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Abstract Background Hepatocellular Carcinoma (HCC) can be classified as one of the most common malignancies worldwide. There is scarcity of the published data on the risk factors for HCC in the Gulf Cooperation Council countries specifically Kuwait. Therefore, this case-control study sought to examine the risk factors associated with HCC in Kuwait. Methods Fifty-three histopathologically confirmed HCC cases were recruited from the Kuwait Cancer Control Center Registry. One hundred ninety-six controls (1:4 ratio) were selected from medical and/ or surgical outpatient’s clinics at all six public hospitals of Kuwait. A structured questionnaire was used to collect the data both from cases and controls through face-to-face interviews. A multivariable logistic regression model was fitted to the case-control data. Adjusted odds ratios (ORadj) and their 95% confidence intervals (CI) were computed using the parameters’ estimates of the final model and used for interpretation of the model. Results The HCC cases compared with the controls were 41.6 times more likely to have had the history of non-alcoholic fatty liver disease (NAFLD) (ORadj = 41.6; 95% CI: 8.9–193.5; p

Background: Hepatocellular Carcinoma (HCC) can be classified as one of the most common malignancies worldwide. There is scarcity of the published data on the risk factors for HCC in the Gulf Cooperation Council countries specifically Kuwait. Therefore, this case-control study sought to examine the risk factors associated with HCC in Kuwait. Methods: Fifty-three histopathologically confirmed HCC cases were recruited from the Kuwait Cancer Control Center Registry. One hundred ninety-six controls (1:4 ratio) were selected from medical and/ or surgical outpatient's clinics at all six public hospitals of Kuwait. A structured questionnaire was used to collect the data both from cases and controls through face-to-face interviews. A multivariable logistic regression model was fitted to the case-control data. Adjusted odds ratios (ORadj) and their 95% confidence intervals (CI) were computed using the parameters' estimates of the final model and used for interpretation of the model. Results: The HCC cases compared with the controls were 41.6 times more likely to have had the history of non-alcoholic fatty liver disease (NAFLD) (ORadj = 41.6; 95% CI: 8.9–193.5; p < 0.001). The cases compared with the controls were more likely to have reported the history of heavy alcohol drinking (ORadj = 14.2; 95% CI: 1.2–173.4; p = 0.038). Furthermore, compared with the controls, the HCC cases tended to frequently consume milk and/or milk substitutes (≥ 3 glass/ week) (ORadj = 7.2; 95% CI: 1.2–43.4). Conversely however, there was a significant protective effect if the participants reportedly have had regularly used olive oil in their routine diet as a source of fat (ORadj = 0.17; 95% CI: 0.04–0.80) or regularly used non-steroid anti-inflammatory drugs (NSAIDs) (ORadj = 0.20; 95% CI: 0.05–0.71). Conclusions: This study showed that heavy alcohol consumption, NAFLD history, and excessive consumption of milk/ milk substitutes were associated with a significantly increased HCC risk. Conversely however, regular use of olive oil in the diet as a source of fat or regular use of NSAIDs had a significantly protective effect against HCC risk. Adapting healthy dietary habits and preventing/ treating NAFLD may minimize the HCC risk. Future research with a larger sample size may contemplate validating the results of this study and unraveling additional risk factors contributing to HCC risk. The resultant data may help design and implement evidence-based educational programs for the prevention of HCC in this and other similar settings. [ABSTRACT FROM AUTHOR]

Abstract Aims The use of non-steroid anti-inflammatory drugs (NSAIDs) is conventional in management of postoperative pain in cancer patients, and further investigations have reported that some of these drugs correlated with the outcome in cancers. However, the prognostic value of the use of NSAIDs during surgery in non-small cell lung cancer (NSCLC) patients has been less addressed. Methods NSCLC patients staged I–III are retrospectively enrolled, and the data of the use of NSAIDs during surgery are collected. Patients are divided into two subgroups according to the use intensity (UI) (low or high) of the NSAIDs, which was calculated by the accumulate dosage of all the NSAIDs divided by the length of hospitalization. The differences of the clinical features among these groups were checked. And the disease-free survival (DFS) and overall survival (OS) differences in these groups were compared by Kaplan–Meier analysis; risk factors for survival were validated by using a Cox proportional hazards model. Results The UI was significant in predicting the DFS (AUC = 0.65, 95% CI: 0.57–0.73, P = 0.001) and OS (AUC = 0.70, 95% CI: 0.59–0.81, P = 0.001). Clinical features including type of resection (P = 0.001), N stages (P

Post-marketing hepatotoxicity findings are more common or occur much later. NSAIDs (non-steroidal anti-inflammatory drugs) like ibuprofen are consumed in large quantities around the world. NSAIDs have a low incidence of hepatotoxicity but their wide use makes them a major contributor to drug-induced liver injury. Hepatitis is linked to systemic oxidative stress which results in cellular necrosis and fibrosis, as well as tissue lipoprotein peroxidation and glutathione depletion. Given the lack of safe and effective anti-hepatitis drugs in medicine today, natural substances appear to be a promising and safe alternative. Propolis and chitosan are considered natural substances that have a protective effect on the hepatocytes. The purpose of this study was to validate the protective effect of propolis/chitosan nanoparticle extracts on ibuprofen-induced hepatotoxicity. Thirty (30) albino rats were used for the experiment. Animals were exposed to ibuprofen (400 mg/kg body weight/day) for 4 weeks (7 days/week) followed by treatment with propolis (200 mg/kg body weight/day) and chitosan extract (200 mg/kg body weight/day) separately and also in combination for consecutive 4 weeks. This study revealed a significant increase in serum transaminases, alkaline phosphatase, albumin, and total bilirubin in serum, as well as an increase in lipid peroxidation (MDA) and nitric oxide (NO). Furthermore, GSH, GST, and SOD decreased significantly in the group that was exposed to ibuprofen. Furthermore, there was a significant increase in pro-inflammatory parameters such as IL-1β and NF-ĸB, as well as low levels of anti-inflammatory parameters such as IL-6 and BCl-2. These alterations were improved by propolis and chitosan extracts, which was further confirmed in experimental animals. This study demonstrated that propolis and chitosan nanoparticle extracts have the potential to protect against hepatotoxicity induced by ibuprofen, due to their ability to regulate anti-inflammatory and anti-oxidative defense activities. [ABSTRACT FROM AUTHOR]

Aims: The use of non-steroid anti-inflammatory drugs (NSAIDs) is conventional in management of postoperative pain in cancer patients, and further investigations have reported that some of these drugs correlated with the outcome in cancers. However, the prognostic value of the use of NSAIDs during surgery in non-small cell lung cancer (NSCLC) patients has been less addressed. Methods: NSCLC patients staged I–III are retrospectively enrolled, and the data of the use of NSAIDs during surgery are collected. Patients are divided into two subgroups according to the use intensity (UI) (low or high) of the NSAIDs, which was calculated by the accumulate dosage of all the NSAIDs divided by the length of hospitalization. The differences of the clinical features among these groups were checked. And the disease-free survival (DFS) and overall survival (OS) differences in these groups were compared by Kaplan–Meier analysis; risk factors for survival were validated by using a Cox proportional hazards model. Results: The UI was significant in predicting the DFS (AUC = 0.65, 95% CI: 0.57–0.73, P = 0.001) and OS (AUC = 0.70, 95% CI: 0.59–0.81, P = 0.001). Clinical features including type of resection (P = 0.001), N stages (P < 0.001), and TNM stages (P = 0.004) were significantly different in UI low (< 74.55 mg/day) or high (≥ 74.55 mg/day) subgroups. Patients in UI-high subgroups displayed significant superior DFS (log rank = 11.46, P = 0.001) and OS (log rank = 7.63, P = 0.006) than the UI-low ones. At last, the UI was found to be an independent risk factor for DFS (HR: 0.52, 95% CI: 0.28–0.95, P = 0.034). Conclusions: The use of NSAIDs during radical resection in NSCLC patients correlated with the outcome and patients with a relative high UI has better outcome. [ABSTRACT FROM AUTHOR]

We have designed a new compound from the non-steroidal anti-inflammatory drug (NSAID) ketoprofen (Ket) and 2-amino-2-(hydroxymethyl)-1,3-propanediol (Tris) precursors, with the aim to reduce the gastrointestinal (GI) side effects of NSAID therapies. We investigated mucosal reactions in a standard rat model of colitis together with methane generation as a possible indicator of pro-inflammatory activation under this condition (approval number: V./148/2013). Whole-body methane production (photoacoustic spectroscopy) and serosal microcirculation (intravital videomicroscopy) were measured, and mucosal damage was assessed (conventional histology; in vivo laser-scanning endomicroscopy). Inflammatory markers were measured from tissue and blood samples. Colitis induced an inflammatory response, morphological colonic damage and increased methane output. Ket treatment lowered inflammatory activation and colonic mucosal injury, but macroscopic gastric bleeding and increased methane output were present. Ket-Tris reduced inflammatory activation, methane emission and colonic mucosal damage, without inducing gastric injury. Conjugation with Tris reduces the GI side effects of Ket and still decreases the inflammatory response in experimental colitis. Methane output correlates with the mucosal inflammatory response and non-invasively demonstrates the effects of anti-inflammatory treatments. [ABSTRACT FROM AUTHOR]

Simple Summary: Tumor evasion of immune surveillance is a hallmark of cancer posing challenges to effective cancer treatment. Herein we review the contributions of prostaglandins in shaping tumor microenvironments to modulate immune responses and cancer progression. Opportunities to target prostaglandins and their signaling receptors in improving cancer therapy, particularly immunotherapy, are explored. Prostaglandins, the bioactive lipids generated from the metabolism of arachidonic acid through cyclooxygenases, have potent effects on many constituents of tumor microenvironments. In this review, we will describe the formation and activities of prostaglandins in the context of the tumor microenvironment. We will discuss the regulation of cancer-associated fibroblasts and immune constituents by prostaglandins and their roles in immune escapes during tumor progression. The review concludes with future perspectives on improving the efficacy of immunotherapy through repurposing non-steroid anti-inflammatory drugs and other prostaglandin modulators. [ABSTRACT FROM AUTHOR]

Post-marketing hepatotoxicity findings are more common or occur much later. NSAIDs (non-steroidal anti-inflammatory drugs) like ibuprofen are consumed in large quantities around the world. NSAIDs have a low incidence of hepatotoxicity but their wide use makes them a major contributor to drug-induced liver injury. Hepatitis is linked to systemic oxidative stress which results in cellular necrosis and fibrosis, as well as tissue lipoprotein peroxidation and glutathione depletion. Given the lack of safe and effective anti-hepatitis drugs in medicine today, natural substances appear to be a promising and safe alternative. Propolis and chitosan are considered natural substances that have a protective effect on the hepatocytes. The purpose of this study was to validate the protective effect of propolis/chitosan nanoparticle extracts on ibuprofen-induced hepatotoxicity. Thirty (30) albino rats were used for the experiment. Animals were exposed to ibuprofen (400 mg/kg body weight/day) for 4 weeks (7 days/week) followed by treatment with propolis (200 mg/kg body weight/day) and chitosan extract (200 mg/kg body weight/day) separately and also in combination for consecutive 4 weeks. This study revealed a significant increase in serum transaminases, alkaline phosphatase, albumin, and total bilirubin in serum, as well as an increase in lipid peroxidation (MDA) and nitric oxide (NO). Furthermore, GSH, GST, and SOD decreased significantly in the group that was exposed to ibuprofen. Furthermore, there was a significant increase in pro-inflammatory parameters such as IL-1β and NF-ĸB, as well as low levels of anti-inflammatory parameters such as IL-6 and BCl-2. These alterations were improved by propolis and chitosan extracts, which was further confirmed in experimental animals. This study demonstrated that propolis and chitosan nanoparticle extracts have the potential to protect against hepatotoxicity induced by ibuprofen, due to their ability to regulate anti-inflammatory and anti-oxidative defense activities.

The new coronavirus infection (COVID-19) is associated with a wide spectrum of various clinical manifestations including involvement of the musculoskeletal system which can persist for a long time after the infection. Supposedly, pathogenesis of musculoskeletal manifestations of COVID-19 is primarily caused by systemic inflammation accompanied by cytokine hyperexpression (interferon γ, interleukins 1β, 6, 8, 17, tumor necrosis factor α), as well as hypoxia leading to overproduction of inflammatory cytokines, activation of bone reabsorption by osteoclasts and subsequent decrease of mineral bone density and osteonecrosis in some cases. Additionally, some drugs prescribed to patients with COVID-19 (some antiviral drugs and glucocorticoids) should also be taken into account as they can lead to development of musculoskeletal pathology. In the acute period of COVID-19, myalgias are common, but in rare cases myositis with proximal muscular weakness and increased levels of creatine phosphokinase, lactate dehydrogenase can occur. Arthralgias in the acute period of COVID-19 are rarer than myalgias. In the studies of clinical manifestation of COVID-19, frequency of arthralgias and myalgias in the acute period is between 15.5 and 50 %. After COVID-19, frequency of arthralgias and myalgias gradually decreases, however there are cases of long-term joint and muscle pains, as well as post-viral arthritis, development of arthritis in the context of various autoimmune disorders. Myalgias and arthralgias during COVID-19 usually regress spontaneously and in most patients do not require prescription of antipain medications, but in some cases pain management is necessary. Use of non-steroid anti-inflammatory drugs and vitamin D during COVID-19 is a safe and effective method of pain management, including myalgia and arthralgia. Rehabilitation programs play an important role in improvement of functional state and patient recovery after moderate and severe COVID-19.

Neurodegenerative diseases (NDDs) are characterized by progressive deterioration of the structure and function of cells and their networks in the nervous system. There are currently no drugs or other treatments that can stop the progression of NDDs. NDDs have many similarities and common pathways, e.g., formation of misfolded amyloid proteins, intra- and extracellular amyloid deposits, and chronic inflammation. Initially, the inflammation process has a cytoprotective function; however, an elevated and prolonged immune response has damaging effects and causes cell death. Neuroinflammation has been a target of drug development for treating and curing NDDs. Treatment of different NDDs with non-steroid anti-inflammatory drugs (NSAIDs) has failed or has given inconsistent results. The use of NSAIDs in diagnosed Alzheimer's disease is currently not recommended. Sigma-1 receptor (Sig-1R) is a novel target for NDD drug development. Sig-1R plays a key role in cellular stress signaling, and it regulates endoplasmic reticulum stress and unfolded protein response. Activation of Sig-1R provides neuroprotection in cell cultures and animal studies. Clinical trials demonstrated that several Sig-1R agonists (pridopidine, ANAVEX3-71, fluvoxamine, dextrometorphan) and their combinations have a neuroprotective effect and slow down the progression of distinct NDDs. [ABSTRACT FROM AUTHOR]

Although NSAIDs possess notable therapeutic and pharmaceutical qualities, it's essential to acknowledge that excessive doses can result in toxicity within the human body. Moreover, the importance lies in identifying and measuring their trace amounts. Due to their existence within intricate matrices, the creation of novel electrospun nanofibers as sorbents for electrically-assisted solidphase microextraction (EA-SPME) becomes vital. This innovation caters to the requirement for the effective pre-treatment of NSAID samples, providing a strategic approach to managing the complexities associated with trace quantities found in various matrices. First, polyvinylalcohol/casein/tannic acid/polyaniline/titanium dioxide nanoparticles (PVA/CAS/TA/PANI/TiO 2 NPs) electrospun nanofibers were prepared for EA-SPME on pewter rode and then, trace amounts of six NSAIDs (Acetaminophen, Caffeine, Naproxen, Celecoxib, Ibuprofen and mefenamic acid) were adsorbed chemically on these nanofibers. In the next step, the desorption of six NSAIDs was electrochemically done from prepared electrospun nanofibers on a pewter rod which was as working electrode at three electrodes system. Finally, these drugs were quantified from different human plasma samples with HPLC-UV. The synthesis of electrospun nanofibers was confirmed through a series of analytical techniques including field emission-scanning electron microscopy (FE-SEM), energy-dispersive X-ray spectroscopy with elemental mapping analysis (EDX-Mapping), X-ray diffraction (XRD), and Fourier transform-infrared (FT-IR). The optimal percentage of additive compounds to PVA/CAS for electrospinning, as well as the factors influencing adsorption and desorption processes, were determined through both of Design Expert software and MATLAB programming language. Under optimum conditions, the wide linear range was 27–8000 ng mL−1 with R2 ≥ 0.9897, low detection limits were ranged from 8 to 27.3 ng mL−1 based on S/N = 3 and significant enrichment factors were acquired. The intra-day and inter-day RSDs% were obtained within the 4.51% - 5.68% and 4.28%–5.45%, respectively. Finally, The effectiveness of the EA-SPME-HPLC-UV method was assessed for determining NSAIDs in plasma samples, demonstrating good recoveries ranging from 90.2% to 105.2%. [Display omitted] • Six NSAIDs with various pKa values were pretreated simultaneously by EA-SPME. • The electrospun nanofibers were used as a sorbent in EA-SPME method. • The chemical adsorption and electrochemical desorption process were performed. • The amounts of six NSAIDs were determined in human plasma samples. • The optimization step was accomplished with both of the design-expert and Matlab. [ABSTRACT FROM AUTHOR]

Periorbital emphysema is rare and associated with facial trauma. Its main distinguishing feature is crepitation on palpation of the edema. It resolves spontaneously in a few days, but there are cases of orbital compartment syndrome that can lead to loss of vision. Here we present the case of a 55-year-old male who came to the emergency department for bilateral periorbital edema associated with non-steroidal anti-inflammatory drug (NSAID) usage, for pain following a fall from a ladder. He was treated with antihistamines and corticosteroids, for presumed allergic reaction, but without response, and subsequently developed acute onset dyspnea. Chest x-ray revealed a left pneumothorax in the context of chest trauma. Chest CT scan after drain placement shows extensive subcutaneous emphysema. In the differential diagnosis of periorbital edema, in addition to allergic, inflammatory, and systemic causes, the traumatic ones should not be excluded., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Manata et al.)

• NSAIDs inhibiting COX-1 mainly holds many gastric side-effects. • To minimize their side-effects, ten NSAIDs were converted to amide derivatives. • The new derivatives showed good anti-inflammatory and analgesic activity. • Best drug candidates were subjected to comprehensive toxicological investigation. • Selectivity of some COX-1 inhibitors shifted to COX-2. Today, usage of NSAIDs (nonsteroidal anti-inflammatory drugs) is very common. However, it has been proven by many studies that NSAIDs with free carboxylic acid group damage the GI (gastrointestinal) system. Our aim was to mask the acidic groups of NSAIDs to prevent or reduce their side effects while preserving their pharmacological effects. In this study, new amide derivatives of known NSAIDs, compounds 11 – 20 , were synthesized to investigate their analgesic and anti-inflammatory effects using in vivo models. While compound 11 showed the most remarkable anti-inflammatory activity by 60.9% inhibition value at 200 mg/kg dose, compounds 11, 12, 15 and 18 had almost the same analgesic activity to that of acetylsalicylic acid (100 mg/kg) and flurbiprofen (100 mg/kg). In addition, all test compounds used at high dose (200 mg/kg, p.o) did not show any acute toxicity. COX-1 and COX-2 inhibition properties of all compounds were measured by biochemical methods and the interaction of the most active compounds with COX enzymes is elucidated by computer-assisted virtual screening methods. It was determined by in vitro enzyme inhibition studies that compound 11 and 13 , synthesized from selective COX-1 inhibitors dexketoprofen and flurbiprofen, are selective COX-2 inhibitors. Moreover, compounds 11 – 13 were found to be non-mutagenic according to the mutagenicity assay using Salmonella TA98 and TA100 strains with and without metabolic activation. Finally, the prediction of ADMET profile and drug-likeness properties of compounds 11 – 20 were examined and the obtained results were evaluated. [Display omitted] [ABSTRACT FROM AUTHOR]

Drug repurposing is a strategy used to develop new treatments based on approved or investigational drugs outside the scope of their original clinical indication. Since this approach benefits from the original toxicity data of the repurposed drugs, the drug-repurposing strategy is timesaving, and inexpensive. It has a higher success rate compared to traditional drug discovery. Several repurposing candidates have been identified in silico screening and in vitro methodologies. One of the best examples is non-steroidal anti-inflammatory drugs (NSAIDs). Tumor-promoting inflammation is one of the hallmarks of cancer, revealing a connection between inflammatory processes and tumor progression and development. This explains why using NSAIDs in the context of neoplasia has become a topic of interest. Indeed, identifying NSAIDs with antitumor activity has become a promising strategy for finding novel cancer treatment opportunities. Indeed, several commercial anti-inflammatory drugs, including aspirin, ibuprofen, diclofenac, celecoxib, tepoxalin and cyclovalone, naproxen, and indomethacin have presented antitumor activity, and some of them are already in clinical trials for cancer treatment. However, the benefits and complications of using NSAIDs for cancer treatment must be carefully evaluated, particularly for cancer patients with no further therapeutic options available. This review article provides insight into the drug repurposing strategy and describes some of the well-known NSAIDs that have been investigated as repurposed drugs with potential anticancer activity., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)