Apocrine sweat gland adenocarcinoma (ASGAC) is a rare skin carcinoma in cats. In some cases, this tumor occurs in anatomical sites of challenging wide surgical resection, which increases the need for adjuvant therapies for residual disease. These would include radiotherapy or electrochemotherapy (ECT), local treatments for invasive tumors in companion animals often associated with surgery. However, the current literature for ASGAC treatment is limited and there are no reports of ECT as an adjuvant therapy. In this case report, we account for the case of an 11-year-old cat with a history of a non-ulcerated recurrent ASGAC, measuring 1.3 × 1.0 cm, located by the rostral mandibular region. Surgical resection was performed and included the angularis oris axial flap for facial reconstruction associated with electroporation of the surgical bed and, post-operatively, in the surgical scar. Histopathological results confirm the presence of a recurrent ASGAC. Immunostaining revealed cyclooxygenase 2 (COX-2) expression with a score of 6, 50% positivity in Ki-67 and positive for pan-cytokeratin (PCK AE-1/ AE-3). A selective COX-2 inhibitor was initiated along with systemic chemotherapy with chlorambucil. The local approach including surgery and ECT was chosen due to the unfavorable anatomical site for extensive resection and the unavailability of radiotherapy. Subsequently, carboplatin chemotherapy was required due to metastasis in the mandibular lymph node. This case report supports the effectiveness of a multimodal treatment including surgery, ECT and chemotherapy in a cat with recurrent ASGAC.

Aim To examine the relationship between tumor differentiation, parametrial, and lymphovascular invasion, as well as the differential expression pattern of cyclooxygenase-2 (COX-2) in cervical intraepithelial neoplasia and various forms of cervical cancer. Methods Histologically diagnosed cases of in-situ and malignant lesions of the cervix were included in the study. Two sections were cut from paraffin blocks. One section was stained with Haematoxylin and Eosin (H&E) for morphologic diagnosis, and the other sections were subjected to COX-2 immunohistochemical staining. Cases of colon carcinoma were taken as positive controls. Cytoplasmic and membrane staining of tumor cells were considered as positive staining, and grading was done. Results Out of the 62 patients, 40 cases (64.5%) showed positive expression of COX-2 in squamous cell carcinoma when compared to in-situ cervical intraepithelial neoplasia and adenocarcinoma. The results were statistically significant, with a p-value of 0.003. Conclusion COX-2 expression is directly proportional to the level of grading of the tumor. The higher the grading, the higher the expression of COX-2. Selective COX-2 inhibitors increase the efficacy of chemotherapy or radiotherapy.

Cancer is highlighted as a major global health challenge in the XXI century. The cyclooxygenase-2 (COX-2) enzyme rises as a widespread tumor progression marker. Celecoxib (CXB) is a selective COX-2 inhibitor used in adjuvant cancer therapy, but high concentrations are required in humans. In this sense, the development of nanocarriers has been proposed once they can improve the biopharmaceutical, pharmacokinetic and pharmacological properties of drugs. In this context, this article reviews the progress in the development of CXB-loaded nanocarriers over the past decade and their prospects. Recent advances in the field of CXB-loaded nanocarriers demonstrate the use of complex formulations and the increasing importance of in vivo studies. The types of CXB-loaded nanocarriers that have been developed are heterogeneous and based on polymers and lipids together or separately. It was found that the work on CXB-loaded nanocarriers is carried out using established techniques and raw materials, such as poly (lactic-co-glicolic acid), cholesterol, phospholipids and poly(ethyleneglycol). The main improvements that have been achieved are the use of cell surface ligands, the simultaneous delivery of different synergistic agents, and the presence of materials that can provide imaging properties and other advanced features. The combination of CXB with other anti-inflammatory drugs and/or apoptosis inducers appears to hold effective pharmacological promise. The greatest advance to date from a clinical perspective is the ability of CXB to enhance the cytotoxic effects of established chemotherapeutic agents.

The global incidence of recurrent aphthous stomatitis in 2018 reached 5-66 % of the population, while in Indonesia 8 %. Moreover, the prevalence of oral mucosal fibrosis and recurrent aphthous stomatitis among male doctors and nurses in China was 21.24 % and 24.27 %, respectively. Our previous study has shown that the ethanol extract of Kaempferia galanga L. rhizome (EKGR) revealed an accelerated wound-healing effect in the oral mucosa ulcer of Wistar rats. This study aims to explore the effects of EKGR on the expression of NF-kappaB-p65 and COX-2 in the tongue tissue of male Wistar rats by Western blot analysis and immunohistochemistry technique, its safety towards the vascular membrane of the egg chorioallantoic membrane, and its single-dose application on the skin of male rabbits. The rats were randomly assigned into 7 groups: the normal control; the negative control; the positive control (treated with triamcinolone acetonide); and 4 treatment groups of EKGR (0.5 %; 1 %; 2 %; 4 %). Western blot and immunohistochemistry methods were used to measure the expression of NF-kappaB-p65 and COX-2. The hen\'s egg test-chorioallantoic membrane assay was employed to predict the safety of EKGR towards the vascular membrane. Moreover, the effect of 200 mg/kg BW EKGR application on the dorsal skin of male albino rabbits was also evaluated. EKGR inhibits the expression of NF-kappaB-p65 and COX-2 as proven by WB and IHC results. In the HET-CAM assay, all concentrations of EKGR do not induce irritation responses, which elicits the safety of EKGR. The administration of EKGR causes mild irritation to the dorsal skin of male rabbits but does not induce erythema and edema, no significant changes in BW, no toxic effects on organ macroscopic examination or histopathology, and does not induce abnormalities in the hematological profile of male albino rabbits. EKGR has confirmed its anti-inflammatory activity by suppressing the expression of COX-2 and NF-kappaB-p65 in the oral mucosa ulcer of Wistar rats. EKGR is safe as it does not exhibit irritating potential and harmful effects.

OBJECTIVE: Uterine serous carcinoma (USC) is a highly aggressive and frequently recurring subtype of endometrial cancer with limited treatment options for advanced or recurrent stages. Sulindac, a classic non-steroidal anti-inflammatory drug, has demonstrated anti-tumor activity in several pre-clinical tumor models. This study aims to evaluate the effect of sulindac on cell proliferation and invasion in USC cells.
METHODS: Human USC cell lines ARK-1 and SPEC2 were treated with different concentrations of sulindac. Cell proliferation was assessed using MTT and colony formation assays. ELISA assays measured cellular stress, cleaved caspase 3 activity, antioxidant ability, and adhesion. Cell cycle arrest was evaluated by Cellometer. The invasive capability was detected by wound healing assay. Western blotting was used to analyze the changes in protein expression induced by sulindac.
RESULTS: Exposure to sulindac decreased cellular viability in a dose-dependent manner in ARK-1 and SPEC2 cells. Sulindac effectively inhibited cell cycle progression, increased cellular stress, caused apoptosis, and reduced cell adhesion and invasion in USC cells. Additionally, sulindac decreased the expression of COX-2 and blocked phosphorylation of NF-κB induced by TNF-α.
CONCLUSIONS: Sulindac is a potential therapeutic agent for USC that deserves further exploration in pre-clinical studies and potentially future clinical trials.

OBJECTIVE: Molecular alterations of diabetic gastroenteropathy are poorly identified. This study investigates the effects of prolonged GABA supplementation on key protein expression levels of trypsin-1, PAR-1, PAR-2, PAR-3, PI3K, Akt, COX-2, GABAA, and GABAB receptors in the gastric tissue of type 2 diabetic rats (T2DM).
METHODS: -To induce T2DM, a 3-month high-fat diet and 35 mg/kg of streptozotocin was used. Twenty-four male Wistar rats were divided into 4 groups: (1) control, (2) T2DM, (3) insulin-treated (2.5 U/kg), and (4) GABA-treated (1.5 g/kg GABA). Blood glucose was measured weekly. The protein expressions were assessed using western blotting. Histopathological changes were examined by H&E and Masson\'s staining.
RESULTS: -Diabetic rats show reduced NOS1 and elevated COX-2 and trypsin-1 protein expression levels in gastric tissue. Insulin and GABA therapy restored the NOS1 and COX-2 levels to control values. Insulin treatment increased PI3K, Akt, and p-Akt and, decreased trypsin-1, PAR-1, PAR-2, and PAR-3 levels in the diabetic rats. Levels of GABAA and GABAB receptors normalized following insulin and GABA therapy. H&E staining indicated an increase in mucin secretion following GABA treatment.
CONCLUSIONS: -These results suggest that GABA by acting on GABA receptors may regulate the trypsin-1/PARs/Akt/COX-2 pathway and thereby improve complications of diabetic gastroenteropathy.

Introduction Breast cancer is considered the most common cancer among women. According to the literature, cyclooxygenase-2 (COX-2) expression in breast carcinoma is associated with aggressive tumor biology and acts as an independent prognostic marker. As COX-2 is a newly identified marker, studies are required to understand its immunoexpression and correlation with hormone receptor status and other prognostic factors, which helps in the therapeutic management of patients. Hence, this study evaluates the expression of COX-2 in breast carcinoma. Methods A hospital-based cross-sectional study was done on 55 mastectomy specimens collected at the Histopathology and Surgical Pathology Section of the Department of Pathology. The patient\'s age, histological type, tumor size, lymph node status, histological grade, and vascular invasion were noted. Immunohistochemical staining for estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2/neu protooncogene (HER2/neu), and COX-2 markers was performed, and its results were compared with these clinicopathological and prognostic parameters. Results were subjected to statistical analysis. Results COX-2 expression was seen in 37 out of 55 cases (67.2%). Expression of COX-2 showed a statistically significant correlation with vascular invasion, ER-negative status, and PR-negative status. No statistical association was found between other parameters like age, tumor size, histological type, histological grade, lymph node status, and HER2/neu status. Conclusion The expression of COX-2 correlated strongly with well-established poor prognostic markers, such as vascular invasion, ER-negative status, and PR-negative status. Thus, expression of COX-2 suggests aggressive tumor biology, and it can be used as an independent prognostic marker.

Inflammation management presents a critical challenge in modern medicine, with nonsteroidal anti-inflammatory drugs (NSAIDs) being a widely used therapeutic option. However, their efficacy is often accompanied by significant gastrointestinal adverse effects, necessitating the exploration of safer alternatives, particularly through the investigation of cyclooxygenase-2 (COX-2) inhibitors. This study endeavors to address this imperative through the synthesis and evaluation of pyrazoline-phenoxyacetic acid derivatives. Among the synthesized compounds, 6a and 6c emerged as promising candidates, demonstrating potent COX-2 inhibition with IC50 values of 0.03 µM for both and selectivity index = 365.4 and 196.9, respectively. Furthermore, these compounds exhibited efficacy in mitigating formalin-induced edema in male Wistar rats, accompanied by favorable safety profiles upon histological examination of vital organs. Comprehensive safety assessments, including evaluation of creatinine, AST, and ALT enzymatic as well as troponin T and creatine kinase-MB levels, further reinforce the promising attributes of the synthetic candidates. Molecular docking studies endorsed by molecular dynamic simulations corroborate the biological findings, elucidating significant protein-ligand interactions at COX-2 active sites indicative of therapeutic potential.

The oil of Carapa guianensis showed leishmanicidal activity, with its activity being related to limonoids, but fatty acids are the major constituents of this oil. The present study evaluated the physicochemical, pharmacokinetic, and toxicity profiles of limonoids and fatty acids already identified in the species. Based on these results, 2 limonoids (methyl angosinlate, 6-OH-methyl angosinlate) and 2 fatty acids (arachidic acid; myristic acid) were selected for the prediction of possible targets and molecular docking. Included in this study were: Gedunin, 6α-acetoxygedunin, Methyl angosenlato, 7-deacetoxy-7-oxogedunin, Andirobin, 6-hydroxy-angolensate methyl, 17β-hydroxyazadiradione, 1,2-dihydro-3β-hydroxy-7-deacetoxy-7-oxogedunin, xyllocensin k, 11beta-Hydroxygedunin, 6α,11-11β-diacetoxygedunin, Oleic Acid, Palmitic Acid, Stearic Acid, Arachidic Acid, Myristic Acid, Palmitoleic Acid, Linoleic Acid, Linolenic Acid, and Beenic Acid. Regarding physicochemical aspects, fatty acids violated LogP, and only limonoid 11 violated Lipinski\'s rule. A common pharmacokinetic aspect was that all molecules were well absorbed in the intestine and inhibited CYP. All compounds showed toxicity in some model, with fatty acids being mutagenic and carcinogenic, and limonoids not being mutagenic and carcinogenic at least for rats. In in vivo models, fatty acids were less toxic. Molecular dockings were performed on COX-2 steroids (15 and 16) and hypoxia-inducible factor 1 alpha for limonoids (3,6), with this target being essential for the intracellular development of leishmania. Limonoids 3 and 6 appear to be promising as leishmanicidal agents, and fatty acids are promising as wound healers.

BACKGROUND: Septic cardiomyopathy is a component of multiple organ dysfunction in sepsis. Mitochondrial dysfunction plays an important role in septic cardiomyopathy. Studies have shown that cyclooxygenase-2 (COX-2) had a protective effect on the heart, and prostaglandin E2 (PGE2), the downstream product of COX-2, was increasingly recognized to have a protective effect on mitochondrial function.
OBJECTIVE: This study aims to demonstrate that COX-2/PGE2 can protect against septic cardiomyopathy by regulating mitochondrial function.
METHODS: Cecal ligation and puncture (CLP) was used to establish a mouse model of sepsis and RAW264.7 macrophages and H9C2 cells were used to simulate sepsis in vitro. The NS-398 and celecoxib were used to inhibit the activity of COX-2. ZLN005 and SR18292 were used to activate or inhibit the PGC-1α activity. The mitochondrial biogenesis was examined through the Mitotracker Red probe, mtDNA copy number, and ATP content detection.
RESULTS: The experimental data suggested that COX-2 inhibition attenuated PGC-1α expression thus decreasing mitochondrial biogenesis, whereas increased PGE2 could promote mitochondrial biogenesis by activating PGC-1α. The results also showed that the effect of COX-2/PGE2 on PGC-1α was mediated by the activation of cyclic adenosine monophosphate (cAMP) response element binding protein (CREB). Finally, the effect of COX-2/PGE2 on the heart was also verified in the septic mice.
CONCLUSIONS: Collectively, these results suggested that COX-2/PGE2 pathway played a cardioprotective role in septic cardiomyopathy through improving mitochondrial biogenesis, which has changed the previous understanding that COX-2/PGE2 only acted as an inflammatory factor.