Highly sensitive colorimetric and paper-based detection for sildenafil in functional food based on monodispersed spherical magnetic graphene composite nanozyme.

BACKGROUND: Sildenafil (SIL) is regarded as an illegal adulterant in functional foods. Some functional foods doped with SIL have posed significant concern about their safety risks. However, the facile colorimetric detection of SIL is rarely investigated. RESULTS: Herein, we prepared a monodispersed spherical composite nanozyme (Fe3O4-NH2/GONRs), possessing excellent peroxidase-like (POD-like) and catalase-like (CAT-like) activities and strong superparamagnetic property. The enzyme-like activities of Fe3O4-NH2/GONRs can be selectively inhibited by SIL due to the synergistic effect of hydrogen bonds and π-π stacking between Fe3O4-NH2/GONRs and SIL. Leveraging this mechanism, a highly sensitive and selective colorimetric detection for SIL with a detection limit (LOD) of 0.26 ng/mL was developed. In addition, we prepared a three-dimensional paper-based analytical device (3D-PAD) for SIL colorimetric detection with naked-eyes and the semi-quantitative analysis with a LOD of 88 ng/mL. SIGNIFICANCE: The proposed colorimetric and PAD detections demonstrated the advantages of low-cost, highly sensitive and selective, thus have promise application potential in the rapid detection of adulterated functional foods.

Melatonin Rinsing Treatment Associated with Storage in a Controlled Atmosphere Improves the Antioxidant Capacity and Overall Quality of Lemons.

Antioxidant capacity is one of the most important biological activities in fruits and vegetables and is closely related to human health. In this study, 'Eureka' lemons were used as experimental materials and stored at 7-8 °C MT (melatonin, 200 µmol, soaked for 15 min) and CA (controlled atmosphere, 2-3% O2 + 15-16% CO2) individually or in combination for 30 d. The changes in lemon fruits' basic physicochemical properties, enzyme activities, and antioxidant capacities were studied. Comparing the combined treatment to the control, the outcomes demonstrated a significant reduction in weight loss, firmness, stomatal opening, and inhibition of polyphenol oxidase (PPO) and peroxidase (POD) activities. Additionally, the combined treatment maintained high levels of titratable acidity (TA), vitamin C (VC), total phenolic content (TPC), and antioxidant capacity and preserved the lemon aroma. Meanwhile, the correlation between fruit color, aroma compounds, and antioxidant capacity was revealed, providing valuable insights into the postharvest preservation of lemons. In conclusion, the combined treatment (MT + CA) was effective in maintaining the quality and antioxidant capacity of lemons.

Crosslinked Biodegradable Hybrid Hydrogels Based on Poly(ethylene glycol) and Gelatin for Drug Controlled Release.

A series of hybrid hydrogels of poly(ethylene glycol) (PEG) were synthesized using gelatin as a crosslinker and investigated for controlled delivery of the first-generation cephalosporin antibiotic, Cefazedone sodium (CFD). A commercially available 4-arm-PEG-OH was first modified to obtain four-arm-PEG-succinimidyl glutarate (4-arm-PEG-SG), which formed the gelatin-PEG composite hydrogels (SnNm) through crosslinking with gelatin. To regulate the drug delivery, SnNm hydrogels with various solid contents and crosslinking degrees were prepared. The effect of solid contents and crosslinking degrees on the thermal, mechanical, swelling, degradation, and drug release properties of the hydrogels were intensively investigated. The results revealed that increasing the crosslinking degree and solid content of SnNm could not only enhance the thermal stability, swelling ratio (SR), and compression resistance capacity of SnNm but also prolong the degradation and drug release times. The release kinetics of the SnNm hydrogels were found to follow the first-order model, suggesting that the transport rate of CFD within the matrix of hydrogels is proportional to the concentration of the drug where it is located. Specifically, S1N1-III showed 90% mass loss after 60 h of degradation and a sustained release duration of 72 h. The cytotoxicity assay using the MTT method revealed that cell viability rates of S1N1 were higher than 95%, indicating excellent cytocompatibility. This study offers new insights and methodologies for the development of hydrogels as biomedical composite materials.

Exploring You-gui Pill for the Treatment of Diabetic Erectile Dysfunction: Data Mining Analysis, Network Pharmacology and Experiments In Vitro.

INTRODUCTION: The You-gui pill (YGP) is a classical compound used for treating antidiabetic erectile dysfunction (DMED). However, the specific active ingredients responsible for its effects on DMED and their mechanisms remain unclear. METHODS: In this paper, we used data mining techniques to analyze high-frequency herbs and herb combinations used in Chinese medicine for the treatment of DMED based on existing literature. Using network pharmacology to study the active components and mechanism of action of YGP against DMED, molecular docking was used to analyze the interactions of the active components with major structural proteins, nonstructural proteins, and mutants. Also, the therapeutic effect of YGP on hyperglycemic modelling and its underlying mechanisms were experimentally validated in CCEC cells by analyzing the expression of its relevant target mRNAs. RESULTS: Network pharmacological analysis identified the three core components of YGP as quercetin, kaempferol, and ß-sitosterol, and constructed a PPI network map of common targets of YGP and DMED, which included HIF-1α, ALB, Bcl-2, INS, IL-1ß, IL-6, TNF-α, CASP3, and TP53. Combined with molecular docking results, these targets had a strong binding affinity between them and the active ingredient compounds, with the highest affinity for HIF-1α and TNF-α. During the in vitro cellular assay validation, the HIF-1α, ALB, Bcl-2, TNF-α, and IL-6 mRNA in CCECs cells showed positive regulation after YGP intervention. CONCLUSION: The combination of "data mining - network pharmacology - molecular docking - experimental validation" provides a powerful methodological basis for the study of the main active components and mechanism of action of YGP against DMED, as well as the development and application of the drug.

Effect of Tourmaline Addition on the Anti-Poisoning Performance of MnCeOx@TiO2 Catalyst for Low-Temperature Selective Catalytic Reduction of NOx.

In view of the flue gas characteristics of cement kilns in China, the development of low-temperature denitrification catalysts with excellent anti-poisoning performance has important theoretical and practical significance. In this work, a series of MnCeOx@TiO2 and tourmaline-containing MnCeOx@TiO2-T catalysts was prepared using a chemical pre-deposition method. It was found that the MnCeOx@TiO2-T2 catalyst (containing 2% tourmaline) exhibited the best low-temperature NH3-selective catalytic reduction (NH3-SCR) performance, yielding 100% NOx conversion at 110 °C and above. When 100-300 ppm SO2 and 10 vol.% H2O were introduced to the reaction, the NOx conversion of the MnCeOx@TiO2-T2 catalyst was still higher than 90% at 170 °C, indicating good anti-poisoning performance. The addition of appropriate amounts of tourmaline can not only preferably expose the active {001} facets of TiO2 but also introduce the acidic SiO2 and Al2O3 components and increase the content of Mn4+ and Oα on the surface of the catalyst, all of which contribute to the enhancement of reaction activity of NH3-SCR and anti-poisoning performance. However, excess amounts of tourmaline led to the formation of dense surface of catalysts that suppressed the exposure of catalytic active sites, giving rise to the decrease in catalytic activity and anti-poisoning capability. Through an in situ DRIFTS study, it was found that the addition of appropriate amounts of tourmaline increased the number of Brønsted acid sites on the catalyst surface, which suppressed the adsorption of SO2 and thus inhibited the deposition of NH4HSO4 and (NH4)2HSO4 on the surface of the catalyst, thereby improving the NH3-SCR performance and anti-poisoning ability of the catalyst.

Double-side role of short chain fatty acids on host health via the gut-organ axes.

Short chain fatty acids (SCFA) exist in dietary foods and are produced by the fermentation of gut microbiota, and are considered an important element for regulating host health. Through blood circulation, SCFA produced in the gut and obtained from foods have an impact on the intestinal health as well as vital organs of the host. It has been recognized that the gut is the "vital organ" in the host. As the gut microbial metabolites, SCFA could create an "axis" connecting the gut and to other organs. Therefore, the "gut-organ axes" have become a focus of research in recent years to analyze organism health. In this review, we summarized the sources, absorption properties, and the function of SCFA in both gut and other peripheral tissues (brain, kidney, liver, lung, bone and cardiovascular) in the way of "gut-organ axes". Short chain fatty acids exert both beneficial and pathological role in gut and other organs in various ways, in which the beneficial effects are more pronounced. In addition, the beneficial effects are reflected in both preventive and therapeutic effects. More importantly, the mechanisms behinds the gut and other tissues provided insight into the function of SCFA, assisting in the development of novel preventive and therapeutic strategies for maintaining the host health.

Evaluation of Pericoronary Fat Attenuation Index to Better Identify Culprit Lesions in Acute Coronary Syndrome According to Stenosis Severity.

OBJECTIVE: To investigate the incremental value of pericoronary fat attenuation index (FAI) in routine coronary artery computed tomography angiography (CCTA) to identify culprit lesions in acute coronary syndrome (ACS). METHODS: We reviewed the CCTA data from 80 ACS patients and 40 individuals with stable coronary atherosclerosis. ACS patient plaques were categorized into culprit and nonculprit groups. The plaque-specific pericoronary FAI was assessed using the Perivascular Fat Analysis Tool. We applied a default prespecified window of -190 to -30 Hounsfield units (HU) and a broader prespecified window of -190 to 20 HU. FAI values within these prespecified windows and the types and severity of plaque stenosis were compared across the 3 groups. Additionally, we investigated high-risk characteristics of plaques in the ACS group and their correlation with FAI. The effectiveness and worthiness of FAI in identifying culprit lesions were analyzed based on the receiver operating characteristic curve. RESULTS: The FAI values under the 2 prespecified windows were higher in the culprit group than in the nonculprit and control groups (all P < 0.001). The culprit group showed the most mixed plaques and the most severe stenosis (all P < 0.001). In the ACS group, the FAI value was significantly lower around calcified lesions (-85.00 ± 9.97 HU) than around noncalcified (-78.00 ± 11.52 HU) and mixed plaques (-78.00 ± 9.24 HU) (both P < 0.001). The culprit group had more high-risk plaques, and high-risk plaques had higher FAI values than those without high-risk characteristics (-70.00 ± 7.67 HU vs -82.00 ± 10.16 HU, P < 0.001). The efficacy of FAI under the default prespecified window in identifying culprit lesions was higher compared than that under the broader prespecified window (area under the curve = 0.799 vs 0.761, P = 0.042), and the diagnostic cutoff values were -77 versus -58 HU. The FAI under the default prespecified window exhibited an incremental value for identifying culprit lesions, as compared with stenosis severity (area under the curve = 0.970 vs 0.939, P < 0.001). CONCLUSION: The culprit lesions have higher FAI than the nonculprit lesions and the controls. FAI is a worthy parameter for identifying culprit lesions in routine CCTA according to stenosis severity, and the default prespecified window is a better option.

Tofacitinib prevents depressive-like behaviors through decreased hippocampal microgliosis and increased BDNF levels in both LPS-induced and CSDS-induced mice.

Depressive disorders are a global mental health challenge that is closely linked to inflammation, especially in the post-COVID-19 era. The JAK-STAT pathway, which is primarily associated with inflammatory responses, is not fully characterized in the context of depressive disorders. Recently, a phase 3 retrospective cohort analysis heightened that the marketed JAK inhibitor tofacitinib is beyond immune diseases and has potential for preventing mood disorders. Inspired by these clinical facts, we investigated the role of the JAK-STAT signaling pathway in depression and comprehensively assessed the antidepressant effect of tofacitinib. We found that aberrant activation of the JAK-STAT pathway is highly conserved in the hippocampus of classical depressive mouse models: LPS-induced and chronic social defeat stress (CSDS)-induced depressive mice. Mechanistically, the JAK-STAT pathway mediates proinflammatory cytokine production and microgliosis, leading to synaptic defects in the hippocampus of both depressive models. Remarkably, the JAK inhibitor tofacitinib effectively reverses these phenomena, contributing to its antidepressant effect. These findings indicate that the JAK/STAT pathway could be implicated in depressive disorders, and suggest that the JAK inhibitor tofacitinib has a potential translational implication for preventing mood disorders far beyond its current indications.

Benzodiazole-Based Covalent Organic Frameworks for Enhanced Photocatalytic Dehalogenation of Phenacyl Bromide Derivatives.

Covalent organic frameworks (COFs) have garnered significant interest within the scientific community due to their distinctive ability to act as organic semiconductors responsive to visible light. This unique attribute makes them up-and-coming candidates for facilitating photocatalytic organic reactions. Herein, two donor-acceptor COFs, TPE-BSD-COF and TPE-BD-COF, have been designed and synthesized by incorporating electron-rich tetraphenylethylene and electron-deficient benzoselenadiazole and benzothiadiazole units into the framework through a Schiff-base polycondensation reaction. Both COFs exhibit exceptional crystallinity and enduring porosity. TPE-BSD-COF and TPE-BD-COF exhibit broad light absorption capabilities, a narrow optical band gap, and low electrochemical impedance spectrum (EIS) levels, indicating that the two COFs are effective heterogeneous photocatalysts for the reductive dehalogenation of phenacyl bromide derivatives under blue LED irradiation. A high photocatalytic yield of 98% and 95% was achieved by TPE-BSD-COF and TPE-BD-COF catalysts, respectively, within only one hour.

Induced Extracellular Ice Nucleation Protects Cocultured Spheroid Interior and Exterior during Cryopreservation.

Spheroids and other 3D cellular models more accurately recapitulate physiological responses when compared to 2D models and represent potential alternatives to animal testing. The cryopreservation of spheroids remains challenging, limiting their wider use. Standard DMSO-only cryopreservation results in supercooling to low subzero temperatures, reducing viability, shedding surface cells, and perforating spheroid interiors. Here, cocultured spheroids with differentially labeled outer cell layers allow spatial evaluation of the protective effect of macromolecular ice nucleators by microscopy and histology. Extracellular nucleation is shown to reduce damage to both interior and exterior regions of the spheroids, which will support the development of "off-the-shelf" 3D models.

From bioinformatics to clinical applications: a novel prognostic model of cuproptosis-related genes based on single-cell RNA sequencing data in hepatocellular carcinoma.

OBJECTIVE AND METHODS: To ascertain the connection between cuproptosis-related genes (CRGs) and the prognosis of hepatocellular carcinoma (HCC) via single-cell RNA sequencing (scRNA-seq) and RNA sequencing (RNA-seq) data, relevant data were downloaded from the GEO and TCGA databases. The differentially expressed CRGs (DE-CRGs) were filtered by the overlaps in differentially expressed genes (DEGs) between HCC patients and normal controls (NCs) in the scRNA-seq database, DE-CRGs between high- and low-CRG-activity cells, and DEGs between HCC patients and NCs in the TCGA database. RESULTS: Thirty-three DE-CRGs in HCC were identified. A prognostic model (PM) was created employing six survival-related genes (SRGs) (NDRG2, CYB5A, SOX4, MYC, TM4SF1, and IFI27) via univariate Cox regression analysis and LASSO. The predictive ability of the model was validated via a nomogram and receiver operating characteristic curves. Research has employed tumor immune dysfunction and exclusion as a means to examine the influence of PM on immunological heterogeneity. Macrophage M0 levels were significantly different between the high-risk group (HRG) and the low-risk group (LRG), and a greater macrophage level was linked to a more unfavorable prognosis. The drug sensitivity data indicated a substantial difference in the half-maximal drug-suppressive concentrations of idarubicin and rapamycin between the HRG and the LRG. The model was verified by employing public datasets and our cohort at both the protein and mRNA levels. CONCLUSION: A PM using 6 SRGs (NDRG2, CYB5A, SOX4, MYC, TM4SF1, and IFI27) was developed via bioinformatics research. This model might provide a fresh perspective for assessing and managing HCC.

A robust polyaniline hydrogel electrode enables superior rate capability at ultrahigh mass loadings.

Simultaneously achieving high mass loading and superior rate capability in electrodes is challenging due to their often mutually constrained nature, especially for pseudocapacitors for high-power density applications. Here, we report a robust porous polyaniline hydrogel (PPH) prepared using a facile ice-templated in situ polymerization approach. Owing to the conductive, robust, and porous nanostructures suitable for ultrafast electron and ion transport, the self-supporting pure polyaniline hydrogel electrode exhibits superior areal capacitance without sacrificing rate capability and gravimetric capacitance at an ultrahigh mass loading and notable current density. It achieves a high areal capacitance (15.2 F·cm-2 at 500 mA·cm-2) and excellent rate capability (~92.7% retention from 20 to 500 mA·cm-2) with an ultrahigh mass loading of 43.2 mg cm-2. Our polyaniline hydrogel highlights the potential of designing porous nanostructures to boost the performance of electrode materials and inspires the development of other ultrafast pseudocapacitive electrodes with ultrahigh loadings and fast charge/discharge capabilities.

Effect of resistance exercise on physical fitness, quality of life, and fatigue in patients with cancer: a systematic review.

Objective: The purpose of this study is to conduct a systematic review to assess the effects of different forms of resistance exercises (resistance exercise, resistance exercise combined with aerobic exercise, and resistance exercise combined with other exercises) on physical fitness, quality of life (QOL), and fatigue of patients with cancer. Methods: We conducted a systematic review using the Cochrane Handbook for Systematic Reviews of Interventions guidelines. We searched PubMed, Web of Science, and Scopus databases for the studies from the establishment of the database to September 2023, including randomized controlled trials and clinical trials that evaluated the effects of different resistance exercise on physical fitness, QOL, and fatigue in all patients with cancer. Two reviewers independently assessed the quality of all the included studies using the Cochrane Handbook for Systematic Reviews of Interventions and MINORS scale. We divided the intervention into three types: resistance exercise, resistance exercise combined with aerobic exercise, and resistance exercise combined with other exercises. Results: In total, 48 studies (3,843 participants) met the inclusion criteria. The three exercise intervention forms have significant effects on physical fitness and QOL, but the improvement effect on fatigue is not clear. A total of 34 studies reported significant and beneficial effects of resistance exercise on physical fitness across all types of cancer. There were 28 studies that reported significant or borderline improvement effects of resistance on QOL, and only 10 studies reported significant effects of resistance exercise interventions on fatigue improvement in patients with cancer. Conclusions: Resistance exercise, resistance exercise combined with aerobic exercise, and resistance exercise combined with other exercises all have a positive effect on improving fitness and QOL in patients with cancer. Resistance exercise has an advantage in improving muscle strength, while combined resistance exercise has an advantage in improving QOL; however, there are no consistent findings in improving fatigue, although low-intensity resistance exercise is effective. Systematic review registration: www.inplasy.com, identifier INPLASY2023110034.

Exploration of iodine adsorption performance of pyrene-based two-dimensional covalent organic frameworks.

Radioiodine (mainly 129I and 131I) is known to be dangerous nuclear waste due to its high toxicity, fast mobility and long radioactive half-life. As an emerging class of novel porous organic polymers, covalent organic frameworks (COFs) have demonstrated tremendous application potential in the field of radioactive iodine capture because of their high specific surface area and tunable pore structure. Herein, three π-conjugated pyrene-based COFs, namely PyTTA-BPDA-COF, PyTTA-BPY-COF, and PyTTA-BT-COF, have been successfully prepared and used as highly efficient adsorbents for iodine capture. The experimental results show that the three COFs displayed excellent adsorption performance, with adsorption capacity of 5.03, 4.46, and 3.97 g g-1 for PyTTA-BPDA-COF, PyTTA-BPY-COF, and PyTTA-BT-COF, respectively. Additionally, the release rate of iodine-loaded COFs in methanol solution and recyclability were also impressive, demonstrating their potential for practical applications. The mechanism investigation reveals that both imine linkage and π-conjugated structure of the COFs may contribute to their high iodine adsorption capability. This work is instructive as a guide for designing and synthesizing COFs as a solid-phase adsorbent for iodine uptake.

In situ visualization of the cellular uptake and sub-cellular distribution of mussel oligosaccharides.

Unlike chemosynthetic drugs designed for specific molecular and disease targets, active small-molecule natural products typically have a wide range of bioactivities and multiple targets, necessitating extensive screening and development. To address this issue, we propose a strategy for the direct in situ microdynamic examination of potential drug candidates to rapidly identify their effects and mechanisms of action. As a proof-of-concept, we investigated the behavior of mussel oligosaccharide (MOS-1) by tracking the subcellular dynamics of fluorescently labeled MOS-1 in cultured cells. We recorded the entire dynamic process of the localization of fluorescein isothiocyanate (FITC)-MOS-1 to the lysosomes and visualized the distribution of the drug within the cell. Remarkably, lysosomes containing FITC-MOS-1 actively recruited lipid droplets, leading to fusion events and increased cellular lipid consumption. These drug behaviors confirmed MOS-1 is a candidate for the treatment of lipid-related diseases. Furthermore, in a high-fat HepG2 cell model and in high-fat diet-fed apolipoprotein E (ApoE) -/- mice, MOS-1 significantly promoted triglyceride degradation, reduced lipid droplet accumulation, lowered serum triglyceride levels, and mitigated liver damage and steatosis. Overall, our work supports the prioritization of in situ visual monitoring of drug location and distribution in subcellular compartments during the drug development phase, as this methodology contributes to the rapid identification of drug indications. Collectively, this methodology is significant for the screening and development of selective small-molecule drugs, and is expected to expedite the identification of candidate molecules with medicinal effects.

A ginseng polysaccharide protects intestinal barrier integrity in high-fat diet-fed obese mice.

A novel polysaccharide, GPH1, was extracted and isolated from ginseng. Structural analysis of GPH1 revealed a molecular weight of 7.321 × 105 Da and the presence of glucose and galactose components in a 30.2: 1 molar ratio. Results of methylation and NMR analyses indicated the GPH1 backbone consisted of →1)-α-Glc-(3→ and →1)-α-Glc-(6→. The anti-obesity activity of GPH1 was assessed by HFD-induced obesity mouse model. GPH1 was found to significantly reduced body weight, alleviated liver lipid accumulation and inflammatory damage. Meanwhile, GPH1 treatment increased the expression of tight junction proteins, including zonula occludens-1 (ZO-1) and claudin-1, while also regulating the intestinal microbiota of obese mice by promoting proliferation of beneficial bacteria with known anti-obesity effects, including s_Akkermansia muciniphila, s_Lactobacillus intestinalis, s_Lactobacillus reuteri, s_Streptococcus hyointestinalis, and s_Lactococcus garvieae. Our findings demonstrated that GPH1 is a practical natural dietary supplement with potential therapeutic effects on obesity.

Isorhamnetin improves diabetes-induced erectile dysfunction in rats through activation of the PI3K/AKT/eNOS signaling pathway.

Erectile dysfunction is a complex and common complication of diabetes mellitus, which lacks an effective treatment. The repairing role of vascular endothelium is the current research hotspot of diabetic mellitus erectile dysfunction (DMED), and the activation of PI3K/AKT/eNOS pathway positively affects the repair of vascular endothelium. The herbal extract isorhamnetin has significant vasoprotective effects and has great potential in treating DMED. This study aimed to clarify whether isorhamnetin has an ameliorative effect on DMED and to investigate the modulation of the PI3K/AKT/eNOS signaling pathway by isorhamnetin to discover its potential mechanism of action. In vivo experiments were performed using a streptozotocin-induced diabetic rat model, and efficacy was assessed after 4 weeks of isorhamnetin gavage administration at 10 mg/kg or 20 mg/kg. Erectile function in rats was assessed by maximum intracavernous pressure/mean arterial pressure (ICPmax/MAP), and changes in corpus cavernosum (CC) fibrosis, inflammation levels, oxidative stress levels, and apoptosis were assessed by molecular biology techniques. In vitro experiments using high glucose-induced corpus cavernosum endothelial cells were performed to further validate the anti-apoptotic effect of isorhamnetin and its regulation of the PI3K/AKT/eNOS pathway. The findings demonstrated that isorhamnetin enhanced erectile function, decreased collagen content, and increased smooth muscle content in the CC of diabetic rats. In addition, isorhamnetin decreased the serum levels of pro-inflammatory factors IL-6, TNF-α, and IL-1ß, increased the levels of anti-inflammatory factors IL-10 and IL-4, increased the activities of SOD, GPx, and CAT as well as the levels of NO, and decreased the levels of MDA in corpus cavernosum tissues. Isorhamnetin also increased the content of CD31 in CC tissues of diabetic rats, activated the PI3K/AKT/eNOS signaling pathway, and inhibited apoptosis. In conclusion, isorhamnetin exerts a protective effect on erectile function in diabetic rats by reducing the inflammatory response, attenuating the level of oxidative stress and CC fibrosis, improving the endothelial function and inhibiting apoptosis. The mechanism underlying these effects may be linked to the activation of the PI3K/AKT/eNOS pathway.

Ginseng total saponin improves red blood cell oxidative stress injury by regulating tyrosine phosphorylation and glycolysis in red blood cells.

BACKGROUND: Oxidative stress is the main cause of many diseases, but because of its complex pathogenic factors, there is no clear method for treating it. Ginseng total saponin (GTS) an important active ingredients in Panax ginseng C.A. Mey (PG) and has potential therapeutic ability for oxidative stress due to various causes. However, the molecular mechanism of GTS in the treating oxidative stress damage in red blood cells (RBCs) is still unclear. PURPOSE: This study aimed to examine the protective effect of GTS on RBCs under oxidative stress damage and to determine its potential mechanism. METHODS: The oxidative stress models of rat RBCs induced by hydrogen peroxide (H2O2) and exhaustive swimming in vivo and in vitro was used. We determined the cell morphology, oxygen carrying capacity, apoptosis, antioxidant capacity, and energy metabolism of RBCs. The effect of tyrosine phosphorylation (pTyr) of Band 3 protein on RBCs glycolysis was also examined. RESULTS: GTS reduced the hemolysis of RBCs induced by H2O2 at the lowest concentration. Moreover, GTS effectively improved the morphology, enhanced the oxygen carrying capacity, and increased antioxidant enzyme activity, adenosine triphosphate (ATP) levels, and adenosine triphosphatase (ATPase) activity in RBCs. GTS also promoted the expression of membrane proteins in RBCs, inhibited pTyr of Band 3 protein, and further improved glycolysis, restoring the morphological structure and physiological function of RBCs. CONCLUSIONS: This study shows, that GTS can protect RBCs from oxidative stress damage by improving RBCs morphology and physiological function. Changes in pTyr expression and its related pTyr regulatory enzymes before and after GTS treatment suggest that Band 3 protein is the main target of GTS in the treating endogenous and exogenous oxidative stress. Moreover, GTS can enhance the glycolytic ability of RBCs by inhibiting pTyr of Band 3 protein, thereby restoring the function of RBCs.

Butyrate improves recovery from experimental necrotizing enterocolitis by metabolite hesperetin through potential inhibition the PI3K-Akt pathway.

Necrotizing enterocolitis (NEC) is one of the most common and serious intestinal illnesses in newborns and seriously affects their long-term prognosis and survival. Butyrate is a short-chain fatty acid that can relieve intestinal inflammation, but its mechanism of action is unclear. Results from an in vivo neonatal rat model has shown that butyrate caused an improved recovery from NEC. These protective effects were associated with the metabolite of hesperetin, as determined by metabolomics and molecular biological analysis. Furthermore, transcriptomics combined with inhibitor assays were used to investigate the mechanism of action of hesperetin in an in vitro NEC model (IEC-6 cells exposed to LPS) to further investigate the mechanism by which butyrate attenuates NEC. The transcriptomics analysis showed that the PI3K-Akt signaling pathway was involved in the anti-NEC effect of hesperitin. Subsequently, the results using an inhibitor of PI3K (LY294002) indicated that the suppression could be explained by the hesperetin-induced expression of tight junction (TJ) proteins by potentially blocking the PI3K-Akt signaling pathway. In summary, the present study demonstrated that butyrate could improve recovery from NEC with a hesperetin metabolite, causing potential inhibition of the phosphorylation of the PI3K-Akt signaling pathway, resulting in the increased expression of TJ proteins. These findings reveal a potential new therapeutic pathway for the treatment of NEC.

Testis-Specific Protein, Y-Encoded-Like 2 Activates JAK2/STAT3 Pathway in Hypothalamic Paraventricular Nucleus to Sustain Hypertension.

BACKGROUND: In the hypothalamic paraventricular nucleus (PVN) of spontaneously hypertensive rats (SHRs), the expression of the testis-specific protein, Y-encoded-like 2 (TSPYL2) and the phosphorylation level of Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) are higher comparing with the normotensive Wistar Kyoto rats (WKY). But how they are involved in hypertension remains unclear. TSPYL2 may interact with JAK2/STAT3 in PVN to sustain high blood pressure during hypertension. METHODS: Knockdown of TSPYL2 via adeno-associated virus (AAV) carrying shRNA was conducted through bilateral microinjection into the PVN of SHR and WKY rats. JAK2/STAT3 inhibition was achieved by intraperitoneally or PVN injection of AG490 into the SHRs. Blood pressure (BP), plasma norepinephrine (NE), PVN inflammatory response, and PVN oxidative stress were measured. RESULTS: TSPYL2 knock-down in the PVN of SHRs but not WKYs led to reduced BP and plasma NE, deactivation of JAK2/STAT3, decreased expression of pro-inflammatory cytokine IL-1ß, and increased expression of anti-inflammatory cytokine IL-10 in the PVN. Meanwhile, AG490 administrated in both ways reduced the BP in the SHRs and deactivated JAK2/STAT3 but failed to change the expression of TSPYL2 in PVN. AG490 also downregulated expression of IL-1ß and upregulated expression of IL-10. Both knockdown of TSPYL2 and inhibition of JAK2/STAT3 can reduce the oxidative stress in the PVN of SHRs. CONCLUSION: JAK2/STAT3 is regulated by TSPYL2 in the PVN of SHRs, and PVN TSPYL2/JAK2/STAT3 is essential for maintaining high BP in hypertensive rats, making it a potential therapeutic target for hypertension.