Modulation Of Inflammatory Response Research Articles

Regenerative Inflammation: The Mechanism Explained from the Perspective of Buffy-Coat Protagonism and Macrophage Polarization.

The buffy-coat, a layer of leukocytes and platelets obtained from peripheral blood centrifugation, plays a crucial role in tissue regeneration and the modulation of inflammatory responses. This article explores the mechanisms of regenerative inflammation, highlighting the critical role of the buffy-coat in influencing macrophage polarization and its therapeutic potential. Macrophage polarization into M1 and M2 subtypes is pivotal in balancing inflammation and tissue repair, with M1 macrophages driving pro-inflammatory responses and M2 macrophages promoting tissue healing and regeneration. The buffy-coat's rich composition of progenitor cells, cytokines, and growth factors-such as interleukin-10, transforming growth factor-β, and monocyte colony-stimulating factor-supports the transition from M1 to M2 macrophages, enhancing tissue repair and the resolution of inflammation. This dynamic interaction between buffy-coat components and macrophages opens new avenues for therapeutic strategies aimed at improving tissue regeneration and managing inflammatory conditions, particularly in musculoskeletal diseases such as osteoarthritis. Furthermore, the use of buffy-coat-derived therapies in conjunction with other regenerative modalities, such as platelet-rich plasma, holds promise for more effective clinical outcomes.

Isoorientin Improves Excisional Skin Wound Healing in Mice

Background/Objectives: Wound healing relies on a coordinated process with the participation of different mediators. Natural products are a source of active compounds with healing potential. Isoorientin is a natural flavone recognized as having several pharmacological properties, such as anti-inflammatory effects, making it a potential treatment for wounds. We investigated the effect of isoorientin on the healing of excisional skin wounds. Methods: Male Swiss mice were subjected to the induction of excisional skin wounds (6 mm diameter) and treated with a vehicle (2% dimethyl sulfoxide in propylene glycol) or 2.5% isoorientin applied topically once a day for 14 days. The wound area was measured on days 0, 3, 7, and 14. Histopathological analyses were performed on the cicatricial tissue after 14 days. The myeloperoxidase activity and the interleukin-1β, tumoral necrosis factor (TNF)-α, and interleukin-6 concentrations were determined on the third day. Results: We observed that 3 days after the topical application of isoorientin, the lesion area was significantly smaller when compared to those of the vehicle (p < 0.01) and control (p < 0.05) groups. No difference was observed after 7 and 14 days of induction. Despite this, on day 14, histological analysis of cicatricial tissue from the animals treated with isoorientin showed reduced epidermal thickness (p < 0.001) and increased collagen deposition (p < 0.001). These effects were accompanied by decreased myeloperoxidase activity and interleukin-1β concentration on the third day of induction, without alteration in TNF-α and interleukin-6. Conclusions: The treatment with isoorientin promoted better tissue repair in excisional wounds in mice, which may be linked to the modulation of the early inflammatory response.

Juruaça virus taxonomy, tolerance and resistance to infection, and inflammatory response modulation in murine model

Juruaça virus (JUAV), previously unclassified, was isolated from bats and administered to neonatal and adult BALB/c mice to investigate acute and chronic disease progression. In this study, we conducted genomic sequencing to achieve taxonomic classification and utilized these models to explore the inflammatory response and sickness behavior in both neonatal and adult mice. Neonates received a single intranasal instillation of infected brain homogenate (20 µL), whereas 31-day-old mice were given the same volume intranasally for three consecutive days. Control groups were administered equal volumes of uninfected brain homogenate. Our findings reveal that intranasal JUAV infection-induced acute meningoencephalitis and death in neonates, while adult mice exhibited chronic infection with variable clinical signs, inflammatory mediator production, histopathological changes, and neuropathological features. Interestingly, only some adult mice showed sickness behavior post-infection, and among these, a subset continued to decline and die. The differential tissue damage observed in mice with and without overt disease symptoms suggests mechanisms of resistance or tolerance, where exceeding tolerance capacity resulted in pathological outcomes, including chronic dysfunction or death. This study provides the first evidence of JUAV’s capability to infect mammals, demonstrating its distinct impact on bats and variable effects in neonatal and adult mice. We provisionally classified JUAV as closely related to the clade containing tombus-like virus 6 found in mute swan feces. Our research highlights the importance of understanding viral–host interactions and the inflammatory responses that contribute to disease variability, offering insights into tolerance and resistance mechanisms based on inflammatory response modulation.

Bothrops atrox snake venom decreased MHC-II and CD86 expression in bone marrow-derived dendritic cells

The effect of Bothrops atrox venom (BaV) on the maturation of bone marrow-derived dendritic cells (BMDCs) from mice was investigated, with a focus on selected cell markers, TAP1 expression, and the release of pro-inflammatory cytokines during this process. The objective was to evaluate BaV's impact on dendritic cell (DC) function, as DCs are pivotal in antigen presentation and responsible for initiating the immune response mediated by naïve T cells, as well as regulating the immune system. Bone marrow cells were obtained from Swiss mice, and hematopoietic precursors were differentiated into BMDCs using GM-CSF and IL-4. On the 7th day, BaV and LPS were introduced into the culture, and the cells were analyzed 24 h later. BaV's ability to stimulate BMDC maturation was assessed through the analysis of surface marker expression. The findings demonstrated that BMDCs are highly influenced by culture environment factors, such as GM-CSF and IL-4, and are sensitive to additional stimuli like LPS and BaV. Mature DCs exhibited elevated levels of critical markers for T cell activation, such as MHC-II, CD80, and CD86, displaying specific phenotypic characteristics. However, the observed reduction in MHC-II and CD86 expression following BaV exposure suggests a substantial impact on the immunological activation capacity of these cells, potentially interfering with the adaptive immune response. Furthermore, the selective release of cytokines, such as IL-6, but not TNF-α or IL-1β, indicates differentiated modulation of inflammatory responses by DCs under various stimulation conditions.

The Impact of Preoperative and Postoperative Nutritional Interventions on Treatment Outcomes and Quality of Life in Colorectal Cancer Patients-A Comprehensive Review.

Colorectal cancer (CRC) is one of the most prevalent cancers worldwide, with high morbidity and mortality rates. Nutritional status has emerged as a significant factor influencing the prognosis and survival of CRC patients. This comprehensive literature review examines the role of nutritional support in improving treatment outcomes, including the efficacy of interventions, patient quality of life (QoL), and the modulation of inflammatory responses. The findings suggest that tailored nutritional interventions improve clinical outcomes, enhance QoL, and reduce treatment-related complications, particularly by attenuating inflammation. Furthermore, the review highlights the cost-effectiveness of nutritional strategies and identifies key methods to enhance patient compliance with dietary recommendations. In conclusion, integrating nutritional support into CRC treatment plans is crucial for optimizing clinical management and improving patient well-being.

Yeast β-glucan attenuates dextran sulfate sodium-induced colitis: Involvement of gut microbiota and short-chain fatty acids

Yeast β-glucan intervention offers a promising strategy for managing colitis; however, the mechanisms remain unknown. In the present work, the protective effects of yeast β-glucan on DSS-induced colitis in mice was evaluated, focusing on its interaction with gut microbiota. The result showed yeast β-glucan significantly alleviated colitis symptoms, evidenced by reduced weight loss, lower disease activity index (DAI) scores, and minimized intestinal damage. It enhanced intestinal barrier integrity via upregulation of tight junction proteins, suppressed lipopolysaccharide (LPS) release, and decreased pro-inflammatory cytokines production. Additionally, yeast β-glucan boosted short-chain fatty acids (SCFAs) production, and activated their receptors, increased the relative abundances of beneficial microbes like Lactobacillus and Lachnospiraceae_UCG-006. Transcriptomic analyses suggest that yeast β-glucan mitigates inflammation by downregulating gene expression related to IL-17 pathway. Our findings highlight potential of yeast β-glucan as a therapeutic agent for colitis through modulation of gut microbiota and inflammatory responses.

Mesenchymal Stem Cell-Conditioned Media-Loaded Microparticles Enhance Acute Patency in Silk-Based Vascular Grafts.

Coronary artery disease leads to over 360,000 deaths annually in the United States, and off-the-shelf bypass graft options are currently limited and/or have high failure rates. Tissue-engineered vascular grafts (TEVGs) present an attractive option, though the promising mesenchymal stem cell (MSC)-based implants face uncertain regulatory pathways. In this study, "artificial MSCs" (ArtMSCs) were fabricated by encapsulating MSC-conditioned media (CM) in poly(lactic-co-glycolic acid) microparticles. ArtMSCs and control microparticles (Blank-MPs) were incubated over 7 days to assess the release of total protein and the vascular endothelial growth factor (VEGF-A); releasates were also assessed for cytotoxicity and promotion of smooth muscle cell (SMC) proliferation. Each MP type was loaded in previously published "lyogel" silk scaffolds and implanted as interposition grafts in Lewis rats for 1 or 8 weeks. Explanted grafts were assessed for patency and cell content. ArtMSCs had a burst release of protein and VEGF-A. CM increased proliferation in SMCs, but not after encapsulation. TEVG explants after 1 week had significantly higher patency rates with ArtMSCs compared to Blank-MPs, but similar to unseeded lyogel grafts. ArtMSC explants had lower numbers of infiltrating macrophages compared to Blank-MP explants, suggesting a modulation of inflammatory response by the ArtMSCs. TEVG explants after 8 weeks showed no significant difference in patency among the three groups. The ArtMSC explants showed higher numbers of SMCs and endothelial cells within the neotissue layer of the graft compared to Blank-MP explants. In sum, while the ArtMSCs had positive effects acutely, efficacy was lost in the longer term; therefore, further optimization is needed.

Exploration of compounds to inhibit the Panton-Valentine leukocidin of Staphylococcus aureus

The Panton-Valentine leukocidin (PVL) of Staphylococcus aureus is associated with necrotizing infections. After binding to complement 5a receptor (C5aR/CD88) and CD45 it causes cytolysis in polymorphonuclear neutrophils (PMNs) as well as inflammasome activation in monocytes. The objective of this study was to test if (ant)agonists of C5aR and CD45 can attenuate the effect of PVL on PMNs and monocytes. We tested the effect of various concentrations of six C5aR (ant)agonists (avacopan, BM213, DF2593A, JPE-1375, PMX205 and W-54011) and one CD45 antagonist (NQ301) to attenuate the cytotoxic effect of PVL on human PMNs and monocytes in vitro. Shifts in the half-maximal effective concentration (EC50) of PVL to achieve a cytotoxic effect on PMNs and modulation of inflammatory cytokine response from monocytes were determined by flow cytometry and IL-1β detection. Pre-treatment of PMNs with avacopan, PMX205 and W-54,011 resulted in 3.6- to 4.3-fold shifts in the EC50 for PVL and were able to suppress IL-1β secretion by human monocytes in the presence of PVL. BM213, DF2593A and NQ301 were unable to change the susceptibility of PMNs towards PVL or reduce inflammasome activation in monocytes. Avacopan, PMX205 and W-54,011 showed protection against PVL-induced cytotoxicity and suppressed IL-1β secretion by monocytes. Clinical studies are needed to prove whether these substances can be used therapeutically as repurposed drugs.

Protective effects of α-Pinene against carbon tetrachloride-induced cardiac injury in Wistar rats: modulation of antioxidant and inflammatory responses

Protective effects of α-Pinene against carbon tetrachloride-induced cardiac injury in Wistar rats: modulation of antioxidant and inflammatory responses

Potential role of bacterial pathogens in the immunopathogenesis of ovarian cancer

The development of next-generation sequencing (NGS) techniques allowed conducting research with greater efficiency and determining the microbial pattern of niches in the human body that were previously considered sterile. Observed changes in the microbiome composition of patients with cancer lesions increasingly indicate the role of microorganisms in the tumour induction and progression. Overgrowth of certain pathogenic strains within the tissue may cause inflammation, which in its chronic form may lead to destabilization of host genome. Such changes may result in altering the expression of genes encoding proteins involved in significant metabolic pathways and promote pathogenic cell functions such as proliferation stimulation, apoptosis inhibition and modulation of inflammatory response. Consequently, these events may lead to tissue destruction, disruption of physiological processes and development of disease states including cancer. In light of emerging reports on the role of changes in the composition of the microbiota in tumorigenesis induction and the presence of pathogenic strains in the ovarian cancer (OC) tumour microenvironment (TME), the hypothesis of a potential role for bacteria in the pathogenesis of this cancer is also gaining interest. The following review presents a summary of scientific research indicating potential role of TME bacteria in the immunopathogenesis of OC.

NFAT5 counters long-term IFN-1 responses in hematopoietic stem cells to preserve reconstitution potential

AbstractHematopoietic stem cells (HSCs) readily recover from acute stress, but persistent stress can reduce their viability and long-term potential. Here, we show that the nuclear factor of activated T cells 5 (NFAT5), a transcription modulator of inflammatory responses, protects the HSC pool under stress. NFAT5 restrains HSC differentiation to multipotent progenitors after bone marrow transplantation and bone marrow ablation with ionizing radiation or chemotherapy. Correspondingly, NFAT5-deficient HSCs fail to support long-term reconstitution of hematopoietic progenitors and mature blood cells after serial transplant. Evidence from competitive transplant assays shows that these defects are HSC intrinsic. NFAT5-deficient HSCs exhibit enhanced expression of type 1 interferon (IFN-1) response genes after transplant, and suppressing IFN-1 receptor prevents their exacerbated differentiation and cell death after reconstitution and improves long-term regeneration potential. Blockade of IFN-1 receptor also prevented the overdifferentiation of NFAT5-deficient HSCs after bone marrow ablation. These findings show that long-term IFN-1 responses to different hematopoietic stressors drive HSCs toward more differentiated progenitors, and that NFAT5 has an HSC-intrinsic role, limiting IFN-1 responses to preserve reconstitution potential. Our identification of cell-intrinsic mechanisms that strengthen the resistance of HSCs to stress could help to devise approaches to protect long-term stemness during the treatment of hematopoietic malignancies.

Vitamin D and Sarcopenia in the Senior People: A Review of Mechanisms and Comprehensive Prevention and Treatment Strategies.

This article reviews the mechanisms and prevention strategies associated with vitamin D and sarcopenia in older adults. As a geriatric syndrome, sarcopenia is defined by a notable decline in skeletal muscle mass and strength, which increases the risk of adverse health outcomes such as falls and fractures. Vitamin D, an essential fat-soluble vitamin, is pivotal in skeletal muscle health. It affects muscle function through various mechanisms, including regulating calcium and phosphorus metabolism, promoting muscle protein synthesis, and modulation of muscle cell proliferation and differentiation. A deficiency in vitamin D has been identified as a significant risk factor for the development of sarcopenia in older adults. Many studies have demonstrated that low serum vitamin D levels are significantly associated with an increased risk of sarcopenia. While there is inconsistency in the findings, most studies support the importance of vitamin D in maintaining skeletal muscle health. Vitamin D influences the onset and progression of sarcopenia through various pathways, including the promotion of muscle protein synthesis, the regulation of mitochondrial function, and the modulation of immune and inflammatory responses. Regarding the prevention and treatment of sarcopenia, a combination of nutritional, exercise, and pharmacological interventions is recommended. Further research should be conducted to elucidate the molecular mechanism of vitamin D in sarcopenia, to study genes related to sarcopenia, to perform large-scale clinical trials, to investigate special populations, and to examine the combined application of vitamin D with other nutrients or drugs. A comprehensive investigation of the interconnection between vitamin D and sarcopenia will furnish a novel scientific foundation and productive strategies for preventing and treating sarcopenia. This, in turn, will enhance the senior people's quality of life and health.

The PDIA3-STAT3 protein complex regulates IBS formation and development via CTSS/MHC-II pathway-mediated intestinal inflammation

Irritable bowel syndrome (IBS) is a persistent functional gastrointestinal disorder characterised by abdominal pain and altered patterns of defecation. This study aims to clarify an increase in the expression and interaction of protein disulfide-isomerase A3 (PDIA3) and Signal Transducer and Activator of Transcription 3 (STAT3) within the membrane of dendritic cells (DCs) from individuals with IBS. Mechanistically, the heightened interaction between PDIA3 and STAT3 at the DC membrane results in reduced translocation of phosphorylated STAT3 (p-STAT3) into the nucleus. The reduction of p-STAT3 to nuclear transport subsequently increased the levels of cathepsin S (CTSS) and major histocompatibility complex class II (MHC-II). Consequently, activated DCs promote CD4+ T cell proliferation and cytokine secretion, including interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-9 (IL-9), and tumour necrosis factor-alpha (TNF-α), thereby contributing to the development of IBS. Importantly, the downregulation of PDIA3 and the administration of punicalagin (Pun), a crucial active compound found in pomegranate peel, alleviate IBS symptoms in rats, such as increased visceral hypersensitivity and abnormal stool characteristics. Collectively, these findings highlight the involvement of the PDIA3-STAT3 protein complex in IBS, providing a novel perspective on the modulation of immune and inflammatory responses. Additionally, this research advances our understanding of the role and mechanisms of PDIA3 inhibitors, presenting new therapeutic possibilities for managing IBS.

Exploring the Role of the Gut Microbiota in Modulating Colorectal Cancer Immunity.

The gut microbiota plays an essential role in maintaining immune homeostasis and influencing the immune landscape within the tumor microenvironment. This review aims to elucidate the interactions between gut microbiota and tumor immune dynamics, with a focus on colorectal cancer (CRC). The review spans foundational concepts of immuno-microbial interplay, factors influencing microbiome composition, and evidence linking gut microbiota to cancer immunotherapy outcomes. Gut microbiota modulates anti-cancer immunity through several mechanisms, including enhancement of immune surveillance and modulation of inflammatory responses. Specific microbial species and their metabolic byproducts can significantly influence the efficacy of cancer immunotherapies. Furthermore, microbial diversity within the gut microbiota correlates with clinical outcomes in CRC, suggesting potential as a valuable biomarker for predicting response to immunotherapy. Conclusions: Understanding the relationship between gut microbiota and tumor immune responses offers potential for novel therapeutic strategies and biomarker development. The gut microbiota not only influences the natural history and treatment response of CRC but also serves as a critical modulator of immune homeostasis and anti-cancer activity. Further exploration into the microbiome's role could enhance the effectiveness of existing treatments and guide the development of new therapeutic modalities.

Beyond Anticoagulation: A Comprehensive Review of Non-Vitamin K Oral Anticoagulants (NOACs) in Inflammation and Protease-Activated Receptor Signaling.

Non-vitamin K oral anticoagulants (NOACs) have revolutionized anticoagulant therapy, offering improved safety and efficacy over traditional agents like warfarin. This review comprehensively examines the dual roles of NOACs-apixaban, rivaroxaban, edoxaban, and dabigatran-not only as anticoagulants, but also as modulators of inflammation via protease-activated receptor (PAR) signaling. We highlight the unique pharmacotherapeutic properties of each NOAC, supported by key clinical trials demonstrating their effectiveness in preventing thromboembolic events. Beyond their established anticoagulant roles, emerging research suggests that NOACs influence inflammation through PAR signaling pathways, implicating factors such as factor Xa (FXa) and thrombin in the modulation of inflammatory responses. This review synthesizes current evidence on the anti-inflammatory potential of NOACs, exploring their impact on inflammatory markers and conditions like atherosclerosis and diabetes. By delineating the mechanisms by which NOACs mediate anti-inflammatory effects, this work aims to expand their therapeutic utility, offering new perspectives for managing inflammatory diseases. Our findings underscore the broader clinical implications of NOACs, advocating for their consideration in therapeutic strategies aimed at addressing inflammation-related pathologies. This comprehensive synthesis not only enhances understanding of NOACs' multifaceted roles, but also paves the way for future research and clinical applications in inflammation and cardiovascular health.

Multiple sclerosis: the NLRP3 inflammasome, gasdermin D, and therapeutics.

Multiple sclerosis (MS) stands as a chronic inflammatory disease characterized by its neurodegenerative impacts on the central nervous system. The complexity of MS and the significant challenges it poses to patients have made the exploration of effective treatments a crucial area of research. Among the various mechanisms under investigation, the role of inflammation in MS progression is of particular interest. Inflammatory responses within the body are regulated by various cellular mechanisms, one of which involves the nucleotide-binding oligomerization domain (NOD)-, leucine-rich repeat (LRR)-, and pyrin domains (PYD)-containing protein 3 (NLRP3). NLRP3 acts as a sensor within cells, playing a pivotal role in controlling the inflammatory response. Its activation is a critical step leading to the assembly of the NLRP3 inflammasome complex, a process that has profound implications for inflammatory diseases like MS. The NLRP3 inflammasome's activation is intricately linked to the subsequent activation of caspase 1 and gasdermin D (GsdmD), signaling pathways that are central to the inflammatory process. GsdmD, a prominent member of the Gasdermin protein family, is particularly noteworthy for its role in pyroptotic cell death, a form of programmed cell death that is distinct from apoptosis and is characterized by its inflammatory nature. This pathway's activation contributes significantly to the pathology of MS by exacerbating inflammatory responses within the nervous system. Given the detrimental effects of unregulated inflammation in MS, therapeutics targeting these inflammatory processes offer a promising avenue for alleviating the symptoms experienced by patients. This review delves into the intricacies of the pyroptotic pathways, highlighting how the formation of the NLRP3 inflammasome induces such pathways and the potential intervention points for therapeutic agents. By inhibiting key steps within these pathways, it is possible to mitigate the inflammatory response, thereby offering relief to those suffering from MS. Understanding these mechanisms not only sheds light on the pathophysiology of MS but also paves the way for the development of novel therapeutic strategies aimed at controlling the disease's progression through the modulation of the body's inflammatory response.

Evaluation of the effect of roasting and digestion on biological activity of compounds of coffee extracts - in vitro assessment of the bioavailability, cytoprotective properties and modulation of inflammatory response

Coffee is the most consumed beverage in the world. Consumption of phenolic compounds present in coffee protects the body against oxidative stress generation, inflammatory response, and cancer development. The aim of the study was evaluation of biological activity of coffee extracts (obtained from green, as well as light and dark roasted Robusta and Arabica beans) and isolated fractions on human colon adenocarcinoma Caco-2 cells, which are used as a cellular model of intestinal barrier in bioavailability studies. Additionally, impact of coffee phenolics on oxidative stress level and anti-inflammatory activity has been studied with RAW 264.7 macrophages used in immunomodulatory research. It was demonstrated that the coffee constituents protection against oxidative stress, lipotoxicity and secretion of proinflammatory mediators is correlated with the presence of mono- and dichlorogenic acids and roasting process. It was demonstrated that coffee phytochemicals can decrease cells proliferation and bind to topoisomerase IIα being a dietary tool in cancer prevention.

Effect of toxins from different periodontitis-associated bacteria on human platelet function.

Periodontitis is caused by a dysbiosis of oral bacteria resulting in alveolar bone destruction and teeth loss. The role of platelets in pathogenesis of periodontitis is a subject of research. The release of toxins from periodontitis-associated bacteria may influence platelet function and contribute to the modulation of hemostatic or inflammatory responses. Therefore, we explored platelet function upon exposure to defined toxins: leukotoxin A from Aggregatibacter actinomycetemcomitans (LtxA), a synthetic version of the C14-Tri-LAN-Gly peptide from Fusobacterium nucleatum (C14), and lipopolysaccharides from Porphyromonas gingivalis (LPS). Light transmission aggregometry was performed after the addition of toxins to platelet-rich plasma in different doses. Flow cytometry was used to identify inhibitory effects of toxins by measuring phosphorylation of the vaso-dilator-stimulated phosphoprotein or to identify activating effects by the detection of CD62P expression. The release of chemokines derived from washed platelets was determined by immunoassays. Collagen-induced threshold aggregation values were diminished upon incubation with LtxA and C14, accompanied with an increase of vaso-dilator-stimulated phosphoprotein (VASP) phosphorylation, indicating platelet inhibition. In contrast, LPS did not affect aggregation but slightly enhanced CD62P expression under co-stimulation with low-dose thrombin pointing to slight platelet activation. The three toxins did not relevantly influence the secretion of chemokines. Although weak, the investigated toxins differently influenced human platelet function. LtxA and C14 mediated inhibitory effects, whereas LPS contributed to a slight activation of platelets. Further analysis of specific cellular responses mediated by bacterial toxins may render novel targets and suggestions for the treatment of periodontitis.

Mechanistic exploration of 6-shogaol’s preventive effects on azoxymethane and dextran sulfate sodium -induced colorectal cancer: involvement of cell proliferation, apoptosis, carcinoembryonic antigen, wingless-related integration site signaling, and oxido-inflammation

Colorectal cancer (CRC) poses a significant global health burden, being the third most prevalent cancer and the second most significant contributor to cancer-related deaths worldwide. Preventive strategies are crucial to combat this rising incidence. 6-shogaol, derived from ginger, has shown promise in preventing and treating various cancers. This study investigated the preventive effects of 6-shogaol on azoxymethane (AOM) and dextran sulfate sodium (DSS)-induced CRC in mice. Forty male BALB/c mice were randomly divided into control, 6-shogaol, AOM + DSS, and 6-shogaol + AOM + DSS. Mice in the control group received corn oil for 16 weeks, while those in the 6-Shogaol group were administered 20 mg/kg of 6-shogaol for 16 weeks. The AOM + DSS group received a single intraperitoneal dose (ip) of 10 mg/kg of AOM, followed by three cycles of 2.5% DSS in drinking water. The 6-shogaol + AOM + DSS group received both 6-shogaol for 16 weeks and a single ip of 10 mg/kg of AOM, followed by three cycles of 2.5% DSS in drinking water. The AOM + DSS-treated mice exhibited reduced food consumption, colon weight, and colon length, along with increased tumor formation. Co-administration of 6-shogaol effectively reversed these changes, inhibiting CRC development. Histopathological analysis revealed protective effects of 6-shogaol against colonic insults and modulation of inflammatory responses. 6-shogaol significantly reduced Carcinoembryonic antigen and Kiel 67 levels, indicating inhibition of tumor cell proliferation. Mechanistically, 6-shogaol promoted apoptosis by upregulating protein 53 and caspase-3 expression, and it effectively restored the balance of the Wingless-related integration site signaling pathway by regulating β-catenin and adenomatous polyposis coli levels. Moreover, 6-shogaol demonstrated anti-inflammatory effects, reducing myeloperoxidase, Tumor necrosis factor alpha, and cyclooxygenase-2 levels in AOM/DSS-treated mice. Additionally, 6-shogaol restored redox homeostasis by reducing lipid peroxidation and nitrosative stress and enhancing antioxidant enzyme activities. The findings suggest that 6-shogaol inhibits cell proliferation, induces apoptosis, regulates Wnt signaling, suppresses inflammation, and restores redox homeostasis, providing comprehensive insights into its potential therapeutic benefits for CRC.

The Antiviral Potential of Perilla frutescens: Advances and Perspectives.

Viruses pose a significant threat to human health, causing widespread diseases and impacting the global economy. Perilla frutescens, a traditional medicine and food homologous plant, is well known for its antiviral properties. This systematic review examines the antiviral potential of Perilla frutescens, including its antiviral activity, chemical structure and pharmacological parameters. Utilizing bioinformatics analysis, we revealed the correlation between Perilla frutescens and antiviral activity, identified overlaps between Perilla frutescens target genes and virus-related genes, and explored related signaling pathways. Moreover, a classified summary of the active components of Perilla frutescens, focusing on compounds associated with antiviral activity, provides important clues for optimizing the antiviral drug development of Perilla frutescens. Our findings indicate that Perilla frutescens showed a strong antiviral effect, and its active ingredients can effectively inhibit the replication and spread of a variety of viruses in this review. The antiviral mechanisms of Perilla frutescens may involve several pathways, including enhanced immune function, modulation of inflammatory responses, and inhibition of key enzyme activities such as viral replicase. These results underscore the potential antiviral application of Perilla frutescens as a natural plant and provide important implications for the development of new antiviral drugs.