Nonsteroidal Research Articles

Exploring COX-Independent Pathways: A Novel Approach for Meloxicam and Other NSAIDs in Cancer and Cardiovascular Disease Treatment

As a fundamental process of innate immunity, inflammation is associated with the pathologic process of various diseases and constitutes a prevalent risk factor for both cancer and cardiovascular disease (CVD). Studies have indicated that several non-steroidal anti-inflammatory drugs (NSAIDs), including Meloxicam, may prevent tumorigenesis, reduce the risk of carcinogenesis, improve the efficacy of anticancer therapies, and reduce the risk of CVD, in addition to controlling the body’s inflammatory imbalances. Traditionally, most NSAIDs work by inhibiting cyclooxygenase (COX) activity, thereby blocking the synthesis of prostaglandins (PGs), which play a role in inflammation, cancer, and various cardiovascular conditions. However, long-term COX inhibition and reduced PGs synthesis can result in serious side effects. Recent studies have increasingly shown that some selective COX-2 inhibitors and NSAIDs, such as Meloxicam, may exert effects beyond COX inhibition. This emerging understanding prompts a re-evaluation of the mechanisms by which NSAIDs operate, suggesting that their benefits in cancer and CVD treatment may not solely depend on COX targeting. In this review, we will explore the potential COX-independent mechanisms of Meloxicam and other NSAIDs in addressing oncology and cardiovascular health.

The Efficacy of Non-Steroidal Anti-Inflammatory Drugs in Athletes for Injury Management, Training Response, and Athletic Performance: A Systematic Review

(1) Background: The purpose of this systematic review is to investigate the prevalent use of non-steroidal anti-inflammatory drugs (NSAIDs) in athletes and to comprehensively review the effectiveness and the results of these medications as it relates to injury management, training response, and overall sport performance. (2) Methods: An electronic literature search was performed in accordance with the recommendations and guidelines of the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) protocol. A total of 7 randomized controlled studies met the review’s specific inclusion criteria from the 2250 studies initially identified within the PubMed database. (3) Results: In total, 346 adult female and male athletes from a variety of sporting activities and fitness levels were observed, of which 175 athletes were treated with either oral, topical, or local muscular infusion of an NSAID. Depending on study design, the outcomes focused on results obtained through physical exam findings, questionnaires, various performance metrics, and direct tissue sampling from microdialysis or biopsies. Across the 7 total studies, 2 articles focused on injured athletes and their varying pain responses with NSAIDs; 2 studies assessed the limited impact of NSAIDs on performance; and 3 articles revealed the use of NSAIDs correlating to no increases in either collagen synthesis or satellite cell activity after exercise. (4) Conclusions: The systematic review affirmed that NSAIDs can be effective for managing acute pain. However, their value appears to diminish when treating chronic injuries or if NSAIDs are expected to improve performance or have other ergogenic effects in athletes, as the aggregate data did not support such benefits. (5) Practical applications: NSAIDs can be beneficial for athletes in the right situation, but the fact that there are risks and possible disadvantageous results with their use highlights the importance of promoting appropriate expectations and the judicious use of these medications with the athletic community.

Case series: Cervical far-lateral and combined cervical far lateral/ foraminal intervertebral disk extrusions in 10 dogs

Far-lateral intervertebral disk extrusions (IVDEs) have been reported infrequently in dogs in veterinary literature, mostly affecting the caudal lumbar intervertebral disks. We describe the clinical findings, computed tomography (CT) and magnetic resonance imaging (MRI) findings, treatment, and outcome in 10 dogs with cervical far-lateral IVDEs. Patient databases of 3 small animal hospitals and 1 veterinary teleradiology service were retrospectively searched for patients in which imaging studies (CT or MRI) identified the presence of intervertebral disk material outside the limits of the intervertebral foramen. Presenting clinical signs included: episodic signs of cervical pain (6/10, 30%), persistent signs of cervical pain (3/10, 50%), nerve root signature or lameness (5/10, 50%), and abnormal cervical posture only (excluding nerve root signature) (1/10, 10%). Affected IVD spaces (for 11 IVDEs in 10 dogs) included: C3-4 (6/11, 55%), C5-6 (3/11, 27%), and C2-3 (2/11, 18%). Nerve root signature was not reported for C2-3 IVDEs. All cases were managed medically (without surgery). The top 3 used medications were gabapentinoids (10/10, 100%), non-steroidal anti-inflammatory drugs (NSAIDs) (10/10, 100%), and paracetamol (3/10, 30%). Median treatment duration was 25 days (range 10–84). Short-term outcome (<3 months) was recorded in 9/10 (90%) cases. Resolution of clinical signs was reported in 7/9 (78%) cases. Long-term follow-up was available for 6/10 (60%) cases (median 11.5 months, range 5.5–30 months); 5/6 (83%) showed resolution of clinical signs. Recurrence of clinical signs was reported in 1 case (9 months later), managed medically again, with successful outcome. In conclusion, cervical far-lateral disk extrusions are a rare clinical entity in dogs, but can result in severe, persistent or episodic, pain. Medical management is associated with a positive short- and long-term outcome in most cases.

Establishment of a human 3D in vitro liver-bone model as a potential system for drug toxicity screening.

Drug toxicity is an important cause of chronic liver damage, which in the long term can lead to impaired bone homeostasis through an imbalance in the liver-bone axis. For instance, non-steroidal anti-inflammatory drugs (e.g., diclofenac), which are commonly used to control pain during orthopaedic interventions, are known to reduce bone quality and are the most prevalent causes of drug-induced liver damage. Therefore, we used human cell lines to produce a stable, reproducible, and reliable in vitro liver-bone co-culture model, which mimics the impaired bone homeostasis seen after diclofenac intake in vivo. To provide the best cell culture conditions for the two systems, we tested the effects of supplements contained in liver and bone cell culture medium on liver and bone cell lines, respectively. Additionally, different ratios of culture medium combinations on bone cell scaffolds and liver spheroids' viability and function were also analysed. Then, liver spheroids and bone scaffolds were daily exposed to 3-6µM diclofenac alone or in co-culture to compare and evaluate its effect on the liver and bone system. Our results demonstrated that a 50:50 liver:bone medium combination maintains the function of liver spheroids and bone scaffolds for up to 21days. Osteoclast-like cell activity was significantly upregulated after chronic exposure to diclofenac only in bone scaffolds co-cultured with liver spheroids. Consequently, the mineral content and stiffness of bone scaffolds treated with diclofenac in co-culture with liver spheroids were significantly reduced. Interestingly, our results show that the increase in osteoclastic activity in the system is not related to the main product of diclofenac metabolism. However, osteoclast activation correlated with the increase in oxidative stress and inflammation associated with chronic diclofenac exposure. In summary, we established a long-term stable liver-bone system that represents the interaction between the two organs, meanwhile, it is also an outstanding model for studying the toxicity of drugs on bone homeostasis.

Gastric-like (pseudopyloric and pseudofoveolar) metaplasia and Paneth cell hyperplasia-neglected histological features of chronic ileal inflammation.

Architectural distortion and basal plasmacytosis are the most widely recognized histologic features of chronic ileal inflammation. However, these features might be difficult to assess in small, poorly oriented, or superficial biopsies. Additional features of chronic mucosal damage, including pseudopyloric or pseudofoveolar metaplasia and Paneth cell hyperplasia, have been less commonly reported, and their broader appreciation could facilitate the diagnosis of chronic ileal inflammatory conditions. The prevalence of gastric-like (pseudopyloric and pseudofoveolar) metaplasia and Paneth cell hyperplasia was evaluated in 102 ileal biopsies obtained from patients with Crohn's disease (n = 47), ulcerative colitis with endoscopically normal ileum (n = 20) or with backwash ileitis (n = 20), and nonsteroidal anti-inflammatory drugs- (NSAIDs-) induced ileitis (n = 15). Gastric-like metaplasia was identified in 23% of CD and 13% of NSAID-induced ileitis cases, whereas it was absent among all ulcerative colitis cases. Pseudopyloric metaplasia, pseudofoveolar metaplasia, or a combination of both was documented in 13%, 2%, and 9% of Crohn's disease cases, respectively. NSAID-associated cases showed only pseudopyloric metaplasia. Paneth cell hyperplasia was detected in 43% of Crohn's disease cases, 13% of NSAID-induced ileitis cases, and 5% of backwash ileitis cases. Accordingly, pseudofoveolar metaplasia, pseudopyloric metaplasia, and Paneth cell hyperplasia are not uncommon in conditions causing chronic ileal inflammation. They are most frequently detected in Crohn's disease, but may also be present in NSAID-induced ileitis, whereas they are significantly less common in backwash ileitis and absent in normal ileum. Given the surface localization of pseudofoveolar metaplasia, its identification can be particularly helpful when dealing with poorly oriented or superficial samples.

Use of Transverse Abdominis block for Post Operative pain management in Patients undergoing Emergency Cesarean Sections : a prospective study

INTRODUCTION Postoperative pain management is an essential aspect of perioperative care for patients undergoing emergency Cesarean sections. Adequate pain control not only improves patient comfort and satisfaction but also facilitates early mobilization, reduces the risk of complications, and shortens hospital stays. Transverse abdominis plane (TAP) block is a well-established technique for providing analgesia to the anterior abdominal wall, which can significantly reduce postoperative pain. In recent years, ultrasound guidance has been increasingly used to improve the accuracy and safety of TAP block. This research article aims to review the use of ultrasound-guided TAP block for postoperative analgesia in patients undergoing emergency Cesarean Sections. Methodology : A total of 60 patients who underwent Emergency Cesarean Sections were included in the study. All received bilateral US-guided TAP blocks with either ropivacaine 0.5% 20 ml on each side i. e. 40 ml total or saline. All participants received a spinal anaesthetic with bupivacaine, followed by postoperative acetaminophen, non-steroidal anti-inflammatory drugs, and patient-controlled i.v. tramadol . Each patient was assessed 24 h after delivery for PCA Tramadol usage, average pain score, nausea, vomiting, itch and duration of hospital stay. Results and Conclusion Out of the total 60 patients , 30 were in the study group and 30 in placebo group. Total PCA Tramadol use in 24 h was reduced in the study group compared with the placebo group ( P<0.05). The active group reported improved satisfaction with their pain relief measured by visual analogue scale as compared with the placebo group ( P=0.008). There were no local complications attributable to the TAP block. Transverse abdominis plane block was effective in providing analgesia with a substantial reduction in tramadol use during 24h after cesarean section when used as adjunctive to standard analgesia.

Dual-Modality Accurate Visualization of Drug Synergy Based on Mass Spectrometry and Fluorescence Imaging.

There is a potential synergistic effect between nonsteroidal anti-inflammatory drugs and hydrogen sulfide (H2S), but direct evidence for the study is lacking. With a single fluorescence detection method, it is difficult to accurately confirm the effectiveness of the synergistic effect. In this study, the fluorescent probe and the nonsteroidal anti-inflammatory drug naproxen were combined via different self-immolative spacer groups to obtain a diagnostic and therapeutic integrated fluorescent probe Nap-NP-NSB, which can release H2S. The quantitative release of H2S by Nap-NP-NSB was evaluated in vitro and in cells, and the synergistic effect of H2S and naproxen was confirmed by monitoring the treatment process of cellular inflammation and oxidative damage of gastric mucosa cells. Finally, in vivo fluorescence imaging and mass spectrometry imaging of the liver and stomach tissues and their sections were performed in the mouse model of acute hepatitis. The dual-modal detection method not only confirmed that Nap-NP-NSB had better anti-inflammatory activity and less gastric mucosal damage, but also enabled a more accurate visualization of the drug synergistic effect of naproxen and H2S. This work provides a dual visualization imaging method combining fluorescence and mass spectrometry imaging and develops a new idea for studying drug synergies based on self-immolative structures.

Enhanced 3D-printed Matrix for Electrocatalytic Detection: A Practical and Simple Electrochemical Platform

AbstractIn this work, we proposed a novel 3D-printed manufactured electrode system. A project was developed and optimized, compatible with commercially available potetiostats. Additive manufacturing included the modification of the pseudo-reference electrode by electrodeposition of silver and its subsequent oxidation to the Ag/AgCl form. Then the system was tested using electrochemical techniques to check the application as a universal electroactive platform. As an example, we checked the detection of paracetamol as a common substance from non-steroidal anti-inflammatory drugs (NSAIDs). Finally, the system was compared to available commercial carbon electrodes, considering the screen-printed electrode (SPE no.1 and SPE no.2) and the glassy carbon electrode (GCE), showing higher sensitivity and linearity range compared to commercial screen-printed systems. The novelty of the proposed platform unveils a new way of common, simple, budget, and fast obtaining a universal electroactive platform for electrochemical research, keeping high-performance parameters.

Risk stratification of residual abscess after surgical treatment for gastroduodenal perforation

AbstractAimsResidual abscess is a major complication after emergency surgery for gastroduodenal (GD) perforation. However, there is little evidence regarding potential risk factors contributing to its development. Establishing a risk stratification strategy would be valuable for the entire management process.MethodsThis single‐center, retrospective study analyzed 115 consecutive patients who underwent surgery for GD perforation between 2010 and 2023 at a secondary emergency care hospital. Patients were divided into two groups based on the presence or absence of residual abscesses. Potential risk factors for abscess formation were evaluated from various aspects.ResultsThe incidence of residual abscesses was 19.1% (22 of 115). Multivariable analysis revealed that current use of nonsteroidal antiinflammatory drugs (odds ratio [OR] 3.76, p = 0.037), cancer chemotherapy (OR 13.56, p = 0.005), and preoperative renal dysfunction (OR 4.72, p = 0.018) were independent predictors. A potential scoring model could be created using these three parameters, and the number of risk factors correlated with the likelihood of developing a residual abscess (0 vs. 1 vs. ≥2; 6.2% vs. 29.4% vs. 50.0%, p < 0.001). From a bacteriological point of view, the presence of Enterococcus in the ascites culture was closely related to its occurrence with 100% probability. Moreover, regarding early detection of this complication, C‐reactive protein on postoperative d 5 had the highest predictive ability with an area under the curve of 0.818.ConclusionThe risk of residual abscess formation after surgical treatment of GD perforation can be assessed utilizing both preoperative and postoperative information.

Renal injury in NSAIDs: a real-world analysis based on the FAERS database.

This study aims to evaluate the reporting risk of renal injury associated with non-steroidal anti-inflammatory drugs (NSAIDs), with a particular focus on the reporting risk levels and onset times of different NSAIDs. A pharmacovigilance study was conducted using data from the FAERS database from January 2004 to December 2023. Reports of renal injury were identified, and signal detection was performed using reporting odds ratio (ROR) and Bayesian confidence propagation neural network (BCPNN) methods. The study compared the incidence, mortality rates, and onset times of renal injury across five NSAIDs. Among the 7436 cases of NSAID-associated renal injury analyzed, elderly patients are at an increased risk of renal injury associated with NSAID usage. Ibuprofen had the highest number of reports (3475 cases, 46.7%), while celecoxib had the lowest (542 cases, 7.3%). Ibuprofen showed the highest signal with renal injury (ROR 3.3, IC025 1.7), whereas celecoxib exhibited the lowest (ROR 1.4, IC025 0.4). Aspirin had the highest mortality rate associated with renal injury (18.7%), while ibuprofen had the lowest (3.8%). The median onset time for renal injury was 6days, with 79.3% of adverse events occurring within the first 30days of use. The study indicates that ibuprofen presents the highest signal of renal injury, while celecoxib shows the lowest signal. The likelihood of NSAID-associated renal injury is heightened in elderly patients, and all five studied NSAIDs are linked to an increased likelihood of acute renal injury. NSAID-related renal damage tends to occur early in the treatment process, potentially leading to serious consequences. Due to the inherent limitations of pharmacovigilance studies, certain findings require additional validation like cohort studies. Nonetheless, the potential for an increased risk of renal injury must be taken into account in patient care.

Study of Correlation between H. pylori, Life Habits, and Risk Factors among Adult Patients in Gharyan, Libya

Helicobacter pylori (H. pylori) is a bacterium that can live in the human stomach and is one of the most common pathogens worldwide. The aim of this study was to evaluate the relationship between H. pylori infection and risk factors and life style habits, such as non-steroidal anti-inflammatory drugs, alcohol ingestion, and smoking. The study was conducted in two centers in Gharyan, Libya (private clinics). The case study took place over three months from July to September 2024 and utilized a validated questionnaire. All participants had confirmed H. pylori infections. A total of 50 cases with positive H. pylori infections were included in this study. They completed the questionnaire and data was analyzed using simple statistics. The questionnaire consisted of three parts. The prevalence of H. pylori infection was higher in females than males in this study. The findings suggested that certain habits, such as perceived stress, frequency of physical activity per week, and duration of physical activity, may influence the presence of H. pylori infection. Additionally, adults with below-normal levels of vitamin D had a higher risk of H. pylori infection.

The Role of Pain Medications in Modulating Peripheral Nerve Injury Recovery.

Peripheral nerve injuries (PNIs) are common, costly, and cause significant pain. Effective management of PNIs involves tailoring medications to the injury type as well as understanding the pharmacokinetics/pharmacodynamics to support nerve regeneration and reduce pain. Opioids act on opioid receptors to significantly reduce pain for many patients, but there are significant addiction risks and side effects. In addition, opioids may exacerbate pain sensitivity and affect nerve regeneration. Non-steroidal anti-inflammatory drugs or acetaminophen act on cyclooxygenase enzymes and are commonly used for nerve pain, with 34.7% of people using them for neuropathic pain. While effective for mild pain, they are often combined with opioids, gamma-aminobutyric acid (GABA) analogs, lidocaine, or corticosteroids for more severe pain. Corticosteroids, mimicking adrenal hormones like cortisol, treat PNI-related inflammation and pain. Their pharmacokinetics are complex, often requiring local injections in order to minimize systemic risks while effectively treating PNIs. Lidocaine, a common local anesthetic, blocks ion channels in the central nervous system (CNS) and peripheral nerves, providing strong analgesic and anti-inflammatory effects. If used improperly, lidocaine can cause neuronal toxicity instead of anesthetic effect. GABA acts as an inhibitory neurotransmitter in the CNS and its drug analogs like pregabalin and gabapentin can alleviate neuropathic pain by binding to voltage-gated Ca2+ channels, inhibiting neurotransmitter release. These pain medications are commonly prescribed for PNIs despite a limited guidance on their effects on nerve regeneration. This review will discuss these drug's mechanisms of action, pharmacokinetics/pharmacodynamics, and their clinical application to highlight their effect on the PNI recovery.

Clinical effect and contributing factors of acupuncture for knee osteoarthritis: a systematic review and pairwise and exploratory network meta-analysis.

This study aims to evaluate (1) the effect and safety of acupuncture in patients with knee osteoarthritis (KOA) and explore (2) whether the effect of acupuncture differed according to acupuncture type, acupuncture dose and follow-up time. Systematic review and pairwise and exploratory network meta-analysis. PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, VIP Database for Chinese Technical Periodicals and Wanfang from inception to 13 November 2023. Randomised controlled trials comparing acupuncture with sham acupuncture, non-steroidal anti-inflammatory drugs (NSAIDs), usual care or waiting list groups, intra-articular (IA) injection and blank groups in patients with KOA. Eligible interventions included manual acupuncture (MA) and electroacupuncture (EA). The primary outcome was pain intensity at the end of treatment. 80 trials (9933 participants) were included. Very low certainty evidence suggested that acupuncture may reduce pain intensity compared with sham acupuncture (standardised mean difference, SMD -0.74, 95% CI -1.08 to -0.39, corresponded to a difference in Visual Analogue Scale of -18.50 mm, -27.00 to -9.75), NSAIDs (SMD -0.86 to -1.26 to -0.46, corresponded to -21.50 mm, -31.50 to -11.50), usual care or waiting list groups (SMD -1.01, -1.47 to -0.54, corresponded to -25.25 mm, -36.75 to -13.50) and blank groups (SMD -1.65, -1.99 to -1.32, corresponded to -41.25 mm, -49.75 to -33.00), but not IA injection. Similar results were also found in other outcomes. For most of the subgroup analyses, acupuncture type, acupuncture dose and follow-up time did not show a significant relative effect. Only when compared with NSAIDs, a higher dose of acupuncture may provide greater pain relief (interaction p<0.001). The network meta-analysis revealed that electroacupuncture (SMD -0.75, 95% CI -1.34 to -0.17) had a greater effect on pain relief in patients with KOA compared with manual acupuncture. The findings suggest that acupuncture may provide clinically important effects in reducing pain and improving physical function in patients with KOA, but the certainty of evidence was very low. Electroacupuncture and higher dose of acupuncture probably are two potential contributing factors. CRD42021232177.

An eco-friendly strategy for emerging contaminants removal in water: Study of the adsorption properties and kinetics of self-polymerized PHEMA in green solvents

Water contaminants severely affect human health and aquatic ecosystems, and adsorption poses an economic, available, and feasible technology for remediation that needs to be accompanied by eco-friendly and sustainable materials. This study proposes an eco-friendly strategy for removing emerging contaminants using polyhydroxyethyl methacrylate polymers synthesized by self-polymerization with hydrophilic first-generation deep eutectic solvents. The polymers were characterized using structural and physical characterization techniques and their adsorption capacity against four emerging contaminants: a non-steroidal anti-inflammatory drug, an antibiotic, a pesticide, and a non-ionic surfactant. The experimental results showed high adsorption capacity for the urea: choline chloride-derived polymer with 6.21, 7.19, 6.01, and 6.99 mg⋅g-1 for paracetamol, ciprofloxacin, glyphosate, and triton X-100, respectively; these values are comparable to those obtained for similar systems. Kinetic, isothermal, and thermodynamics were also studied using various mathematical models to understand the adsorption mechanism, further complemented by DFT analysis. Chemisorption was found to be the primary mechanism by exothermic and ordered processes, which is thermodynamically favored. The study demonstrated for the first-time the effectiveness of self-polymerized PHEMA without chemical modification as a reusable adsorbent material and its ability to remove different types of emerging contaminants, thereby offering a promising solution for water treatment in environmental science.

Response of crop seed germination and primary root elongation to a binary mixture of diclofenac and naproxen.

Non-steroidal anti-inflammatory drugs, diclofenac (DCF) and naproxen (NPX), represent a group of environmental contaminants often detected in various water and soil samples. This work aimed to assess possible phytotoxic effects of DCF and NPX in concentrations 0.1, 1 and 10 mg/L, both individually and in binary mixtures, on the seed germination and primary root elongation of crops, monocots Allium porrum and Zea mays, and dicots Lactuca sativa and Pisum sativum. Results proved that the seed germination was affected by neither individual drugs nor their mixture. The response of primary root length in monocot and dicot species to the same treatment was different. The Inhibition index (%) comparing the root length of drug-treated plants to controls proved to be approximately 10% inhibition in the case of dicots lettuce and pea, and nearly 20% inhibition in monocot leek, but almost 20% stimulation in monocot maize. Assessment of the binary mixture effect confirmed neither synergistic nor antagonistic interaction of DCF and NPX on early plant development in the applied concentration range.

Radiation Therapy for the Treatment of Osteoarthritis.

Osteoarthritis is a common cause of pain and disability in the United States. Many patients experience pain that is refractory or unable to be treated by traditional treatments such as exercise, physical therapy, nonsteroidal anti-inflammatory drugs, and/or cyclooxygenase-2 inhibitors. For patients with medically refractory disease, intra-articular corticosteroid therapy, hyaluronic acid, or surgery can be considered. However, for many older patients with significant impairment in quality of life related to osteoarthritis, radiation therapy is a noninvasive treatment option that has a long history of global use. In this topic discussion, we review the clinical evidence supporting treatment of osteoarthritis, as well as considerations for how to select which patient and joint to treat. We discuss technical considerations for treatment including dose and immobilization, assessment of treatment response, and the role of retreatment.

Therapeutic strategies to modulate gut microbial health: Approaches for sarcopenia management.

Sarcopenia is a progressive and generalized loss of skeletal muscle and functions associated with ageing with currently no definitive treatment. Alterations in gut microbial composition have emerged as a significant contributor to the pathophysiology of multiple diseases. Recently, its association with muscle health has pointed to its potential role in mediating sarcopenia. The current review focuses on the association of gut microbiota and mediators of muscle health, connecting the dots between the influence of gut microbiota and their metabolites on biomarkers of sarcopenia. It further delineates the mechanism by which the gut microbiota affects muscle health with progressing age, aiding the formulation of a multi-modal treatment plan involving nutritional supplements and pharmacological interventions along with lifestyle changes compiled in the review. Nutritional supplements containing proteins, vitamin D, omega-3 fatty acids, creatine, curcumin, kefir, and ursolic acid positively impact the gut microbiome. Dietary fibres foster a conducive environment for the growth of beneficial microbes such as Bifidobacterium, Faecalibacterium, Ruminococcus, and Lactobacillus. Probiotics and prebiotics act by protecting against reactive oxygen species (ROS) and inflammatory cytokines. They also increase the production of gut microbiota metabolites like short-chain fatty acids (SCFAs), which aid in improving muscle health. Foods rich in polyphenols are anti-inflammatory and have an antioxidant effect, contributing to a healthier gut. Pharmacological interventions like faecal microbiota transplantation (FMT), non-steroidal anti-inflammatory drugs (NSAIDs), ghrelin mimetics, angiotensin-converting enzyme inhibitors (ACEIs), and butyrate precursors lead to the production of anti-inflammatory fatty acids and regulate appetite, gut motility, and microbial impact on gut health. Further research is warranted to deepen our understanding of the interaction between gut microbiota and muscle health for developing therapeutic strategies for ameliorating sarcopenic muscle loss.

New Binary Adducts of Panobinostat with Different Carboxylic Acid Based NSAIDs: Structural Analysis and Physicochemical Properties Investigation

AbstractAdoption of multitarget, cost‐effective fixed‐dose medication combinations can help lower the pill load without increasing the risk of adverse events. In this study, three new 1:1 drug‐drug binary solid forms of panobinostat (PNB) and nonsteroidal anti‐inflammatory drugs (NSAIDs) were effectively synthesized by liquid‐assisted grinding and slow evaporation crystallization techniques. The obtained solid forms were extensively characterized by various analytical techniques. The structural investigation revealed that all molecular adducts formed salt with a comparable (10) graph set pattern created by heteromeric interactions formed between PNB and corresponding salt formers. To determine the dissolving behavior of the newly developed adducts, solubility tests were performed at various pH levels (pH 1.2 and pH 7), and the results indicated that the solubility of all forms is increased at pH 7.0, particularly PNB.NIF has a solubility of 0.195 mg/mL, which is seven times higher than the parent drug. Furthermore, PXRD was used to assess the stability of the synthesized adduct at varied temperature and humidity levels and it was found that all the adducts are stable. Based on the findings, we hope that the newly found PNB drug‐drug binary adducts have possible potential to broaden the use of drug combinations without changing the chemical structures.

Total knee arthroplasty combined with simultaneous open reduction and internal fixation in the treatment of knee osteoarthritis with patellar fracture: a case report and review of the literature

BackgroundPatients with severe knee osteoarthritis combined with patellar fracture are rare, and it is unclear whether single-stage surgery affects the enhanced recovery after surgery.Case presentationThis case report describes two patients of Han nationality. A 69-year-old male patient was previously diagnosed with severe knee osteoarthritis of the left knee joint and was treated conservatively with long-term oral nonsteroidal antiinflammatory drugs and intraarticular injection of sodium hyaluronate. He was hospitalized for acute left knee injury owing to a fall from a height. He was diagnosed with knee osteoarthritis of the left knee joint and patellar fracture. Another 74-year-old female patient was previously diagnosed with severe knee osteoarthritis, long-term oral nonsteroidal antiinflammatory drugs and topical Chinese medicine to relieve the pain. A month ago, she fell down the stairs and fractured the patella in her left knee, she was diagnosed with severe left knee osteoarthritis combined with an old left patella fracture. Both patients were successfully treated by single-stage primary total knee arthroplasty and fixation of the patellar fracture. They both carried out early functional exercise normally and successfully achieved enhanced recovery.ConclusionSuccessful single stage total knee replacement with patella management can not only reduce the number of operations, but also enable patients to achieve rapid postoperative recovery. However, single stage may increase the risk of local surgical complications. Therefore, for most patients, especially those with low risk of anesthesia related complications, standard of treatment remains first fixing the patellar fracture and when the fracture is healed proceed with the total knee arthroplasty.

Electrochemical Carboxylation: Green Synthesis of Atrolactic Acid Using Boron-Doped Diamond Electrodes

Electrochemical CO2 fixation is vital for sustainability in the chemical industry, yet the selective synthesis of multi-carbon products remains challenging. Organic electrosynthesis offers promise by enabling precise control over reaction conditions and facilitating novel reactivity patterns. One such technique, electrochemical carboxylation, involves coupling CO2 with organic molecules to produce carboxylic acids. Specifically, electro-carboxylation of acetophenone yields atrolactic acid, a valuable precursor for nonsteroidal anti-inflammatory drugs, providing a greener alternative to traditional production methods. This study focuses on the synthesis and characterization of boron-doped diamond (BDD) films using the microwave plasma-assisted chemical vapor deposition (MP-CVD) method and synthesized BDD electrodes were then used for the electrolytic carboxylation of acetophenone. Various analytical techniques, including X-ray diffraction (XRD), Raman spectroscopy, and laser microscopy, etc. were employed to characterize the BDD films. Various BDD films synthesized for different durations were utilized in the electrolytic carboxylation of acetophenone, with the highest yield of atrolactic acid (25%) achieved using a BDD film synthesized over 6 hours. Also, the effect of BDD surface modification i.e. oxygen and hydrogen terminated BDD on the synthesis of atrolactic acid. Additionally, different electrolytes were employed in the synthesis process of atrolactic acid. A comparative study between Pt and BDD electrodes for the electrolytic carboxylation of acetophenone was conducted, and a mechanism for the formation of atrolactic acid was proposed.