Folic Acid and Taurine Alleviate the Impairment of Redox Status, Immunity, Rumen Microbial Composition and Fermentation of Lambs under Heat Stress.

The aim of this study was to investigate if the supplementation of folic acid and taurine can relieve the adverse effects of different levels of heat stress (HS) on growth performance, physiological indices, antioxidative capacity, immunity, rumen fermentation and microbiota. A total of 24 Dorper × Hu crossbred lambs (27.51 ± 0.96 kg) were divided into four groups: control group (C, 25 °C), moderate HS group (MHS, 35 °C), severe HS group (SHS, 40 °C), and the treatment group, under severe HS (RHS, 40 °C, 4 and 40 mg/kg BW/d coated folic acid and taurine, respectively). Results showed that, compared with Group C, HS significantly decreased the ADG of lambs (p < 0.05), and the ADG in the RHS group was markedly higher than in the MHS and SHS group (p < 0.05). HS had significant detrimental effects on physiological indices, antioxidative indices and immune status on the 4th day (p < 0.05). The physiological indices, such as RR and ST, increased significantly (p < 0.05) with the HS level and were significantly decreased in the RHS group, compared to the SHS group (p < 0.05). HS induced the significant increase of MDA, TNF-α, and IL-ß, and the decrease of T-AOC, SOD, GPx, IL-10, IL-13, IgA, IgG, and IgM (p < 0.05). However, there was a significant improvement in these indices after the supplementation of folic acid and taurine under HS. Moreover, there were a significant increase in Quinella and Succinivibrio, and an evident decrease of the genera Rikenellaceae_RC9_gut_group and Asteroleplasma under HS (p < 0.05). The LEfSe analysis showed that the genera Butyrivibrio, Eubacterium_ventriosum_group, and f_Bifidobacteriaceae were enriched in the MHS, SHS and RHS groups, respectively. Correlated analysis indicated that the genus Rikenellaceae_RC9_gut_group was positively associated with MDA, while it was negatively involved in IL-10, IgA, IgM, and SOD (p < 0.05); The genus Anaeroplasma was positively associated with the propionate and valerate, while the genus Succinivibrio was negatively involved in TNF-α (p < 0.05). In conclusion, folic acid and taurine may alleviate the adverse effects of HS on antioxidant capacity, immunomodulation, and rumen fermentation of lambs by inducing changes in the microbiome that improve animal growth performance.

Semiconducting polymer dots for multifunctional integrated nanomedicine carriers.

The expansion applications of semiconducting polymer dots (Pdots) among optical nanomaterial field have long posed a challenge for researchers, promoting their intelligent application in multifunctional nano-imaging systems and integrated nanomedicine carriers for diagnosis and treatment. Despite notable progress, several inadequacies still persist in the field of Pdots, including the development of simplified near-infrared (NIR) optical nanoprobes, elucidation of their inherent biological behavior, and integration of information processing and nanotechnology into biomedical applications. This review aims to comprehensively elucidate the current status of Pdots as a classical nanophotonic material by discussing its advantages and limitations in terms of biocompatibility, adaptability to microenvironments in vivo, etc. Multifunctional integration and surface chemistry play crucial roles in realizing the intelligent application of Pdots. Information visualization based on their optical and physicochemical properties is pivotal for achieving detection, sensing, and labeling probes. Therefore, we have refined the underlying mechanisms and constructed multiple comprehensive original mechanism summaries to establish a benchmark. Additionally, we have explored the cross-linking interactions between Pdots and nanomedicine, potential yet complete biological metabolic pathways, future research directions, and innovative solutions for integrating diagnosis and treatment strategies. This review presents the possible expectations and valuable insights for advancing Pdots, specifically from chemical, medical, and photophysical practitioners' standpoints.

Dendrobium officinale Polysaccharide (DOP) inhibits cell hyperproliferation, inflammation and oxidative stress to improve keratinocyte psoriasis-like state.

PURPOSE: Psoriasis is a skin disease characterized by excessive proliferation, inflammation and oxidative stress in keratinocytes. The present study aimed to investigate the therapeutic effects of Dendrobium officinale polysaccharide (DOP) on keratinocyte psoriasis-like models. METHODS: The HaCaT keratinocyte inflammation models were induced by interleukin (IL)-22 or lipopolysaccharide (LPS), respectively, and oxidative stress damage within cells was elicited by H2O2 and treated using DOP. CCK-8 and EdU were carried out to detect cell proliferation. ELISA, qRT-PCR, and Western blot were conducted to measure the expression of pro-inflammatory cytokines IL17A, IL-23, IL1ß, tumor necrosis factor alpha (TNF-α), and IL-6. Reactive oxygen species (ROS) level in keratinocytes was detected by flow cytometry. Cell proliferation-associated proteins (PCNA, Ki67, Cyclin D1) and pathway proteins (p-AKT and AKT), and oxidative stress marker proteins (Nrf-2, CAT, SOD1) were detected by Western blot. RESULT: DOP did not affect the proliferation of normal keratinocytes, but DOP was able to inhibit the proliferative activity of IL-22-induced overproliferating keratinocytes and suppress the expression of proliferation-related factors PCNA, Ki67, and Cyclin D1 as well as the proliferation pathway p-AKT. In addition, DOP treatment was able to inhibit IL-22 and LPS-induced inflammation and H2O2-induced oxidative stress, including the expression of IL17A, IL-23, IL1ß, TNF-α, IL-6, and IL1ß, as well as the expression levels of intracellular ROS levels and cellular oxidative stress-related indicators SOD, MDA, CAT, Nrf-2 and SOD1. CONCLUSION: DOP inhibits keratinocyte hyperproliferation, inflammation and oxidative stress to improve the keratinocyte psoriasis-like state.

Dendrobium polysaccharide (DOP) ameliorates the LL-37-induced rosacea by inhibiting NF-κB activation in a mouse model.

BACKGROUND: Rosacea, a common chronic inflammatory skin disease worldwide, is currently incurable with complex pathogenesis. Dendrobium polysaccharide (DOP) may exert therapeutic effects on rosacea via acting on the NF-κB-related inflammatory and oxidative processes. MATERIALS AND METHODS: In this study, an LL-37-induced rosacea-like mouse model was established. HE staining was used to assess the skin lesions, erythema severity scores, pathological symptoms, and inflammatory cell numbers of mice in each group. The inflammation level was quantitatively analyzed using enzyme-linked immunosorbent assay (ELISA) and reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR). The expression levels of TLR4 and p-NF-κB were finally detected. RESULTS: DOP improved skin pathological symptoms of rosacea mice. DOP also alleviated the inflammation of rosacea mice. Moreover, the TLR4/NF-κB pathway was observed to be inhibited in the skin of mice after DOP application. These findings evidenced the anti-inflammatory effects of DOP on the LL-37-induced rosacea mouse model. DOP could inhibit NF-κB activation, suppress neutrophil infiltration, and reduce pro-inflammatory cytokines production, which may be the reason for DOP protecting against rosacea. CONCLUSION: This study may propose an active candidate with great potential for rosacea drug development and lay a solid experimental foundation for promoting DOP application in rosacea therapy.

NEK2 overexpression aggravates IL-22-induced keratinocyte proliferation and cytokine level increases and IMQ-induced psoriasis-like dermatitis.

BACKGROUND: Psoriasis is a common inflammatory skin disease characterized by the excessive proliferation and abnormal differentiation of keratinocytes. Protein kinases could act on intracellular signaling pathways associated with cell proliferation. OBJECTIVE: Identifying more hub protein kinases affecting cellular and molecular processes in psoriasis, and exploring the dynamic effects of baicalin and NEK2 on the IL-22-induced cellular inflammation and IMQ-induced psoriasis-like mice. METHODS AND RESULTS: In this study, differentially expressed protein kinases playing a hub role in psoriasis initiation and development were identified using integrative bioinformatics analyses, and NEK2 has been chosen. NEK2 was significantly up-regulated in psoriatic samples according to online datasets and experimental analyses. In IL-22-induced cellular inflammation model in HaCaT cells, NEK2 overexpression promoted, whereas NEK2 knockdown partially abolished IL-22-induced alterations in cell viability, DNA synthesis, cytokine levels, as well as STAT3 phosphorylation and p-RB, cyclin D1, CDK4, and CDK6 protein contents. Baicalin treatment partially suppressed IL-22-induced HaCaT cell viability, DNA synthesis, and increases in cytokine levels, whereas NEK2 overexpression significantly abolished Baicalin-induced protection against cellular inflammation. In IMQ-induced psoriasis-like skin inflammation model in mice, baicalin markedly ameliorated IMQ-induced psoriasis-like symptoms and local skin inflammation, whereas NEK2 overexpression partially eliminated the therapeutic effects of baicalin. CONCLUSION: NEK2, up-regulated in psoriatic lesion skin, could aggravate IMQ-induced psoriasis-like dermatitis and attenuate the therapeutic efficiency of baicalin through promoting keratinocyte proliferation and cytokine levels. The STAT3 signaling might be involved.

Acupuncture Alleviates CUMS-Induced Depression-Like Behaviors by Restoring Prefrontal Cortex Neuroplasticity.

Purpose: To explore the therapeutic efficiency of acupuncture and the related molecular mechanism of neural plasticity in depression. Methods: Chronic unpredictable mild stress- (CUMS-) induced rats were established for the depression animal model. There were a total of four rat groups, including the control group, the CUMS group, the CUMS+acupuncture group, and the CUMS+fluoxetine group. The acupuncture group and the fluoxetine group were given a 3-week treatment after the modeling intervention. The researcher performed the open-field, elevated plus maze, and sucrose preference tests to evaluate depressive behaviors. The number of nerve cells, dendrites' length, and the prefrontal cortex's spine density were detected using Golgi staining. The prefrontal cortex expression, such as BDNF, PSD95, SYN, and PKMZ protein, was detected using the western blot and RT-PCR. Results: Acupuncture could alleviate depressive-like behaviors and promote the recovery of the neural plasticity functions in the prefrontal cortex, showing the increasing cell numbers, prolonging the length of the dendrites, and enhancing the spine density. The neural plasticity-related proteins in the prefrontal cortex, including BDNF, PSD95, SYN, and PKMZ, were all downregulated in the CUMS-induced group; however, these effects could be partly reversed after being treated by acupuncture and fluoxetine (P < 0.05). Conclusion: Acupuncture can ameliorate depressive-like behaviors by promoting the recovery of neural plasticity functions and neural plasticity-related protein upregulation in the prefrontal cortex of CUMS-induced depressed rats. Our study provides new insights into the antidepressant approach, and further studies are warranted to elucidate the mechanisms of acupuncture involved in depression treatment.

Matrine regulates Th1/Th2 inflammatory responses by inhibiting the Hsp90/NF-κB signaling axis to alleviate atopic dermatitis.

Atopic dermatitis (AD) is a common inflammatory skin disease. Matrine is the main component of the traditional Chinese medicine Sophora flavescens, and it poses good therapeutic effects on inflammatory diseases. This study aimed to explore the pharmacological effects of matrine on AD and its underlying mechanism. An AD mouse model and inflamed human epidermal keratinocyte cells (HaCaT) cells were established. Histopathological aspects were examined using hematoxylin and eosin staining, toluidine blue staining, and immunohistochemistry. The mRNA and protein expressions were assessed using quantitative real-time polymerase chain reaction and Western blot, respectively. The secretions of cytokines and chemokines were examined by enzyme-linked immunosorbent assay. Flow cytometry was carried out to analyze the proportions of T-helper (Th) 1 and Th2 cells. Herein, our results displayed that matrine diminished AD symptoms and decreased heat shock protein 90 (Hsp90) expression. Matrine decreased the Th2 cytokine levels in the ear tissues and serum, and it also significantly repressed inflammatory cytokines (thymus activation regulated chemokine and interleukin-6) secretions by repressing the Hsp90/NF-κB signaling axis in inflamed HaCaT cells. Furthermore, matrine inhibited Th2 differentiation of CD4+ T cells when co-cultured with inflamed HaCaT cells. Matrine can regulate the Th1/Th2 inflammatory response by inhibiting the Hsp90/NF-κB signaling axis to alleviate AD. Therefore, it may be a candidate for AD treatment.

Dexmedetomidine prevents spatial learning and memory impairment induced by chronic REM sleep deprivation in rats.

The study was attempted to investigate the effect on and mechanisms of action of dexmedetomidine with regard to learning and memory impairment in rats with chronic rapid eye movement (REM) sleep deprivation. A total of 50 male Sprague Dawley rats were randomly divided into five groups. Modified multiple platform method was conducted to cause the sleep deprivation of rats. Dexmedetomidine and midazolam were administered by intraperitoneal injection. Learning and memory ability was assessed through Morris water maze. Morphological changes of rat hippocampal neurons and synaptic were detected by transmission electron microscope and Golgi staining. The gene expression in hippocampus of each group was detected by RNA-seq and verified by RT-PCR and western blot. REM Sleep-deprived rats exhibited spatial learning and memory deficits. Furthermore, there was decreased density of synaptic spinous in the hippocampal CA1 region of the sleep deprivation group compared with the control. Additionally, transmission electron microscopy showed that the synaptic gaps of hippocampal neurons in REM sleep deprivation group were loose and fuzzy. Interestingly, dexmedetomidine treatment normalized these events to control levels following REM sleep deprivation. Molecular biological methods showed that Alox15 expression increased significantly after REM sleep deprivation as compared to control, while dexmedetomidine administration reversed the expression of Alox15. Dexmedetomidine alleviated the spatial learning and memory dysfunction induced with chronic REM sleep deprivation in rats. This protective effect may be related to the down-regulation of Alox15 expression and thereby the enhancement of synaptic structural plasticity in the hippocampal CA1 area of rats. Supplementary Information: The online version contains supplementary material available at 10.1007/s41105-023-00450-8.

Intraperitoneal ozone injection prevents REM sleep deprivation - induced spatial learning and memory deficits by suppressing the expression of Sema3A in the hippocampus in rats.

Objectives: Sleep deprivation is a common health problem in modern society and is negatively associated with deleterious effects on cognitive functions such as learning and memory ability. This study was undertaken to provide a detailed account of the effect of chronic ozone intraperitoneal injection on the deleterious effects of sleep deprivation on brain function in rats. Materials and Methods: Sleep deprivation was induced using the modified multiple platform model. The rats received REM sleep deprivation with an intraperitoneal injection of ozone or midazolam for 28 days. The effects of ozone on REM sleep deprivation-induced hippocampus-dependent learning and memory deficits were studied by the following approaches: Morris water maze (MWM) tests were used to evaluate spatial learning and memory of rats. Morphological changes in the brain were evaluated using hematoxylin and eosin (HE) staining. RNA-sequence was performed to seek a common mechanism. The expression of the targeted gene was examined by qPCR and Western blotting. Results: Ozone intraperitoneal injection reversed spatial learning and memory deficits associated with REM sleep deprivation, ameliorating pathological brain damage and down-regulating the hippocampal expression of Sema3A in rats after REM sleep deprivation. Conclusion: Ozone intraperitoneal injection alleviated sleep deprivation-induced spatial learning and memory deficits by protecting hippocampal neurons via down-regulation of the expression of Sema3A in the hippocampus.

Neuropathic Pain Creates Systemic Ultrastructural Changes in the Nervous System Corrected by Electroacupuncture but Not by Pregabalin.

PURPOSE: It is unclear whether neuropathological structural changes in the peripheral nervous system and central nervous system can occur in the spared nerve injury model. In this study, we investigated the pathological changes in the nervous system in a model of neuropathic pain as well as the effects of electroacupuncture (EA) and pregabalin (PGB) administration as regards pain relief and tissue repair. PATIENTS AND METHODS: Forty adult male SD rats were equally and randomly divided into 4 groups: spared nerve injury group (SNI, n = 10), SNI with electroacupuncture group (EA, n = 10), SNI with pregabalin group (PGB, n =10) and sham-operated group (Sham, n=10). EA and PGB were given from postoperative day (POD) 14 to 36. EA (2 Hz and 100 Hz alternating frequencies, intensities ranging from 1-1.5-2 mA) was applied to the left "zusanli" (ST36) and "Yanglingquan" (GB34) acupoints for 30 minutes. The mechanical withdrawal thresholds (MWTs) were tested with von Frey filaments. Moreover, the organizational and structural alterations of the bilateral prefrontal cortex, hippocampus, sciatic nerves and the thoracic, lumbar spinal cords and dorsal root ganglions (DRGs) were examined via light and electron microscopy. RESULTS: MWTs of left hind paw demonstrated a remarkable decrease in the SNI model (P < 0.05). In the SNI model, ultrastructural changes including demyelination and damaged neurons were observed at all levels of the peripheral nervous system (PNS) and central nervous system (CNS). In addition, EA improved MWTs and restored the normal structure of neurons. However, the effect was not found in the PGB treatment group. CONCLUSION: Chronic pain can induce extensive damage to the central and peripheral nervous systems. Meanwhile, EA and PGB can both alleviate chronic pain syndromes in rats, but EA also restores the normal cellular structures, while PGB is associated with no improvement.

Acupuncture Can Play an Antidepressant Role by Regulating the Intestinal Microbes and Neurotransmitters in a Rat Model of Depression.

BACKGROUND Acupuncture, which has many good effects and few adverse effects, is widely recognized as an alternative therapy for depression in clinical practice. This study aimed to explore the mechanism of acupuncture in antidepressant treatment. MATERIAL AND METHODS In this experiment, Sprague-Dawley rats were randomly divided into 4 groups: control, chronic unpredictable mild stress (CUMS), acupuncture, and fluoxetine groups. The CUMS, acupuncture, and fluoxetine groups were orphaned and subjected to chronic unpredictable stress for 6 weeks, and the acupuncture and fluoxetine groups were treated with their respective intervention in weeks 4-6. The body weight of rats was monitored weekly. After behavioral tests were completed, serum, feces, and hippocampal tissue of rats were collected. RESULTS The results showed that the acupuncture and fluoxetine treatments could alleviate the behavioral changes caused by CUMS. The treatments increased the total distance of rat crossing in the open-field test, prolonged the activity time of the open cross maze in the open arm, and improved the rate of sucrose consumption in the sucrose preference test. In addition, both the decreased level of dopamine (DA) and 5-hydroxytryptamine (5-HT) in serum and hippocampus caused by CUMS were improved after the treatments with acupuncture and fluoxetine, and the decreased expression of brain-derived neurotrophic factor signaling and the astrocytes in the hippocampus caused by CUMS were increased after the treatments with acupuncture and fluoxetine. Acupuncture and fluoxetine also decreased the ß isoform of calmodulin-dependent protein kinase II in the hippocampus, which was increased by CUMS. Furthermore, acupuncture regulated intestinal microbial disorders caused by CUMS, which reduced the relative abundance ratio of Bacteroidetes/Firmicutes in rats. CONCLUSIONS Our experimental results indicate that acupuncture can alleviate depression-like performance in CUMS rats by regulating intestinal microbes and neurotransmitters.

Renal-clearable hyaluronic acid functionalized NaGdF4 nanodots with enhanced tumor accumulation.

Integration of high tumor-targeting capacity, controlling in vivo transport and low normal tissue retention into one engineered nanoparticle is a critical issue for future clinically translatable anti-cancer nanomedicines. Herein, hyaluronic acid functionalized 3.8 nm NaGdF4 nanodots (named NaGdF4 ND@HAs) have been prepared through conjugation of tryptone capped NaGdF4 nanodots (NaGdF4 ND@tryptone) with hyaluronic acid (HA, a naturally occurring glycosaminoglycan), which can recognize the overexpressed CD44 on cancer cell membranes. The as-prepared NaGdF4 ND@HAs have good paramagnetic properties (longitudinal relaxivity (r 1) = 7.57 × 10-3 M S-1) and low cytotoxicity. The in vivo experimental results demonstrate that the NaGdF4 ND@HAs can not only efficiently accumulate in mouse-bearing MDA-MB-231 tumors (ca. 5.3% injection dosage (ID) g-1 at 2 h post-injection), but also have an excellent renal clearance efficiency (ca. 75% injection dosage (ID) at 24 h post-injection). The as-prepared NaGdF4 ND@HAs have good paramagnetic properties with enhanced tumor-targeting capacity, which provides a useful strategy for the preparation of renal clearable magnetic resonance imaging (MRI) contrast agents for tumors.