Extrusion modification of prolamins from distiller's grains to facilitate the construction of biopolymer films.

BACKGROUND: Distiller's grains (DGs), which are rich in natural ingredients such as prolamins, are often used as low-value feed or discarded directly, resulting in great environmental pollution and resource waste. Prolamins from DGs (PDGs) were found to be a potential material for the construction of biopolymer films due to their good film-forming properties. In this study, extrusion processing was conducted to modify the physicochemical and structural properties of PDGs to facilitate the construction of biopolymer films with superior characteristics. RESULTS: Results indicated that extrusion led to improved solubility (17.91% to 39.95%) and increased disulfide bonds (1.46 to 6.13 µmol g-1) in PDGs. The total and sulfur amino acid contents of extruded PDGs were increased by 13.26% and 38.83%, respectively. New aggregation patterns were formed after extrusion according to the results of scanning electron microscopy, Fourier transform infrared spectroscopy and X-ray diffraction. Extrusion resulted in reduced surface hydrophobicity of PDGs (10 972 to 3632), sufficient evidence for which could be also found from structure analyses of PDGs. Finally, PDGs extruded at 110 °C were found to facilitate the forming of biopolymer films with superior mechanical properties, water resistance and thermal stability. CONCLUSIONS: Physicochemical and structural properties of PDGs were effectively modified by extrusion processing, and extrusion modification of PDGs could be a great way to facilitate the construction of biopolymer films with superior characteristics. It could provide more possibilities to extend the applications of DGs to alleviate the problems of environmental pollution and resource waste. © 2024 Society of Chemical Industry.

The effect of chronic academic stress on intentional forgetting.

This study investigated whether chronic academic stress could affect the directed forgetting (DF) process. Both the stress group (undergoing preparation for a major academic examination) and the control group performed a DF task. A forgetting cue was presented after a to-be-forgotten (TBF) word, whereas no cue appeared after a to-be-remembered (TBR) item in the study phase. An old/new recognition test was used in the test phase. The results showed that (1) the stress group showed a higher level of self-reported stress, state anxiety, negative affect, and decreased cortisol awakening response (CAR) compared with the control group, suggesting a higher level of stress for the stress group. (2) Both groups showed superior recognition performance of TBR than TBF items, suggesting a DF effect. (3) The stress group showed inferior recognition performance of TBF items and an enhanced DF effect compared with the control group. These results demonstrated that the intentional memory control process might be enhanced under chronic academic stress.

Influence of magnetic field on gluten aggregation behavior and quality characteristics of dough enriched with potato pulp.

This study investigated the effect of varying magnetic field intensities (ranging from 0 to 10 mT) on the quality characteristics of dough with 40 % potato pulp substitution (DPP). The results indicated that the DPP fermented with a 4 mT magnetic field exhibited a significant enhancement in the combination of water and substrate, thereby elevating the viscoelastic properties of DPP through reinforcing the stability of gluten network. Meanwhile, DPP treated with a 4 mT magnetic field exhibited the highest amount of disulfide bonds (11.64 µmol SS/g sample). This is accompanied by a prominent cross-linkage structure, as evidenced by SDS-PAGE and CLSM. Notably, the application of a magnetic field substantially augments the dough's capacity to retain gas during fermentation. In addition, the application of magnetic field significantly increased the wet gluten content (20.85 %, P < 0.05) in DPP, which improved tensile properties and an acceptable color profile. The introduction of a magnetic field induces gluten aggregation, which in turn results in heightened particle size distribution and ζ-potential values. In conclusion, this study emphasize the potential of magnetic field technology as a viable method to enhance the overall quality attributes of dough enriched with potato pulp substitution.

A syndrome differentiation model of TCM based on multi-label deep forest using biomedical text mining.

Syndrome differentiation and treatment is the basic principle of traditional Chinese medicine (TCM) to recognize and treat diseases. Accurate syndrome differentiation can provide a reliable basis for treatment, therefore, establishing a scientific intelligent syndrome differentiation method is of great significance to the modernization of TCM. With the development of biomdical text mining technology, TCM has entered the era of intelligence that based on data, and model training increasingly relies on the large-scale labeled data. However, it is difficult to form a large standard data set in the field of TCM due to the low degree of standardization of TCM data collection and the privacy protection of patients' medical records. To solve the above problem, a multi-label deep forest model based on an improved multi-label ReliefF feature selection algorithm, ML-PRDF, is proposed to enhance the representativeness of features within the model, express the original information with fewer features, and achieve optimal classification accuracy, while alleviating the problem of high data processing cost of deep forest models and achieving effective TCM discriminative analysis under small samples. The results show that the proposed model finally outperforms other multi-label classification models in terms of multi-label evaluation criteria, and has higher accuracy in the TCM syndrome differentiation problem compared with the traditional multi-label deep forest, and the comparative study shows that the use of PCC-MLRF algorithm for feature selection can better select representative features.

Carbon and nitrogen sources consumption by ale and lager yeast strains: a comparative study during fermentation.

The rapid and efficient consumption of carbon and nitrogen sources by brewer's yeast is critical for the fermentation process in the brewing industry. The comparison of the growth characterizations of typical ale and lager yeast, as well as their consumption preference to carbon and nitrogen sources were investigated in this study. Results showed that the ale strain grew faster and had a more extended stationary phase than the lager strain. However, the lager strain was more tolerant to the stressful environment in the later stage of fermentation. Meanwhile, the ale and lager yeast strains possessed varying preferences for metabolizing the specific fermentable sugar or free amino acid involved in the wort medium. The lager strain had a strong capacity to synthesize the extracellular invertase required for hydrolyzing sucrose as well as a strong capability to metabolize glucose and fructose. Furthermore, the lager strain had an advantage in consuming Lys, Arg, Val, and Phe, whereas the ale strain had a higher assimilation rate in consuming Tyr. These findings provide valuable insights into selecting the appropriate brewer's yeast strain based on the wort components for the industrial fermentation process. KEY POINTS: • The lager strain is more tolerant to the stressful environment. • The lager strain has the great capability to synthesize the extracellular invertase. • The assimilation efficiency of free amino acid varies between ale and lager.

Discovery of NAFLD-Improving Agents by Promoting the Degradation of Keap1.

Activating Nrf2 through inhibiting Keap1 has been proven to alleviate oxidative stress and related diseases, including nonalcoholic fatty liver disease (NAFLD). Traditional Keap1 inhibitors could not avoid the "off-target" effects, but using proteolysis targeting chimera (PROTAC) technology to induce Keap1 degradation might be an effective strategy to find potential NAFLD improving agents. Thus, several PROTACs were designed and synthesized by harnessing CDDO as the Keap1 ligand in this study. PROTAC I-d exhibited optimal Keap1 degradation activity, which could increase the Nrf2 level and alleviate oxidative stress in free fatty acid-induced AML12 cells and the liver of mice fed with a methionine-choline-deficient diet. Moreover, compared with CDDO, PROTAC I-d displayed significant advantages in inhibiting hepatic steatosis, steatohepatitis, and fibrosis in the in vivo and in vitro models of NAFLD. In addition, PROTAC I-d also showed lower in vivo toxicity than CDDO. All these results suggested that PROTAC I-d might be a potential improving agent for NAFLD.

Left dorsolateral prefrontal cortex activation can accelerate stress recovery: A repetitive transcranial stimulation study.

In this study, a single high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) session was applied over the left dorsolateral prefrontal cortex (DLPFC) after a moderate-to-intense stressor to investigate whether left DLPFC stimulation could regulate cortisol concentration after stress induction. Participants were randomly divided into three groups (stress-TMS, stress, and placebo-stress). Stress was induced in both the stress-TMS and stress groups using the Trier Social Stress Test (TSST). The placebo-stress group received a placebo TSST. In the stress-TMS group, a single HF-rTMS session was applied over the left DLPFC after TSST. Cortisol was measured across the different groups, and each group's responses to the stress-related questionnaire were recorded. After TSST, both the stress-TMS and stress groups reported increased self-reported stress, state anxiety, negative affect, and cortisol concentration compared with the placebo-stress group, indicating that TSST successfully induced a stress response. Compared with the stress group, the stress-TMS group exhibited reduced cortisol levels at 0, 15, 30, and 45 min after HF-rTMS. These results suggest that left DLPFC stimulation after stress induction might accelerate the stress recovery.

14-3-3ζ Plays a key role in the modulation of neuroplasticity underlying the antidepressant-like effects of Zhi-Zi-Chi-Tang.

BACKGROUND: Zhi-Zi-Chi-Tang (ZZCT) is an effective traditional Chinese medicinal formula. ZZCT has been used for the treatment of depression for centuries. Its clinical efficacy in relieving depression has been confirmed. However, the molecular mechanisms of ZZCT regarding neuroplasticity in the pathogenesis of depression have not yet been elucidated. PURPOSE: The present study aimed to examine the effects of ZZCT on neuroplasticity in mice exposed to chronic unpredictable mild stress (CUMS), and to explore the underlying molecular mechanisms. METHODS: For this purpose, a murine model of depression was established using the CUMS procedure. Following the intragastric administration of ZZCT or fluoxetine, classic behavioral experiments were performed to observe the efficacy of ZZCT as an antidepressant. Immunofluorescence was used to label and quantify microtubule-associated protein (MAP2) and postsynaptic density protein (PSD95) in the hippocampus. Golgi staining was applied to visualize the dendritic spine density of neurons in the hippocampi. Isolated hippocampal slices were prepared to induce long-term potentiation (LTP) in the CA1 area. The hippocampal protein expression levels of glycogen synthase kinase-3ß (GSK-3ß), p-GSK-3ß (Ser9), cAMP response element binding protein (CREB), p-CREB (Ser133), brain-derived neurotrophic factor (BDNF) and 14-3-3ζ were detected using western blot analysis. The interaction of 14-3-3ζ and p-GSK-3ß (Ser9) was examined using co-immunoprecipitation. LV-shRNA was used to knockdown 14-3-3ζ by an intracerebroventricular injection. RESULTS: ZZCT (6 g/kg) and fluoxetine (20 mg/kg) alleviated depressive-like behavior, restored hippocampal MAP2+ PSD95+ intensity, and reversed the dendritic spine density of hippocampal neurons and LTP in the CA1 region of mice exposed to CUMS. Both low and high doses of ZZCT (3 and 6 g/kg) significantly promoted the binding of 14-3-3ζ to p-GSK-3ß (Ser9) in the hippocampus, and ZZCT (6 g/kg) significantly promoted the phosphorylation of GSK-3ß Ser9 and CREB Ser133 in the hippocampus. ZZCT (3 and 6 g/kg) upregulated hippocampal BDNF expression in mice exposed to CUMS. LV-sh14-3-3ξ reduced the antidepressant effects of ZZCT. CONCLUSION: ZZCT exerted antidepressant effects against CUMS-stimulated depressive-like behavior mice. The knockdown of 14-3-3ζ using lentivirus confirmed that 14-3-3ζ was involved in the ZZCT-mediated antidepressant effects through GSK-3ß/CREB/BDNF signaling. On the whole, these results suggest that the antidepressant effects of ZZCT are attributed to restoring damage by neuroplasticity enhancement via the 14-3-3ζ/GSK-3ß/CREB/BDNF signaling pathway.

Curcumin: a natural organic component that plays a multi-faceted role in ovarian cancer.

Curcumin, a natural organic component obtained from Curcuma longa's rhizomes, shows abundant anti-tumor, antioxidant and anti-inflammatory pharmacological activities, among others. Notably the anti-tumor activity has aroused widespread attention from scholars worldwide. Numerous studies have reported that curcumin can delay ovarian cancer (OC), increase its sensitivity to chemotherapy, and reduce chemotherapy drugs' side effects. It has been shown considerable anticancer potential by promoting cell apoptosis, suppressing cell cycle progression, inducing autophagy, inhibiting tumor metastasis, and regulating enzyme activity. With an in-depth study of curcumin's anti-OC mechanism, its clinical application will have broader prospects. This review summarizes the latest studies on curcumin's anti-OC activities, and discusses the specific mechanism, hoping to provide references for further research and applications.

Metabolomic analysis-identified 2-hydroxybutyric acid might be a key metabolite of severe preeclampsia.

This study set out to determine the key metabolite changes underlying the pathophysiology of severe preeclampsia (PE) using metabolic analysis. We collected sera from 10 patients with severe PE and from 10 healthy pregnant women of the same trimester and analyzed them using liquid chromatography mass spectrometry. A total of 3,138 differential metabolites were screened, resulting in the identification of 124 differential metabolites. Kyoto encyclopedia of genes and genomes pathway analysis revealed that they were mainly enriched in the following metabolic pathways: central carbon metabolism in cancer; protein digestion and absorption; aminoacyl-transfer RNA biosynthesis; mineral absorption; alanine, aspartate, and glutamate metabolism; and prostate cancer. After analysis of 124 differential metabolites, 2-hydroxybutyric acid was found to be the most critical differential metabolite, and its use allowed the differentiation of women with severe PE from healthy pregnant women. In summary, our analysis revealed that 2-hydroxybutyric acid is a potential key metabolite for distinguishing severe PE from healthy controls and is also a marker for the early diagnosis of severe PE, thus allowing early intervention.

Modification mechanism of protein in rice adjuncts upon extrusion and its effects on nitrogen conversion during mashing.

The traditional production of wort with adjunct-introduced was achieved by double mashing procedure, which hindered the utilization of proteins in adjunct and led to a deficiency of nitrogen in wort. In this study, the modification mechanism of the extrusion pretreatment on the structure characterization of rice flour protein was investigated. The decoction mashing procedure was performed to enhance the nitrogen conversion of the extruded rice adjunct. Decreased solubility along with disrupted secondary and tertiary structures of rice protein were observed after extrusion. As a result, the total nitrogen, free amino nitrogen, and free amino acids content of wort with extruded rice adjunct-introduced were improved by 23.28 %, 34.67 %, and 7.33 %, respectively, which could be verified by the electrophoretic patterns of the wort protein. The application of extrusion as a pretreatment of adjuncts can promote the protein availability of adjuncts in the decoction mashing stage.

A natural carotenoid crocin exerts antidepressant action by promoting adult hippocampal neurogenesis through Wnt/ß-catenin signaling.

INTRODUCTION: Adult hippocampal neurogenesis (AHN) is acknowledged to play a critical role in depression. Emerging evidence suggests that the Wnt/ß-catenin pathway can modulate hippocampal neurogenesis. Crocin, a natural carotenoid, possesses antidepressant property. Yet, how it affects neurogenesis and exerts antidepressant response remains unknown. OBJECTIVE: To explore the role of AHN and Wnt/ß-catenin in the antidepressant action of crocin. METHODS: Depressive-related behaviors, including sucrose preference test (SPT), tail suspension test (TST), forced swimming test (FST), and sexual behaviors were performed following crocin treatment. Neurogenesis was characterized via immunohistochemistry, immunofluorescence, Golgi staining and electrophysiology approach. Wnt/ß-catenin signaling was examined with western blot analysis. The role of AHN Wnt/ß-catenin cascade in crocin's antidepressant response was assessed by conditional removal of glial fibrillary acidic protein (GFAP)-expressing newborn neural cells, temozolomide administration, microinfusion of Dkk1 or viral-mediated shRNA of Wnt3a. RESULTS: Crocin decreased the immobility duration in TST and FST without impairing the performance in sexual behaviors. Crocin boosted the proliferation and differentiation of progenitors, and promoted dendritic maturation and functional integration of hippocampal newborn neurons. Conditional removal of GFAP-expressing neural cells or temozolomide administration impaired the antidepressant response of crocin. Additionally, Wnt/ß-catenin signaling was promoted following crocin treatment. In chronic unpredictable mild stress (CUMS) murine model, crocin treatment displayed antidepressant response in SPT, FST and TST, and restored the neurogenesis levels and Wnt/ß-catenin signaling impaired by CUMS. Infusion of Dickkopf-1 (DKK1) or knockdown of Wnt3a in the hippocampus impaired the antidepressant response of crocin. CONCLUSION: Crocin exerted antidepressant response, which was dependent on enhancement of AHN and activation of the Wnt/ß-catenin pathway.

Study of ultrasonic treatment on the structural characteristics of gluten protein and the quality of steamed bread with potato pulp.

Physicochemical properties and microstructure of gluten protein, and the structural characteristics of steamed bread with 30 % potato pulp (SBPP) were investigated by ultrasonic treatments. Results showed that 400 W ultrasonic treatment significantly (P < 0.05) increased the combination of water and substrate in the dough with 30 % potato pulp (DPP). The contents of wet gluten, free sulfhydryl (SH), and disulfide bond (SS) were influenced by ultrasonic treatment. Moreover, UV-visible and fluorescence spectroscopy demonstrated that the conformation of gluten protein was changed by ultrasonic treatment (400 W). Fourier transform infrared (FT-IR) illustrated that the ß-sheet content was significantly (P < 0.05) increased (42 %) after 400 W ultrasonic treatment, and the surface hydrophobicity of gluten protein in SBPP increased from 1225.37 (0 W ultrasonic treatment) to 4588.74 (400 W ultrasonic treatment). Ultrasonic treatment facilitated the generation of a continuous gluten network and stabilized crumb structure, further increased the specific volume and springiness of SBPP to 18.9 % and 6.9 %, respectively. Those findings suggested that ultrasonic treatment would be an efficient method to modify gluten protein and improve the quality of SBPP.

G6PD promotes cell proliferation and dexamethasone resistance in multiple myeloma via increasing anti-oxidant production and activating Wnt/ß-catenin pathway.

BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD) as the rate-limiting enzyme in the pentose phosphate pathway (PPP) is well-established as an aberrantly expressed protein in numerous clinical diseases; however, its role in cancer, specifically in multiple myeloma (MM) remains elusive. METHODS: In this study, serum metabolites in 70 normal people and 70 newly diagnosed MM patients were analyzed using untargeted metabolomics and the results were verified using ELISA. The survival analysis of multiple clinical datasets was performed to identify a potential target gene in MM. The oncogenic role of G6PD was investigated using lentivirus-based overexpression or knockdown of G6PD using RNAi or an inhibitor in vitro, and in a xenograft mouse model in vivo. The mechanisms of induced Dexamethasone (Dexa)-resistance of G6PD were further explored using the above established MM cell lines in vitro. RESULTS: Based on the screening of potential genes, PPP was shown to be involved in the occurrence of MM, which was evidenced by the differential expression of serum metabolites of G6P and Dehydroepiandrosterone sulfate (DHEAS, the more stable sulfate ester form of an endogenously uncompetitive G6PD inhibitor known as DHEA). Elevated G6PD promoted MM cell proliferation. Mechanistically, high G6PD expression enhanced enzymatic generation of the antioxidant NADPH via the PPP and decreased the production of reactive oxygen species (ROS), thus inducing the proliferation and Dexa resistance in MM cells. Furthermore, canonical Wnt/ß-catenin signaling also participated in regulating G6PD-induced drug resistance and cellular redox levels of ROS. Intriguingly, DHEA treatment could enhance the sensitivity of MM cells to Dexa primarily through augmenting cellular oxidative stress. CONCLUSIONS: Our data demonstrate that G6PD enhances the generation of the enzymatic anti-oxidant NADPH and decreases ROS generation, thereby promoting resistance to Dexa-induced apoptosis via the enzymatic PPP and non-enzymatic Wnt/ß-catenin signaling pathway in MM. Targeting G6PD to harness cellular redox may serve as a promising novel strategy for the management of MM.

The Influence of Parental Environmental Exposure and Nutrient Restriction on the Early Life of Offspring Growth in Gambia-A Pilot Study.

BACKGROUND: The role of the germline in epigenetic transgenerational inheritance starts with environmental factors, acting on the first generation of a gestating mother. These factors influence the developing second-generation fetus by altering gonadal development, thereby reprogramming the primordial germ cell DNA methylation and leading to consequences that might be seen along generations. OBJECTIVE: Despite these epigenetic factors now surfacing, the few available studies are on animal-based experiments, and conducting a follow-up on human intergenerational trials might take decades. To this response, this study aimed to determine the influence of parental energy, toxicant exposure, age, and nutrient restriction on the early life of offspring growth in Gambia. METHOD: This pilot study was based on population observation and combined both maternal and paternal factors across the country between August and October 2021. It captures the lifestyle and health detailed account of 339 reproductive parents and their last born (child under 5 years) using a structured interview questionnaire performed by nurses and public health officers. RESULTS: This study showed that parents who worked in industrial areas were more likely to have offspring with poor psychosocial skills. In addition, mothers who are exposed to oxidative stress and high temperatures are more likely to have offspring with poor psychosocial skills. Mothers who consume a high-protein diet were almost three times more likely to have infants with good psychosocial skills in their offspring. Furthermore, there was a negative correlation between maternal stress during pregnancy and the psychosocial skills of offspring. CONCLUSION: This study was able to ascertain if the maternal diet during gestation, toxicant exposure, maternal stress, and parental smoking habits have an influence on the early life of offspring. While the study recommends a large sample size study to eliminate selection bias, there should be an increased level of awareness of mothers of their offspring's health and their husbands' lifestyles that might influence the adulthood health of their offspring.

A functional near-infrared spectroscopy investigation of item-method directed forgetting.

Whether directed forgetting is passive or active remains debated. Using functional near-infrared spectroscopy (fNIRS), blood-oxygen level-dependent responses of intentional forgetting were investigated in the item-method directed forgetting (DF) paradigm. During the study phase, each word was followed by a random remembering or forgetting cue indicating whether the word is to be remembered (TBR) or to be forgotten (TBF). A recognition test was used in the test phase and four cue-response conditions were obtained: remembering/forgetting cues associated with the subsequently remembered (TBR-r/TBF-r) or forgotten (TBR-f/TBF-f) words. Data from 16 healthy adult participants showed a DF effect. The fNIRS data revealed that, during the 5-9 s time window, the oxygenate hemoglobin (oxy-Hb) levels were higher during intentional forgetting compared to intentional remembering in the left inferior frontal (TBF-f vs. TBR-f) and right superior frontal gyrus (TBF-r vs. TBR-r), indicating more frontal inhibition involved during intentional forgetting. During the 9-11 s time window, the oxy-Hb level in the frontal and parietal gyrus was higher for forgetting than remembering cues, indicating that the TBF words might be automatically encoded. In sum, the TBF words might receive inhibition control triggered by forgetting cues and then be automatically encoded with the increase of the post-cue interval.

The ERP correlates of color-based center-surround inhibition in working memory.

The color-based center-surround inhibition (CSI) in working memory (WM) refers to that remembering a color inhibits the memory of similar colors but not of distinct colors. This study aimed to investigate the neural activity of color-based CSI in WM. Two WM items (distance 0°, 10°, 20°, 30°, 40°, 50°, or 60° in color space) were displayed sequentially, then one of them was retrieved to compare with a later probe. Behavioral results revealed that participants showed longer RTs for distances 20° and 30° than distances 0° and 40°, suggesting a CSI between similar items. ERP results revealed that: 1) WM item-induced late positive component (LPC) was more positive for distance 30° than the other distances, suggesting an enhanced resource allocation process for encoding similar items; 2) Cue-induced LPC was more positive for distances 20° and 30° than distances 0° and 60°, suggesting a greater difficulty for retrieving similar items; Cue-induced contingent negative variation was less negative for distance 20° than distances 40°, 50°, and 60°, suggesting a reduced response preparation process during retrieving similar items; 3) Probe-induced LPC was more positive for distances 20° and 30° than distances 50° and 60°, suggesting a greater effort for comparing probe with one item retrieved from two similar items. These results revealed a colored-based CSI during WM encoding and retrieval processes. An enhanced top-down control might be required to resolve the greater interference between similar items than identical or distinct items conditions.

lncRNA STAT4-AS1 Inhibited TH17 Cell Differentiation by Targeting RORγt Protein.

Objective: From our previous study, we obtained long noncoding RNA (lncRNA) STAT4-AS1, which is related to asthma through high-throughput screening. However, we could not determine the specific mechanism involved and in response to this. We further designed this study. Results: First, we found that lncRNA STAT4-AS1 was downregulated in T cells from patients with asthma when compared to healthy controls. Next, we confirmed that lncRNA STAT4-AS1 was significantly negatively correlated with T helper 17 (TH17) differentiation in vitro experiments. The decreases of STAT4-AS1 promoted TH17 differentiation, while the increases of STAT4-AS1 inhibited TH17 differentiation. Subsequently, through RNA pull-down, RNA-binding protein immunoprecipitation (RIP), and dual luciferase reporter assay, we found that STAT4-AS1 could inhibit the binding of retinoid-related orphan receptor-γt (RORγt) protein with an IL-17A promoter after binding with RORγt protein. Fluorescence in situ hybridization (FISH) and nuclear-cytoplasmic separation assay showed that STAT4-AS1 is bonded to RORγt in the cytoplasm, preventing RORγt from entering the nucleus. Conclusion: Overall, STAT4-AS1 directly targets RORγt protein, inhibits the mutual binding of RORγt and IL-17 gene promoter, and eventually inhibits TH17 differentiation. To this end, STAT4-AS1 as a potential target may confer applications in the clinical treatment and diagnosis of TH17-related diseases.

The Protective Effect of Pilose Antler Peptide on CUMS-Induced Depression Through AMPK/Sirt1/NF-κB/NLRP3-Mediated Pyroptosis.

Background: Pilose antler peptide (PAP), prepared from the pilose antler of Cervus nippon Temminck, is widely used in traditional Chinese medicine (TCM) against various inflammatory disorders. TCM prescriptions containing pilose antler are often prescribed clinically to treat depression. However, the pharmacological mechanisms of how PAP, against inflammation, prevents and treats depression remain poorly understood. Methods: PAP was identified by de novo sequencing and database searching. Then, behavioral tests were conducted to investigate the effect of PAP on CUMS-exposed mice. In parallel, Nissl staining and Golgi-Cox staining were used for exploring the effect of PAP on neural cells and dendritic spine density. Additionally, the expression of key proteins of the AMPK/Sirt1/NF-κB/NLRP3 pathway was analyzed by Western blot. Finally, the CUMS procedure was conducted for 6 weeks. At the 5th week, PAP and fluoxetine (Flu) were intragastrically treated for 2 weeks. The silencing information regulator-related enzyme 1 (Sirt1) inhibitor EX-527 and the AMP-activated protein kinase (AMPK) inhibitor dorsomorphin were employed to investigate the effects of Sirt1 and AMPK on PAP-mediated depression. Results: PAP attenuated the behavior alteration caused by CUMS stimulation, decreased the number of neurons, and restored the dendritic spine density. PAP treatment effectively upregulated the expressions of p-AMPK and Sirt1 and suppressed the expressions of Ac-NF-κB, NLRP3, Ac-Caspase-1, GSDMD-N, Cleaved-IL-1ß, and Cleaved-IL-18. Moreover, selectively inhibited Sirt1 and AMPK were able to compromise the therapeutic effect of PAP on depression. Conclusion: The present work indicated that PAP has a protective effect on CUMS-induced depression. In addition, AMPK and Sirt1 played critical roles in the PAP-relieved depression. PAP might be a potential therapeutic option for treating depression.