UNASSIGNED: Breast cancer is the most prevalent cancer among women worldwide and is a well-known cause for cancer mortality in females. COX-2 (cyclooxygenase) plays a vital role in development of some human cancers such as lung, colon and breast. It is a potent enzyme that is important for the conversion of arachidonic acid into prostaglandins. These prostaglandins mediate cellular proliferation, apoptosis and angiogenesis which contributes to carcinogenesis. Overexpression of COX-2 has been detected in several malignancies including breast cancer. COX-2 overexpression is regarded as a poor prognostic marker of breast cancer.The present study will aim to study the immunohistochemical expression of COX-2 in breast cancer and compare it with known histopathological parameters thus assessing its prognostic value.
UNASSIGNED: This will be an observational study conducted in the Department of Pathology, JNMC, Wardha (Sawangi). Radical mastectomy specimens will be studied for COX-2 expression by immunohistochemistry in patients diagnosed with breast carcinoma. COX-2 expression will be quantified as immunohistochemical score and results will be correlated with various histopathological parameters.
UNASSIGNED: The expected result of our study will suggest an association of COX-2 expression to the factors associated with poor prognosis in breast carcinoma. A positive correlation is expected between larger tumor size, positive lymph node status, higher T stage and N stage and lymphovascular invasion.
UNASSIGNED: Conclusions will be drawn from the obtained results of the immunohistochemical study by using COX-2- for detection of overexpression of COX-2 when evaluated with TNM staging, histological grading and molecular types of breast cancer.

Complications of the worldwide use of non-steroidal anti-inflammatory drugs (NSAIDs) sparked scientists to design novel harmless alternatives as an urgent need. So, a unique hybridization tactic of quinoline/pyrazole/thioamide (4a-c) has been rationalized and synthesized as potential COX-2/15-LOX dual inhibitors, utilizing relevant reported studies on these pharmacophores. Moreover, we extended these preceding hybrids into more varied functionality, bearing crucial thiazole scaffolds(5a-l). All the synthesized hybrids were evaluatedin vitroas COX-2/15-LOX dual inhibitors. Initially, series4a-cexhibited significant potency towards 15-LOX inhibition (IC50 = 5.454-4.509 μM) compared to meclofenamate sodium (IC50 = 3.837 μM). Moreover, they revealed reasonable inhibitory activities against the COX-2 enzyme in comparison to celecoxib.Otherwise, conjugates 5a-ldisclosed marked inhibitory activity against 15-LOX and strong inhibitory to COX-2. In particular, hybrids5d(IC50 = 0.239 μM, SI = 8.95), 5h(IC50 = 0.234 μM, SI = 20.35) and 5l (IC50 = 0.201 μM, SI = 14.42) revealed more potency and selectivity outperforming celecoxib (IC50 = 0.512 μM, SI = 4.28). In addition, the most potentcompounds, 4a, 5d, 5h, and 5l have been elected for further in vivoevaluation and displayed potent inhibition of edema in the carrageenan-induced rat paw edema test that surpassed indomethacin. Further, compounds5d, 5h, and 5l decreased serum inflammatory markers including oxidative biomarkersiNO, and pro-inflammatory mediators cytokines like TNF-α, IL-6, and PGE. Ulcerogenic liability for tested compounds demonstrated obvious gastric mucosal safety. Furthermore, a histopathological study for compound 5l suggested a confirmatory comprehensive safety profile for stomach, kidney, and heart tissues. Docking and drug-likeness studies offered a good convention with the obtained biological investigation.

The current study aimed to find out the anti-arthritic activity and safety study of Coronopus didymus aqueous extract (CDAE) as well as its chemical characterization by HPLC-DAD. Safety study including acute and subacute toxicity studies of the plant aqueous extract was also performed. In complete Freund\'s adjuvant-induced arthritic model (CFA), 0.15 ml CFA was injected in the left hind paw at day 1 in all rats except normal rats. Treatment with CDAE at 200, 400, and 800 mg/kg and methotrexate (1 mg/kg) was administered at day 8 and continued till 28th day using oral gavage. The CDAE considerably (p < 0.05) reduced the paw swelling and arthritic score, and reinstated the body weight and blood parameters. The CDAE considerably modulated superoxide dismutase, catalase, reduced glutathione, and malondialdehyde level in liver homogenate in contrast to disease control. The CDAE at 400 mg/kg considerably reduced IL-6, IL -1β, COX-2, and NF-ĸβ, whereas elevated IL-10, IL-4, and I-kappa β as equated to disease and standard groups. The LD50 of CDAE > 2000 mg/kg. In subacute toxicity study, CDAE at 200-800 mg/kg did not exhibit clinical signs of toxicity, mortality, hematological, biochemical, and histological alteration in the liver heart, kidney, and lungs in contrast to the normal group. It was concluded that the presence of delphinidine-3-glucoside, diosmetin, 3-feruloyl-4,5-dicaffeoyl quinic acid, and gallic acid in CDAE might be accountable for its anti-arthritic activity and safe use for a long period.

Perfluorooctane sulfonate (PFOS) has harmful impacts on various organs, including the intestine. Lemongrass essential oil (LGEO) has anti-inflammatory, anti-oxidant, antibacterial, and immunomodulatory effects. This study investigated the impact of PFOS on the mucosa of the jejunum of rats and evaluated LGEO\'s protective impact. Four groups of rats were created: control, LGEO (100 mg/kg/day), PFOS (5 mg/kg/day), and LGEO-PFOS group. The agents were given orally for 28 days. Oxidative stress parameters, pro-inflammatory cytokines, and caspase-3 were measured in jejunal homogenates. Rat jejunal sections were evaluated histologically (light and electron microscopic examination) and immunohistochemically [for tumor necrosis factor-α (TNF-α), Proliferating cell nuclear antigen (PCNA), cyclooxygenase-2 (COX2), and Bcl2]. PFOS significantly elevated oxidative stress, pro-inflammatory cytokines, caspase-3, and gene expression of nuclear factor kappa B (NF-kB) and inducible nitric oxide synthetase (iNOS). The disturbed architecture of jejunal villi and crypts was demonstrated. Immunohistochemically, a significant rise in TNF-α, PCNA, and COX2 and a significant decrease in Bcl2 expression were revealed compared to control group. Further ultrastructural alterations included dilated RER, mitochondria with destroyed cristae, vacuolated cytoplasm, and shrunken condensed nuclei of enterocytes. LGEO treatment significantly reduced these harmful effects. LGEO protected against PFOS-induced jejunal damage by reducing the oxidative, inflammatory, and apoptotic impacts.

Pancreatic cancer is a highly aggressive malignancy and a leading cause of cancer-related deaths worldwide. Moreover, the incidence and mortality rates for pancreatic cancer are projected to keep increasing. A major challenge in the treatment of pancreatic cancer is the lack of effective screening approaches, which contributes to its poor prognosis, indicating the need for new treatment regimens and alternative therapies, such as herbal medicine. The medicinal plant A. strigosa, which is widely distributed in the Eastern Mediterranean region, is a short prickly plant from the Boraginaceae family that has been widely used in traditional medicine for treating various diseases. Nevertheless, its effect on human pancreatic cancer remains poorly investigated. In the present study, we screened the phytochemical content of Anchusa strigosa aqueous extracts obtained by maceration and ultrasound-assisted methods (ASM and ASU, respectively) and evaluated their antioxidant effects. We also investigated their anticancer effects and possible underlying mechanisms. The results show that both extracts were rich in bioactive molecules, with slight differences in their composition. Both extracts exhibited remarkable antioxidant potential and potent radical-scavenging activity in vitro. Additionally, non-cytotoxic concentrations of both extracts attenuated cell proliferation in a time- and concentration-dependent manner, which was associated with a decrease in the proliferation marker Ki67 and an induction of the intrinsic apoptotic pathway. Furthermore, the extracts increased the aggregation of pancreatic cancer cells and reduced their migratory potential, with a concomitant downregulation of integrin β1. Finally, we showed that the ASM extract caused a significant decrease in the levels of COX-2, an enzyme that has been linked to inflammation, carcinogenesis, tumor progression, and metastasis. Taken together, our findings provide evidence that A. strigosa extracts, particularly the extract obtained using the maceration method, have a potential anticancer effect and may represent a new resource for the design of novel drugs against pancreatic cancer.

BACKGROUND: Inflammation-provoked disorders including cancer are arbitrated by cyclooxygenase-2 (COX-2). Celecoxib and niflumic acid are among the potent and selective inhibitors of this enzyme while aspirin (acetylsalicylic acid) and sodium salicylate are its non-selective and lesser potent inhibitors. Despite these proven studies, the comparative structural study of these selective and non-selective molecules at atomistic scale in complex state with COX-2 that may answer this differential inhibitory behavior has not been accomplished spotlighting the imperative need of additional research in this area. Thus, this study was framed to provide a strong explanation for the enigma of higher inhibitory activity of celecoxib-niflumic acid duo in comparison to aspirin and sodium salicylate towards COX-2.
METHODS: A contemporary approach including advanced molecular docking against COX2, molecular dynamics of receptor-ligand complexes, simulation-trajectory-backed MMGBSA for different time points, radius of gyration (Rg) calculations, and e-pharmacophores approach was employed to attain a rational conclusion.
RESULTS: Our findings demonstrated the higher binding affinity of celecoxib and niflumic acid over aspirin and sodium salicylate against COX-2. Although both selective and non-selective COX-2 inhibitors manifested nearly the same stability in the active site of this enzyme but the e-pharmocophoric features found in the case of selective inhibitors scored over non-selective ones. Thus, our findings excluded the differential stability to be the cause of stronger potency of selective inhibitors but attributed their potency to greater number of complementary features present in these inhibitors against the active site of inflammation engendering COX-2.

Ulcerative colitis (UC) is considered a long-term inflammatory disorder worldwide. Its pathogenesis is associated with reduced antioxidant capacity. Lycopene (LYC) is a powerful antioxidant with strong free radical scavenging property. The present work has done to assess changes of colonic mucosa in induced UC and the possible ameliorative effects of LYC. Forty-five adult male albino rats were randomly divided into four groups: group I (control), group II was given 5 mg/kg/day (LYC) by oral gavage for 3 weeks. Group III (UC) was received single intra-rectal injection of acetic acid. Group IV (LYC+UC) received LYC in same dose and duration as before and acetic acid on 14th day of the experiment. UC group showed loss of surface epithelium with destructed crypts. Congested blood vessels with heavy cellular infiltration were observed. Significant decrease in goblet cell numbers and the mean area percentage of ZO-1 immunoexpression were noticed. Significant increase in the mean area percentage of collagen and the mean area percentage of COX-2 were also noticed. Ultrastructural changes were matched with light microscopic results that showed abnormal destructive columnar and goblet cells. Histological, immunohistochemical, and ultrastructural findings in group IV supported the ameliorative role of LYC against destructive changes induced by UC.

OBJECTIVE: This study aims to investigate the anti-inflammatory mechanism of monoamine oxidase inhibitor (MAOI) in carrageenan (CARR) induced inflammation models to reprofile their use. We also aimed to explore the role of monoamine oxidase (MAO)-mediated H2O2-NF-κB-COX-2 pathway in acute inflammation.
METHODS: In vitro anti-inflammatory activity and hydrogen peroxide (H2O2) scavenging activity were performed according to the established procedure. Inflammation was induced using CARR in BALB/c mice at the foot paw and peritoneal cavity. Hourly measurement of paw swelling was performed. The level of nitric oxide (NO), myeloperoxidase (MPO), cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2) and nuclear factor κB (NF-κB) was determined using enzyme-linked immunosorbent assay (ELISA). Peritoneal fluid was collected to investigate total count, differential count of leukocytes, and capillary permeability.
RESULTS: In vitro anti-inflammatory evaluations revealed the potential role of MAOI to inhibit heat-induced protein denaturation and human red cell membrane destabilization. H2O2 inhibition activity of MAOI also proved their powerful role as an H2O2 scavenger. Treatment with MAOI in CARR-induced mice significantly reduced paw edema, leukocyte extravasation, and total and differential leukocyte count. The result of ELISA showed MAOI effectively reduce the level of COX-2, PGE2 and NF-κB in inflamed tissue.
CONCLUSIONS: In short, this study demonstrates that inhibition of H2O2 by MAOI alleviates CARR-induced paw edema possibly by inhibiting the H2O2-mediated NF-κB-COX-2 pathway. The present investigation identifies MAOI might reprofile for the treatment of acute inflammation also, the MAO enzyme may use as a novel therapeutic target to design and develop new class of anti-inflammatory agents.

BACKGROUND: Colorectal cancer (CRC) is the fourth most common cancer in Nigeria, and it affects mostly persons in their middle age. In a bid to gain some insight into the molecular characteristics of CRC in our environment, we set out to investigate the expression of COX-2 and HER-2 among Nigerian subjects.
OBJECTIVE: To evaluate the expression of COX-2 and HER-2 and determine their correlation with clinicopathologic parameters in surgically resected histologically diagnosed cases of colorectal cancer.
METHODS: Fifty-three paraffin-embedded tissue blocks of colorectal resections and corresponding patient information were retrieved from the archives of the Anatomic and Molecular Pathology Department of Lagos University Teaching Hospital. A 4-micron slide section was obtained from each specimen and immunohistochemistry for COX-2 and HER-2 expression was performed.
RESULTS: Mean age of cases was 53.9years with an almost equal M:F ratio of 1.12:1. Half of the cases were moderately differentiated adenocarcinoma and 17% were high grade tumors. Eighty three percent of the tumours showed positive cytoplasmic COX-2 expression and extremely low membranous HER-2 positivity was observed in 2%. There was no significant correlation between COX-2 expression and age, gender, tumour location, tumour size, depth of invasion or lymph node status. However, COX-2 expression revealed a significant correlation with tumour grade (p= 0.013).
CONCLUSIONS: This study detects a high COX-2 and low HER- 2 expression in colorectal cancer using immunohistochemistry, suggesting a possible role for COX-2 in CRC pathogenesis. This report should trigger further investigations of both markers vis-à-vis the management of CRC in our environment.
BACKGROUND: Le cancer colorectal (CCR) est le quatrième cancer le plus fréquent au Nigeria et il touche surtout les personnes d’âge moyen. Dans le but de mieux comprendre les caractéristiques moléculaires du CCR dans notre environnement, nous avons entrepris d’étudier l’expression de COX-2 et de HER-2 chez les sujets nigérians.
OBJECTIVE: Évaluer l’expression de COX-2 et HER-2 et déterminer leur corrélation avec les paramètres clinicopathologiques dans les cas de cancer colorectal diagnostiqués histologiquement et réséqués chirurgicalement.
UNASSIGNED: Cinquante-trois blocs de tissus inclus en paraffine provenant de résections colorectales et les informations correspondantes sur les patients ont été récupérés dans les archives du département de pathologie anatomique et moléculaire du Lagos University Teaching Hospital. Une section de lame de 4 microns a été obtenue de chaque spécimen et une immunohistochimie pour l’expression de COX-2 et HER-2 a été réalisée.
UNASSIGNED: L’âge moyen des cas était de 53,9 ans avec un rapport M:F presque égal de 1,12:1. La moitié des cas étaient des adénocarcinomes modérément différenciés et 17% des tumeurs de haut grade. Quatre-vingt-trois pour cent des tumeurs présentaient une expression cytoplasmique positive de la COX-2 et une positivité HER-2 membranaire extrêmement faible a été observée dans 2 % des cas. Il n’y avait pas de corrélation significative entre l’expression de la COX-2 et l’âge, le sexe, la localisation de la tumeur, la taille de la tumeur, la profondeur de l’invasion ou le statut des ganglions lymphatiques. Cependant, l’expression du COX-2 a révélé une corrélation significative avec le grade de la tumeur (p= 0,013).
CONCLUSIONS: Cette étude détecte une forte expression de COX- 2 et une faible expression de HER-2 dans le cancer colorectal en utilisant l’immunohistochimie, suggérant un rôle possible de COX-2 dans la pathogenèse du CCR. Ce rapport devrait déclencher des investigations plus poussées des deux marqueurs vis-à-vis de la gestion du CRC dans notre environnement.

Background Diosgenin, extracted from Dioscorea esculenta, has been reported to decrease prostaglandin E2 (PGE2) levels and any other inflammatory cytokine in rodents. However, it is still unclear whether D. esculenta intake suppressed PGE2 production and menstrual pain and premenstrual syndrome (PMS) in younger female. Aim This study aims to investigate the effect of D. esculenta intake on PGE2 and cytochrome c oxidase subunit 2 (COX-2) levels and on menstrual pain and PMS in young women. This is a randomized, double-blind, placebo-controlled, crossover study. Methods Ten healthy young females were administered either a placebo or D. esculenta (300 mg/day) for 4 weeks, followed by a 4-week washout period. Fasting blood sample was taken from the fingertips on the second day of menstrual cycle began and obtained 24h before the last D. esculenta to avoid acute effects. Participants then switched treatments for 4 weeks as a second trial. Plasma PGE2 and COX-2 levels were measured before and after each trial. The visual analogue scale (VAS), McGill pain questionnaire (MPQ), and Daily Record of Severity of Problems (DRSP) were also evaluated. The study was set and conducted from 2019 to 2020. Results PGE2 and COX-2 levels significantly decreased after D. esculenta intake compared to placebo (p = 0.038, p = 0.042 each). The VAS and DRSP scores were also significantly lower after D. esculenta intake (p = 0.046, p = 0.035 each). Conclusion Four-week D. esculenta intake suppressed PGE2 and COX-2 levels resulting in an improvement in PMS symptoms and menstrual pain in young women.