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الملخص: أهداف البحث: يتطور الإجهاد التأكسدي بسبب اضطراب في توازن مضادات الأكسدة الداعمة للأول ويمكن وصفه بأنه اضطراب في إشارات الأكسدة والاختزال والتحكم فيها. يعد السيليكوكسيب، وهو مثبط انتقائي لـ''كوكس-2''، دواء فعالا لتسكين الألم والالتهاب. ومع ذلك، ثبت أن السيليكوكسيب يسبب إصابة مؤكسدة للأنسجة الكبدية عن طريق بيروكسيد الدهون المعزز الذي يؤدي إلى الإنتاج المفرط لأنواع الأكسجين التفاعلية. ولذلك فإن استخدامه المتكرر أو على المدى الطويل قد يؤدي إلى آثار جانبية كبدية وكلوية وغيرها من الآثار الجانبية الملحوظة. الليكوبين (لايكو) هو أحد مضادات الأكسدة القوية التي تتواجد بشكل طبيعي في الفواكه والخضروات المصبوغة. وهو مزيل نشط للأكسجين المفرد والجذور الحرة الأخرى وبالتالي حماية الخلايا من هدم غشاء البلازما الذي تسببه الجذور الحرة. طريقة البحث: افترضت الدراسة أن اللايكو قد يحمي خلايا كبد الفئران من الإجهاد التأكسدي الناجم عن السيليكوكسيب، مما يقلل من تسلل الدهون واستنفاد الجليكوجين. تم تقسيم الفئران بشكل عشوائي إلى ثلاث مجموعات (10 فئران / مجموعة): المجموعة الضابطة أ (المحلول الملحي فقط)، المجموعة ب السيليكوكسيب (50 مجم / كجم، عن طريق الفم)، المجموع ج السيليكوكسيب+اللايكو (50 مجم / كجم، عن طريق الفم) لمدة 30 يوما. بعد ذلك، تم فحص أنسجة الكبد لمعرفة متوسط وزن الكبد والتغيرات النسيجية في محتوى الدهون والجليكوجين. النتائج: خفف اللايكو من تلف خلايا الكبد في الفئران المعالجة بـ السيليكوكسيب، مما قلل من تراكم الدهون وفقدان الجليكوجين، على الأرجح من خلال خصائصه المضادة للأكسدة. يمكن أن يؤدي تناول اللايكو و السيليكوكسيب المصاحب إلى منع الآثار الجانبية السامة للكبد فيما يتعلق بالإصابة التأكسدية التي يتبعها مرض الكبد الدهني غير الكحولي، وهو أحد مكونات متلازمة التمثيل الغذائي الرئيسية. علاوة على ذلك، كشف اتجاه ربط اللايكوبين في موقع الربط لإنزيم ''كوكس-2'' أن المركب المرسى أظهر قوة ربط كبيرة. الاستنتاجات: في الختام، تكشف دراستنا عن سلوك حماية اللايكوبين ضد تلف الكبد الناجم عن السيليكوكسيب عن طريق تقليل استنزاف الدهون والجليكوجين. Abstract: Objective: Oxidative stress develops because of a shift in the prooxidant–antioxidant balance toward the former, because of disturbances in redox signaling and control. Celecoxib (Cb), a selective COX-2 inhibitor, is a drug that effectively decreases pain and inflammation. However, Cb causes oxidative injury to hepatic tissues via enhanced lipid peroxidation, thus resulting in excessive production of reactive oxygen species. Consequently, frequent or long-term Cb use may lead to hepatic, renal, and other noticeable adverse effects. Lycopene (lyco), a potent antioxidant naturally occurring in pigmented fruits and vegetables, actively eradicates singlet oxygen and other free radicals, thereby protecting cells against destruction of the plasma membrane by free radicals. Methods: We hypothesized that lyco might protect rat liver cells against Cb-induced oxidative stress, thus reducing fatty infiltration and glycogen depletion. Rats were randomized into three groups (with ten rats each) receiving control (group A, saline only), Cb (group B, 50 mg/kg, orally), or Cb + lyco (group C, 50 mg/kg, orally) for 30 days. Subsequently, liver tissues were examined, and the average liver weight and histological changes in fat and glycogen content were determined. Results: Lyco mitigated hepatocyte damage in Cb-treated rats, reducing fat accumulation and glycogen loss, probably through its antioxidant properties. Concomitant lyco and Cb intake prevented hepatotoxic adverse effects due to oxidative injury, as well as non-alcoholic fatty liver disease (NAFLD), a key component of metabolic syndrome. Moreover, the binding orientation of lyco in the binding site of COX-2 enzyme revealed that the docked complex had noteworthy binding strength. Conclusion: In conclusion, our study revealed lyco's protective effects against Cb-induced hepatic damage by reducing fat and glycogen depletion.

Objective: To evaluate the efficacy and safety of Jiawei Simiao powder (JWSMP) combined with celecoxib for the treatment of acute gouty arthritis by conducting a meta-analysis of randomized controlled trials (RCTs). Methods: The Chinese National Knowledge Infrastructure Databases, Chinese Scientific Journal Database, Wanfang, Cochrane Library, EMBASE, PubMed, and Web of Science databases were searched from inception until December 2023. Continuous variables were analyzed using the mean difference (MD) for analysis, and dichotomous variables were used as risk ratios. Data with similar characteristics were pooled for meta-analysis, and heterogeneity was assessed using I2. The Cochrane Handbook was used to assess the risk of bias and quality. RevMan 5.3 software was used to perform the meta-analysis. Results: Thirteen RCTs involving 1007 patients were included in the study. The quality of the included studies was low (unclear randomization processes and insufficient blinding reporting). The group receiving JWSMP combined with celecoxib showed significantly lower levels of serum uric acid (SUA, MD = −66.32, 95% confidence interval (CI): −80.97 to −51.67, P

Introduction: Different lines of evidence confirm the involvement of the immune system in the pathophysiology of major depressive disorder. Up to 30% of depressed patients present with an immune-mediated subtype, characterized by peripheral inflammation (high-sensitive C-reactive protein (hsCRP) ≥ 3 mg/l) and an atypical symptom profile with fatigue, anhedonia, increased appetite, and hypersomnia. This immune-mediated subtype of MDD is associated with poorer response to first-line antidepressant treatment. Consequently, strategies for immune-targeted augmentation should be prioritised towards patients with this subtype. Meta-analyses have shown modest but heterogeneous treatment effects with immune-targeted augmentation in unstratified MDD cohorts, with celecoxib and minocycline as most promising first-line treatment options. However, no study has prospectively evaluated the effectiveness of a priori stratification by baseline inflammation levels for add-on celecoxib or minocycline in MDD. Methods: The INSTA-MD trial is a multicentre, 12-week, randomised, double-blind, placebo-controlled, parallel-group stratified clinical trial of adjunctive minocycline or celecoxib to treatment-as-usual for patients with MDD. Two hundred forty adult patients with Major Depressive Disorder who failed to remit with one or two trials of antidepressant treatment will be enrolled and allocated to high-hsCRP (hsCRP ≥3 mg/L) or low-hsCRP (hsCRP

Objective: Endometriosis is an estrogen-dependent chronic inflammatory disease in women of reproductive age. A review of the literature revealed that cytokines and inflammatory factors are associated with endometriosis-associated infertility. Interleukin 33 (IL-33) is a strong inducer of other pro-inflammatory cytokines. Vascular cell adhesion molecule-1 (VCAM-1) plays a central role in recruiting inflammatory cells, whose expression facilitates leukocyte adhesion and is rapidly induced by pro-inflammatory cytokines. Many studies have indicated that VCAM-1 expression is high in endometriosis; however, whether the expression of VCAM-1 is related to IL-33 is unclear. Materials and methods: Human ovarian endometriotic stromal cells (hOVEN-SCs) were treated with IL-33 to enable investigation of cell characterization, gene and protein expression, and signal pathways. Proliferation potential was measured using an MTT assay. Gene expression was analyzed using reverse transcription-polymerase chain reaction. Protein expression assay was performed using western blot analysis. Results: This study investigated the effects of IL-33 on VCAM-1 and COX-2 expression in hOVEN-SCs. First, the results revealed that the IL-33/ST2/mitogen-activated protein kinase (MAPK) signaling pathway could increase the expression of VCAM-1 and COX-2 in hOVEN-SCs. Second, we discovered that COX-2 expression was essential for IL-33-induced VCAM-1 expression because the effects could be negated through NS398, a selective COX-2 inhibitor. Finally, treatment of IL-33-treated hOVEN-SCs with celecoxib significantly and dose-responsively decreased VCAM-1 expression. Conclusion: Taken together, these results indicate that IL-33 can upregulate VCAM-1 expression in hOVEN-SCs through the IL-33/ST2/MAPK/COX-2 signaling pathway and thereby contribute to endometriosis.

Due to the large cost of joint replacement for surgical treatment of knee osteoarthritis, there are many complications in elderly patients, and there are many contraindications to surgery, and conservative treatment is still based on drugs. To further evaluate the efficacy and safety of sodium hyaluronate combined with celecoxib for the treatment of osteoarthritis of the knee. In total, 202 studies were screened, with a final selection of 9 RCTs involving 2339 participants; of these, 9 RCTs were included in the final meta-analysis. Treatment group reduces VAS (SMD = −1.61; 95 % CI [−2.25, −0.98]; I2 = 95 %; P

Objective: To explore the effective targets of Celecoxib in the treatment of heterotopic ossification using network pharmacology methods. Methods: Potential molecules related to heterotopic ossification were obtained by retrieving the GEO and CTD databases and intersecting them. Potential binding targets of Celecoxib were acquired from the STITCH database. A protein-protein interaction network was constructed between potential binding targets of Celecoxib and potential related molecules of heterotopic ossification using the STRING database. Molecules in the protein-protein interaction network were further analyzed using GO and KEGG enrichment analysis in R software, followed by enrichment analysis of active molecules in the Celecoxib-heterotopic ossification target dataset. Hub genes were selected based on the “degree” value and enrichment within the protein-protein interaction network. The binding affinity of hub genes to Celecoxib was observed using molecular docking techniques. Finally, in vitro experiments were conducted to validate the effectiveness of hub genes and explore their regulatory role in the progression of heterotopic ossification. Additionally, the therapeutic effect of Celecoxib, which modulates the expression of the hub genes, was investigated in the treatment of heterotopic ossification. Results: 568 potential molecules related to heterotopic ossification and 76 potential binding targets of Celecoxib were identified. After intersection, 13 potential functional molecules in Celecoxib's treatment of heterotopic ossification were obtained. KEGG analysis suggested pathways such as Rheumatoid arthritis, NF-kappa B signaling pathway, Pathways in cancer, Antifolate resistance, MicroRNAs in cancer play a role in the treatment of heterotopic ossification by Celecoxib. Further enrichment analysis of the 13 potential functional molecules identified 5 hub genes: IL6, CCND1, PTGS2, IGFBP3, CDH1. Molecular docking results indicated that Celecoxib displayed excellent binding affinity with CCND1 among the 5 hub genes. Experimental validation found that CCND1 is highly expressed in the progression of heterotopic ossification, promoting heterotopic ossification in the early stages and inhibiting it in the later stages, with Celecoxib's treatment of heterotopic ossification depending on CCND1. Conclusion: In the process of treating heterotopic ossification with Celecoxib, immune and inflammatory signaling pathways play a significant role. The therapeutic effect of Celecoxib on heterotopic ossification depends on the hub gene CCND1, which plays different roles at different stages of the progression of heterotopic ossification, ultimately inhibiting the occurrence of heterotopic ossification.

Celecoxib (CLX), a selective inhibitor for cyclooxygenase 2 (COX-2), has manifested potential activity against diverse types of cancer. However, low bioavailability and cardiovascular side effects remain the major challenges that limit its exploitation. In this work, we developed ultra-elastic nanovesicles (UENVs) with pH-triggered surface charge reversal traits that could efficiently deliver CLX to colorectal segments for snowballed tumor targeting. CLX-UENVs were fabricated via a thin-film hydration approach. The impact of formulation factors (Span 80, Tween 80, and sonication time) on the nanovesicular features was evaluated using Box–Behnken design, and the optimal formulation was computed. The optimum formulation was positively coated with polyethyleneimine (CLX-PEI-UENVs) and then coated with Eudragit S100 (CLX-ES-PEI-UENVs). The activity of the optimized nano-cargo was explored in 1,2-dimethylhydrazine-induced colorectal cancer in Wistar rats. Levels of COX-2, Wnt-2 and β-catenin were assessed in rats' colon. The diameter of the optimized CLX-ES-PEI-UENVs formulation was 253.62 nm, with a zeta potential of −23.24 mV, 85.64% entrapment, and 87.20% cumulative release (24 h). ES coating hindered the rapid release of CLX under acidic milieu (stomach and early small intestine) and showed extended release in the colon section. In colonic environments, the ES coating layer was removed due to high pH, and the charge on the nanovesicular corona was shifted from negative to positive. Besides, a pharmacokinetics study revealed that CLX-ES-PEI-UENVs had superior oral bioavailability by 2.13-fold compared with CLX suspension. Collectively, these findings implied that CLX-ES-PEI-UENVs could be a promising colorectal-targeted nanoplatform for effective tumor management through up-regulation of the Wnt/β-catenin pathway.

Loading drugs in drug delivery systems can increase their retention time and control their release within the knee cavity. Hence, we aimed to improve the therapeutic efficacy of celecoxib and kartogenin (KGN) through their loading in chitosan nanoparticles (CS NPs). Celecoxib-loaded nanoparticles (CNPs) and KGN-loaded nanoparticles (K-CS NPs) were prepared using the absorption method and covalent attachment, respectively, through an ionic gelation process. The morphology, particle size, zeta potential, polydispersity index (PDI), conjugation efficiency (CE), encapsulation efficiency (EE), the in vitro release of the drug from NPs, as well as MTT and hemolysis assays, were evaluated. Then, the IL-1β-stimulated chondrocytes were treated with CNPs and K-CS NPs, individually or in combination, to explore their potential chondroprotective and anti-inflammatory effects. CNPs and K-CS NPs showed sizes of 352.6 ± 22.5 and 232.7 ± 4.5 nm, respectively, suitable for intra-articular (IA) injection. Based on the hemolysis results, both NPs exhibited good hemocompatibility within the studied range. Results showed that treating IL-1β-pretreated chondrocytes with CNPs or K-CS NPs remarkably limited the negative effects of IL-1β, especially when both types of NPs were used together. Therefore, injecting these two NPs into the knee cavity may improve drug bioavailability, rapidly suppress inflammation and pain, and promote cartilage regeneration. Meanwhile, for the first time, the study investigated the effect of the simultaneous use of celecoxib and KGN to treat osteoarthritis (OA).

المخلص: أهداف البحث: يلعب تولد الأوعية دورا مهما في مختلف الحالات الفسيولوجية والمرضية. إنه ضروري لنمو الورم ورم خبيث. الهدف من هذه الدراسة هو تقييم تأثير تركيبة فانديتانيب وسيليكوكسيب على تكوين الأنبوب الوعائي وتأثيره على الجينات المولدة للأوعية (م.م.ب -2 و م.م.ب -9) باستخدام نموذج مختبري للإنسان. الخلايا البطانية للوريد السري. طرق البحث: تم استنبات الخلايا البطانية للوريد السري البشري والتحقق منها عن طريق قياس التدفق الخلوي. عولجت الخلايا البطانية في الوريد السري البشري بفانديتانيب وسيليكوكسيب ومزيج من العقارين ، وتم تحديد قابلية بقاء الخلية وموت الخلايا المبرمج باستخدام مقايسة م.ت.ت وقياس التدفق الخلوي. تم تحليل عملية تكوين الأوعية باستخدام اختبار تكوين الأنبوب، وتم تحديد التأثير على الجينات المولدة للأوعية باستخدام النسخ العكسي لتفاعل البلمرة المتسلسل الكمي في الوقت الحقيقي. النتائج: كانت الخلايا البطانية للوريد السري البشري موجبة لـ سي.دي-144 وسلبية لـ سي.دي-14. أدى فانديتانيب وسيليكوكسيب وتركيبهما إلى تثبيط بقاء الخلايا البطانية للوريد السري البشري بطريقة تعتمد على الجرعة. كان معدل موت الخلايا المبرمج 13.1٪، 9٪ و 23.7٪، عند العلاج بـ فانديتانيب، سيليكوكسيب، أو مزيج من كلا العقارين. منع فانديتانيب تشكيل الأنبوب بنسبة 43.7٪ ، والسيليكوكسيب بنسبة 21٪، ومزيجهم بنسبة 77.3٪ على التوالي. النسخ العكسي من تفاعل البوليميراز المتسلسل الكمي في الوقت الحقيقي. أظهر أن كلا من فاندتانيب وسيليكوكسيب يقللان من مستويات التعبير عن م.م.ب -2 و م.م.ب -9، وأظهر الجمع بينهما مستوى أعلى من الانخفاض في التعبير المستوى الذي وجد أنه ذو دلالة إحصائية. الاستنتاجات: سيليكوكسيب يعزز تأثير فانديتانيب في تثبيط تكوين الأوعية في المختبر، وقد أظهر الجمع بينهما مستويات أعلى من التثبيط مقارنة باستخدام فانديتانيب وحده. Abstract: Objective: Angiogenesis plays an important role in various physiological and pathological conditions and is essential for tumor growth and metastasis. The aim of this study was to evaluate the effect of a combination of vandetanib and celecoxib on angiogenic tube formation and its effect on angiogenic genes (MMP-2 and MMP-9) using an in vitro model of human umbilical vein endothelial cells (HUVECs). Methods: HUVECs were cultured and verified by flow cytometry. HUVECs were then treated with vandetanib, celecoxib, and the combination of both drugs. Then, we investigated cell viability and cell apoptosis by MTT assays and flow cytometry. The process of angiogenesis was analyzed by tube formation assays, and the effect on angiogenic genes was determined by RT-qPCR. Results: HUVECs were positive for CD144 and negative for CD14. Vandetanib, celecoxib, and their combination inhibited HUVEC viability in a dose-dependent manner (p

Transarterial chemoembolization (TACE) is a first-line treatment for intermediate to advanced-stage liver cancer, with drug-eluting microspheres commonly used as embolic agents. However, currently available drug-eluting microspheres suffer from low drug-loading capacity and limited drug options. In this work, we developed polydopamine-modified polyvinyl alcohol dual-drug-loaded microspheres encapsulating celecoxib and cisplatin (referred to as PCDMS). Physicochemical characterization revealed that the surface of the microspheres displayed increased roughness after polydopamine modification, and celecoxib and cisplatin were successfully loaded onto the microsphere surface. In vitro cell experiments demonstrated that the PCDMS significantly inhibited the proliferation and migration of highly metastatic human liver cancer cells (MHCC-97H) and human liver cancer cells (SMMC-7721). Furthermore, the dual-loaded microspheres exhibited remarkable tumor growth inhibition and reshaped the tumor microenvironment in both subcutaneous H22 liver cancer model in Balb/c mice and intrahepatic VX2 tumor model in New Zealand rabbits, demonstrating a synergistic antitumor effect where 1 + 1>2. This work provides a potential therapeutic approach for the treatment of refractory liver cancer and holds significant translational potential.

This study aims to clarify the molecular mechanism by which celecoxib (CXB) interacts with poly (lactic acid), (PLA), microparticles using calculations from density functional theory (DFT), time-dependent density functional theory (TDDFT), and molecular docking. Chemical reactivity and binding energy parameters indicate that the interaction of CXB through the pyrazole ring with PLA (state A: -1.52 eV) is stronger due to hydrogen bonding than in states B (-0.36 eV) and C (-0.44 eV) due to weak hydrogen bonding interactions. The infrared (IR) and Ultraviolet-Visible (UV–Vis) absorption spectra reveal that both pure PLA and CXB experience shifts as a result of the interaction between CXB and PLA. The interaction between CXB (5.07 Debye) and PLA (7.33 Debye) results in an increase in the dipole moment (B: 39.86 Debye), an improvement in solubility, and a reduction in the energy gap (Eg). In comparison to free molecules, the designed models, including CXB and PLA, showed greater stability in the protein's active pocket based on molecular docking calculations. Therefore, CXB interacting with PLA acts as a potent inhibitor of tumor necrosis factor-alpha (TNF-α), cyclooxygenase-2 (COX-2), and human epidermal growth factor receptor-2 (HER2).and can be used to treat breast cancer patients as well as immune-inflammatory diseases like rheumatoid arthritis (RA).

Purpose: The purpose of this study was to determine if preoperative celecoxib treatment raises the risk of postoperative 1) myocardial infarctions, 2) thromboembolic complications, 3) acute kidney injuries, 4) transfusions, and 5) readmissions. Materials and methods: Using the administrative claims database, PearlDiver, a retrospective study from January 2010 to October 2020 was conducted. Patients undergoing total knee or hip arthroplasty for osteoarthritis with recent celecoxib prescription were included, excluding those with MI history. Propensity score matched 230,587 patients (TKA: 38,433 celecoxib, 192,154 control; THA: 21,603 celecoxib, 108,008 control). Outcomes evaluated: 90-day myocardial infarction, DVT, PE, VTE, AKIs, transfusion, readmission. Multivariate logistic regression calculated odds ratios, 95 % CIs, p-values. Welch's t-tests assessed differences in stay lengths, costs (p

Backgrounds and aims: Carcinogenesis is characterized by an unlimited growth of cells exacerbated by Cox-2 overexpression. Cox-2 inhibitors have been proven effective in preventing and treating tumors. In our previous studies, we found that 4-Amino-2-Trifluoromethylphenyl Retinate (ATPR) induces cell apoptosis and inhibits cell proliferation to exhibit anti-cancer properties. The use of ATRA as well as Cox-2 inhibitors in clinical settings can cause adverse reactions. It is unknown what the effects and mechanisms of co-administration of ATPR and Cox-2 inhibitors are. Results: A combination of ATPR and Cox-2 inhibitors, Celecoxib, inhibited pharyngeal cancer cell proliferation in vitro and induced apoptosis. The cell cycle was arrested at G0/G1 by activating P53 and CDNA1. By activating MAPK/JNK pathways, ATPR and Celecoxib led to intrinsic and extrinsic apoptosis in pharyngeal cancer cells. ATPR/Celecoxib combined treatment suppressed tumor growth in the pharyngeal cancer cell-derived xenograft mouse model by increasing the number of apoptotic cells. The expression of the RARA and PTGS2 genes was significantly increased in tumor tissue compared to non-tumor tissue in the clinical analysis of the head and neck squamous cell carcinoma dataset. An association was found between this and the level of intrinsic apoptotic signals. Furthermore, a survival analysis conducted over a period of five years indicated that higher levels of RARA expression were associated with a better clinical outcome. Conclusion: ATPR and celecoxib inhibit the proliferation of cancer cells as well as induce apoptosis. Co-administration of ATPR and Cox-2 inhibitors has the potential to be a novel treatment plan for cancer.

Background: : Anger can worsen a person's emotions and increase the severity of an individual's mood state, notably depression. The State-Trait Anger Expression Inventory (STAXI) assessment tool is useful for assessing the experience, expression, and control of anger in normal individuals, and in evaluating anger experienced by patients with a variety of psychological and medical disorders. Since its creation, STAXI has been utilized in various studies involving substance abuse and major depressive disorder; however, anger has never been studied systematically in bipolar depression. Scientific evidence supports the hypothesis that immune system activation, reflected in its inflammatory response, contributes to the pathophysiology and phenomenology of bipolar disorder. However, there is limited research showing how the treatment of bipolar disorder is enhanced with an anti-inflammatory agent and how it affects anger, which prompted this investigation. The current clinical study tested the hypothesis that co-administration of a specific anti-inflammatory agent, Celecoxib, along with Escitalopram, a selective serotonin reuptake inhibitor, would be beneficial in patients with treatment resistant bipolar depression. In comparison to patients receiving Escitalopram monotherapy, it was hypothesized that the combination therapy would lead to an augmented response in alleviating bipolar depression. In addition, the combination therapy would result in a greater percentage of responders and remitters. It also was hypothesized that the combination therapy would reduce anger symptoms as assessed by STAXI from beginning to end of treatment. Method: : In this double-blind, two-arm, placebo-controlled study, 65 consenting patients diagnosed with treatment resistant bipolar depression were randomized to receive either Escitalopram (10 mg twice/day) + Celecoxib (200 mg twice/day), or Escitalopram + placebo (twice/day). There were 47 completers: 27 in the Celecoxib, and 20 in the Placebo arm. The 17-item Hamilton Depression Rating Scale was used to assess response to treatment, with a 50% reduction from baseline indicating treatment response and a score < 7 indicating remission. The Beck Depression Index also was used as a self-report measure of depression. Levels of state and trait anger were assessed using the 57-item STAXI scale. Measures of depression, anger and perceived stress were collected at baseline and at week 8 of treatment. Results: : A multiple regression analysis of baseline data indicated that the Hamilton depression score was significantly related to the feelings subscale of the state STAXI. However, the baseline Beck score was found to be predicted by perceived stress. To test treatment effects, an analysis of covariance revealed that the week 8 Hamilton depression score was significantly lower for patients receiving the combination therapy, controlling for baseline differences. The week 8 Beck score also was lower for those in the combination therapy group, but was not statistically significant. In comparison to the monotherapy group, those receiving the combination therapy showed a statistically higher proportion of responders and remitters. Significant differences in state or trait anger subscales were found only responders to the CBX add-on arm at week 8. Limitations: : Limitations of the study include small sample size and short period of treatment. Conclusion: : An analysis of baseline data suggest that depression is associated with state feelings of anger and perceived stress. In comparison to receiving Escitalopram alone, the combination therapy was more effective in lowering Hamilton depression scores and was associated with greater proportions of responders and remitters. Anti-inflammatory combination therapy reduced state and trait anger by the end of treatment.

Background: Affective illness has been associated with a proinflammatory state, and it is generally accepted that the immune system plays a key role in the pathophysiology of mood disorders. Since inflammatory biomarkers are elevated in bipolar disorder, anti-inflammatory combination therapies may enhance response and reverse treatment resistance. Purpose: In the present study we investigated the possible impact of single nucleotide polymorphisms (SNPs) within the CRP gene on CRP blood levels, treatment response and level-of-stress perception in our cohort of treatment-resistant bipolar-depressed patients receiving escitalopram and celecoxib, or escitalopram and placebo, as previously reported (Halaris et al., 2020). Methods: Study design, clinical findings, and CRP blood levels have been reported previously (Halaris et al., 2020; Edberg et al., 2018). In this follow-up study we extracted DNA from blood cells collected at baseline. Genome-wide genotyping was performed for all subjects using the Infinium Multi-Ethnic Global-8 v1.0 Kit. Based on reports in the literature indicating possible associations with psychiatric conditions, ten previously reported CRP gene polymorphisms were evaluated in a preliminary analysis. We focused on rs3093059 and rs3093077 were in complete LD. Carriers were defined as those possessing at least one C allele for rs3093059, or at least one G allele for rs3093077. Additionally, we determined blood levels of the medications administered. Results: Non-carriers of rs3093059 and rs3093077 had significantly lower baseline CRP blood levels than carriers (p = 0.03). Increased rates of HAM-D17 response (p = 0.21) and remission (p = 0.13) and lower PSS-14 scores (p = 0.13) were observed in non-carriers among subjects receiving celecoxib but they did not reach statistical significance. When examining all subjects, nominally significant associations between carrier-status and remission (p = 0.04) and PSS-14 scores (p = 0.04) were observed after correcting for treatment arm. Non-carriers receiving celecoxib had the highest rates of response and remission, and the lowest stress scores. Conclusions: Carriers of the CRP SNPs may have higher baseline CRP levels, although non-carriers appear to benefit more from celecoxib co-therapy. Determination of the carrier status in conjunction with pretreatment blood CRP level measurement may contribute to personalized psychiatric practice, but replication of the present findings is needed.

Objective: An important issue in adolescent idiopathic scoliosis (AIS) correction surgery is postoperative pain management due to the procedure’s relatively high invasiveness. Although celecoxib is widely used as an analgesic for post-surgical pain, there have been several reports of drug eruptions. Such side effects may similarly occur in AIS patients following posterior spinal fusion (PSF). However, no studies have specifically addressed perioperative rash from analgesics in scoliosis surgery. We investigated the incidence of drug eruptions in PSF for AIS and their patient-related risk factors. Methods: We retrospectively reviewed the medical records of 134 consecutive patients who underwent PSF for AIS. Sixty-six patients had received celecoxib and 68 had taken NSAIDs, acetaminophen, or other painkillers after surgery. We investigated the incidence of drug eruptions between patients who took celecoxib (celecoxib group) or other painkillers (others group) and searched for factors associated with rash after surgery by means of a logistic regression model. Results: The overall incidence of drug eruptions after PSF for AIS was 11.9%. The incidence of eruptions in the celecoxib group (18.2%) was significantly higher than in the others group (5.9%) (p = 0.034). The patient-related factors of celecoxib intake and allergic history had significant associations with drug eruptions in multivariate analysis, with odds ratios of 3.88 and 3.53, respectively. Conclusion: In PSF surgery for AIS, patients who receive celecoxib and/or have a history of allergies are significantly more likely to exhibit a rash and should be observed closely for drug eruptions.

Celecoxib and tramadol have been combined in a novel FDA-approved medication to address acute pain disorders requiring opioid treatment when other analgesics proved either intolerable or ineffective. The absorbance spectra of celecoxib and tramadol exhibit significant overlap, posing challenges for their individual quantification. This study introduces a spectrophotometric quantification approach for celecoxib and tramadol using a principle component regression assistive model to assist resolving the overlapped spectra and quantifying both drugs in their binary mixture. The model was constructed by establishing calibration and validation sets for the celecoxib and tramadol mixture, employing a five-level, two-factor experimental design, resulting in 25 samples. Spectral data from these mixtures were measured and preprocessed to eliminate noise in the 200-210 nm range and zero absorbance values in the 290-400 nm range. Consequently, the dataset was streamlined to 81 variables. The predicted concentrations were compared with the known concentrations of celecoxib and tramadol, and the errors in the predictions were evidenced calculating root mean square error of cross-validation and root mean square error of prediction. Validation results demonstrate the efficacy of the models in predicting outcomes; recovery rates approaching 100 % are demonstrated with relative root mean square error of prediction (RRMSEP) values of 0.052 and 0.164 for tramadol and celecoxib, respectively. The selectivity was further evaluated by quantifying celecoxib and tramadol in the presence of potentially interfering drugs. The model demonstrated success in quantifying celecoxib and tramadol in laboratory-prepared tablets, producing metrics consistent with those reported in previously established spectrophotometric methods., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Multiple anti-inflammatory medications have helped treat inflammatory bowel disease (IBD). However, oral administration has minimal absorption and systemic side effects. This study aims to investigate the potential of encapsulating anti-inflammatory drug celecoxib (Cele) within microbeads for the treatment of IBD. Microbeads were formed by cross-linking carboxymethyl chitosan (CMCs) with sodium alginate (Alg) through the ionic gelation method and optimized through response surface methodology. Additionally, the study revealed a mucoadhesivity value of 59.32 ± 0.74 % for the optimized microbead system. The drug release study demonstrated the sustained release of Cele CMCs/Alg microbeads upto 24 h compared to quick release of the free drug. The results of the cell viability assay indicated that the Cele-Alg/CMCs microbeads exhibited a non-toxic nature within the concentration range of 100-250 μM. A significant decrease in nitric oxide (NO) generation (61.14 ± 3.67 %) was seen in HCT-116 cells stimulated with lipopolysaccharide (LPS) upon treatment with Cele-250 μM /CMCs/Alg microbeads. The results of the reactive oxygen species and wound healing assay suggest that Cele-250 μM /CMCs/Alg microbeads had improved anti-inflammatory characteristics comparable to those of free drug treatment. The western blot analysis demonstrated that the microbeads composed of CMCs/Alg-Cele possess the capacity to inhibit the expression of COX-2 in vitro supressing inflammation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Even though toxoplasmosis is a worldwide parasitic disease caused by Toxoplasma gondii (T. gondii), the available drugs used for the treatment of symptomatic toxoplasmosis have multiple drawbacks. So, there is a considerable need to discover new potential therapeutic agents. The current study aimed to assess the effect of celecoxib (CELE) alone or combined with spiramycin against chronic toxoplasmosis in experimentally infected mice. The study documented the reduction rate of T. gondii cysts in brain tissues and ultrastructural changes through transmission electron microscopy after treatment. We also investigated pathological changes in the brain, liver, lung, and spleen, as well as the expression of TGF-β, iNOS, and pSTAT-1 in brain tissues. Other markers for kidney function and serum levels of interleukins 10 and 12 were also assessed. The study reported a reduction rate of T. gondii brain cyst count of 32.9 % after CELE treatment, 71.7 % after spiramycin treatment, and 75.7 % after combined treatment. Furthermore, the CELE and spiramycin combination improved the ultrastructure and histopathology in brain tissues while decreasing TGF-β, iNOS, and pSTAT-1 expression. The combined therapy ameliorated the inflammation of the liver, lung, and spleen, upregulated the IL-12 level, reduced the IL-10 level, and was accompanied by a reduction in creatinine and urea in serum. In conclusion, CELE increased spiramycin therapeutic efficacy, and their combination showed a better response than spiramycin alone. Thus, the CELE combination with spiramycin represents a hopeful therapy against chronic toxoplasmosis., Competing Interests: Declaration of competing interest The authors have no relevant competing interests to report about the contents of this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Celecoxib, a selective COX-2 inhibitor non-steroidal anti-inflammatory drug (NSAID), exhibits analgesic and anti-inflammatory properties similar to piperine, the secondary metabolite of Piper nigrum L. Unfortunately, celecoxib has a low compressibility and low dissolution rate in aqueous medium. This study aimed to prepare a cocrystal of celecoxib and piperine to enhance the dissolution rate and compressibility properties of celecoxib. The cocrystal was synthesized using the seeding method and thoroughly characterized using Powder X-ray diffraction (XRD), differential scanning calorimetry (DSC), infrared spectrophotometry, and single-crystal X-ray diffraction techniques. The complete change in PXRD, decrease in melting point in DSC measurements, and shift in the N-H stretching band in the FT-IR spectrum suggested the formation of cocrystals phase. Single-crystal XRD confirmed the formation of an equimolar ratio of cocrystals of celecoxib and piperine. The intrinsic dissolution test was conducted to confirm the impact on the cocrystal to dissolution, and it showed a slight increase compared to intact celecoxib. To assess the physico-mechanical properties, the cocrystal powders were compressed into tablets with varying forces. The results demonstrated a significant improvement in compressibility compared with intact celecoxib owing to the slip plane in the crystal lattice of the cocrystal. In conclusion, our novel celecoxib-piperine cocrystal exhibited distinct physicochemical characteristics compared to intact celecoxib, showing enhanced dissolution rate and compressibility., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Background: Major depressive disorder (MDD) is a highly prevalent condition with a substantial incidence of relapse or treatment resistance. A subset of patients show evidence of low-grade inflammation, with these patients having a higher likelihood of more severe or difficult to treat courses of illness. Anti-inflammatory treatment of MDD has been investigated with mixed results, and no known studies have included assessments beyond cessation of the anti-inflammatory agent, meaning it remains unknown if any benefit from treatment persists. The objective of the present study was to investigate treatment outcomes up to 29 weeks post-cessation of celecoxib or placebo augmentation of an antidepressant, and how concentrations of selected inflammatory markers change over the same period., Methods: The PREDDICT parallel-group, randomised, double-blind, placebo-controlled trial (University of Adelaide, Australia) ran from December 2017 to April 2020. Participants with MDD were stratified into normal range or elevated inflammation strata according to screening concentrations of high sensitivity C-reactive protein (hsCRP). Participants were randomised to treatment with vortioxetine and celecoxib or vortioxetine and placebo for six weeks, and vortioxetine alone for an additional 29 weeks (35 total weeks). Following a previous publication of results from the six-week RCT phase, exploratory analyses were performed on Montgomery-Åsberg Depression Rating Scale (MADRS) scores, response and remission outcomes, and selected peripheral inflammatory markers across the entire study duration up to week 35., Results: Participants retained at each observation were baseline N=119, week 2 N=115, week 4 N=103, week 6 N=104, week 8 N=98, week 22 N=81, and week 35 N=60. Those in the elevated hsCRP celecoxib-augmented group had a statistically significantly greater reduction in MADRS score from baseline to week 35 compared to all other groups, demonstrating the greatest clinical improvement long-term, despite no group or strata differences at preceding time points. Response and remission outcomes did not differ by treatment group or hsCRP strata at any time point. Changes in hsCRP between baseline and week 35 and Tumour Necrosis Factor-α (TNF-α) concentrations between baseline and week 6 and baseline and week 35 were statistically significantly associated with MADRS scores observed at week 6 and week 35 respectively, with reducing TNF-α concentrations associated with reducing MADRS scores and vice versa in each case. A post-hoc stratification of the participant cohort by baseline TNF-α concentrations led to significant prediction by the derived strata on clinical response at weeks 6, 8 and 35, with participants with elevated baseline TNF-α less likely to achieve clinical response., Interpretation: The present analysis suggests for the first time a possible longer-term clinical benefit of celecoxib augmentation of vortioxetine in inflammation-associated MDD treatment. However, further research is needed to confirm the finding and to ascertain the reason for such a delayed effect. Furthermore, the trial suggests that TNF-α may have a stronger relationship with anti-inflammatory MDD treatment outcomes than hsCRP, and should be investigated further for potential predictive utility., Clinical Trials Registration: Australian New Zealand Clinical Trials Registry (ANZCTR), ACTRN12617000527369p. Registered on 11 April 2017, http://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12617000527369p., (Copyright © 2024. Published by Elsevier Inc.)

In this study, we aimed to develop a solid self-nanoemulsifying drug delivery system (S-SNEDDS) and a solid self-nanoemulsifying granule system (S-SNEGS) to enhance the solubility and oral bioavailability of celecoxib. This process involved the preparation of a liquid SNEDDS (L-SNEDDS) and its subsequent solidification into a S-SNEDDS and a S-SNEGS. The L-SNEDDS consisted of celecoxib (drug), Captex® 355 (Captex; oil), Tween® 80 (Tween 80; surfactant) and D-α-Tocopherol polyethylene glycol 1000 succinate (TPGS; cosurfactant) in a weight ratio of 3.5:25:60:15 to produce the smallest nanoemulsion droplet size. The S-SNEDDS and S-SNEGS were prepared with L-SNEDDS/Ca-silicate/Avicel PH 101 in a weight ratio of 103.5:50:0 using a spray dryer and 103.5:50:100 using a fluid bed granulator, respectively. We compared the two novel developed systems and celecoxib powder based on their solubility, dissolution rate, physicochemical properties, flow properties and oral bioavailability in rats. S-SNEGS showed a significant improvement in solubility and dissolution rate compared to S-SNEDDS and celecoxib powder. Both systems had been converted from crystalline drug to amorphous form. Furthermore, S-SNEGS exhibited a significantly reduced angle of repose, compressibility index and Hausner ratio than S-SNEDDS, suggesting that S-SNEGS was significantly superior in flow properties. Compared to S-SNEDDS and celecoxib powder, S-SNEGS increased the oral bioavailability (AUC value) in rats by 1.3 and 4.5-fold, respectively. Therefore, S-SNEGS wolud be recommended as a solid self-nanoemulsifying system suitable for poorly water-soluble celecoxib., Competing Interests: Declaration of Competing Interest The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Pharmacological inhibition of cyclooxygenase-2 (COX-2) activity ameliorated the severity of non-alcoholic steatohepatitis (NASH) rats. It is not completely understood that the role of COX-2 inhibitor celecoxib on adiponectin receptors (Adipo-R1/R2) expression in different tissues in NASH rats. Sprague-Dawley male NASH rats induced by a high-fat diet (HFD) were administrated with or without celecoxib for 8 weeks. Biochemical parameters of liver function, glucose, and lipid metabolism, and the levels of adiponectin, tumor necrosis factor-alpha (TNF-α), prostaglandin E2 (PGE2) in the serum or liver were collected according to the standard protocols. The mRNA and protein levels of Adipo-R1, Adipo-R2, and COX-2 in the liver, muscle, and visceral fat were performed by quantitative real-time polymerase chain reaction (q-PCR) and Western blot analysis, respectively. The results showed that celecoxib ameliorated the various clinical indicators and pathological characteristics in the NASH rats, including body weight, liver function, liver index, and redox activities in serum and hepatic samples. The serum concentrations of adiponectin and TNF-α and PGE2 were negatively correlated. As expected, these ameliorative effects of celecoxib were associated with the gene and protein levels up-regulation of Adipo-R1, Adipo-R2 in the liver and visceral fat tissues, and seeming to be compensatory down-regulation expression in muscle tissues (P

Background: Use of anti-inflammatory medications (NSAIDs) is an important component of multimodal pain control after orthopedic procedures to avoid opioid overutilization and abuse. However, the deleterious effects of NSAIDs on tendon healing are of particular concern in rotator cuff repair (RCR). The purpose of this study was to evaluate the effect of celecoxib or placebo on healing rates after RCR when administered in the perioperative and immediate postoperative period using MRI evaluation at one year postoperatively. A secondary aim was to determine whether clinical differences existed between patients with intact or non-intact repairs. Methods: Patients aged ≤65 years with partial- or full-thickness rotator cuff tear (

Coronavirus-triggered pulmonary and systemic disease, i.e. systemic inflammatory response to virally triggered lung injury, named COVID-19, and ongoing discussions on refining immunomodulation in COVID-19 without COX2 inhibition prompted us to search the related literature to show a potential target (COX2) and a weapon (celecoxib). The concept of selectively targeting COX2 and closely related cascades might be worth trying in the treatment of COVID-19 given the substantial amount of data showing that COX2, p38 MAPK, IL-1b, IL-6 and TGF-β play pivotal roles in coronavirus-related cell death, cytokine storm and pulmonary interstitial fibrosis. Considering the lack of definitive treatment and importance of immunomodulation in COVID-19, COX2 inhibition might be a valuable adjunct to still-evolving treatment strategies. Celecoxib has properties that should be evaluated in randomized controlled studies and is also available for off-label use.

Intracerebral hemorrhage (ICH) may be caused by trauma, aneurysm and arteriovenous malformation, as can any bleeding within the intracranial vault, including brain parenchyma and adjacent meningeal spaces (aneurism and atreovenous malformation). ICH is the cerebral stroke with the least treatable form. Over time, intraventricular hemorrhage (IVH) is associated with ICH, which contributes to hydrocephalus, and the major cause of most hemorrhagic death (Due to the cerebral hemorrhage and post hemorrhagic surgeries). Most patients suffer from memory impairment, grip strength, posture, and cognitive dysfunctions attributable to cerebral hemorrhage or post-brain hemorrhagic surgery. Nevertheless, a combined model of ICH based IVH is not present pre-clinically. Autologous blood (ALB) injection (20 μl/5 min) in the rat brain triggers hemorrhage, such as factors that further interfere with the normal functioning of neuroinflammatory cytokines, oxidative stress, and neurotransmitter dysfunction, such as CoQ10 insufficiency and dysregulation of mitochondrial ETC-complexes. For the prevention of post-brain hemorrhagic behavioral and neurochemical dysfunctions, there is no specific drug treatment available, only available therapy used to provide symptomatic relief. The current study reveals that long-term administration of Solanesol (SNL) 40 and 60 mg/kg alone and in combination with available drug therapy Donepezil (DNP) 3 mg/kg, Memantine (MEM) 20 mg/kg, Celecoxib (CLB) 20 mg/kg, Pregabalin (PGB) 30 mg/kg, may provide the neuroprotective effect by improving behavioral and neurochemical deficits, and gross pathological changes in ALB induced combined experimental model of ICH-IVH in post brain hemorrhagic conditions in rats. Thus, SNL can be a potential therapeutic approach to improve neuronal mitochondrial dysfunction associated with post brain hemorrhagic behavioral and neurochemical alterations.

Celecoxib is used widely for the acute treatment of pain and for pain relief in various diseases. Furthermore, it shows potential in chemoprevention, although chronic treatment with celecoxib could lead to adverse effects like cardiovascular events. New derivatives of celecoxib were synthesised that may be suitable as chemopreventive agent without inducing adverse effects.Critical endpoint for a safe use of pharmaceuticals is genotoxicity after application. A standard test for the assessment of genotoxicity is the cytokinesis-block micronucleus assay, that evaluates the number micronuclei after treatment of cells with a test compound as biomarker for DNA damage. Various promising derivatives of celecoxib have been assessed with the cytokinesis-block micronucleus assay in HeLa-H2B-GFP cells. It could be demonstrated, that neither celecoxib nor its derivatives were genotoxic in this assay and therefore celecoxib derivatives could be developed further for a safe use as chemopreventive agent.

Present study offers great prospects for the adsorption of anti-inflammatory celecoxib molecule (CXB) over the surface of zinc oxide (Zn12O12) and magnesium oxide (Mg12O12) nanoclusters in several environments by performing robust theoretical calculations. Density functional theory (DFT), time-dependent density functional theory (TDDFT) and molecular docking calculations have been extensively carried out to predict the foremost optimum site of CXB adsorption. It has been observed that the CXB molecule prefers to be adsorbed by its SO2 site on the Zn-O and Mg-O bonds of the Zn12O12 and Mg12O12 nanoclusters instead of NH2 and NH sites, where electrostatic interactions dominate over the bonding characteristics of the conjugate complexes. Furthermore, the presence of interactions between the CXB molecule and nanoclusters has also been evidenced by the UV–Vis absorption spectra and IR spectra. Molecular docking analysis has revealed that both adsorption states including CXB/Zn12O12 and CXB/Mg12O12 have good inhibitory potential against protein tumor necrosis factor alpha (TNF-α) and Interleukin-1 (IL-1), and human epidermal growth factor receptor 2 (HER2). Hence they might be explored as efficient TNF-α, IL-1, and HER2 inhibitors. Hence from the study, it can be anticipated that these nanoclusters can behave as an appropriate biomedical carrier for the CXB drug delivery.

Pancreatic cancer generates resistance to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) by downregulating death receptors and switching pro-apoptosis to anti-apoptosis through caspases blockers like X-linked inhibitor of apoptosis proteins (XIAPs) and survivin. From this perspective, a self-sustaining nanoplatform (SSN) was prepared to reverse the downregulation of death receptors and remove blockage of XIAPs and survivin as a source-broadening and expenditure-reducing strategy to coactivate extrinsic and intrinsic apoptosis in TRAIL-resistant pancreatic cancer. After administration, efficient tumor accumulation and cellular uptake of SSN would be achieved by elongated circulation time of PEG shell and active targeting ability of novel multifunctional R6ST protein equipped with cell-penetrating peptide R6 and active targeting of soluble TRAIL fragment, and further enhanced through interaction with the death receptors upregulated by the encapsulated celecoxib in SSN, which could be served as a positive feedback loop. This positive feedback loop not only broadened the source of death receptors but also reduced the expenditure of caspases by counteracting the inhibition of XIAPs and survivin via tetrapeptides AVPI in R6ST and celecoxib respectively, to synchronously relieve and promote exogenous and endogenous apoptotic pathway. Consequently, SSN exhibited synergistic effect to overcome TRAIL-resistance of pancreatic cancer through this source-broadening and expenditure-reducing strategy.

A novel series of pyrazole derivatives with urea/thiourea scaffolds 16a-l as hybrid sorafenib/erlotinib/celecoxib analogs was designed, synthesized and tested for its VEGFR-2, EGFR WT , EGFR T790M tyrosine kinases and COX-2, pro-inflammatory cytokines TNF-α and IL-6 inhibitory activities. All the tested compounds showed excellent COX-2 selectivity index in range of 18.04-47.87 compared to celecoxib (S.I. = 26.17) and TNF-α and IL-6 inhibitory activities (IC 50  = 5.0-7.50, 6.23-8.93 respectively, compared to celecoxib IC 50  = 8.40 and 8.50, respectively). Screening was carried out against 60 human cancer cell lines by National Cancer Institute (NCI), compounds 16a, 16c, 16d and 16 g were the most potent inhibitors with GI% ranges of 100 %, 99.63-87.02 %, 98.98-43.10 % and 98.68-23.62 % respectively, and with GI 50 values of 1.76-15.50 µM, 1.60-5.38 µM, 1.68-7.39 µM and 1.81-11.0 µM respectively, in addition, of showing good safety profile against normal cell line (F180). Moreover, compounds 16a, 16c, 16d and 16 g had cell cycle arrest at G2/M phase with induced necrotic percentage compared to sorafenib of 2.06 %, 2.47 %, 1.57 %, 0.88 % and 1.83 % respectively. Amusingly, compounds 16a, 16c, 16d and 16 g inhibited VEGFR-2 with IC 50 of 25 nM, 52 nM, 324 nM and 110 nM respectively, compared to sorafenib (IC 50  = 85 nM), and had excellent EGFR WT and EGFR T790M kinase inhibitory activities (IC 50  = 94 nM, 128 nM, 160 nM, 297 nM), (10 nM, 25 nM, 36 nM and 48 nM) respectively, compared to both erlotinib and osimertinib (IC 50  = 114 nM, 56 nM) and (70 nM, 37 nM) respectively and showed (EGFR wt /EGFR T790M S.I.) of (range: 4.44-9.40) compared to erlotinib (2.03) and osmertinib (1.89)., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Adjunctive inflammatory treatments improve response and remission rates in treatment-resistant bipolar depression (TRBDD), but underlying mechanisms remain unclear. Given the association between hypothalamic-pituitary-adrenal (HPA) axis dysregulation and treatment-resistant depression, we investigated the pre-treatment HPA-axis profile in relation to treatment response. Methods: This is a secondary analysis of 31 TRBDD patients with moderately severe depression scores as assessed with the Hamilton Depression Rating Scale 17 (HAMD17), who were randomized to receive either escitalopram (ESC) (10–40 mg daily) + celecoxib (CBX) (200 mg twice daily), or ESC (10–40 mg daily) + placebo (PBO) (twice daily). Salivary cortisol was measured at baseline. A multivariate linear regression model was applied to evaluate whether depression scores at Week 8 were related to CBX and baseline salivary cortisol, adjusting for sex, age, BMI, and baseline depression scores. We utilized the HAMD17 and Montgomery-Asberg Depression Rating Scale (MADRS). Results: Coefficient of determination (R2) for week 8 MADRS and HAMD17 scores were 0.907 and 0.624 (both p-value

Objective: Endometriosis is an estrogen-dependent chronic inflammatory disease in women of reproductive age. A review of the literature revealed that cytokines and inflammatory factors are associated with endometriosis-associated infertility. Interleukin 33 (IL-33) is a strong inducer of other pro-inflammatory cytokines. Vascular cell adhesion molecule-1 (VCAM-1) plays a central role in recruiting inflammatory cells, whose expression facilitates leukocyte adhesion and is rapidly induced by pro-inflammatory cytokines. Many studies have indicated that VCAM-1 expression is high in endometriosis; however, whether the expression of VCAM-1 is related to IL-33 is unclear., Materials and Methods: Human ovarian endometriotic stromal cells (hOVEN-SCs) were treated with IL-33 to enable investigation of cell characterization, gene and protein expression, and signal pathways. Proliferation potential was measured using an MTT assay. Gene expression was analyzed using reverse transcription-polymerase chain reaction. Protein expression assay was performed using western blot analysis., Results: This study investigated the effects of IL-33 on VCAM-1 and COX-2 expression in hOVEN-SCs. First, the results revealed that the IL-33/ST2/mitogen-activated protein kinase (MAPK) signaling pathway could increase the expression of VCAM-1 and COX-2 in hOVEN-SCs. Second, we discovered that COX-2 expression was essential for IL-33-induced VCAM-1 expression because the effects could be negated through NS398, a selective COX-2 inhibitor. Finally, treatment of IL-33-treated hOVEN-SCs with celecoxib significantly and dose-responsively decreased VCAM-1 expression., Conclusion: Taken together, these results indicate that IL-33 can upregulate VCAM-1 expression in hOVEN-SCs through the IL-33/ST2/MAPK/COX-2 signaling pathway and thereby contribute to endometriosis., Competing Interests: Conflict of interest The authors have no conflicts of interest relevant to this article., (Copyright © 2024. Published by Elsevier B.V.)

Osteoarthritis is a long-term degenerative condition of the joints that is characterized by the breakdown of cartilage and inflammation of the synovial membrane. The presence of an inflammatory microenvironment and the degradation of the extracellular matrix produced by chondrocytes leads to the aggravation of cartilage injury, hindering the treatment of osteoarthritis. A promising approach to address this issue is to apply a combined strategy that is sensitive to the specific conditions in osteoarthritic joints and possesses properties that can reduce inflammation and promote cartilage healing. Here, inspired by the structure of chocolate-covered peanuts, we developed an injectable, environment-responsive bilayer hydrogel microsphere using microfluidics technology. The microsphere applied chondroitin sulfate methacryloyl (ChsMA) as its core and was coated with a methacryloyl gelatin (GelMA) shell that was loaded with celecoxib (CLX) liposomes (ChsMA+CLX@Lipo@GelMA). CLX was released from the liposomes when the GelMA shell rapidly degraded in response to the osteoarthritic microenvironment and suppressed the generation of inflammatory agents, demonstrating a beneficial impact of the outer shell in reducing inflammation. While the inner methacryloyl microsphere core degraded, chondroitin sulfate was released to promote chondrocyte anabolism and facilitate cartilage repair. Thus, the synthesized bilayer hydrogel microspheres hold great potential for treating osteoarthritis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Due to the large cost of joint replacement for surgical treatment of knee osteoarthritis, there are many complications in elderly patients, and there are many contraindications to surgery, and conservative treatment is still based on drugs. To further evaluate the efficacy and safety of sodium hyaluronate combined with celecoxib for the treatment of osteoarthritis of the knee. In total, 202 studies were screened, with a final selection of 9 RCTs involving 2339 participants; of these, 9 RCTs were included in the final meta-analysis. Treatment group reduces VAS (SMD = -1.61; 95 % CI [-2.25, -0.98]; I 2  = 95 %; P < 0.00001) and adverse reactions (OR = 0.45; 95 % CI [0.22,0.94]; I 2  = 0 %; P < 0.33); Meanwhile, improving Lysholm knee scores (SMD = 0.19; 95 % CI [-0.06, -0.44]; I 2  = 76 %; P = 0.0004) and Clinical efficiency (OR = 0.31; 95 % CI [0.19,0.50]; I 2  = 0 %; P < 0.00001). All indicators were superior to the control group. Our primary findings suggest that KOA treatment with celecoxib combined with sodium hyaluronate reduces VAS, while improving Lysholm scores and Clinical efficiency. In addition, we found that celecoxib combined with sodium hyaluronate treatment had fewer adverse effects than the control group, indicating that the combination is safe and effective in the treatment of KOA., Competing Interests: Declaration of competing interest None of the authors have any competing interests., (Copyright © 2024 Asian Surgical Association and Taiwan Robotic Surgery Association. Published by Elsevier B.V. All rights reserved.)

Non-steroidal anti-inflammatory drugs (NSAIDs) have been shown to impair bone healing. We previously reported that in colon cancer cells, celecoxib, a COX-2-selective NSAID, inhibited the canonical Wnt/β-catenin signaling pathway. Since this pathway also plays an important role in osteoblast growth and differentiation, we examined the effect of celecoxib on maturation of osteoblast-like cell line MC3T3-E1. Celecoxib induced degradation of transcription factor 7-like 2, a key transcription factor of the canonical Wnt pathway. Subsequently, we analyzed the effect of celecoxib on two osteoblast differentiation markers; runt-related transcription factor 2 (RUNX2) and alkaline phosphatase (ALP), both of which are the products of the canonical Wnt pathway target genes. Celecoxib inhibited the expression of both RUNX2 and ALP by suppressing their promoter activity. Consistent with these observations, celecoxib also strongly inhibited osteoblast-mediated mineralization. These results suggest that celecoxib inhibits osteoblast maturation by suppressing Wnt target genes, and this could be the mechanism that NSAIDs inhibit bone formation and fracture healing.

For chemical modification, p-aminobenzoic acid was incorporated into chitosan Schiff base (ACsSB) and chitosan (ACs). Two ACs-based CuO nanoparticles composites; ACs/CuONPs-1 % and ACs/CuONPs-5 %, were also synthesized. Their structures were emphasized utilizing several analytical techniques; elemental analysis, FTIR, 1 H NMR, XRD, SEM, EDX and TEM. Compared with standard cyclooxygenase (COX) inhibitor, Celecoxib, the prepared biomaterials showed in vitro selective inhibitory effectiveness against COX-2 enzyme that could be sorted, according to their MIC values that produce 50 % inhibition of COX-2 enzyme activity, as follows: Celecoxib (0.28 μg/mL) > ACs/CuONPs-5 % (4.1 μg/mL) > ACs/CuONPs-1 % (14.8 μg/mL) > ACs (38.5 μg/mL) > ACsSB (58.9 μg/mL) > chitosan (>125 μg/mL). Further, ACs/CuONPs-5 % has more in vitro inhibition efficiency towards Helicobacter pylori (H. pylori) than the other prepared biomaterials. Interestingly, the MIC value of 100 % growth inhibition of H. pylori for ACs/CuONP-5 % is equal to that of drug Clarithromycin (1.95 μg/mL). Thus, ACs/CuONPs-5 % has a promising potential as anti-H. pylori and selective anti-inflammatory agent. ACs/CuONPs-5 % is safe on the human gastric normal cells (GES-1). Therefore, amalgamation of both p-aminobenzoic acid and CuONPs into chitosan extremely promoted its anti-inflammatory and anti-H. pylori activity. This is a promising approach to achieve methods successful to compete the conventional antibiotics., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The pathogenesis of venous malformation needs to be clarified and, although various treatment modalities are available, an optimal treatment has not been established. A 19-year-old girl presented with venous malformation of the rectosigmoid colon. She showed severe anemia due to rectal hemorrhage; her hemoglobin (Hb) level was 4.9 g/dl. A large venous malformation connected to an internal hemorrhoid was evident by endoscopy. Neither surgical resection nor sclerotherapy was indicated because of high blood flow in the venous malformation. Octreotide was initiated. However, the bleeding continued and she required persistent blood transfusions. We started propranolol in the 5th week of hospitalization. Celecoxib, which was started for her knee pain was found to be predictably effective, and we administered it regularly. Propranolol and celecoxib were gradually increased, the rectal bleeding decreased, and her anemia improved. Five months after the initiation of propranolol and celecoxib, she could maintain Hb at 15 g/dl without transfusion. Propranolol can contract blood vessels and celecoxib can inhibit vascular endothelial growth factor (VEGF) to result in anti-angiogenesis. This combination therapy might be useful for controlling intractable venous malformation.

Recombinant human prostaglandin endoperoxide H synthase-1 (huPGHS-1) was characterized. huPGHS-1 has a single high-affinity heme binding site per dimer and exhibits maximal cyclooxygenase (COX) activity with one heme per dimer. Thus, huPGHS-1 functions as a conformational heterodimer having a catalytic monomer (Ecat) with a bound heme and an allosteric monomer (Eallo) lacking heme. The enzyme is modestly inhibited by common FAs including palmitic, stearic, and oleic acids that are not COX substrates. Studies of arachidonic acid (AA) substrate turnover at high enzyme-to-substrate ratios indicate that nonsubstrate FAs bind the COX site of Eallo to modulate the properties of Ecat. Nonsubstrate FAs slightly inhibit huPGHS-1 but stimulate huPGHS-2, thereby augmenting AA oxygenation by PGHS-2 relative to PGHS-1. Nonsubstrate FAs potentiate the inhibition of huPGHS-1 activity by time-dependent COX inhibitors, including aspirin, all of which bind Ecat. Surprisingly, preincubating huPGHS-1 with nonsubstrate FAs in combination with ibuprofen, which by itself is a time-independent inhibitor, causes a short-lived, time-dependent inhibition of huPGHS-1. Thus, in general, having a FA bound to Eallo stabilizes time-dependently inhibited conformations of Ecat. We speculate that having an FA bound to Eallo also stabilizes Ecat conformers during catalysis, enabling half of sites of COX activity.

Background. Cyclooxygenase-2 (COX-2) enzyme over expression is reported in many human HCC cell line studies and is linked to tumor cell resistance to chemotherapy-induced apoptosis. We hypothesized that adding a COX-2 inhibitor would improve the therapeutic benefits in patients with HCC. COX-2 is often increased and involved in drug resistance and poor prognosis.Method. Between January 2001 and December 2007, 15 patients with MDR-positive-HCC from 34 HCC patients based on tissue and serum liver of glypican-3 and fitting the preset eligibility criteria, were treated with a combination regimen with intravenous infusion of (5-FU) 750 mg once per week, 100mg/day cyclophosphamide (Endoxan) and 400 mg/day celecoxib taken orally in divided doses, while the rest of the patients received only 5-FU and Endoxan. Twenty-one patients (62%) had liver disease associated with hepatitis C virus (HCV) and 5 patients with hepatitis B virus (62%). Results. We found that celecoxib reduced P-glycoprotein with activation of caspase-3 and marked regression of tumor sizes. Sera angiogenic factors (VEGF & bFGF) levels measurement in HCC patients indicated that, the sera levels of both angiogenic factors were reduced significantly (p < 0.05) after treatment. Based on the tumor markers AFP & Glypican-3, 11 of the patients had a PR (11/15), including 3 patients who had normalization of AFP, and four patients had CR (4/15).Conclusions. These data suggest that the combination of 5-FU, Endoxan and Celecoxib is highly effective palliative regimen for patients with HCC with good performance status (score ≤ 3). The study suggests a framework for Celecoxib-based combination treatment of HCC.

A new series of 2,3-diaryl-1,3thiazolidin-4-one derivatives was designed, synthesized, and evaluated for their cytotoxicity and COXs inhibitory activities. Among these derivatives, compounds 4 k and 4j exhibited the highest inhibitory activities against COX-2 at IC 50 values of 0.05 and 0.06 μM, respectively. Compounds 4a, 4b, 4e, 4 g, 4j, 4 k, 5b, and 6b, which exhibited the highest inhibition% against COX-2, were evaluated for their anti-inflammatory activity in rats. Results showed 41.08-82.00 % inhibition of paw edema thickness by the test compounds compared to celecoxib (inhibition% = 89.51 %). In addition, compounds 4b, 4j, 4 k, and 6b exhibited better GIT safety profiles compared to celecoxib and indomethacin. The four compounds were also evaluated for their antioxidant activity. The results revealed the highest antioxidant activity for 4j (IC 50  = 45.27 μM) comparable to torolox (IC 50  = 62.03 μM). The antiproliferative activity of the new compounds was evaluated against HePG-2, HCT-116, MCF-7, and PC-3 cancer cell lines. The results showed the highest cytotoxicity for compounds 4b, 4j, 4 k, and 6b (IC 50  = 2.31-27.19 μM), with 4j being the most potent. Mechanistic studies revealed the ability of 4j and 4 k by inducing marked apoptosis and cell cycle arrest at the G1 phase in HePG-2 cancer cells. These biological results may also suggest a role for COX-2 inhibition in the antiproliferative activity of these compounds. The results of the molecular docking study for 4 k and 4j into the active site of COX-2 revealed good fitting and correlation with the results of the in vitro COX‑2 inhibition assay., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: Prostaglandin E2 (PGE2), a product of cyclooxygenase (COX) pathway of arachidonic acid, exerts inhibitory impacts on dendritic cell (DC) activity to repress anti-tumor immune responses. Therefore, targeting COX during DC vaccine generation may enhance DC-mediated antitumor responses. We aimed to investigate the impacts of DC vaccine treated with celecoxib (CXB), a selective COX2 inhibitor, on some T cell-related parameters., Materials and Methods: Breast cancer (BC) was induced in BALB/c mice, and then they received DC vaccine treated with lipopolysaccharide (LPS-mDCs), LPS with a 5 ​μM dose of CXB (LPS/CXB5-mDCs) and LPS with a 10 ​μM dose of CXB (LPS/CXB10-mDCs). The frequency of splenic Th1 and Treg cells and amounts of IFN-γ, IL-12 and TGF-β production by splenocytes, as well as, the expression of Granzyme-B, T-bet and FOXP3 in tumors were determined using flow cytometry, ELISA, and real-time PCR, respectively., Results: Compared with untreated tumor group (T-control), treatment with LPS/CXB5-mDCs and LPS/CXB10-mDCs decreased tumor growth (P ​= ​0.009 and P ​< ​0.0001), escalated survival rate (P ​= ​0.002), increased the frequency of splenic Th1 cells (P ​= ​0.0872, and P ​= ​0.0155), increased the IFN-γ (P ​= ​0.0003 and P ​= ​0.0061) and IL-12 (P ​= ​0.001 and P ​= ​0.0009) production by splenocytes, upregulated T-bet (P ​= ​0.062 and P ​< ​0.0001) and Granzyme-B (P ​= ​0.0448 and P ​= ​0.4485), whereas decreased the number of Treg cells (P ​= ​0.0014, and P ​= ​0.0219), reduced the amounts of TGF-β production by splenocytes (P ​= ​0.0535 and P ​= ​0.0169), and reduced the expression of FOXP3 (P ​= ​0.0006 and P ​= ​0.0057) in comparison with T-control group., Conclusions: Our findings show that LPS/CXB-treated DC vaccine potently modulated antitumor immune responses in a mouse BC model., Competing Interests: Declaration of competing interest The authors declare no conflict of interests., (Copyright © 2023 Medical University of Bialystok. Published by Elsevier B.V. All rights reserved.)

Recent evidences suggest key roles of abnormal neurogenesis and astrogliosis in the pathogenesis of epilepsy. Alterations in the microenvironment of the stem cell, such as microglial activation and cyclooxygenase-2 induction may cause ectopic neurogenesis or astrogliosis. Here, we examined if inflammatory blockade with celecoxib, a selective cyclooxygenase-2 inhibitor, could modulate the altered microenvironment in the epileptic rat brain. Celecoxib attenuated the likelihood of developing spontaneous recurrent seizures after pilocarpine-induced prolonged seizure. During the latent period, celecoxib prevented neuronal death and microglia activation in the hilus and CA1 and inhibited the generation of ectopic granule cells in the hilus and new glia in CA1. The direct inhibition of precursor cells by celecoxib was further demonstrated in human neural stem cells culture. These findings raise the evidence of COX-2 induction to act importantly on epileptogenesis and suggest a potential therapeutic role for COX-2 inhibitors in chronic epilepsy.