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Ethnopharmacological Relevance: Developing effective drugs is urgent for preventing platelet activation and atherosclerotic diseases. Qihuang Zhuyu formula (QHZYF) is a curative medical plants formula in clinic while its molecular mechanism remains to be further elucidated., Aim of the Study: To investigate how QHZYF, via the sirtuin 1 (SIRT1)/peroxisome proliferator-activated receptor alpha (PPARα) pathway, mediates the endocannabinoid system, regulates mitochondrial function, and inhibits platelet activation, thereby offering novel strategies for the prevention and treatment of cardiovascular diseases., Methods: The chemical constituents of QHZYF were characterized by ultra-performance liquid chromatography tandem with quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF-MS). For the in vivo experiments, an atherosclerosis rat model was developed. Platelet activation and endocannabinoid levels were assessed by ELISA, while the expression of PPARα was evaluated by immunofluorescence. Additionally, the expression of endocannabinoid-degrading enzymes was analyzed by Western blotting. In the in vitro studies, the protein-protein interaction between SIRT1 and PPARα was initially investigated using co-immunoprecipitation (Co-IP). Thereafter, platelets were co-cultured with human umbilical vein endothelial cells (HUVECs) stimulated by oxidized low-density lipoprotein (ox-LDL). The mitochondrial function of platelets was examined by flow cytometry. Platelet activation and endocannabinoid levels were quantified using ELISA, and the expression of PPARα, endocannabinoid-degrading enzymes and proteins reflecting mitochondrial function were determined by Western blotting. Subsequently, QHZYF was incorporated into the aforementioned system, and the entire experimental protocol was replicated to explore how QHZYF influences platelet activation through the SIRT1/PPARα pathway-mediated endocannabinoid system., Results: In the in vivo experiments, it was observed that QHZYF significantly augmented the levels of PPARα, concurrently with a decrease in the expression of endocannabinoid-degrading enzymes. This was paralleled by a rise in endogenous cannabinoid levels and a reduction in platelet activation, a process that was found to be regulated by SIRT1. The co-immunoprecipitation (Co-IP) analysis substantiated the cooperative interaction between SIRT1 and PPARα, underscoring their role in mediating the endocannabinoid system, regulating mitochondrial function, and consequently influencing platelet activation. In the in vitro studies, a co-culture system involving platelets and HUVECs stimulated with ox-LDL was employed. It was noted that the SIRT1/PPARα pathway mediates the endocannabinoid system in regulating mitochondrial function, which in turn affects platelet activation. The incorporation of QHZYF-containing serum into this system produced outcomes consistent with those observed in the in vivo experiments. These findings suggest that QHZYF operates by modulating the endocannabinoid system via the SIRT1/PPARα pathway, thereby controlling mitochondrial function and inhibiting platelet activation., Conclusion: SIRT1 may mediate endocannabinoid signaling through its interaction with PPARα, regulating mitochondrial function and subsequently influencing platelet activation. QHZYF effectively modulates the endocannabinoid system via the SIRT1/PPARα pathway, thereby inhibiting platelet activation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Gastrointestinal disorders manifest through disruptions in gastrointestinal functionality accompanied by dysbiosis within the microbiome. Probiotics are considered biological agents with potential therapeutic efficacy in managing gastrointestinal pathologies by modulating the gut microbiota. Nevertheless, several hurdles, such as safety considerations, resilience to stressors, post-colonization quantifications, and evaluative modalities, may impede the adoption of probiotics for gastrointestinal disorders. Herein, we performed online research using 6 databases: Scopus, ScienceDirect, PubMed, Web of Science, Cochrane Library, and Ovid. Inclusion criteria were mostly articles published in the years 2015-2024, concerning the association between probiotics and gastrointestinal diseases. This review aimed to provide comprehensive data regarding the latest studies in this area. Additionally, this review delineates the various aspects of probiotic use, including both the positive and negative aspects, as well as the role of probiotics in immune system modulation and the prevention of various diseases. Also, we comprehensively discuss the prophylactic and supportive therapeutic role of probiotics in the management of COVID-19. Given the extensive adoption of probiotic formulations as microecological interventions for gastrointestinal disorders, a comprehensive understanding of the challenges inherent in their application and the implementation of contemporary methodologies to enhance probiotic colonization and evaluation systems are paramount for harnessing probiotics as viable biotherapeutic agents. However, there is a need for additional studies to confirm the potential role of probiotics as a suitable target in the treatment of gastrointestinal diseases.

Background: C16:0 and cis-9 C18:1 may have different effects on animal growth and health due to unique metabolism in vivo. This study was investigated to explore the different effects of altering the ratio of C16:0 and cis-9 C18:1 in fat supplements on growth performance, lipid metabolism, intestinal barrier, cecal microbiota, and inflammation in fattening bulls. Thirty finishing Angus bulls (626 ± 69 kg, 21 ± 0.5 months) were divided into 3 treatments according to the randomized block design: (1) control diet without additional fat (CON), (2) CON + 2.5% palmitic acid calcium salt (PA, 90% C16:0), and (3) CON + 2.5% mixed fatty acid calcium salt (MA, 60% C16:0 + 30% cis-9 C18:1). The experiment lasted for 104 d, after which all the bulls were slaughtered and sampled for analysis., Results: MA tended to reduce 0-52 d dry matter intake compared to PA (DMI, P = 0.052). Compared with CON and MA, PA significantly increased 0-52 d average daily gain (ADG, P = 0.027). PA tended to improve the 0-52 d feed conversion rate compared with CON (FCR, P = 0.088). Both PA and MA had no significant effect on 52-104 days of DMI, ADG and FCR (P > 0.05). PA tended to improve plasma triglycerides compared with MA (P = 0.077), significantly increased plasma cholesterol (P = 0.002) and tended to improve subcutaneous adipose weight (P = 0.066) when compared with CON and MA. Both PA and MA increased visceral adipose weight compared with CON (P = 0.021). Only PA increased the colonization of Rikenellaceae, Ruminococcus and Proteobacteria in the cecum, and MA increased Akkermansia abundance (P < 0.05). Compared with CON, both PA and MA down-regulated the mRNA expression of Claudin-1 in the jejunum (P < 0.001), increased plasma diamine oxidase (DAO, P < 0.001) and lipopolysaccharide (LPS, P = 0.045). Compared with CON and MA, PA down-regulated the ZO-1 in the jejunum (P < 0.001) and increased plasma LPS-binding protein (LBP, P < 0.001). Compared with CON, only PA down-regulated the Occludin in the jejunum (P = 0.013). Compared with CON, PA and MA significantly up-regulated the expression of TLR-4 and NF-κB in the visceral adipose (P < 0.001) and increased plasma IL-6 (P < 0.001). Compared with CON, only PA up-regulated the TNF-α in the visceral adipose (P = 0.01). Compared with CON and MA, PA up-regulated IL-6 in the visceral adipose (P < 0.001), increased plasma TNF-α (P < 0.001), and reduced the IgG content in plasma (P = 0.035). Compared with CON, PA and MA increased C16:0 in subcutaneous fat and longissimus dorsi muscle (P < 0.05), while more C16:0 was also deposited by extension and desaturation into C18:0 and cis-9 C18:1. However, neither PA nor MA affected the content of cis-9 C18:1 in longissimus dorsi muscle compared with CON (P > 0.05)., Conclusions: MA containing 30% cis-9 C18:1 reduced the risk of high C16:0 dietary fat induced subcutaneous fat obesity, adipose tissue and systemic low-grade inflammation by accelerating fatty acid oxidative utilization, improving colonization of Akkermansia, reducing intestinal barrier damage, and down-regulating NF-κB activation., (© 2024. The Author(s).)

Animal nutritionists have incessantly worked towards providing livestock with high-quality plant protein feed resources. Soybean meal (SBM) has been an essential and predominantly adopted vegetable protein source in livestock feeding for a long time; however, several SBM antinutrients could potentially impair the animal's performance and growth, limiting its use. Several processing methods have been employed to remove SBM antinutrients, including fermentation with fungal or bacterial microorganisms. According to the literature, fermentation, a traditional food processing method, could improve SBM's nutritional and functional properties, making it more suitable and beneficial to livestock. The current interest in health-promoting functional feed, which can enhance the growth of animals, improve their immune system, and promote physiological benefits more than conventional feed, coupled with the ban on the use of antimicrobial growth promoters, has caused a renewed interest in the use of fermented SBM (FSBM) in livestock diets. This review details the mechanism of SBM fermentation and its impacts on animal health and discusses the recent trend in the application and emerging advantages to livestock while shedding light on the research gap that needs to be critically addressed in future studies. FSBM appears to be a multifunctional high-quality plant protein source for animals. Besides removing soybean antinutrients, beneficial bioactive peptides and digestive enzymes are produced during fermentation, providing probiotics, antioxidants, and immunomodulatory effects. Critical aspects regarding FSBM feeding to animals remain uncharted, such as the duration of fermentation, the influence of feeding on digestive tissue development, choice of microbial strain, and possible environmental impact., Competing Interests: We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, and there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the content of this paper., (© 2024 The Authors.)

Aberrant expression of serine/arginine-rich splicing factor 2 (SRSF2) can lead to tumorigenesis, but its molecular mechanism in colorectal cancer is currently unknown. Herein, we found SRSF2 to be highly expressed in human colorectal cancer (CRC) samples compared with normal tissues. Both in vitro and in vivo, SRSF2 significantly accelerated the proliferation of colon cancer cells. Using RNA-seq, we screened and identified 33 alternative splicing events regulated by SRSF2. Knockdown of SLMAP-L or CETN3-S splice isoform could suppress the growth of colon cancer cells, predicting their role in malignant proliferation of colon cancer cells. Mechanistically, the in vivo crosslinking immunoprecipitation assay demonstrated the direct binding of the RNA recognition motif of SRSF2 protein to SLMAP and CETN3 pre-mRNAs. SRSF2 activated the inclusion of SLMAP alternative exon 24 by binding to constitutive exon 25, while SRSF2 facilitated the exclusion of CETN3 alternative exon 5 by binding to neighboring exon 6. Knockdown of SRSF2, its splicing targets SLMAP-L, or CETN3-S caused colon cancer cells to arrest in G1 phase of the cell cycle. Rescue of SLMAP-L or CETN3-S splice isoform in SRSF2 knockdown colon cancer cells could effectively reverse the inhibition of cell proliferation by SRSF2 knockdown through mediating cell cycle progression. Importantly, the percentage of SLMAP exon 24 inclusion increased and CETN3 exon 5 inclusion decreased in CRC samples compared to paired normal samples. Collectively, our findings identify that SRSF2 dysregulates colorectal carcinoma proliferation at the molecular level of splicing regulation and reveal potential splicing targets in CRC patients., Competing Interests: Conflict of interest All the authors declare that they have no conflicts of interest with the contents of the article., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

We aimed to clarify the therapeutic effects of imperatorin (IMP) on knee osteoarthritis (KOA). Thirty 3-month-old SD male rats were randomly divided into Normal, monosodium iodoacetate (MIA) and MIA+IMP groups. Their synovial tissues were subjected to histopathological analysis. Primary synovial fibroblasts obtained from additional normal rats were treated by lipopolysaccharide (LPS) and then IMP. The mRNA and protein expressions of factors related to synovitis and synovial fibrosis were detected by qRT-PCR and Western blotting, respectively. The concentrations of inflammatory factors IL-1β and IL-18 were measured by ELISA. IMP reduced HIF-1α, NLR family pyrin domain-containing 3 inflammasome expression and IL-1β, IL-18 production in synovial fibroblasts induced by LPS. IMP also downregulated synovial fibrosis markers. In vitro study revealed that MIA-induced synovitis and synovial fibrosis were relieved by IMP. IMP relieves the inflammation associated with synovitis and synovial fibrosis. It reduces the production of pro-inflammatory mediators and cytokines and inhibits TGF-β1, TIMP-1 and VEGF expressions that promote synovial fibrosis.

Increasing evidence has shown that NLRP3 inflammasome activation participates in chronic aseptic inflammation and is related to tissue fibrosis. Our last study also revealed the vital role of NLRP3 inflammasome, highly associated with tissue hypoxia, in the onset and development of knee osteoarthritis (KOA). In this study, we tried to find a possible benign intervention for that pathological process. Agnuside (AGN), a nontoxic, natural small molecule isolated from the extract of Vitex negundo L. (Verbenaceae), has been demonstrated to have antioxidation, anti-inflammatory, analgesia, and many other properties as an iridoid glycoside, although its specific target is still unclear. Therefore, we established MIA-induced KOA model rats and investigated the effects of AGN oral gavage on oxygen-containing state, NLRP3 inflammasome, synovitis, and fibrosis in KOA. Pimonidazole staining and HIF-1 α immunohistochemical assay both showed that AGN at the oral dose of 6.25 mg/kg can effectively relieve local hypoxia in synovial tissue. Besides, we observed a decrease of HIF-1 α , caspase-1, ASC, and NLRP3 after AGN intervention, both in the mRNA and protein levels. In addition, rats treated with the AGN showed less inflammatory reaction and fibrosis, not only in the expression of NLRP3, inflammasome downstream factors IL-1 β and IL-18, and fibrosis markers TGF- β , TIMP1, and VEGF but also in the observation of HE staining, anatomical characteristics, Sirius Red staining, and type I collagen immunohistochemistry. Subsequently, we established LPS-induced models of fibroblast-like synoviocytes (FLSs) mimicking the inflammatory environment of KOA and activating NLRP3 inflammasome. FLSs treated with AGN (3  μ M) resulted in a downregulation of HIF-1 α and the components required for NLRP3 inflammasome activation. Meanwhile, the content of proinflammatory factors IL-1 β and IL-18 in FLS supernatant was also reduced by AGN. In addition, both mRNA and protein levels of the fibrotic markers were significantly decreased after AGN management. To conclude, this study demonstrates that AGN alleviates synovitis and fibrosis in experimental KOA through the inhibition of HIF-1 α accumulation and NLRP3 inflammasome activation. Additionally, not only does it reveal some novel targets for anti-inflammatory and antioxidant effects of AGN but also announces its potential value in treating KOA in humans., Competing Interests: All authors declare that there are no actual or potential conflicts of interest, including any financial, personal, or other relationships with other people or organizations that could inappropriately influence, or be perceived to influence our work., (Copyright © 2021 Li Zhang et al.)

Objectives : Synovitis plays an important role in knee osteoarthritis (KOA) pain. The activation of the NOD-like receptor protein 3 (NLRP3) inflammasome in fibroblast-like synoviocytes (FLSs) promotes KOA development. In this study, we aimed to investigate whether vanillic acid (VA), a monomer derived from Chinese herbal medicines, could target NLRP3 inflammasome-related synovitis to reduce pain. Methods : Rats in the KOA and KOA + VA groups were injected with monosodium iodoacetate (MIA) in the knee to induce KOA. From day 14, the KOA + VA group was given VA at 30 mg/kg every day via gastric intubation. FLSs were collected from the synovial tissues. We examined both the protein and gene expression of caspase-1, apoptosis-associated speck-like protein with a caspase recruitment domain (ASC), NLRP3, components of the NLRP3 inflammasome, and interleukin-1β (IL-1β) and IL-18 in vivo and in vitro . Results : The upregulation of caspase-1, ASC, and NLRP3 in the KOA model were reduced by VA. VA also lowered the level of IL-1β and IL-18 in the KOA model. In addition, VA relieved pain-related behavior of KOA model rats and downregulated the pain mediators CGRP, NGF, and TrkA in FLSs. Interestingly, we also observed reduced synovial fibrosis in the animal experiments. Conclusion : Our research showed that VA reduces synovitis and pain-related behaviors in a rat model of KOA, which provides the basis for further investigations into the potential therapeutic impact of VA in KOA., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Ma, Huang, Zhang, Li, Xu, Xiao, Shi, Zhang, Liao and Wang.)

An easily fabricated Fabry-Perot optical fiber humidity sensor with high performance was presented by filling Graphene Quantum Dots (GQDs) into the Fabry-Perot resonator, which consists of two common single mode optical fibers. The relative humidity sensing performance was experimentally investigated by an interference spectrum drift between 11 %RH to 85 %RH. 0.567 nm/%RH sensitivity and 0.99917 linear correlation were found in experiments that showed high sensitivity, good and wide-range linear responding. Meanwhile, its good responding repeatability was demonstrated by two circle tests with increasing and decreasing relative humidity. For investigating the measurement influence caused by a temperature jitter, the temperature responding was experimentally investigated, which showed its linear responding with 0.033 nm/°C sensitivity. The results demonstrate the humidity sensitivity is greatly higher than the temperature sensitivity. The wavelength shift influence is 0.0198 nm with 0.6 °C max temperature jitter in the experiment, which can be ignored in humidity experiments. The fast-dynamic responses at typical humidity were demonstrated in experiments, with 5.5 s responding time and 8.5 s recovering time. The sensors with different cavity lengths were also investigated for their humidity response. All sensors gave good linear responding and high sensitivity. In addition, the relation curve between cavity length and response sensitivity also had good linearity. The combination of GQDs and single mode optical fibers showed easy fabrication and good performance for an optical fiber relative humidity sensor.

Knee osteoarthritis (KOA) is a disabling chronic inflammatory disease that is closely associated with synovium tissue hypoxia and synovial fibrosis. Casticin, a compound purified from the Chinese herb Viticis Fructus, has been proved effective in preventing inflammation and fibrosis in previous studies. However, the effect of casticin on synovial fibrosis in KOA is not clear. In present study, we aimed to investigate how did casticin affect synovial fibrosis on monoiodoacetic acid (MIA)-induced KOA in rats. The MIA-induced knee osteoarthritis model and lipopolysaccharide (LPS) stimulated primary synovial fibroblasts inflammation model were established. Pathological and morphological changes in synovial tissue were observed by H&E and sirius red staining. The hypoxia of synovium was detected by pimonidazole staining and immunohistochemistry of hypoxia-inducible factors 1α (HIF-1α). The levels of nucleotide oligomerization domain-like receptor protein 3 (NLRP3) inflammasome components, fibrogenic markers (TGF-β, COL1A1 and TIMP1) and inflammatory cytokines were examined by western blotting, qRT-PCR or ELISA in both KOA rat models and primary synovial fibroblasts. Our data suggested that casticin improved hypoxia and inflammation in synovium tissue, as well the synovial fibrosis in rats. Besides, casticin inhibited the activation of NLRP3 inflammasome in MIA-induced KOA rats and synovial fibroblasts. In conclusion, our findings demonstrated that casticin alleviated MIA-induced KOA by inhibiting of HIF-1α/NLRP3 inflammasome activation. Therefore, casticin could be a potential treatment strategy for KOA., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflicts of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The radiation sensitivity of tumor cells is closely related to tumor cell hypoxia. Hypoxia-inducible factor-1α (HIF-1α) is considered a key transcription factor which regulates the sensitivity of hypoxic tumor cells to radiotherapy. On the other hand, some studies have shown that gold nanomaterials improve radiation sensitivity. However, studies on the effect of gold nanomaterials carrying HIF-1αsiRNA on tumor radiotherapy, and the underlying mechanisms are limited. Thus, the present study was aimed at investigating the effect of gold nanocomposites (AuNRs) carrying HIF-1αsiRNA (AuNRs-HIF-1αsiRNA) on the radiation sensitivity of nasopharyngeal carcinoma (NPC) hypoxia cells. The effect of AuNRs-HIF-1αsiRNA on radiation sensitivity of hypoxic NPC cells was determined under X-ray irradiation. The results showed that Au-HIF-1αsiRNA improved the radio-sensitivity of NPC tumor. Thus, this study has demonstrated that gold nanomaterials carrying HIF-1αsiRNA effectively increased the radio-sensitivity of hypoxic tumor, thereby improving the effect of radiotherapy on NPC cells.

Purpose: Our recent reports have revealed that inhibiting NLRP3 activation reduces synovial inflammation and fibrosis in knee osteoarthritis (KOA). Synovial inflammation is involved the entire process of KOA and promotes the progression of KOA. Natural flavonoid Chrysin from Scutellariae Radix, a traditional Chinese medicine, exhibits multifarious biological activities and potentially has protective activity against osteoarthritis. However, the mechanism of Chrysin in the treatment of synovial inflammation remains elusive. The purpose of our research was to explore the anti-inflammatory effects of Chrysin on KOA, which was induced by monoiodoacetic acid (MIA) in rats by targeting the NLRP3 inflammasome in the hopes of identifying an effective drug to treat KOA., Methods: The MIA-induced KOA model was used to evaluate the cold pain threshold and paw withdrawal threshold (PWT) of joints after MIA (40 mg/mL) injection into the knee joints. Microscopically, we used LPS (5 ug/mL) and ATP (4 mmol/L) to stimulate fibroblast-like synovial cells (FLSs) to explore the underlying mechanisms and effects of Chrysin. Two staining methods, H&E and Sirius Red, were applied to assess histopathological changes in synovial membranes. Cellular signal transduction was determined by qRT-PCR and WB. Cytokine expression (inflammatory cytokines and pain-related cytokines) was detected by ELISA. The degree of chronic inflammatory pain was evaluated by c-Fos immunofluorescence., Results: The results showed that Chrysin not only attenuated synovial inflammation but also reduced the secretion of pain-related factors and increased the PWT and cold pain threshold in rats. Chrysin also inhibited NLRP3 inflammasome activation and increased IL-1β levels to alleviate the synovitis., Conclusion: Chrysin can relieve knee synovial inflammation and improve pain behavior in KOA rats, which may be related to the ability of Chrysin to inhibit NLRP3 inflammasome activation. Therefore, Chrysin may be developed as a new drug for the treatment of KOA., Competing Interests: The authors declare that they have no competing interests., (© 2020 Liao et al.)