Timeframe Analysis of Novel Synthetic Cannabinoids Effects: A Study on Behavioral Response and Endogenous Cannabinoids Disruption.

This study investigates the impact of SCs consumption by assessing the effects of three novel synthetic cannabinoids (SCs); MDMB-CHMINACA, 5F-ADB-PINACA, and APICA post-drug treatment. SCs are known for their rapid onset (<1 min) and prolonged duration (≥5 h). Therefore, this research aimed to assess behavioral responses and their correlation with endocannabinoids (ECs) accumulation in the hippocampus, and EC's metabolic enzymes alteration at different timeframes (1-3-5-h) following drug administration. Different extents of locomotive disruption and sustained anxiety-like symptoms were observed throughout all-encompassing timeframes of drug administration. Notably, MDMB-CHMINACA induced significant memory impairment at 1 and 3 h. Elevated levels of anandamide (AEA) and 2-arachidonoyl glycerol (2-AG) were detected 1 h post-MDMB-CHMINACA and 5F-ADB-PINACA administration. Reduced mRNA expression levels of fatty acid amide hydrolase (FAAH), monoacylglycerol lipase (MAGL) (AEA and 2-AG degrading enzymes, respectively), and brain-derived neurotrophic factor (BDNF) occurred at 1 h, with FAAH levels remaining reduced at 3 h. These findings suggest a connection between increased EC content and decreased BDNF expression following SC exposure. Cognitive disruption, particularly motor coordination decline and progressive loss manifested in a time-dependent manner across all the analyzed SCs. Our study highlights the importance of adopting a temporal framework when assessing the effects of SCs.

Optical amplification enables a huge sensitivity improvement to laser heterodyne radiometers for high-resolution measurements of atmospheric gases.

A novel, to the best of our knowledge, performance-enhanced laser heterodyne radiometer has been developed by utilizing a semiconductor optical amplifier to amplify the collected weak solar radiation in an optical fiber. High-spectral-resolution measurements of atmospheric carbon dioxide column absorption are used to validate the technique and performance of the developed instrument. The implementation of optical amplification led to a 9-times improvement in sensitivity according to the Allan variance analysis for noise fluctuations, and resulted in a 7.7-times enhancement in measurement precision for atmospheric carbon dioxide. The promising results showed the great potential of employing this type of compact fiber-optics-based spectral radiometer for applications such as atmospheric greenhouse gas sensing.

Quality assessment and traceability study of Angelicae Sinensis Radix via binary chromatography, triple quadrupole tandem mass spectrometry, and multivariate statistical analysis.

Angelicae Sinensis Radix is a world-renowned herbal medicine originating in China. Owing to many environmental and geographical factors, Angelicae Sinensis Radix from various origins may have a difference in the content of ingredients, which made the confusion in the clinical practice and market. Herein, a binary chromatographic fingerprinting analysis method is developed via hydrophilic interaction chromatography and reversed-phase liquid chromatography to obtain more chemical information. Following that, an ultra-performance liquid chromatography with a triple quadrupole mass spectrometry method is furnished to simultaneously detect 17 ingredients of Angelicae Sinensis Radix gathered from six geographic zones in China. Eventually, the principal component analysis is successfully carried out to classify and differentiate the Angelicae Sinensis Radix from different origins, meanwhile the quantitative volcano plots was used to observe the changes of ingredient trends vividly. Accordingly, the proposed binary chromatography and triple quadrupole tandem mass spectrometry coupled with multivariate statistical analysis can be utilized as a facile and reliable method for origin tracing and quality control of Angelicae Sinensis Radix.

Exposure to PM2.5 during pregnancy causes lung inflammation in the offspring: Mechanism of action of mogrosides.

Epidemiological and toxicological studies have demonstrated that exposure to fine particulate matter (PM2.5) during pregnancy is harmful to the tissues of the offspring. However, the mechanism by which PM2.5 exposure causes lung damage in the offspring or potential dietary therapy for this condition remains unclear. Mogrosides (MGs) are derived from the traditional plant Siraitia grosvenorii and are used medicinally, where they can moisten the lungs and relieve coughing. In this study, pregnant rats were exposed to PM2.5 by intratracheal instillation and treated with MGs by gavage to model the effect of PM2.5 in the offspring and the interventional effect of MGs on lung tissue. We then used transcriptomics, metabolomics, and RT-qPCR as tools to look for metabolite and genetic changes in the offspring. We found that when compared to the control group, the mRNA levels of the inflammatory mediator Pla2g2d and the metabolites lysophosphatidylcholines (LysoPCs) and arachidonic acid (AA) were up-regulated in the lung tissues of PM2.5 group. In contrast, these inflammatory changes were restored after treatment with MGs during pregnancy. In addition, the levels of AA, LPC 15:0 and LPC 18:0 were elevated in the PM2.5 group compared with control group. This increase was inhibited by co-administration of MGs. The change of PGA1 was adverse. In conclusion, even a relatively low exposure to PM2.5 in rats during pregnancy produces inflammation in the lungs of the male offspring, and an intervention with MGs could significantly alleviate this effect. Furthermore, Pla2g2d may represent a potential target for MGs resulting in the improvement of PM2.5-induced lung injury.

Ablation of Selenbp1 Alters Lipid Metabolism via the Pparα Pathway in Mouse Kidney.

Selenium-binding protein 1 (Selenbp1) is a 2,3,7,8-tetrechlorodibenzo-p-dioxin inducible protein whose function is yet to be comprehensively elucidated. As the highly homologous isoform, Selenbp2, is expressed at low levels in the kidney, it is worthwhile comparing wild-type C57BL mice and Selenbp1-deficient mice under dioxin-free conditions. Accordingly, we conducted a mouse metabolomics analysis under non-dioxin-treated conditions. DNA microarray analysis was performed based on observed changes in lipid metabolism-related factors. The results showed fluctuations in the expression of numerous genes. Real-time RT-PCR confirmed the decreased expression levels of the cytochrome P450 4a (Cyp4a) subfamily, known to be involved in fatty acid ω- and ω-1 hydroxylation. Furthermore, peroxisome proliferator-activated receptor-α (Pparα) and retinoid-X-receptor-α (Rxrα), which form a heterodimer with Pparα to promote gene expression, were simultaneously reduced. This indicated that reduced Cyp4a expression was mediated via decreased Pparα and Rxrα. In line with this finding, increased levels of leukotrienes and prostaglandins were detected. Conversely, decreased hydrogen peroxide levels and reduced superoxide dismutase (SOD) activity supported the suppression of the renal expression of Sod1 and Sod2 in Selenbp1-deficient mice. Therefore, we infer that ablation of Selenbp1 elicits oxidative stress caused by increased levels of superoxide anions, which alters lipid metabolism via the Pparα pathway.

Functional Food XingJiuTang Attenuates Alcohol-Induced Liver Injury by Regulating SIRT1/Nrf-2 Signaling Pathway.

Lipid accumulation, inflammatory responses and oxidative stress have been implicated in the pathology of alcohol-induced liver injury (ALI). In this work, we evaluated the effects of the functional food XingJiuTang (XJT) on ALI and explored the underlying mechanism. We used alcohol-stimulated human normal hepatocytes L02 for in vitro experiments, while for in vivo experiments, 55 % alcohol was intragastrically administrated to C57BL/6 mice at 16 mL/kg with pre-administration of bifendate and XJT. Liver histology and function, along with the inflammatory cytokines, oxidative mediators and SIRT1/Nrf-2 pathway were evaluated. The results showed that XJT treatment significantly alleviated ALI, ameliorated lipid peroxidation, improved the liver function impaired by alcohol and inhibited the hepatocytes apoptosis in vitro and in vivo. In addition, XJT treatment modulated the activation of the SIRT1/Nrf-2 signaling pathway and suppressed the overexpression of NOX4. Overall, the functional food XJT effectively protects against experimental ALI via activating the SIRT1/Nrf-2 pathway.

Protective Effect of the Traditional Chinese Patent Medicine Qing-Xuan Granule against Bleomycin-Induced Pulmonary Fibrosis in Mice.

Pulmonary fibrosis (PF) is a chronic obstructive pulmonary disease without effective clinical drug treatment. Qing-Xuan Granule (QX) as a traditional Chinese patent medicine is clinically used to cure children's cough. This study was designed to investigate the effects of QX and possible molecular mechanisms for bleomycin-induced PF. The work used Western blotting and Q-PCR to explore the vitro and vivo mechanisms of QX treatment, while using HPLC-TOF/MS to explore the composition of QX. QX was given daily orally for two weeks after bleomycin intratracheal instillation. The protective effects of QX on lung function, inflammation, growth factors, hydroxyproline content and deposition of extracellular matrix were investigated. QX decreased expression of Col I and α-SMA in lung tissues by down-regulating TGF-ß1-Smad2/3 signaling and suppressed epithelial-mesenchymal transition and effectively reversed abnormal mRNA levels of MMP-1and TIMP-1 as well as LOXL-2 in lung tissues. HPLC-TOF/MS indicate that six substances could be the main active components, which were reported to protect against experimental lung disease.

Oligosaccharides from Asparagus cochinchinensis for ameliorating LPS-induced acute lung injury in mice.

Asparagi radix is an edible herb with medicinal properties and is now widely used in clinical applications for improving pulmonary inflammation. However, the lung-protective effect and the active constituents of Asparagi radix are yet to be elucidated. Herein, the potential pulmonary protective effect of the oligosaccharides of Asparagi radix was investigated. We firstly identified eighteen oligosaccharides with different degrees of polymerization from Asparagi radix using HPLC-QTOF MS. Oligosaccharides were analysed for 20 samples of Asparagi radix collected from various regions in China using HILIC-ELSD and were found to stably exist in this herb. In this study, we found that AROS significantly reduced NO production and effectively down-regulated the mRNA expression of IL-6, IL-1ß and TNF-α in RAW 264.7 cells, thereby reducing the inflammatory response induced by LPS. AROS also inhibited LPS-stimulated intracellular ROS production. A murine model of lipopolysaccharide (LPS)-induced acute lung injury was used to evaluate the in vivo anti-inflammatory and lung protective efficacies of AROS. AROS ameliorated the damage to the pulmonary cellular architecture pathological injury and lung edema. AROS significantly decreased the levels of cytokines IL-6, TNF-α and IL-1ß; the levels of MPO and MDA; and superoxide dismutase consumption in vivo. This effect of oligosaccharides can explain the traditional usage of Asparagus cochinchinensis as a tonic medicine for respiratory problems, and oligosaccharides from Asparagi radix used as a natural ingredient can play an important role in protecting lung injury.

Protection effect of Dioscoreae Rhizoma against ethanol-induced gastric injury in vitro and in vivo: A phytochemical and pharmacological study.

ETHNOPHARMACOLOGICAL RELEVANCE: Dioscoreae Rhizoma, a kind of Chinese yam, is a medicinal and edible plant used in China for strengthening the spleen and stomach. However, there is a lack of modern pharmacology studies regarding its anti-gastric injury activity. AIM OF THE STUDY: This study aimed to investigate the phytochemical composition of Chinese yam aqueous extract (CYW) and evaluate its gastroprotective effects against ethanol-induced gastric injury in vitro and in vivo. MATERIALS AND METHODS: The active components of CYW were identified using HPLC-QTOF-MS/MS in combination with the GNPS molecular networking and network pharmacology. In vitro studies were performed in the RAW264.7/GES-1 cell coculture system. In vivo study, mice were treated with CYW (0.31, 0.63, and 3.14 g/kg BW, orally) for 14 days, followed by a single oral dose of ethanol (10 mL/kg BW) to induce gastric injury. The biochemical, inflammation and oxidative stress markers were analyzed using commercial kits. Histopathology was used to assess the degree of gastric injury. Gene and protein expressions were studied using RT-qPCR and western blotting, respectively. RESULTS: CYW significantly restored the levels of SOD, GPx and CAT, and reduced the MDA content. Further analyses showed that CYW significantly alleviated the gastric oxidative stress by inhibiting the inflammation via decreasing p-NF-κB and p-IκB-α expression levels and inhibiting the generation of IL-6, TNF-α, and IL-1ß. At the same time, the fraction remarkably upregulated Bcl-2, downregulated Bax and increased growth factor secretion, thereby prevented gastric mucous cell. Besides, The combination of HPLC-QTOF-MS/MS, GNPS molecular networking analysis, and network pharmacology demonstrated that linoleic acid, 3-acetyl-11-keto-beta-boswellic acid, adenosine, aminocaproic acid, tyramine, DL-tryptophan, cycloleucine, lactulose, melibiose, alpha-beta-trehalose, and sucrose would be the main active compounds of CYW against ethanol-induced gastric injury. CONCLUSION: This study showed that CYW is potentially rich source of anti-oxidant and anti-inflammatory bioactive compounds. It showed efficacy against ethanol-induced gastric injury by inhibiting inflammation, oxidative stress, and apoptosis in the stomach. The results of the current work indicate that Dioscoreae Rhizoma could be utilized as a type of natural resource for production of new medicine and functional foods to prevent and/or ameliorate ethanol-induced gastric injury.

Corrigendum: Correlation of mild cognitive impairment with the thickness of retinal nerve fiber layer and serum indicators in type 2 diabetic patients.

[This corrects the article DOI: 10.3389/fendo.2023.1299206.].

Specneuzhenide improves bleomycin-induced pulmonary fibrosis in mice via AMPK-dependent reduction of PD-L1.

BACKGROUND: Pulmonary fibrosis (PF) is an escalating global health issue, characterized by rising rates of morbidity and mortality annually. Consequently, further investigation of potential damage mechanisms and potential preventive strategies for PF are warranted. Specnuezhenide (SPN), a prominent secoiridoid compound derived from Ligustrum lucidum Ait, exhibits anti-inflammatory and anti-oxidative capacities, indicating the potential therapeutic actions on PF. However, the underlying mechanisms of SPN on PF remain unclear. PURPOSE: This work was aimed at investigating the protective actions of SPN on PF and the potential mechanism. METHODS: In vivo, mice were administrated with bleomycin (BLM) to establish PF model. PF mice were treated with SPN (45/90 mg/kg) by gavage. In vitro, we employed TGF-ß1 (10 ng/mL)-induced MLE-12 and PLFs cells, which then were treated with SPN (5, 10, 20 µM). DARTS assay, biofilm interference experiment and molecular docking were performed to investigate the molecular target of SPN. RESULTS: In vivo, we found SPN treatment improved survival rate, alleviated pathological changes through reducing BLM-induced extracellular matrix (ECM) deposition, as well as BLM-induced epithelial-mesenchymal transition (EMT). In vitro, SPN inhibited EMT and lung fibroblast transdifferentiation. Mechanistically, SPN activated the AMPK protein to decrease the abnormally high level of PD-L1. Furthermore, the compound C, known as an AMPK inhibitor, exhibited a significant hindrance to the inhibition of SPN on TGF-ß1-caused fibroblast transdifferentiation and proliferation. This outcome could be attributed to the fact that compound C could eliminate the inhibitory effects of SPN on PD-L1 expression. Interestingly, DARTS assay, biofilm interference experiment and molecular docking results all indicated that SPN could bind to AMPK, which suggested that SPN might be a potential agonist targeting AMPK protein. CONCLUSION: Altogether, the results in our work illustrated that SPN promoted AMPK-dependent reduction of PD-L1 protein, contributing to the inhibition of fibrosis progression. Thus, SPN may represent a potential AMPK agonist for PF treatment.

Berberine-based self-assembly agents with enhanced synergistic antitumor efficacy.

Tumors are still a major threat to people worldwide. Nanodrug delivery and targeting systems can significantly improve the therapeutic efficacy of chemotherapeutic drugs for antitumor purposes. However, many nanocarriers are likely to exhibit drawbacks such as a complex preparation process, limited drug-loading capacity, untargeted drug release, and toxicity associated with nanocarriers. Therefore, new therapeutic alternatives are urgently needed to develop antitumor drugs. Natural products with abundant scaffold diversity and structural complexity, which are derived from medicinal plants, are important sources of new antitumor drugs. Here, two carrier-free berberine (BBR)-based nanoparticles (NPs) were established to increase the synergistic efficacy of tumor treatment. BBR can interact with glycyrrhetinic acid (GA) and artesunate (ART) to self-assemble BBR-GA and BBR-ART NPs without any nanocarriers, respectively, the formation of which is dominated by electrostatic and hydrophobic interactions. Moreover, BBR-GA NPs could lead to mitochondria-mediated cell apoptosis by regulating mitochondrial fission and dysfunction, while BBR-ART NPs induced ferroptosis in tumor cells. BBR-based NPs have been demonstrated to possess significant tumor targeting and enhanced antitumor properties compared with those of simple monomer mixes both in vitro and in vivo. These carrier-free self-assemblies based on natural products provide a strategy for synergistic drug delivery and thus offer broad prospects for developing enhanced antitumor drugs.

Preventive and Therapeutic Effects of Crocetin in Rats with Heart Failure.

Gardenia is both a food and medicine plant. It is widely used for cardiovascular protection, and its main bioactive ingredient is crocetin. This study aims to observe the therapeutic effects of crocetin on chronic heart failure in rats induced by various etiologies. It further compares the efficacy differences between preventative and treatment administration, varying dosages, and treatment durations, to provide improved guidance for medication in heart failure rats and determine which categories of chronic heart failure rats might benefit most from crocetin. Chronic heart failure models induced by abdominal aorta constriction, renal hypertension, and coronary artery ligation were constructed. By examining cardiac function, blood biochemistry, and histopathology, the study assessed the preventive and therapeutic effects of crocetin on load-induced and myocardial ischemia-induced heart failure. The results showed that in all three models, both treatment and preventative administration of crocetin significantly improved chronic heart failure in rats, especially in preventative administration. The results indicate crocetin may be beneficial for improving symptoms and functional capacity in rats with heart failure. Furthermore, long-term administration was more effective than short-term administration across all three rat models, with therapeutic onset observed over 6 weeks.

Design, synthesis and evaluation of flavonoid derivatives as potential multifunctional acetylcholinesterase inhibitors against Alzheimer's disease.

A new series of flavonoid derivatives were designed, synthesized and evaluated as potential multifunctional AChE inhibitors against Alzheimer's disease. Most of them exhibited potent AChE inhibitory activity, high selectivity for AChE over BuChE, and moderate to good inhibitory potency toward Aß aggregation. Specifically, compound 12c was the strongest AChE inhibitor, being 20-fold more potent than galanthamine and twofold more potent than tacrine, and it also had ability to inhibit Aß aggregation (close to the reference compound) and to function as a metal chelator. Molecular modeling and enzyme kinetic study revealed that it targeted both the catalytic active site and the peripheral anionic site of AChE. Consequently, this class of compounds deserved to be thoroughly and systematically studied for the treatment of Alzheimer's disease.

Analysis of 12 Chemical Compounds And Pattern Recognition of Different Parts of Angelicae Sinensis Radix by Liquid Chromatography-Tandem Mass Spectrometry And Chemometrics Methods.

To evaluate the quality and quantify bioactive constituents in different parts of Angelicae Sinensis Radix, an efficient, high-speed, high-sensitivity high-performance liquid chromatography and triple quadrupole mass spectrometry method was used for simultaneous detection of 12 chemical compounds including L-tryptophan, chlorogenic acid, caffeic acid, ferulic acid, isoferulic acid, senkyunolide I, guanosine, proline, L-glutamine, γ-aminobutyric acid, glutamic acid, and arginine in 52 batches of Angelicae Sinensis Radix from Gansu, China. The established methods were validated by good linearity (R2≥0.9921), limits of detection (0.0001-0.0156 µg/mL), limits of quantitation (0.0006-0.0781 µg/mL), stability (RSD≤7.77%), repeatability (RSD≤6.79%), intra- and interday precisions (RSD≤6.00% and RSD≤6.39%, respectively) and recovery (90.90-107.16%). According to the quantitative results, the contents of the hydrophilic compounds were higher in the head, while the medium and weak polar components were mainly concentrated in the tail. Finally, principal component analysis results revealed that Angelicae Sinensis Radix could be divided into different medicinal sites based on polar components such as amino acids, nucleosides. The combination of liquid chromatography-tandem mass spectrometry and principal component analysis is a simple and reliable method for pattern recognition and quality evaluation of Angelicae Sinensis Radix.

Investigation of pulmonary toxicity evaluation on mice exposed to polystyrene nanoplastics: The potential protective role of the antioxidant N-acetylcysteine.

Accumulating evidences show that the hazardous substance atmospheric nanoplastics increase the respiratory risk of individuals, but the inside toxicity mechanisms to lung tissue remain unclear. This study aims at investigating the potential mechanisms of inhaled cationic polystyrene nanoplastics (amine-polystyrene nanoplastics, APS-NPs)-induced pulmonary toxicity on mice. In vivo, the mice intratracheal administrated with APS-NPs suspension (5 mg/kg) were found inflammatory infiltrates in lung tissues through histopathology analysis. Furthermore, transcriptome analysis demonstrated that 1821 differentially expressed mRNA between APS group and control group were dominantly associated with 288 known KEGG pathways, indicating that APS-NPs might cause early inflammatory responses in lung tissue by activating the NLRP3/capase-1/IL-1ß signaling pathway. Moreover, in vitro results also showed that NLRP3 inflammasome could be activated to induce pyroptosis in MLE-12 cells after exposure to APS-NPs. And, MH-S cells after exposure to APS-NPs exhibited increased Irg1 proteins, leading to the increasing generation of ROS and inflammatory factors (e.g., tnf-α, il-6, il-1ß). In conclusion, these results revealed that Irg1/NF-κB/NLRP3/Caspase-1 signaling pathway was activated significantly after exposing to APS-NPs, leading to pulmonary toxicity on mice. Intriguingly, prior administration of the clinical antioxidant N-acetylcysteine (NAC) could serve as a possible candidate for the prevention and treatment of pulmonary toxicity induced by APS-NPs. The study contributes to a better understanding of the potential risks of environmental nanoplastics to humans and its improvement measure.

Modulation of Bleomycin-induced Oxidative Stress and Pulmonary Fibrosis by Ginkgetin in Mice via AMPK.

BACKGROUND: Ginkgetin, a flavonoid extracted from Ginkgo biloba, has been shown to exhibit broad anti-inflammatory, anticancer, and antioxidative bioactivity. Moreover, the extract of Ginkgo folium has been reported on attenuating bleomycin-induced pulmonary fibrosis, but the anti-fibrotic effects of ginkgetin are still unclear. This study was intended to investigate the protective effects of ginkgetin against experimental pulmonary fibrosis and its underlying mechanism. METHODS: In vivo, bleomycin (5 mg/kg) in 50 µL saline was administrated intratracheally in mice. One week after bleomycin administration, ginkgetin (25 or 50 mg/kg) or nintedanib (40 mg/kg) was administrated intragastrically daily for 14 consecutive days. In vitro, the AMPK-siRNA transfection in primary lung fibroblasts further verified the regulatory effect of ginkgetin on AMPK. RESULTS: Administration of bleomycin caused characteristic histopathology structural changes with elevated lipid peroxidation, pulmonary fibrosis indexes, and inflammatory mediators. The bleomycin- induced alteration was normalized by ginkgetin intervention. Moreover, this protective effect of ginkgetin (20 mg/kg) was equivalent to that of nintedanib (40 mg/kg). AMPK-siRNA transfection in primary lung fibroblasts markedly blocked TGF-ß1-induced myofibroblasts transdifferentiation and abolished oxidative stress. CONCLUSION: All these results suggested that ginkgetin exerted ameliorative effects on bleomycininduced oxidative stress and lung fibrosis mainly through an AMPK-dependent manner.

Ginseng saponin metabolite 20(S)-protopanaxadiol relieves pulmonary fibrosis by multiple-targets signaling pathways.

Background: Panax ginseng Meyer is a representative Chinese herbal medicine with antioxidant and anti-inflammatory activity. 20(S)-Protopanaxadiol (PPD) has been isolated from ginseng and shown to have promising pharmacological activities. However, effects of PDD on pulmonary fibrosis (PF) have not been reported. We hypothesize that PDD may reverse inflammation-induced PF and be a novel therapeutic strategy. Methods: Adult male C57BL/6 mice were used to establish a model of PF induced by bleomycin (BLM). The pulmonary index was measured, and histological and immunohistochemical examinations were made. Cell cultures of mouse alveolar epithelial cells were analyzed with Western blotting, co-immunoprecipitation, immunofluorescence, immunohistochemistry, siRNA transfection, cellular thermal shift assay and qRT-PCR. Results: The survival rate of PPD-treated mice was higher than that of untreated BLM-challenged mice. Expression of fibrotic hallmarks, including α-SMA, TGF-ß1 and collagen I, was reduced by PPD treatment, indicating attenuation of PF. Mice exposed to BLM had higher STING levels in lung tissue, and this was reduced by phosphorylated AMPK after activation by PPD. The role of phosphorylated AMPK in suppressing STING was confirmed in TGF-ß1-incubated cells. Both in vivo and in vitro analyses indicated that PPD treatment attenuated BLM-induced PF by modulating the AMPK/STING signaling pathway. Conclusion: PPD ameliorated BLM-induced PF by multi-target regulation. The current study may help develop new therapeutic strategies for preventing PF.

Correlation of mild cognitive impairment with the thickness of retinal nerve fiber layer and serum indicators in type 2 diabetic patients.

Background: Cognitive Impairment arising from type 2 diabetes mellitus (T2DM) has garnered significant attention in recent times. However, there are few studies on the identification and diagnosis of markers of cognitive impairment. Notably, alterations in the Retinal Nerve Fiber Layer's (RNFL) thickness can potentially serve as an indicative measure of central nervous system changes. Further investigations have indicated that the decline in cognitive function within T2DM patients is intricately linked to persistent systemic inflammation and the accumulation of advanced glycosylation end products. Comprehensive studies are warranted to unveil these complex associations. Objective: This study aims to explore the potential of utilizing the RNFL thickness and serological concentrations of IL-18, irisin, CML, and RAGE as diagnostic indicators for Mild Cognitive Impairment (MCI) among individuals with T2DM. Methods: The thickness of RNFL were determined in all patients and controls using optical coherence tomography (OCT). The serum levels of IL-18, irisin, CML and RAGE were detected by ELISA kit. In addition, Cognitive assessment was performed by the Mini-Mental State Examination (MMSE) and the Montreal Cognitive assessment (MoCA). Results: The average RNFL thickness in the right eye were decreased in T2DM and T2DM combined with MCI (T2DM-MCI) patients and were positively correlated with MoCA and MMSE scores. The serum levels of IL-18, CML and RAGE in T2DM and T2DM-MCI increased significantly (p<0.05) and were negative correlated with MoCA and MMSE scores. The level of irisin in T2DM and T2DM-MCI decreased significantly (p<0.05) and were positively correlated with MoCA and MMSE scores. The area under the ROC curve of T2DM-MCI predicted by the average RNFL thickness in the right eye, CML and RAGE were 0.853, 0.874 and 0.815. The diagnostic efficacy of the combination of average RNFL thickness in the right eye, CML, and RAGE for the diagnosis of T2DM-MCI was 0.969. Conclusion: The average RNFL thickness in the right eye, CML and RAGE have possible diagnostic value in T2DM-MCI patients.

α-Lipoic acid eliminates dioxin-induced offspring sexual immaturity by improving abnormalities in folic acid metabolism.

Maternal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) causes developmental and reproductive disorders in pups due to the attenuated luteinizing hormone (LH) production during the perinatal stage; however, the administration of α-lipoic acid (LA) to TCDD-exposed pregnant rats reversed the attenuated LH production. Therefore, reproductive disorders in pups are expected to be ameliorated with LA supplementation. To address this issue, pregnant rats orally received low dose TCDD at gestational day 15 (GD15) and proceeded to parturition. The control received a corn oil vehicle. To examine the preventive effects of LA, supplementation with LA was provided until postnatal day 21. In this study, we demonstrated that maternal administration of LA restored the sexually dimorphic behavior of male and female offspring. TCDD-induced LA insufficiency is likely a direct cause of TCDD reproductive toxicity. In the analysis to clarify the mechanism of the decrease in LA, we found evidence suggesting that TCDD inhibits the synthesis and increases the utilization of S-adenosylmethionine (SAM), a cofactor for LA synthesis, resulting in a decrease in the SAM level. Furthermore, folate metabolism, which is involved in SAM synthesis, is disrupted by TCDD, which may adversely affect infant growth. Maternal supplementation of LA restored SAM to its original level in the fetal hypothalamus; in turn, SAM ameliorated abnormal folate consumption and suppressed aryl hydrocarbon receptor activation induced by TCDD. The study demonstrates that the application of LA could prevent and recover next-generation dioxin reproductive toxicity, which provides the potential to establish effective protective measures against dioxin toxicity.