable linear regression and a generalized additive model. In order to explore the non-linear connection, we employed smoothed curve fitting. Subgroup analysis were also performed. A total of 13,701 participants with an average age of 57.73 ± 10.86 years were enrolled, of whom 51.53% were female. After fully adjustment, SII was negatively associated with serum soluble α-Klotho [ß(95% CI) = - 0.07 (- 0.08, - 0.05)]. Furthermore, we found L-shaped association between SII and klotho protein level, with the inflection point at 255 pg/ml. Subgroup analysis and interaction test revealed that there was no discernible dependence on gender, age, race, smoking, alcohol, diabetes and hypertension (all p for interaction > 0.05). SII level was negatively associated with serum klotho protein concentration in American adults. To verify our findings, more large-scale prospective investigations are still required.

Chemical modification, structure elucidation and antifungal mechanism studies of a peptide extracted from garlic (Allium sativum L.).

BACKGROUND: Garlic is a promising source of antimicrobial peptide separation, and chemical modification is an effective method for activity improvement. The present study aimed to improve the antifungal activity of a peptide extracted from garlic. Chemical modifications were conducted, and the structure-activity relationship and antifungal mechanism were investigated. RESULTS: The results indicated that the cationic charge induced by Lys residue at the N-terminal was important for the antimicrobial activity, and the modified sequence exhibited significant antifungal activity with low mammalian toxicity and a low tendency of drug resistance (p < 0.05). The structure-activity relationship analysis revealed that the modified active peptide had a predominant α-helical structure and an inner cyclic correlation. Transcriptomic analysis showed that peptide KMLKKLFR (Lys-Met-Leu-Lys-Lyse-Leu-Phe-Arg) affected the rRNA processing and carbon metabolism process of Candida albicans. In addition, the membrane potential study indicated a non-membrane destruction mechanism, and molecular docking analysis and a DNA interaction assay suggested promising inner targets. CONCLUSION: The results of the present study indicate that chemical modification by amino acid substitution was effective for antimicrobial activity improvement. The present study would benefit future antimicrobial peptide development and suggests that garlic is a great source of antibacterial peptides and peptide template separations for coping with antibiotic resistance. © 2024 Society of Chemical Industry.