Anti-inflammatory Research Articles

Assessing Blood-Brain Barrier Function in the Context of Pain Management.

One essential component of the neurovascular system is known as the blood-brain barrier (BBB). This highly effective biological barrier plays a pivotal role in regulating the brain's internal microenvironment and carefully controlling the passage of various chemicals into and out of the brain. Notably, it serves as a safeguard for the brain, particularly when it comes to the selective transportation of drugs like opioids and non-steroidal anti-inflammatory medications (NSAIDs), which are commonly used in the management of chronic pain. It's important to note that during the development of chronic pain, the activation of microglia and astrocytes can potentially disrupt or damage the integrity of the BBB. In this comprehensive review, we aim to delve into the intricate interplay between the blood-brain barrier and the transportation of pain-relieving drugs, shedding light on the challenges and mechanisms involved in this process.

Synthesis and characterization of novel magnetic metal organic framework for efficient removal of ketoprofen from aqueous solutions: Mechanism of interaction, adsorption and optimization via BOX-Behnken design

This investigation examines the adsorption and elimination of the anti-inflammatory medication ketoprofen (KTP) in relation to a newly developed magnetic thorium metal-organic framework (MTh-MOF). The study found that KTP absorption on MTh-MOF resulted in a reduction in pore volume, pore size, and surface area, as revealed by N2 adsorption/desorption isotherm analysis used to evaluate the characteristics of the MTh-MOF. Scanning electron microscopy (SEM) showed that the pore radius of MTh-MOF decreased from 1.68 nm to 0.82 nm, demonstrating a consistent and uniform structure. Fourier-transform infrared (FT-IR) spectroscopy was employed to identify the functional groups present in MTh-MOF, while X-ray photoelectron spectroscopy (XPS) was used to confirm the compound's structure. The optimal conditions for achieving a high adsorption capacity were found to be at pH 6 and a MTh-MOF dose of 0.02 g. The results indicated that MTh-MOF displayed a high capacity for absorbing KTP, with the adsorption data fitting well with pseudo-second-order kinetic models and the Langmuir isotherm. The adsorption capacity of MTh-MOF for KTP was determined to be 518 mg/g. The adsorption energy of 28.26 kJ·mol–1 suggested that chemisorption was the predominant mode of adsorption. The process of KTP adsorption on MTh-MOF was observed to be spontaneous, endothermic, and random, as evidenced by the temperature-dependent increases in the thermodynamic parameters (ΔGo, ΔHo, and ΔSo). The adsorption process was optimized using Response Surface Methodology and Box-Behnken design (RSM, BBD). Aromatic rings interact via π-π bonding, while chemisorption involves the development of chemical interactions between the adsorbate and adsorbent. Additionally, electrostatic interactions arise from the attraction or repulsion of charges between the adsorbate and adsorbent, and pore-filling occurs when the adsorbate fills the adsorbent's pores. In order to understand the electrical properties, reactivity, and shape of KTP, density functional theory (DFT) was utilized.

The Emerging Treatment of BCG (Bacillus Calmette-Guérin)-Unresponsive Non–Muscle-Invasive Bladder Cancer

Bacillus Calmette-Guérin (BCG) remains the cornerstone in the treatment of high-risk non-muscle-invasive bladder cancer (NMIBC), effectively preventing recurrence and progression. Unfortunately, a significant proportion of patients are classified as BCG-unresponsive, and there have been no definite alternative treatments for these disease group except for radical cystectomy, which is still challenging and sometimes not applicable. Therefore, there has been a need for alternative bladder-preserving treatments for patients who desire a bladder-sparing approach or are too frail for major surgery. Intravesical therapies, such as gemcitabine, mitomycin C and docetaxel, are mostly studied approaches, showing some promising results. However, no definitive conclusion has be drawn because of the heterogeneity of the studies and protocols and the limited number of patients enrolled in most of these studies. Immunotherapy and anti-inflammatory agents, though promising, require further validation through ongoing clinical trials to ensure their safety and efficacy. Gene therapy is also being explored, though it is in its early stages, with challenges in gene delivery and immune regulation still to be addressed. Photodynamic therapy and hyperthermia, particularly in combination with other treatments like intravesical chemotherapy, have shown potential in improving outcomes for BCG-unresponsive patients, though they are not yet considered first-line treatments. While these novel approaches hold promise, more robust data and clinical trial results are necessary to guide treatment protocols. In conclusion, ongoing research and clinical trials will continue to shape the future of NMIBC management, with the aim of providing more effective and bladder-preserving options for patients.

Comprehensive review on advanced antipyretic and anti-nociceptic agents: Efficacy; safety and emerging therapies

Fever; characterized by an increased core temperature; is a complex physiological reaction to illness involving acute-phase reactants and many physiological; endocrinological; and immunological systems. Antipyretics; chiefly non-steroidal anti-inflammatory Drugs (NSAIDs) and paracetamol; are essential for the management of fever and related discomfort. These medicines primarily function by inhibiting cyclooxygenase enzymes; so diminishing the production of prostaglandin E2 in the hypothalamus and subsequently decreasing the thermal set point. Although paracetamol is acknowledged for its safety when utilized correctly; it presents concerns of hepatic toxicity and overdose; requiring vigilant monitoring; especially in pediatric patients or those with concomitant conditions. Conversely; ibuprofen typically has greater antipyretic efficacy; particularly in pediatric populations; although its application may be constrained by gastrointestinal adverse effects and renal considerations. Recent breakthroughs in this domain concentrate on improving the safety and efficacy of antipyretic drugs; particularly for at-risk populations such as the elderly and children. Innovations like COX-2 selective inhibitors and advanced delivery technologies; including nanomedicine; offer exciting opportunities for enhancing pain management and fever therapy. Future study should emphasize the customization of therapy according to pharmacodynamics; possible drug interactions; and patient attributes to enhance therapeutic results. An interdisciplinary approach is crucial for the appropriate management of fever and pain; enhancing patient welfare and progressing clinical practices in antipyretic and antinociceptive therapies.

Vertebral osteoporotic fractures: differential diagnosis, therapeutic approaches

Osteoporotic vertebral fractures (OVF) are a severe complication of osteoporosis associated adverse outcomes, acute and chronic pain syndrome. If vertebral fractures (deformities) are detected, osteoporosis is diagnosed regardless of bone mineral density and the 10-year absolute fracture risk scale of the Fracture Risk Assessment Tool, but subject to the exclusion of other metabolic osteopathies. The article presents differential diagnosis of OVF with osteopathies such as osteomalacia, tumors or metastatic lesions of the spine, Paget»s disease, myeloma, hyper parathyroid osteodystrophy, post-traumatic vertebral deformities, Scheuermann-Mau disease. Differential diagnosis between different types of osteopathies is based on features of the clinical picture, history, changes in laboratory parameters (calcium, phosphorus, alkaline phosphatase, parathyroid hormone, vitamin D3 and on data from X-ray of the skeleton examination. It is necessary to take into account conditions under which the vertebral fracture occurred, its localization, prevalence, peculiarities of changes in bone structures, presence or absence of osteoporotic background, degenerative-dystrophic changes in the spine. The tactics of managing the patients with OVF is determined by the time after the fracture, its severity, nature of the pain syndrome and includes non-drug and medical measures. Among non-pharmaceutical measures in the acute period of OVF, there are unloading of the spinal column, use of a corset, and physical therapy. Medical measures are aimed at pain relief using injectable and oral forms of nonsteroidal anti-inflammatory drugs, central acting muscle relaxants and anti-osteoporotic therapy. Dexketoprofen (Dexalgin) is the first-line drug for relief of acute pain in OVF which has a rapid and pronounced analgesic effect. For the anti-osteoporotic therapy, the drugs of choice are parenteral bisphosphonates, denosumab and teriparatide.

Advancements in benzotriazole derivatives: from synthesis to pharmacological applications

Benzotriazole derivatives have emerged as significant compounds in medicinal chemistry due to their diverse pharmacological activities and unique structural properties. This review discusses the various synthetic strategies employed to develop these derivatives, including solvent-free techniques for N-alkylation and the synthesis of N-acyl benzotriazoles. Characterization methods such as infrared (IR) and nuclear magnetic resonance (NMR) spectroscopy confirm the successful formation of metal-benzotriazole complexes. The pharmacological profiles of benzotriazole derivatives reveal their potential as antimicrobial agents, particularly against Gram-positive and Gram-negative bacteria, including methicillin-resistant Staphylococcus aureus. Additionally, some derivatives exhibit potent antiprotozoal activity against Acanthamoeba castellanii, as well as analgesic effects that surpass those of standard drugs. Antioxidant studies highlight superior free radical scavenging abilities in certain benzotriazole-substituted compounds, while anti-inflammatory derivatives demonstrate activity comparable to common anti-inflammatory medications. Furthermore, significant antifungal activity against Candida albicans and Aspergillus niger positions these compounds as promising alternatives in addressing prevalent health challenges. The findings underscore the importance of benzotriazole derivatives in drug discovery and their potential in combating issues such as antibiotic resistance and oxidative stress.

Low friction hydrogel with diclofenac eluting ability for dry eye therapeutic contact lenses.

When placed in the eye, contact lenses (CLs) disturb the tear fluid and affect the natural tribological behaviour of the eye. The disruption in the contact mechanics between the ocular tissues can increase frictional shear stress and ocular dryness, causing discomfort. Ultimately, continuous CLs wear can trigger inflammation which is particularly critical for people suffering from dry eye. In this work, a double strategy was followed to obtain therapeutic daily disposable CLs for dry eye: a hydroxyethyl methacrylate (HEMA) based hydrogel was coated with two natural polysaccharides, chitosan (CHI) and hyaluronic acid (HA) and posteriorly loaded with an anti-inflammatory drug (diclofenac, DCF). Material sterilisation was carried out by high hydrostatic pressure (HHP) combined with moderate temperature. The friction coefficient (μ) was determined in the presence of different tear biomolecules (cholesterol, lysozyme and albumin) using a nanotribometer. Drug release experiments were performed in static and in hydrodynamic conditions. The material was extensively characterised, regarding surface morphology/topography, optical properties, water content and swelling behaviour, wettability, ionic and oxygen permeability and mechanical properties. It was found that the coating did not impair the physico-chemical properties relevant for the material's application in CLs. Besides, it also ensured a sustained release of DCF for 24 h in tests performed in hydrodynamic conditions that simulate those found in the eye, increasing significantly the amount of drug released. It reduced friction, improving the lubrication ability of the hydrogel, and presented antibacterial properties against S. aureus, P. aeruginosa and B. Cereus. The coated samples did not reveal any signs of cytotoxicity or potential eye irritation. Overall, the coating of the hydrogel may be useful to produce daily CLs able to alleviate dry eye symptoms and the discomfort of CLs wearers.

Progress in targeted therapy for ankylosing spondylitis: A review.

Ankylosing spondylitis (AS) is a chronic inflammatory disease characterized by axial osteoarticular inflammation and tendon enthesitis with unclear pathogenesis. Nonsteroidal anti-inflammatory drugs and antirheumatic drugs used in the traditional treatment of AS have some problems such as drug intolerance and inadequate treatment response. Since the introduction of biological agents in the treatment of AS, they have completely changed the treatment concept of AS, and because of their safety and good tolerance, they have become the main choice for clinical AS patients. This article systematically summarizes the current status of targeted therapy for AS worldwide, analyzes the advantages and disadvantages of different types of biological agents in the treatment of AS, and provides an objective evaluation of clinical targeted therapy for AS, in order to provide a new perspective for clinical standardized treatment.

Comparative proteomic analysis of human vitreous in rhegmatogenous retinal detachment and diabetic retinopathy reveals a common pathway and potential therapeutic target

BackgroundThe vitreous humor serves as a window into the physiological and pathological processes of the eye, particularly the retina. Diabetic retinopathy (DR), a leading cause of blindness, involves hyperglycemia-induced damage to retinal cells, leading to ischemia and elevated nitric oxide levels, culminating in vascular proliferation. Rhegmatogenous retinal detachment (RD) results from a break in the neuroretina, triggering ischemia, photoreceptor death, and cellular proliferation. Proliferative vitreoretinopathy (PVR) further complicates these conditions through fibrous proliferation. Despite their prevalence and potential for blindness, our understanding of the molecular mechanisms underlying these vitreoretinal diseases is incomplete.Methods and resultsTo elucidate disease mechanisms and identify potential therapeutic targets, we conducted a comparative proteomic analysis of vitreous samples from DR, RD, and macular pucker (P) patients, which were chosen as controls. LC–MS analysis identified 988 quantifiable proteins, with distinct clustering observed among disease groups. Differential expression analysis revealed 202 proteins in RD vs. P and 167 in DR vs. P, highlighting distinct proteomic signatures. Enrichment analysis identified glucose metabolism as an altered process in both diseases, suggesting common pathways despite differing etiologies. Notably, aldo–keto reductase family 1 member B1 (AKR1B1) has emerged as a potential key player in both DR and RD, indicating its role in glucose metabolism and inflammation. In silico drug screening identified diclofenac, an approved ophthalmic non-steroidal anti-inflammatory drug (NSAID), as a potential therapeutic agent targeting AKR1B1.ConclusionOur study revealed distinct proteomic signatures and common pathways in vitreoretinal diseases, highlighting AKR1B1 as a potential therapeutic target. Using diclofenac during diagnosis and postoperative care for diabetic retinopathy or rhegmatogenous retinal detachment may reduce complications, lower costs, and improve quality of life. Future research will focus on confirming AKR1B1’s role in vitreoretinal diseases and understanding diclofenac’s mechanism of action.

Optic neuropathy as an initial manifestation of acute retinal necrosis caused by varicella zoster virus: a case report

BackgroundWe present the treatment and follow-up of a rare patient with acute retinal necrosis (ARN) with optic neuropathy as the first manifestation.Case presentationA 57-year-old male patient first presented with reduced vision and optic neuropathy in his right eye.After 20 days, the vision in the left eye decreased, and the slit-lamp examination showed no remarkable changes in the anterior segment. The right eye showed 2 + cells and flares in the anterior chamber. The iris texture was good, the pupils were round (light reflex), the crystalline lens was slightly opaque, and the vitreous was turbid. An anterior chamber paracentesis was performed to collect aqueous humor for polymerase chain reaction testing. The PCR test showed positive detection of VZV in the right eye, while the content of VZV in the left eye was lower than the reference value. Both eyes of the patient were successively diagnosed with acute retinal necrosis (ARN) due to VZV infection. The patient was treated with topical antiviral and anti-inflammatory eye medication, oral steroids, and general antiviral drugs. After three months, the vision and condition were relatively stable.ConclusionsClinicians should realize that accurate diagnosis and timely antiviral therapy are crucial for treating ARN.

Evaluating diclofenac's risks in COVID-19: strategies for mitigating adverse outcomes.

The use of nonsteroidal anti-inflammatory drugs (NSAIDs), particularly diclofenac, during the COVID-19 pandemic has raised concerns due to its potential to worsen disease progression. This commentary evaluates key risks associated with diclofenac and highlights the critical role of pharmacists in mitigating adverse outcomes through careful medication management and patient education. Diclofenac poses unique risks due to its ability to generate reactive oxygen species (ROS), leading to oxidative stress and mitochondrial dysfunction. In COVID-19, a disease characterized by hyperinflammation, these effects may exacerbate systemic inflammation, contributing to severe outcomes. Moreover, diclofenac's known association with increased cardiovascular risks, such as myocardial infarction and stroke, is especially concerning in patients with COVID-19, who are predisposed to thrombotic complications. The drug's hepatotoxic potential adds another layer of concern, particularly in patients with pre-existing liver dysfunction or those at higher risk due to COVID-19-related liver involvement. Pharmacists play a pivotal role in addressing these risks by conducting thorough medication reviews and assessing patient-specific risk factors. They can guide clinicians and patients toward safer alternatives, such as ibuprofen or naproxen, which demonstrate a lower oxidative and cardiovascular burden. Patient education is equally critical; pharmacists should counsel individuals on potential adverse effects of diclofenac, such as cardiovascular symptoms, renal dysfunction, and liver complications, while advising on lifestyle modifications and adjunctive therapies to reduce NSAID dependence. Additionally, pharmacists contribute to pharmacovigilance by monitoring patients for adverse drug reactions and reporting safety concerns to improve NSAID usage guidelines during the pandemic. By adopting a personalized approach to NSAID therapy, pharmacists can minimize risks and enhance patient safety, ultimately improving outcomes in the management of COVID-19 and other inflammatory conditions. This underscores their indispensable role in optimizing care during complex clinical scenarios.

Impact of Antibiotics and Chronic Medications on Efficacy of Immune Checkpoint Inhibitors in Patients With Hepatocellular Carcinoma.

The interaction of immune checkpoint inhibitors (ICI) and concomitant medications such as antibiotics, metformin, statins, beta-blockers, proton pump inhibitors (PPIs), nonsteroidal anti-inflammatory drugs (NSAIDs), and low-dose aspirin has been studied in other malignancies. Our study aims to investigate the relationship between these medications and ICI efficacy in patients with advanced hepatocellular carcinoma (aHCC). A retrospective review of patients who received at least one dose of ICIs between May 2015 and November 2019 was performed. The primary objectives were to compare the overall survival (OS) and progression-free survival (PFS) between patients with and without medication usage. Log rank test was used to assess for differences in survival. Hazard ratios were reported using Cox proportional hazard regression analysis. The data cutoff date was December 31, 2020. A total of 168 patients were included. Median age was 69 years, 85.7% male, 60.7% ECOG 0, 78.0% Child-Pugh A liver cirrhosis, 57.7% hepatitis B etiology, 8.9% hepatitis C, and 33.3% nonviral. One hundred three patients (61.3%) received ICI monotherapy, while 38.7% received ICI in combination. Sixty-two patients (36.9%) had concomitant antibiotic usage, 26.8% metformin, 30.4% statin, 31.0% beta-blockers, 60.1% PPI, 6.5% NSAIDs, and 11.9% aspirin. Patients with aHCC receiving antibiotics did not have a shorter OS (adjusted HR [aHR] 1.40, 95% CI 0.94-2.09, p=0.096) or shorter PFS (aHR 0.94, 95% CI 0.66-1.34, p=0.73), as compared to those who did not receive antibiotics. However, patients with aHCC of viral hepatitis etiology receiving ICI treatment and concurrent antibiotics had shorter OS (5.5 vs. 14.2 months, aHR 1.93, 95% CI 1.17-3.17, p=0.010) and PFS (1.1 vs. 2.6 months, aHR 2.69, 95% CI 1.28-5.65, p=0.009), as compared to those who did not receive antibiotics. The use of antibiotics may diminish ICI efficacy in patients with aHCC of viral hepatitis etiology, while the use of metformin, statins, beta-blockers, NSAIDs, and aspirin is not associated with significant clinical outcomes.

COLONOSCOPY-RELATED NEPHROPATHY

Colonoscopy is a widely used tool for the diagnosis and treatment of colon disease [1]. It is the gold standart to visualize the large bowel [2]. Acute phosphate nephropathy (APhN) is a clinical entity which causes acute and subsequent chronic renal failure after exposure to oral sodium phosphate (OSP) bowel purgatives. APhN is seen as a result of oral sodium phosphate use in patients undergoing bowel cleansing before colonoscopy [3]. Generally, patients who will undergo colonoscopy are given 45 ml of OSP twice, starting 12-24 hours before the procedure. After intestinal absorption, elevated urea and creatinine, transient hyperphosphatemia, hypocalcemia, hypernatremia, hyponatremia, hypokalemia and high anion gap metabolic acidosis may also be observed [4]. Advanced age, ACEi/ARB use, acute or chronic kidney disese or the presence of a kidney transplant, retention of OSP resulting from poor bowel motility or colitis, female gender, volume depletion, hypertension, diabetes, and diuretic, lithium, or nonsteroidal anti-inflammatory drug use are considered as risk factors [5]. This case report describes a patient who developed nephropathy and required urgent observation and treatment after phosphate administration before colonoscopy.

The Protective Effects of Carvacrol Against Doxorubicin-Induced Cardiotoxicity In Vitro and In Vivo.

Doxorubicin (DOX) is a remarkable chemotherapeutic agent, however, its adverse effect on DOX-induced cardiotoxicity (DIC) is a rising concern. Recent research has identified carvacrol (CAR), an antioxidant and anti-inflammatory agent, as a promising natural compound for protecting against DIC. This study aims to investigate the potential cardioprotective effects properties of CAR in vitro and in vivo. The cardioprotective effect of CAR was assessed by pretreating H9c2 cells with non-toxic CAR for 24h, followed by co-treatment with DOX (10μM) for an additional 24h. The cell viability was determined using an MTT assay. For the in vivo study, male Sprague-Dawley rats (200-250g) were randomly divided into three groups: control, cardiotoxicity (DOX), and treatment (CAR + DOX) groups. CAR (50mg/kg, BW) was administered orally to the CAR + DOX groups for 14days. Then, a single dose of DOX (15mg/kg/i.p, BW) was administered on day 15 for DOX and CAR + DOX groups. The rats were allowed to recover for 3days before being sacrificed. Our results demonstrated that DOX (10µM) significantly reduced H9c2 cell viability by 50% (p < 0.0001), and CAR (0.067µM) protected H9c2 cells from DIC (p = 0.0045). In the rat model, CAR pretreatment effectively mitigated DOX-induced reductions in systolic pressure (p = 0.0007), pulse pressure (p = 0.0213), hypertrophy (p = 0.0049), and cardiac fibrosis (p = 0.0006). However, the pretreatment did not alter the heart function, oxidative stress, and antioxidant enzymes. In conclusion, our results indicate that CAR could potentially serve as an adjuvant to reduce cardiotoxicity by ameliorating myocardial fibrosis and hypertrophy.

Fabrication of curcumin-incorporated human amniotic membrane extracellular matrix-derived scaffold to enhance full-thickness wound healing in diabetic rats.

The multifactorial nature of diabetic wounds necessitates a mixed approach for successful treatment. Compensation of degenerated wound tissue extracellular matrix (ECM) and application of anti-inflammatory and antioxidant agents have been shown to be promising. Here, an attempt was made to fabricate a biocompatible wound dressing from curcumin-incorporated human amniotic membrane (HAM) ECM-derived scaffold to accelerate diabetic wound healing in rats. Therefore, after inducing diabetes, an excisional ischemic wound was created on rat skin, then treatments were administered for a period of 21days. The main groups were the diabetic animals that received an engraftment of HAM scaffold (HAMS group) and the curcumin-incorporated HAMS (HAMS/β/C group). Evaluation at post-wounding days 7, 14, and 21 indicated that the parameters related to regeneration, including wound closure, volume of new epidermis and dermis, proliferating cells, fibroblasts, blood vessels, collagen deposition, and tensile strength, as well as transcripts of Vegf, bFgf, and Tgf-β genes of the healed wound in both HAMS and HAMS/β/C groups were considerably greater than those of the diabetic group. Conversely, the presence of inflammatory cells, i.e., neutrophils and macrophages, and the transcripts of Tnf-α and Il-1β showed a dramatic decrease in the treated groups relative to the diabetic group. Finally, compared to the HAMS group, considerable differences were found with the HAMS/β/C group in almost all evaluated parameters. Overall, these results suggest that using the complementary or synergistic effects of curcumin and HAMS could be a promising approach to improve diabetic wound healing.

Do Major Pharmacovigilance Databases Support Evidence of Second Trimester NSAID and Third Trimester Paracetamol Fetotoxicity?

Background: Paracetamol and non-steroidal anti-inflammatory drugs (NSAIDs) are frequently used during pregnancy. Due to their fetotoxicity, NSAIDs are contraindicated during the third trimester. There is ongoing controversy about the extent to which NSAIDs may cause cardiovascular and renal impairment in the fetus earlier in the second trimester. Paracetamol, used as an effective treatment for closure of patent ductus arteriosus (PDA) after birth, is suspected to cause similar but unwanted effects during the third trimester of pregnancy. Methods: Three major pharmacovigilance databases (VigilanceCentral, EudraVigilance, and VigiBase) were searched for Individual Case Safety Reports (ICSRs; n = 1288) on fetotoxic effects that have been shown to result from NSAID exposure in late pregnancy. Results: In 219/1288 cases, an NSAID and/or paracetamol was taken after the first trimester, and the ICSR was not related to other reported risk factors. Out of these 219 ICSRs, 48 were exposed to NSAIDs in the second but not the third trimester or to paracetamol in the third trimester. Causality assessment was “probable or likely” in four NSAID reports and none of the paracetamol reports. Conclusions: The scarcity of adverse drug reactions (ADRs) in our study and in the literature, despite decades of pharmaceutical marketing and worldwide use of paracetamol as an analgesic of choice in the third trimester and the absence of formal contraindications against NSAIDs in the second trimester, speaks against a substantial cardiovascular and nephrotoxic risk of temporary use of NSAIDs in the second trimester or paracetamol in the third trimester. NSAIDs continue to be contraindicated in the third trimester.

Temperature-Responsive Hydrogel System Integrating Wound Temperature Monitoring and On-demand Drug Release for Sequentially Inflammatory Process Regulation of Wound Healing.

Wound healing faces challenges like inflammation, infection, and limited monitoring capabilities, and traditional dressings often lack the ability to promote healing or provide real-time wound status updates. Early pro-inflammatory responses help clear pathogens and damaged tissue, while timely anti-inflammatory modulation aids tissue regeneration, making sequential inflammation regulation crucial. Additionally, wound temperature, a key infection biomarker, enables real-time monitoring for effective management. We propose a temperature-responsive hydrogel dressing capable of two-stage sequential drug release and wound temperature monitoring. The hydrogel, composed of poly(N-isopropylacrylamide) (PNIPAM) and dopamine/methacrylated-modified hyaluronic acid (HA-MA-DA), allows temperature-based drug release control, sequential regulating pro-inflammatory and anti-inflammatory stages in wound healing. Interleukin-8 (IL-8), a pro-inflammatory molecule, is encapsulated into hydrogel matrix and rapidly released to trigger the initial inflammatory response. Furthermore, photothermally responsive and erastin-loaded polydopamine@PNIPAM nanoparticles (E-PD NPs) are incorporated to release the anti-inflammatory drug erastin upon near-infrared light exposure, terminating inflammation through cytosolic burial, and thus achieve anti-inflammatory effects at the second stage of wound healing. Furthermore, a bluetooth module enables real-time wound temperature monitoring. Combining sequential drug release with temperature monitoring, our hydrogel dressing addresses significant gaps in current wound healing technologies and offers new insights into personalized therapeutic interventions.

Perspective: Pathological transdifferentiation—a novel therapeutic target for cardiovascular diseases and chronic inflammation

Pathological transdifferentiation, where differentiated cells aberrantly transform into other cell types that exacerbate disease rather than promote healing, represents a novel and significant concept. This perspective discusses its role and potential targeting in cardiovascular diseases and chronic inflammation. Current therapies mainly focus on mitigating early inflammatory response through proinflammatory cytokines and pathways targeting, including corticosteroids, TNF-α inhibitors, IL-1β monoclonal antibodies and blockers, IL-6 blockers, and nonsteroidal anti-inflammatory drugs (NSAIDs), along with modulating innate immune memory (trained immunity). However, these approaches often fail to address long-term tissue damage and functional regeneration. For instance, fibroblasts can transdifferentiate into myofibroblasts in cardiac fibrosis, and endothelial cells may undergo endothelial to mesenchymal transition (EndMT) in vascular remodeling, resulting in fibrosis and impaired tissue function. Targeting pathological transdifferentiation represents a promising therapeutic avenue by focusing on key signaling pathways that drive these aberrant cellular phenotypic and transcriptomic transitions. This approach seeks to inhibit these pathways or modulate cellular plasticity to promote effective tissue regeneration and prevent fibrosis. Such strategies have the potential to address inflammation, cell death, and the resulting tissue damage, providing a more comprehensive and sustainable treatment solution. Future research should focus on understanding the mechanisms behind pathological transdifferentiation, identifying relevant biomarkers and master regulators, and developing novel therapies through preclinical and clinical trials. Integrating these new therapies with existing anti-inflammatory treatments could enhance efficacy and improve patient outcomes. Highlighting pathological transdifferentiation as a therapeutic target could transform treatment paradigms, leading to better management and functional recovery of cardiovascular tissues in diseases and chronic inflammation.

Investigation of the effects of a new transdermal formulation of systemic diclofenac on the upper gastrointestinal mucosa in patients with low back pain: A comparative study with oral diclofenac.

Non-steroidal anti-inflammatory drugs (NSAIDs) are associated with gastrointestinal mucosal damage attributed to a topical effect of NSAIDs on the gastrointestinal mucosa after oral administration and cyclooxygenase-1 inhibition. Diclofenac sodium systemic patch (DSSP), a transdermal patch from which diclofenac sodium is absorbed through the skin to exert its effects through the circulating blood, is considered to reduce the occurrence of gastrointestinal mucosal damage compared with oral diclofenac. This study aimed to compare the effect of DSSP on the upper gastrointestinal mucosa with that of an orally administered diclofenac sodium tablet (DST). This randomized, evaluator-blinded study included Japanese patients with low back pain (LBP). The patients were administered with either DSSP (150mg/day) or DST (75mg/day) for 2weeks. The primary endpoint was the incidence of gastroduodenal ulcers and/or erosions on upper gastrointestinal endoscopy after the study treatment. Thirty patients each were randomly assigned to the DSSP and DST groups. The incidence of gastroduodenal ulcers and/or erosions was 26.7% and 86.2% in the DSSP and DST groups, respectively. The difference in the incidence was -59.5% (95% confidence interval: -77.0 to -34.6). No adverse events (AEs) were observed in the DSSP group, and 20.0% (6/30 patients) reported mild AEs in the DST group (excluding ulcers and erosions). DSSP is associated with a lower risk of gastrointestinal mucosal damage than DST, which has the same active ingredient but uses a different route of administration, in patients with LBP.

A review and recommendations on the management of psoriatic arthritis in Australia 2024.

Psoriatic arthritis (PsA) is a progressive, systemic inflammatory disease. It can lead to serious joint damage and disability, increased cardiovascular risk and reduced quality of life. Six experts met to develop the recommendations for the management of PsA in Australia. The final recommendations are approved by all panel members. Management and treatment recommendations have been made under six subheadings: Recommendations for non-steroidal anti-inflammatory drugs and glucocorticoids; Disease-modifying treatment; Screening and monitoring; Family planning; Symptom treatment and extra-articular manifestations; Comorbidities and lifestyle considerations. Our recommendations for the management of PsA in Australia draw heavily on the established global guidelines. These recommendations aim to assist clinicians to make informed, patient-centric choices when delivering treatment to people with PsA.