NLRP1 is predominantly overexpressed in breast cancer tissue, and the evaluated activation of NLRP1 inflammasome is associated with tumor growth, angiogenesis, and metastasis. Therefore, targeting NLRP1 activation could be a crucial strategy in anticancer therapy. In this study, we investigated the hypothesis that NLRP1 pathway may contribute to the cytotoxic effects of celecoxib and nimesulide in MDA-MB-231 cells. First of all, IC50 values and inhibitory effects on the colony-forming ability of drugs were evaluated in cells. Then, the alterations in the expression levels of NLRP1 inflammasome components induced by drugs were investigated. Subsequently, the release of inflammatory cytokine IL-1β and the activity of caspase-1 in drug-treated cells were measured. According to our results, celecoxib and nimesulide selectively inhibited the viability of MDA-MB-231 cells. These drugs remarkably inhibited the colony-forming ability of cells. The expression levels of NLRP1 inflammasome components decreased in celecoxib-treated cells, accompanied by decreased caspase-1 activity and IL-1β release. In contrast, nimesulide treatment led to the upregulation of the related protein expressions with unchanged caspase-1 activity and increased IL-1β secretion. Our results indicated that the NLRP1 inflammasome pathway might contribute to the antiproliferative effects of celecoxib in MDA-MB-231 cells but is not a crucial mechanism for nimesulide.

BACKGROUND: Fu\'s subcutaneous needling (FSN) is a new type of acupuncture that uses subcutaneous tissue to oscillate from side to side to improve muscle pathology status and can be effective in treating Knee osteoarthritis. Nonetheless, whether the clinical effect is similar to that of most commonly used drugs is unclear. Thus, this study aims to determine the pain-relieving effect and improvement in the joint function of the FSN therapy by comparing it with that of a positive control drug (celecoxib). Furthermore, this clinical trial also aims to evaluate the effect of FSN on gait and lower limb muscle flexibility, which can further explore the scientific mechanisms of the FSN therapy.
METHODS: This study is a randomized, parallel-controlled, single-center prospective clinical study that includes 60 participants, with an FSN group (n = 30) and a drug group (n = 30). The Fu\'s subcutaneous needling (FSN) group undergo the FSN therapy 3 times a week for 2 weeks, while the drug group receives 0.2 g/day oral celecoxib for 2 weeks, with a follow-up period of 4 weeks after the completion of treatment. The primary outcome is the difference in the visual analog scale score after 2 weeks of treatment compared with baseline. The Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index, joint active range of motion test, three-dimensional gait analysis, and shear wave elastic imaging technology analysis in lower limb muscles are also performed to demonstrate clinical efficacy.
BACKGROUND: The trial is performed following the Declaration of Helsinki. The study protocol and consent form have been approved by the Ethics Committee of Guangdong Provincial Hospital of Chinese Medicine. All patients will give informed consent before participation and the trial is initiated after approval. The results of this trial will be disseminated through publication in peer-reviewed journals.
BACKGROUND: NCT06328153.

BACKGROUND: Epilepsy poses a significant global health challenge, particularly in regions with limited financial resources hindering access to treatment. Recent research highlights neuroinflammation, particularly involving cyclooxygenase-2 (COX-2) pathways, as a promising avenue for epilepsy management.
METHODS: This study aimed to develop a Cyclooxygenase-2 inhibitor with potential anticonvulsant properties. A promising drug candidate was identified and chemically linked with phospholipids through docking analyses. The activation of this prodrug was assessed using phospholipase A2 (PLA2)-mediated hydrolysis studies. The conjugate\'s confirmation and cytotoxicity were evaluated using Fourier Transform Infrared Spectroscopy (FT-IR), Differential Scanning Calorimetry (DSC), and Sulphoramide B (SRB) assays.
RESULTS: Docking studies revealed that the Celecoxib-Phospholipid conjugate exhibited a superior affinity for PLA2 compared to other drug-phospholipid conjugates. FT-IR spectroscopy confirmed the successful synthesis of the conjugate, while DSC analysis confirmed its purity and formation. PLA2-mediated hydrolysis experiments demonstrated selective activation of the prodrug depending on PLA2 concentration. SRB experiments indicated dose-dependent cytotoxic effects of Celecoxib, phospholipid non-toxicity, and efficient celecoxib-phospholipid conjugation.
CONCLUSIONS: This study successfully developed a Celecoxib-phospholipid conjugate with potential anticonvulsant properties. The prodrug\'s specific activation and cytotoxicity profile makes it a promising therapeutic candidate. Further investigation into underlying mechanisms and in vivo studies is necessary to assess its translational potential fully.

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.

BACKGROUND: Celecoxib, an anti-inflammatory drug, combined therapies using antimicrobials and immune modulator drugs are being studied.
OBJECTIVE: To assess whether Celecoxib has direct in vitro antifungal effect against the Paracoccidioides brasiliensis, the causative agent of Paracoccidioidomycosis-(PCM) and also if it improves the in vivo activity of neutrophils-(PMN) in an experimental murine subcutaneous-(air pouch) model of the disease.
METHODS: The antifungal activity of Celecoxib(6 mg/mL) on P. brasiliensis-(Pb18) was evaluated using the microdilution technique. Splenocytes co-cultured with Pb18 and treated with Celecoxib(6 mg/mL) were co-cultured for 24, 48 and 72-hours. Swiss mice were inoculated with Pb18 and treated with Celecoxib(6 mg/kg) in the subcutaneous air pouch. Neutrophils were collected from the air pouch. Mitochondrial activity, reactive oxygen production, catalase, peroxidase, cytokines and chemokines, nitrogen species, total protein, microbicidal activity of PMNs and viable Pb18 cells numbers were analyzed.
RESULTS: Celecoxib had no cytotoxic effect on splenocytes co-cultured with Pb18, but had a marked direct antifungal effect, inhibiting fungal growth both in vitro and in vivo. Celecoxib interaction with immune system cells in the air pouch, it leads to activation of PMNs, as confirmed by several parameters (mitochondrial activity, reactive oxygen species, peroxidase, KC and IL-6 increase, killing constant and phagocytosis). Celecoxib was able to reduce IL-4, IL-10 and IL-12 cytokine production. The number of recovered viable Pb18 decreased dramatically.
CONCLUSIONS: This is the first report of the direct antifungal activity of Celecoxib against P. brasiliensis. The use of Celecoxib opens a new possibility for future treatment of PCM.

BACKGROUND: In the randomized, phase 3, SUSA-301 trial, celecoxib-tramadol co-crystal (CTC) provided significantly greater analgesia compared with celecoxib, tramadol, or placebo in adults with acute, moderate-to-severe, postoperative pain. This post hoc, secondary analysis further evaluated the use of rescue medication and the incidence of treatment-emergent adverse events (TEAEs).
METHODS: Patients (N = 637) were randomized 2:2:2:1 to receive oral CTC 200 mg twice daily (BID; n = 184), tramadol 50 mg four times daily (QID; n = 183), celecoxib 100 mg BID (n = 181), or placebo QID (n = 89). Post hoc analyses were conducted on the use of rescue medications up to 4 and 48 h post-study drug dose, stratified by baseline pain intensity (moderate/severe), and on the incidence of TEAEs, stratified by rescue medication use.
RESULTS: A significantly lower proportion of patients received any rescue medication within 4 h post-study dose with CTC (49.5%) versus tramadol (61.7%, p = 0.0178), celecoxib (65.2%, p = 0.0024), and placebo (75.3%, p = 0.0001); this was also seen for oxycodone use. Fewer patients in the CTC group received ≥3 doses of rescue medication compared with the other groups, irrespective of baseline pain intensity. In patients who did not receive opioid rescue medication, CTC was associated with a lower incidence of nausea and vomiting TEAEs versus tramadol alone. In patients who received rescue oxycodone, the incidence of nausea was similar in the CTC and tramadol groups, and higher versus celecoxib and placebo.
CONCLUSIONS: Celecoxib-tramadol co-crystal was associated with reduced rescue medication use and an acceptable tolerability profile compared with tramadol or celecoxib alone in adults with acute, moderate-to-severe, postoperative pain.

OBJECTIVE: The aim of this study was to investigate whether multimodal analgesia can decrease postoperative opioid usage in patients undergoing shoulder arthroscopy.
METHODS: Patients diagnosed with subacromial impingement syndrome who underwent acromioplasty at our institution between October 2022 and November 2023 were retrospectively analyzed. Patients were divided into an observation group and a control group based on postoperative pain management methods. The control group received intravenous self-controlled electronic analgesia (sufentanil injection 1 μg/kg + butorphanol injection 4 mg + 0.9% NaCl injection to 100 mL), while the observation group received multimodal analgesia (ropivacaine subacromial pump 3 mL/h, combined with oral celecoxib and acetaminophen). Visual Analog Scale (VAS) scores were recorded preoperatively and at various postoperative time points, and opioid usage, length of hospital stay, and analgesia-related complications within 1 week postoperatively were compared between groups. The 36-item Short Form Health Survey (SF-36) scores and the Constant-Murley score (CMS), were also assessed 1 day and 1 week after treatment.
RESULTS: One hundred thirty-two patients were included in the study, 66 in the observation group and 66 in the control group. In the control group, there were 46 males and 20 females, with a mean age of 55.47 ± 11.42 years and in the observation group 44 males and 22 females, with a mean age of 56.13 ± 12.19 years The observation group consistently reported significantly lower pain intensity compared to the control group at 8 h (T1), 24 (T2), and 48 h (T3) after surgery (p < 0.05). Additionally, the observation group exhibited significantly lower opioid usage and complication rates compared to the control group (p < 0.05). SF-36 scores and CMS scores were significantly higher in the observation group 1 week after treatment compared to the control group (p < 0.05).
CONCLUSIONS: Following shoulder arthroscopy, multimodal analgesia effectively reduces opioid consumption, lowers complication rates, and provides effective short-term pain relief. This approach carries significant implications for improving patient outcomes.

OBJECTIVE: Tonsillectomy and adenoidectomy are common surgical procedures that cause persistent pain, bleeding, and functional limitations. We aimed to investigate the efficacy of celecoxib compared with a placebo for managing post-tonsillectomy or adenoidectomy pain and other adverse events.
METHODS: Systematic review and meta-analysis.
METHODS: We conducted a systematic literature search in the PubMed, Cochrane, and Google Scholar databases from inception until July 2023. Dichotomous outcomes have been reported as risk ratios (RR) while continuous outcomes were reported using mean differences (MD). A funnel plot was drawn to investigate publication bias.
RESULTS: From 1394 records identified, 6 randomised double-blind trials comprising 591 participants undergoing tonsillectomy and/or adenoidectomy were eligible for inclusion. A high dose (400 mg) of celecoxib was effective in decreasing the pain score for \'worst pain\' after the procedure (MD: -10.98, [95% CI: -11.53, -10.42], p < .01, I2 = 0%) while a low dose (200 mg) was not significantly effective (p = 0.31). For managing other outcomes such as vomiting (RR: 1.37 [95% CI: 0.69, 2.68], p = 0.37, I2 = 67%), diarrhoea (RR: 1.41, [95% CI: 0.75, 2.64], p = .29, I2 = 42%), dizziness/drowsiness (RR: 0.90, [95% CI: 0.71, 1.15], p = .48, I2 = 0%), functional recovery time (p = .74), and headache (p = .91), there was no significant difference between the group on celecoxib and the placebo group regardless of dosage. Finally, there was no significant difference (RR: 1.02, [95% CI: 0.91, 1.15], p = .69, I2 = 0%) in the effect of the intervention on minimum bleeding, moderate bleeding, and profuse bleeding.
CONCLUSIONS: This meta-analysis provides robust evidence pooled from high-quality trials and raises questions about the efficacy of celecoxib for tonsillectomy and/or adenoidectomy, challenging existing perceptions.

BACKGROUND: Knee osteoarthritis (KOA) is one of the most common osteoarthritis, imposing substantial economic and medical burdens on both individuals and society. In China, Tuina has been selected as a complementary and alternative therapy to relieve knee pain and dysfunction symptoms. However, the current evidence is insufficient to support the efficacy of Tuina therapy in addressing knee pain and improving physical function. The trial aims to compare the effectiveness of Tuina with celecoxib, which is considered as the standard treatment, and to assess its potential as an alternative therapy through changes in outcome measures.
METHODS: A total of 360 KOA patients aged between 40 and 70 years and classified as Kellgren and Lawrence grades I-II will be recruited from eight subcentral hospitals. The participants will be randomly assigned to either the treatment group (Tuina, Biw) or the control group (celecoxib, Qd), with both groups undergoing a 4-week intervention phase followed by an 8-week follow-up phase. The primary outcome is the change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale at week 4 compared with baseline. Secondary outcomes including WOMAC stiffness and function subscales, WOMAC total score, 36-item Short-Form Health Survey, Timed Up and Go test, Short Physical Performance Battery, gait analysis parameters and pain medication records will be assessed at weeks 4, 8 and 12. Any adverse events that occur during the trial will be promptly recorded.
BACKGROUND: This study has been approved by the Ethics Committee of Shanghai Municipal Hospital of Traditional Chinese Medicine (2023SHL-KY-16-01, 2023SHL-KY-16-02). Written informed consent will be obtained from all participants. Study results will be disseminated through peer-reviewed journals and conference presentations.
BACKGROUND: ChiCTR2300069416.

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.