Background/Objectives: Ovarian aging represents a critically important aspect of female senescence. It not only denotes the loss of fertility but is also accompanied by a series of physiological changes and the aging of other organs. Hydroxytyrosol (HT), a natural polyphenolic phytocompound, has been demonstrated to exhibit remarkable effects in regulating autophagy, inflammation, and the aging process. However, the relationship between HT and ovarian aging, as well as the specific underlying mechanisms, remains poorly understood. Methods: In this study, network pharmacology, molecular docking, and molecular dynamics simulation were employed to explore the regulatory effect of HT on ovarian inflammaging via autophagy-targeted mechanisms. Results: Through network pharmacology analysis, this study successfully identified 10 hub genes associated with ovarian aging regulation. Notably, four out of the top five hub genes were found to be closely related to autophagy regulatory pathways. Further investigation revealed the pivotal role of ATG7: HT may regulate ovarian inflammaging through activating the FIP200 (focal adhesion kinase family interacting protein of 200 kD)-dependent non-canonical selective autophagy pathway. The results of molecular docking indicated that ATG7 has a strong binding ability with HT. Molecular dynamics simulation further verified the binding stability between the two. Conclusions: By analysis, a possible pathway for HT to regulate ovarian inflammaging via non-canonical selective autophagy was explored, providing cues for further research.

Hydroxytyrosol (HT), a principal bioactive phytochemical abundant in Mediterranean dietary sources, has emerged as a molecule of significant scientific interest owing to its multifaceted health-promoting properties. Accumulating evidence suggests that HT's therapeutic potential in metabolic disorders extends beyond conventional antioxidant capacity to encompass mitochondrial regulatory networks. This review synthesizes contemporary evidence from our systematic investigations and the existing literature to delineate HT's comprehensive modulatory effects on mitochondrial homeostasis. We systematically summarized the impact of HT on mitochondrial dynamics (fusion/fission equilibrium), biogenesis and energy metabolism, mitophagy, inter-organellar communication with the endoplasmic reticulum, and microbiota-mitochondria crosstalk. Through this multidimensional analysis, we established HT as a mitochondrial homeostasis modulator with potential therapeutic applications in metabolic syndrome (MetS) and its related pathologies including type 2 diabetes mellitus, obesity-related metabolic dysfunction, dyslipidemia, non-alcoholic steatohepatitis, and hypertension-related complications. Moreover, we further discussed translational challenges in HT research, emphasizing the imperative for direct target identification, mitochondrial-targeted delivery system development, and combinatorial therapeutic strategies. Collectively, this review provides a mechanistic framework for advancing HT research and accelerating its clinical implementation in MetS and its related diseases.

This study aims to explore the protective effect and underlying mechanism of hydroxytyrosol (HT) in fungal keratitis.

Mouse models with Aspergillus fumigatus (A. fumigatus) keratitis, human corneal epithelial cells (HCECs) and RAW 264.7 cells were used in this study. Methods employed included MIC assay, biofilm formation test, hyphal immunofluorescence staining and adhesion test to assess the antifungal activity of HT. The severity of keratitis was evaluated using slit-lamp examination and HE staining. Draize eye test was used to measure corneal tolerance to HT. Corneal macrophages were detected by immunofluorescence staining. Reactive oxygen species (ROS) production in cytoplasm was quantified using DCFH-DA. Mitochondrial membrane potential was detected by JC-1. RT-PCR, ELISA and western blot were used to measure the expression of cytokines, as well as Nrf2 and HO-1 levels.

HT inhibited A. fumigatus growth, biofilm formation and conidial adhesion, and downregulated the expression of genes related to cell-wall assembly and morphogenesis. In fungal keratitis mouse models, HT significantly alleviated corneal inflammation, decreased the expression of cytokines and the accumulation of macrophages. In vitro, HT attenuated A. fumigatus-induced cytokine overexpression in HCECs or RAW 264.7 cells, and this effect was counteracted by an Nrf2 inhibitor. In RAW 264.7 cells stimulated with A. fumigatus, HT downregulated M1 markers expression, upregulated M2 markers expression, reduced ROS production, and restored mitochondrial membrane potential. Notably, these effects of HT were negated by pretreatment with an Nrf2 inhibitor.

This study underscores HT's efficacy against A. fumigatus growth and corneal invasion, its ability to mitigate fungi-induced inflammation, and its capacity to eliminate ROS via activation of the Nrf2/HO-1 signaling pathway. These findings suggest that HT holds therapeutic promise for fungal keratitis.

Inflammatory bowel disease is a multifaceted condition that is influenced by nutritional, microbial, environmental, genetic, psychological, and immunological factors. Polyphenols and polysaccharides have gained recognition for their therapeutic potential. This review emphasizes the biological effects of polyphenols and polysaccharides, and explores their antioxidant, anti-inflammatory, and microbiome-modulating properties in the management of inflammatory bowel disease (IBD). However, polyphenols encounter challenges, such as low stability and low bioavailability in the colon during IBD treatment. Hence, polysaccharide-based encapsulation is a promising solution to achieve targeted delivery, improved bioavailability, reduced toxicity, and enhanced stability. This review also discusses the significance of covalent and non-covalent interactions, and simple and complex encapsulation between polyphenols and polysaccharides. The administration of these compounds in appropriate quantities has proven beneficial in preventing the development of Crohn's disease and ulcerative colitis, ultimately leading to the management of IBD. The use of polyphenols and polysaccharides has been found to reduce histological scores and colon injury associated with IBD, increase the abundance of beneficial microbes, inhibit the development of colitis-associated cancer, promote the production of microbial end-products, such as short-chain fatty acids (SCFAs), and improve anti-inflammatory properties. Despite the combined effects of polyphenols and polysaccharides observed in both in vitro and in vivo studies, further human clinical trials are needed to comprehend their effectiveness on inflammatory bowel disease.

Intestinal fibrosis, a prominent consequence of inflammatory bowel disease (IBD), presents considerable difficulty owing to the absence of licensed antifibrotic therapies. This review assesses the therapeutic potential of phytochemicals as alternate methods for controlling intestinal fibrosis. Phytochemicals, bioactive molecules originating from plants, exhibit potential antifibrotic, anti-inflammatory, and antioxidant activities, targeting pathways associated with inflammation and fibrosis. Compounds such as Asperuloside, Berberine, and olive phenols have demonstrated potential in preclinical models by regulating critical signaling pathways, including TGF-β/Smad and NFκB, which are integral to advancing fibrosis.

The main findings suggest that these phytochemicals significantly reduce fibrotic markers, collagen deposition, and inflammation in various experimental models of IBD. These phytochemicals may function as supplementary medicines to standard treatments, perhaps enhancing patient outcomes while mitigating the adverse effects of prolonged immunosuppressive usage. Nonetheless, additional clinical trials are necessary to validate their safety, effectiveness, and bioavailability in human subjects.

Therefore, investigating phytochemicals may lead to crucial advances in the formulation of innovative treatment approaches for fibrosis associated with IBD, offering a promising avenue for future therapeutic development.

Ulcerative colitis (UC) is a form of chronic inflammatory bowel disease, and UC diagnosis rates continue to rise throughout the globe. The research and development of new drugs for the treatment of UC are urgent, and natural compounds are an important source. However, there is a lack of systematic summarization of natural compounds and their mechanisms for the treatment of UC.

We reviewed the literature in the databases below from their inception until July 2023: Web of Science, PubMed, China National Knowledge Infrastructure, and Wanfang Data, to obtain information on the relationship between natural compounds and UC.

The results showed that 279 natural compounds treat UC through four main mechanisms, including regulating gut microbiota and metabolites (Mechanism I), protecting the intestinal mucosal barrier (Mechanism II), regulating intestinal mucosal immune response (Mechanism III), as well as regulating other mechanisms (Mechanism Ⅳ) such as cellular autophagy modulation and ferroptosis inhibition. Of these, Mechanism III is regulated by all natural compounds. The 279 natural compounds, including 62 terpenoids, 57 alkaloids, 52 flavonoids, 26 phenols, 19 phenylpropanoids, 9 steroids, 9 saponins, 8 quinonoids, 6 vitamins, and 31 others, can effectively ameliorate UC. Of these, terpenoids, alkaloids, and flavonoids have the greatest potential for treating UC. It is noteworthy to highlight that a total of 54 natural compounds exhibit their therapeutic effects by modulating Mechanisms I, II, and III.

This review serves as a comprehensive resource for the pharmaceutical industry, researchers, and clinicians seeking novel therapeutic approaches to combat UC. Harnessing the therapeutic potential of these natural compounds may significantly contribute to the improvement of the quality of life of patients with UC and promotion of disease-modifying therapies in the future.

Polyphenols are natural secondary metabolites found in plants endowed with multiple biological activities (antioxidant, anti-inflammatory, antimicrobial, cardioprotective, and anticancer). In view of these properties, they find many applications and are used as active ingredients in nutraceutical, food, pharmaceutical, and cosmetic formulations. In accordance with green chemistry and circular economy strategies, they can also be recovered from agroindustrial waste and reused in various sectors, promoting sustainable processes. This review described structural characteristics, methods for extraction, biological properties, and applications of polyphenolic extracts obtained from two selected plant materials of the Mediterranean area as olive (Olea europaea L.) and pomegranate (Punica granatum L.) based on recent literature, highlighting future research perspectives.

Salvia officinalis L. has attracted scientific and industrial interest due to its pharmacological properties. However, its detailed phytochemical profile and its correlation with beneficial effects in the human microbiome and oxidative stress remained elusive. To unveil this, S. officinalis was collected from the region of Epirus and its molecular identity was verified with DNA barcoding. Phytochemical profile for both aqueous and ethanol-based extracts was determined by high-pressure liquid chromatography-tandem mass spectrometry and 103 phytochemicals were determined. The effect of S. officinalis extracts as functional regulators of food microbiota by stimulating the growth of Lacticaseibacillus rhamnosus strains and by suppressing evolution of pathogenic bacteria was verified. Furthermore, we recorded that both extracts exhibited a significant cellular protection against H2O2-induced DNA damage. Finally, both extracts exhibited strong inhibitory effect towards LDL oxidation. This study provides a comprehensive characterization of S. officinalis on its phytochemical components as also its potential impact in human microbiome and oxidative stress.

The antioxidant and anti-inflammatory effects of hormetic nutrition for enhancing stress resilience and overall human health have received much attention. Recently, the gut-brain axis has attracted prominent interest for preventing and therapeutically impacting neuropathologies and gastrointestinal diseases. Polyphenols and polyphenol-combined nanoparticles in synergy with probiotics have shown to improve gut bioavailability and blood-brain barrier (BBB) permeability, thus inhibiting the oxidative stress, metabolic dysfunction and inflammation linked to gut dysbiosis and ultimately the onset and progression of central nervous system (CNS) disorders. In accordance with hormesis, polyphenols display biphasic dose-response effects by activating at a low dose the Nrf2 pathway resulting in the upregulation of antioxidant vitagenes, as in the case of heme oxygenase-1 upregulated by hidrox® or curcumin and sirtuin-1 activated by resveratrol to inhibit reactive oxygen species (ROS) overproduction, microbiota dysfunction and neurotoxic damage. Importantly, modulation of the composition and function of the gut microbiota through polyphenols and/or probiotics enhances the abundance of beneficial bacteria and can prevent and treat Alzheimer's disease and other neurological disorders. Interestingly, dysregulation of the Nrf2 pathway in the gut and the brain can exacerbate selective susceptibility under neuroinflammatory conditions to CNS disorders due to the high vulnerability of vagal sensory neurons to oxidative stress. Herein, we aimed to discuss hormetic nutrients, including polyphenols and/or probiotics, targeting the Nrf2 pathway and vitagenes for the development of promising neuroprotective and therapeutic strategies to suppress oxidative stress, inflammation and microbiota deregulation, and consequently improve cognitive performance and brain health. In this review, we also explore interactions of the gut-brain axis based on sophisticated and cutting-edge technologies for novel anti-neuroinflammatory approaches and personalized nutritional therapies.

On exposure to cosmetic pollutants, gastrointestinal dysbiosis, which is characterised by a disturbance in the gut microbiota, has come into focus as a possible contributor to the occurrence of neurotoxic consequences. It is normal practice to use personal care products that include parabens, phthalates, sulphates, triclosans/triclocarbans and micro/nano plastics. These substances have been found in a variety of bodily fluids and tissues, demonstrating their systemic dispersion. Being exposed to these cosmetic pollutants has been linked in recent research to neurotoxicity, including cognitive decline and neurodevelopmental problems. A vital part of sustaining gut health and general well-being is the gut flora. Increased intestinal permeability, persistent inflammation, and impaired metabolism may result from disruption of the gut microbial environment, which may in turn contribute to neurotoxicity. The link between gastrointestinal dysbiosis and the neurotoxic effects brought on by cosmetic pollutants may be explained by a number of processes, primarily the gut-brain axis. For the purpose of creating preventative and therapeutic measures, it is crucial to comprehend the intricate interactions involving cosmetic pollutants, gastrointestinal dysbiosis, and neurotoxicity. This review provides an in-depth understanding of the various hazardous cosmetic pollutants and its potential role in the occurrence of neurological disorders via gastrointestinal dysbiosis, providing insights into various described and hypothetical mechanisms regarding the complex toxic effects of these industrial pollutants.

An adequate intestinal environment before weaning may contribute to diarrhea predisposition and piglet development. This study evaluates how the dietary supplementation of vitamin E (VE) (100 mg/kg), hydroxytyrosol (HXT) (1.5 mg/kg) or the combined administration (VE + HXT) given to Iberian sows from gestation affects the piglet's faecal characteristics, short chain fatty acids (SCFAs), fatty acid profile or intestinal morphology as indicators of gut health; and quantify the contribution of the oxidative status and colostrum/milk composition to the piglet's SCFAs content and intestinal health. Dietary VE increased isobutyric acid (iC4), butyric acid (C4), isovaleric acid (iC5), and ∑SCFAs, whereas HXT increased iC4 and tended to decrease ∑SCFAs of faeces. Piglets from HXT-supplemented sows also tended to have higher faecal C20:4n-6/C20:2 ratio C22:6 proportion and showed lower occludin gene expression in the duodenum. The combination of both antioxidants had a positive effect on iC4 and iC5 levels. Correlation analyses and regression equations indicate that faecal SCFAs were related to oxidative status (mainly plasma VE) and colostrum and milk composition (mainly C20:2, C20:3, C20:4 n-6). This study would confirm the superiority of VE over HXT supplementation to improve intestinal homeostasis, gut health, and, consequently piglet growth.

Obesity, pancreatitis, cardiovascular, gastrointestinal (GI), and liver diseases have all been linked to the Western lifestyle, characterized by increased unhealthy food consumption and decreased physical activity. Besides obesity and pancreatitis, many GI and liver diseases are associated with inflammation. Inflammasomes are multi-protein complexes that mediate acute and restorative inflammatory pathways. However, many aberrations in inflammasome activity originate from shifts in dietary habits. Evidence reveals that dietary polyphenols effectively modulate inflammasome-associated dysfunctions. With a focus on pancreatitis, GI, and liver disorders, this review set out to provide the most relevant evidence for the therapeutic impact of polyphenols via the regulation of the inflammasome pathway. Overall, flavonoid and non-flavonoid polyphenols maintain intestinal eubiosis, downregulate NLRP3 inflammasome canonical pathway, and restore redox status via upregulating Nrf2/HO-1 signaling. These effects at the level of the intestine, the liver, and the pancreas are associated with decreased systemic levels of key pro-inflammatory cytokines, including TNF-α, IL-1β, and IL-6.

The previous documentation has shown the role of resistant starch in promoting intestinal health, while the effect of starch-lipid complex (RS5) on colitis remains unclear. This study aimed to investigate the effect and potential mechanism of RS5 in colitis. We prepared RS5 complexes by combining pea starch with lauric acid. Mice with dextran sulfate sodium-induced colitis were treated with either RS5 (3.25 g/kg) or normal saline (10 mL/kg) for seven days, and the effects of pea starch-lauric acid complex on mice were observed. The RS5 treatment significantly attenuated weight loss, splenomegaly, colon shortening, and pathological damage in mice with colitis. Compare with the DSS group, cytokines levels, such as tumor necrosis factor-α and interleukin-6 in both serum and colon tissue was significantly decreased in RS5 treatment group, while the gene expression of interleukin-10 and the expression of mucin 2, zonula occludens-1, Occludin, and claudin-1 in the colon was significantly upregulated in RS5 treatment group. In addition, RS5 treatment altered the gut microbiota structure of colitis mice by increasing the abundance of Bacteroides and decreasing Turicibacter, Oscillospira, Odoribacter, and Akkermansia. The dietary composition could be exploited to manage colitis by attenuating inflammation, restoring the intestinal barrier, and regulating gut microbiota.

Ongoing research explores the underlying causes of ulcerative colitis and Crohn's disease. Many experts suggest that dysbiosis in the gut microbiota and genetic, immunological, and environmental factors play significant roles. The term "microbiota" pertains to the collective community of microorganisms, including bacteria, viruses, and fungi, that reside within the gastrointestinal tract, with a particular emphasis on the colon. When there is an imbalance or disruption in the composition of the gut microbiota, it is referred to as dysbiosis. Dysbiosis can trigger inflammation in the intestinal cells and disrupt the innate immune system, leading to oxidative stress, redox signaling, electrophilic stress, and inflammation. The Nod-like Receptor (NLR) Family Pyrin Domain Containing 3 (NLRP3) inflammasome, a key regulator found in immunological and epithelial cells, is crucial in inducing inflammatory diseases, promoting immune responses to the gut microbiota, and regulating the integrity of the intestinal epithelium. Its downstream effectors include caspase-1 and interleukin (IL)-1β. The present study investigated the therapeutic potential of 13 medicinal plants, such as Litsea cubeba, Artemisia anomala, Piper nigrum, Morus macroura, and Agrimonia pilosa, and 29 phytocompounds such as artemisitene, morroniside, protopine, ferulic acid, quercetin, picroside II, and hydroxytyrosol on in vitro and in vivo models of inflammatory bowel diseases (IBD), with a focus on their effects on the NLRP3 inflammasome. The observed effects of these treatments included reductions in IL-1β, tumor necrosis factor-alpha, IL-6, interferon-gamma, and caspase levels, and increased expression of antioxidant enzymes, IL-4, and IL-10, as well as regulation of gut microbiota. These effects could potentially provide substantial advantages in treating IBD with few or no adverse effects as caused by synthetic anti-inflammatory and immunomodulated drugs. However, additional research is necessary to validate these findings clinically and to develop effective treatments that can benefit individuals who suffer from these diseases.

Inflammatory bowel diseases (IBD) and colorectal cancer (CRC) are difficult to cure, and available treatment is associated with troubling side effects. In addition, current therapies have limited efficacy and are characterized by high costs, and a large segment of the IBD and CRC patients are refractive to the treatment. Moreover, presently used anti-IBD therapies in the clinics are primarily aimed on the symptomatic control. That is why new agents with therapeutic potential against IBD and CRC are required. Currently, polyphenols have received great attention in the pharmaceutical industry and in medicine due to their health-promoting properties. They may exert anti-inflammatory, anti-oxidative, and anti-cancer activity, via inhibiting production of pro-inflammatory cytokines and enzymes or factors associated with carcinogenesis (e.g., matrix metalloproteinases, vascular endothelial growth factor), suggesting they may have therapeutic potential against IBD and CRC. However, their use is limited under both processing conditions or gastrointestinal interactions, reducing their stability and hence their bioaccessibility and bioavailability. Therefore, there is a need for more effective carriers that could be used for encapsulation of polyphenolic compounds. In recent years, natural polysaccharides have been proposed for creating carriers used in the synthesis of polyphenol encapsulates. Among these, hemicelluloses are particularly noteworthy, being characterized by good biocompatibility, biodegradation, low immunogenicity, and pro-health activity. They may also demonstrate synergy with the polyphenol payload. This review discusses the utility and potential of hemicellulose-based encapsulations of polyphenols as support for treatment of IBD and CRC.

Plantaginis Herba (Plantago asiatica L.) has the effects of clearing heat and diuresis, oozing wet and drenching. As the main active components of Plantaginis Herba (Plantago asiatica L.), plantamajoside have a wide range of antitumor activities but very low bioavailability. The process of interacting between plantamajoside and gut microbiota remains unclear.

To illustrate the process of interacting between plantamajoside and gut microbiota based on high-resolution mass spectrometry and targeted metabolomics methods.

This experiment was divided into two parts. First, metabolites produced from plantamajoside by gut microbiota were identified and quantified based on high-resolution mass spectrometry and LC-MS/MS. Additionally, stimulation of plantamajoside on gut microbiota-derived metabolites was determined by targeted metabolomics and gas chromatography.

We first found that plantamajoside was rapidly metabolized by gut microbiota. Then, we identified metabolites of plantamajoside by high-resolution mass spectrometry and speculated that plantamajoside was metabolized into five metabolites including calceolarioside A, dopaol glucoside, hydroxytyrosol, 3-(3-hydroxyphenyl) propionic acid (3-HPP) and caffeic acid. Among them, we quantitatively analyzed four possible metabolites based on LC‒MS/MS and found that hydroxytyrosol and 3-HPP were final products by the gut microbiota. In addition, we studied whether plantamajoside could affect the short-chain fatty acid (SCFA) and amino acid metabolites. We found that plantamajoside could inhibit the acetic acid, kynurenic acid (KYNA) and kynurenine (KN) produced by intestinal bacteria and promote the indole propionic acid (IPA) and indole formaldehyde (IALD) produced by intestinal bacteria.

An interaction between plantamajoside and gut microbiota was revealed in this study. Unlike the traditional metabolic system, the special metabolic characteristics of plantamajoside in gut microbiota was found. Plantamajoside was metabolized into the following active metabolites: calceolarioside A, dopaol glucoside, hydroxytyrosol, caffeic acid and 3-HPP. Besides, plantamajoside could affect SCFA and tryptophan metabolism by gut microbiota. Especially, the exogenous metabolites hydroxytyrosol, caffeic acid and endogenous metabolites IPA may have potential association with the antitumor activity of plantamajoside.

Inflammaging refers to a chronic, systemic, low-grade inflammation, driven by immune (mainly macrophages) and non-immune cells stimulated by endogenous/self, misplaced or altered molecules, belonging to physiological aging. This age-related inflammatory status is characterized by increased inflammation and decreased macroautophagy/autophagy (a degradation process that removes unnecessary or dysfunctional cell components). Inflammaging predisposes to age-related diseases, including obesity, type-2 diabetes, cancer, cardiovascular and neurodegenerative disorders, as well as vulnerability to infectious diseases and vaccine failure, representing thus a major target for anti-aging strategies. Phenolic compounds-found in extra-virgin olive oil (EVOO)-are well known for their beneficial effect on longevity. Among them, hydroxytyrosol (HTyr) appears to greatly contribute to healthy aging by its documented potent antioxidant activity. In addition, HTyr can modulate inflammation and autophagy, thus possibly counteracting and reducing inflammaging. In this review, we reference the literature on pure HTyr as a modulatory agent of inflammation and autophagy, in order to highlight its possible interference with inflammaging. This HTyr-mediated activity might contribute to healthy aging and delay the development or progression of diseases related to aging.

One of the significant health issues in the world is the prevalence of ulcerative colitis (UC). UC is a chronic disorder that mainly affects the colon, beginning with the rectum, and can progress from asymptomatic mild inflammation to extensive inflammation of the entire colon. Understanding the underlying molecular mechanisms of UC pathogenesis emphasizes the need for innovative therapeutic approaches based on identifying molecular targets. Interestingly, in response to cellular injury, the NLR family pyrin domain containing 3 (NLRP3) inflammasome is a crucial part of the inflammation and immunological reaction by promoting caspase-1 activation and the release of interleukin-1β. This review discusses the mechanisms of NLRP3 inflammasome activation by various signals and its regulation and impact on UC.

In recent years, the phytoconstituents of foods in the Mediterranean diet (MD) have been the subject of several studies for their beneficial effects on human health. The traditional MD is described as a diet heavy in vegetable oils, fruits, nuts, and fish. The most studied element of MD is undoubtedly olive oil due precisely to its beneficial properties that make it an object of interest. Several studies have attributed these protective effects to hydroxytyrosol (HT), the main polyphenol contained in olive oil and leaves. HT has been shown to be able to modulate the oxidative and inflammatory process in numerous chronic disorders, including intestinal and gastrointestinal pathologies. To date, there is no paper that summarizes the role of HT in these disorders. This review provides an overview of the anti-inflammatory and antioxidant proprieties of HT against intestinal and gastrointestinal diseases.

Brucellosis is a well-known and harmful zoonotic disease that poses a severe threat to public health and wild and dairy animals. Due to a lack of monitoring and awareness, disease incidence has increased. Therefore, this study was conducted for the first time to ascertain the status of seroprevalence of brucellosis, hematological, oxidative stress, and antioxidant enzymes in different breeds of cattle reared under tropical-desert conditions in Pakistan. This study comprised 570 cattle of different breeds. We recorded some epidemiological traits, including age and gender. The blood samples were obtained from all the cattle, screened with RBPT, and then confirmed by ELISA and PCR. The results recorded an overall 11.75%, 10.7%, and 9.64% prevalence of brucellosis based on RBPT, ELISA, and PCR. We obtained nonsignificant results in different age and sex groups of cattle. The results showed significantly (P ≤ 0.05) lower values of erythrocyte counts, hemoglobin quantity, hematocrit, lymphocytes, and monocytes in infected cases. The results showed that the total leukocyte and neutrophil cells significantly (P ≤ 0.05) increased. The lipid peroxidation parameters (MDA- and NO-scavenging activity of erythrocyte) increased significantly (P ≤ 0.05) in infected cattle, whereas significantly reduced antioxidant enzymes like SOD, RGSH, and CAT were. Similarly, significantly lower serum albumin levels and total serum proteins were recorded in infected cattle.

Inflammasomes are protein complexes involved in the regulation of different biological conditions. Over the past few years, the role of NLRP3 in different tumor types has gained interest. In breast cancer (BC), NLRP3 has been associated with multiple processes including epithelia mesenchymal transition, invasion and metastization. Little is known about molecular modifications of NLRP3 up-regulation. In this study, in a cohort of BCs, the expression levels of NLRP3 and PYCARD were analyzed in combination with CyclinD1 and MYC ones and their gene alterations. We described a correlation between the NLRP3/PYCARD axis and CyclinD1 (p < 0.0001). NLRP3, PYCARD and CyclinD1’s positive expression was observed in estrogen receptor (ER) and progesterone receptor (PgR) positive cases (p < 0.0001). Furthermore, a reduction of NLRP3 and PYCARD expression has been observed in triple negative breast cancers (TNBCs) with respect to the Luminal phenotypes (p = 0.017 and p = 0.0015, respectively). The association NLRP3+/CCND1+ or PYCARD+/CCND1+ was related to more aggressive clinicopathological characteristics and a worse clinical outcome, both for progression free survival (PFS) and overall survival (OS) with respect to NLRP3+/CCND1− or PYCARD+/CCND1− patients, both in the whole cohort and also in the subset of Luminal tumors. In conclusion, our study shows that the NLRP3 inflammasome complex is down-regulated in TNBC compared to the Luminal subgroup. Moreover, the expression levels of NLRP3 and PYCARD together with the alterations of CCND1 results in Luminal subtype BC’ss poor prognosis.