Pituitary neuroendocrine tumor is the third most common primary intracranial tumor. Its main clinical manifestations include abnormal hormone secretion symptoms, symptoms caused by tumor compression of the surrounding pituitary tissue, pituitary stroke, and other anterior pituitary dysfunction. Its pathogenesis is yet to be fully understood. Surgical treatment is still the main treatment. Despite complete resection, 10%-20% of tumors may recur. While dopamine agonists are effective in over 90% of prolactinomas, prolonged use and individual variations can lead to increased drug resistance and a gradual decline in efficacy, which ultimately requires surgical intervention. Nonsteroidal anti-inflammatory drugs reduce the production of inflammatory mediator prostaglandins by inhibiting the activity of cyclooxygenase and exert antipyretic, analgesic, antiplatelet, and anti-inflammatory effects. In recent years, many in-depth studies have confirmed the potential of nonsteroidal anti-inflammatory drugs as a preventive and antitumor agent. It has been extensively utilized in the prevention and treatment of various types of cancer. However, their specific mechanisms of action still need to be fully elucidated. This article summarizes recent research progress on the expression of cyclooxygenase in pituitary neuroendocrine tumors and the treatment of nonsteroidal anti-inflammatory drugs. It provides a feasible theoretical basis for further research on pituitary neuroendocrine tumors and explores potential therapeutic targets.

UNASSIGNED: The present study investigated the nephron-testicular protective effects of sesamin against cisplatin (CP)-induced acute renal and testicular injuries.
UNASSIGNED: Thirty-two male Wistar rats were allocated to receive carboxymethylcellulose (0.5%, as sesamin vehicle), CP (a single i.p. 5 mg/kg dose), CP plus sesamin at 10 or 20 mg/kg orally for 10 days.
UNASSIGNED: Data analysis showed significant increases in serum urea, creatinine, interleukin (IL)-1, IL-6, and tumor necrosis factor-α (TNF-α), as well as renal and testicular tissue malondialdehyde and nitric-oxide concentrations in CP-intoxicated rats in comparison to control animals. On the contrary, rats treated with CP only exhibited significantly lower (p < .05) serum testosterone, tissue glutathione, and activities of endogenous antioxidant enzymes compared to control rats. Histopathologically examining CP-intoxicated rats\' tissues using H&E and PAS stains showed atrophied glomeruli, interstitial inflammatory cells, atypic tubular epithelium with focal apoptosis, and reduced mucopolysaccharide content. Further, immunohistochemical staining of the same group revealed an increase in p53 and cyclooxygenase-II (Cox-II) expression in renal and testicular tissues. Treatment with sesamin alleviated almost all the changes mentioned above in a dose-dependent manner, with the 20 mg/kg dose restoring several parameters\' concentrations to normal ranges.
UNASSIGNED: In brief, sesamin could protect the kidneys and testes against CP toxicity through its antioxidant, anti-inflammatory, and anti-apoptotic effects.

Thymol (THY), as the natural monoterpene phenol, acts against oxidative stress and inflammatory processes. This study aimed to evaluate the anti-inflammatory effects and possible molecular mechanisms of THY via formalin-induced mouse and egg albumin-induced chick models alongside molecular docking and molecular dynamic (MD) simulations. THY (7.5, 15, and 30 mg/kg) was investigated, compared to celecoxib and ketoprofen (42 mg/kg), as anti-inflammatory standards. THY dose-dependently and significantly (p < 0.05) decreased paw-licking and edema diameter parameters in formalin (phases I and II) and egg albumin-induced models. Moreover, THY (15 mg/kg) exerted better anti-inflammatory effects in combination with the standard drug ketoprofen than alone and with celecoxib. In silico studies demonstrated elevated binding affinities of THY with cyclooxygenase-2 (COX-2) than the COX-1 enzyme, and the ligand binds at a similar location where ketoprofen and celecoxib interact. The results of MD simulations confirmed the stability of the test ligand. THY exerted anti-inflammatory effects on Swiss mice and young chicks, possibly by interacting with COX-2. As a conclusion, THY might be a hopeful drug candidate for the management of inflammatory disorders.

UNASSIGNED: Diagnosing and treating lameness in horses is essential to improving their welfare. In equine orthopedic practice, infrared thermography (IRT) can indirectly detect soreness. Non-steroidal anti-inflammatory drugs can treat painful and inflammatory processes in horses. Using IRT, the efficacy of meloxicam (Maxicam Gel®) was evaluated in pre-treating transient synovitis in horses induced by a middle carpal joint injection of lipopolysaccharides (LPS) from E. coli 055:B5 at a dose of 10 endotoxin units.
UNASSIGNED: In a cross-over design, six healthy horses were randomly assigned to receive either 0.6 mg/kg of oral Maxicam Gel® (MAXVO) or a mock administration (control group, C) following a two-week washout period. IRT of the middle carpal joint, visual lameness assessment and joint circumference were recorded over time. Clinical and hematological evaluations were performed. Synovial fluid aspirates were analyzed for total nucleated cell count, total protein, and prostaglandin E2. A mixed effects analysis of variance was performed for repeated measures over time, followed by Tukey\'s test. A multinomial logistic regression was conducted to determine whether there is a relationship between a thermography temperature change and the lameness score.
UNASSIGNED: There were no changes in joint circumference. The MAXVO group showed a lower rectal temperature 4 h after synovitis induction. The C group presented an increase in neutrophils and a decrease in total hemoglobin and hematocrit 8 h after induction. No changes were observed in the synovial fluid between groups. The horses that received meloxicam did not show clinically significant lameness at any time, while the C group showed an increase in lameness 2, 4, and 8 h after synovitis induction.
UNASSIGNED: IRT indicated that the skin surface temperature of the middle carpal joint was lower in horses who received meloxicam, suggesting a reduction in the inflammatory process induced by LPS. It was observed that the maximum temperature peaks in the dorsopalmar and lateropalmar positions can be utilized to predict the severity of lameness, particularly when the temperature rises above 34°C. Horses pre-treated with meloxicam showed either reduced or no indication of mild to moderate pain and presented a lowehr thermographic temperature, which indicates the effectiveness of Maxicam Gel® as an anti-inflammatory.

Chronic inflammation plays a crucial role in carcinogenesis. High levels of serum prostaglandin E2 and tissue overexpression of cyclooxygenase-2 (COX-2) have been described in breast, urinary, colorectal, prostate, and lung cancers as being involved in tumor initiation, promotion, progression, angiogenesis, and immunosuppression. Non-steroidal anti-inflammatory drugs (NSAIDs) are prescribed for several medical conditions to not only decrease pain and fever but also reduce inflammation by inhibiting COX and its product synthesis. To date, significant efforts have been made to better understand and clarify the interplay between cancer development, inflammation, and NSAIDs with a view toward addressing their potential for cancer management. This review provides readers with an overview of the potential use of NSAIDs and selective COX-2 inhibitors for breast cancer treatment, highlighting pre-clinical in vitro and in vivo studies employed to evaluate the efficacy of NSAIDs and their use in combination with other antineoplastic drugs.

Dramatic postmortem prostanoid (PG) enzymatic synthesis in the brain causes a significant artifact during PG analysis. Thus, enzyme deactivation is required for an accurate in situ endogenous PG quantification. To date, the only method for preventing postmortem brain PG increase with tissue structure preservation is fixation by head-focused microwave irradiation (MW), which is considered the gold standard method, allowing for rapid in situ heat-denaturation of enzymes. However, MW requires costly equipment that suffers in reproducibility, causing tissue loss and metabolite degradation if overheated. Our recent study indicates that PGs are not synthesized in the ischemic brain unless metabolically active tissue is exposed to atmospheric O2. Based on this finding, we proposed a simple and reproducible alternative method to prevent postmortem PG increase by slow enzyme denaturation before craniotomy. To test this approach, mice were decapitated directly into boiling saline. Brain temperature reached 100°C after ∼140 s during boiling, though 3 min boiling was required to completely prevent postmortem PG synthesis, but not free arachidonic acid release. To validate this fixation method, brain basal and lipopolysaccharide (LPS)-induced PG were analyzed in unfixed, MW, and boiled tissues. Basal and LPS-induced PG levels were not different between MW and boiled brains. However, unfixed tissue showed a significant postmortem increase in PG at basal conditions, with lesser differences upon LPS treatment compared to fixed tissue. These data indicate for the first time that boiling effectively prevents postmortem PG alterations, allowing for a reproducible, inexpensive, and conventionally accessible tissue fixation method for PG analysis.

Introduction: There is a growing interest in studying natural products for the identification of novel lead compounds for drug development for treating inflammatory diseases. Although some studies have focused anti-inflammatory activity of benzophenones and xanthones, exploring additional targets such as enzymes and cytokines, involved in their inflammatory response could provide more comprehensive understanding of the compounds\' anti-inflammatory effects. In this study, four xanthones ananixanthone (1), smeathxanthone A (2), smeathxanthone B (3), and 1,3,5,8-tetrahydroxy-2-(3-methybut-2-enyl)-4-(3,7-dimethyloct-2,6-dienyl) xanthone (4); and three benzophenones guttiferone O (5), guttiferone M (6), and aristophenone A (7) from Garcinia smeathmannii (Planch. & Triana) Oliv. were investigated for their effect on nitric oxide production, cyclooxygenase, lipoxygenase inhibition, and Th1/Th2 cytokines production in activated RAW 264.7 macrophages. Methods: The Griess reagent method and the ferrous oxidation-xylenol orange assay were used to evaluate the inhibition of NO production and the 15-lipoxygenase activity respectively. Cyclooxygenase activity was assessed using the fluorometric COX activity assay kit and measurement of Th1/Th2 cytokines was performed using a flow cytometer. Results: All the tested compounds exhibited a dose-dependent inhibition of NO production with varying degrees of inhibitory effects on 15-LOX activity. Compound (6), displays the best inhibitory effect on COX-1/COX-2 activity. A general trend of the tested compounds on cytokines profiles revealed that compound (5) showed a pronounced enhancement of anti-inflammatory cytokines (IL-4 and IL-10). Conclusion: This observation supports future exploration of ananixanthone (1), guttiferone O (5), and guttiferone (6) as potential candidates for the development of anti-inflammatory drugs.

Introduction: The purpose of this study is to delineate anti-inflammatory and antioxidant potential of varenicline, a cigarette smoking cessation aid, on decreasing lipopolysaccharide (LPS)-elevated proinflammatory cytokines in RAW 264.7 murine macrophage cultures which we showed earlier to occur via cholinergic anti-inflammatory pathway (CAP) activation. To this end, we investigated the possible suppressive capacity of varenicline on LPS-regulated cyclooxygenase (COX-1 and COX-2) via α7 nicotinic acetylcholine receptor (α7nAChR) activation using the same in vitro model. Materials and Methods: In order to test anti-inflammatory effectiveness of varenicline, the levels of COX isoforms and products (PGE2, 6-keto PGF1α, a stable analog of PGI2, and TXA2) altered after LPS administration were determined by Enzyme Linked Immunosorbent Assay (ELISA). The antioxidant effects of varenicline were assessed by measuring reductions in reactive oxygen species (ROS) using a fluorometric intracellular ROS assay kit. We further investigated the contribution of nAChR subtypes by using non-selective and/or selective α7nAChR antagonists. The results were compared with that of conventional anti-inflammatory medications, such as ibuprofen, celecoxib and dexamethasone. Results: Varenicline significantly reduced LPS-induced COX-1, COX-2 and prostaglandin levels and ROS to an extent similar to that observed with anti-inflammatory agents used. Discussion: Significant downregulation in LPS-induced COX isoforms and associated decreases in PGE2, 6-keto PGF1α, and TXA2 levels along with reduction in ROS may be partly mediated via varenicline-activated α7nAChRs.

Climate change has contributed to increased frequency and intensity of wildfire. Studying its acute effects is limited due to unpredictable nature of wildfire occurrence, which necessitates readily deployable techniques to collect biospecimens. To identify biomarkers of wildfire\'s acute effects, we conducted this exploratory study in eight healthy campers (four men and four women) who self-collected nasal fluid, urine, saliva, and skin wipes at different time points before, during, and after 4-hour exposure to wood smoke in a camping event. Concentrations of black carbon in the air and polycyclic aromatic hydrocarbons in participants\' silicone wristbands were significantly elevated during the exposure session. Among 30 arachidonic acid metabolites measured, lipoxygenase metabolites were more abundant in nasal fluid and saliva, whereas cyclooxygenase and non-enzymatic metabolites were more abundant in urine. We observed drastic increases, at 8 hours following the exposure, in urinary levels of PGE2 (398%) and 15-keto-PGF2α (191%) (FDR<10%), with greater increases in men (FDR < 0.01%) than in women. No significant changes were observed for other metabolites in urine or the other biospecimens. Our results suggest urinary PGE2 and 15-keto-PGF2α as promising biomarkers reflecting pathophysiologic (likely sex-dependent) changes induced by short-term exposure to wildfire.

This study aimed to investigate the molecular mechanisms underlying the protective effects of cyclooxygenase (cox) inhibitors against myocardial hypertrophy.Rat H9c2 cardiomyocytes were induced by mechanical stretching. SD rats underwent transverse aortic constriction to induce pressure overload myocardial hypertrophy. Rats were subjected to echocardiography and tail arterial pressure in 12W. qPCR and western blot were used to detect the expression of Notch-related signaling. The inflammatory factors were tested by ELISA in serum, heart tissue, and cell culture supernatant.Compared with control, levels of pro-inflammatory cytokines IL-6, TNF-α, and IL-1β were increased and anti-inflammatory cytokine IL-10 was reduced in myocardial tissues and serum of rat models. Levels of Notch1 and Hes1 were reduced in myocardial tissues. However, cox inhibitor treatment (aspirin and celecoxib), the improvement of exacerbated myocardial hypertrophy, fibrosis, dysfunction, and inflammation was parallel to the activation of Notch1/Hes1 pathway. Moreover, in vitro experiments showed that, in cardiomyocyte H9c2 cells, application of ~20% mechanical stretching activated inflammatory mediators (IL-6, TNF-α, and IL-1β) and hypertrophic markers (ANP and BNP). Moreover, expression levels of Notch1 and Hes1 were decreased. These changes were effectively alleviated by aspirin and celecoxib.Cox inhibitors may protect heart from hypertrophy and inflammation possibly via the Notch1/Hes1 signaling pathway.