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The interaction between macrophages and cardiomyocytes plays an important role not only in maintaining cardiac homeostasis, but also in the development of many cardiovascular diseases (CVDs), such as myocardial infarction (MI) and heart failure (HF). In addition to supporting cardiomyocytes, macrophages and cardiomyocytes have a close and complex relationship. By studying their cross-talk, we can better understand novel mechanisms and target pathogenic mechanisms, and improve the treatment of CVDs. We review macrophage-cardiomyocyte communication through connexin 43 (Cx43)-containing gap junctions (GJs) directly, secreted protein factors indirectly, and discuss the implications of these interactions in cardiac homeostasis and the development of various CVDs, including MI, HF, arrhythmia, cardiac fibrosis and myocarditis. In this section, we review various drugs that work by modulating cytokines or other proteins to reduce inflammation in CVDs. The clinical findings from targeting inflammation in CVDs are also discussed. Additionally, we examine the challenges and opportunities for improving our understanding of macrophage-cardiomyocyte coupling as it relates to pathophysiological disease processes, extending our research scope, and helping identify new molecular targets and improve the effectiveness of existing therapies. [ABSTRACT FROM AUTHOR]

Risk factors associated with Helicobacter pylori infection among patients attending private clinics in Borama district, Somaliland, are studied. We specifically investigated the association among the use of non-steroidal anti-inflammatory drugs, the users’ socioeconomic status, and the household hygiene practice of people with H. pylori infection attending the Borama private clinic. Helicobacter pylorus (H. pylori) is a Gram-negative spiral-shaped bacterium that infects gastric-type epithelium, and it is probably the most common bacterial agent in humans after Streptococcus mutans, which causes dental caries. H. pylori infection is now recognized as a worldwide problem and it is the most common cause of chronic gastritis and is strongly linked to peptic ulcer disease and gastric cancer. The prevalence of H. pylori infection is high in less-developed Asian countries like India, Bangladesh, Pakistan, and Thailand, and is acquired at an earlier age than in the more developed Asian countries like Japan and China. H. pylori infection is a global public health problem, affecting over 50% of the population worldwide. [ABSTRACT FROM AUTHOR]

Each life is challenged to adapt to an ever-changing environment with integrity—simply put, to maintain identity. We hypothesize that this mission statement of adaptive homeostasis is particularly poignant in an adaptive response, like inflammation. A maladaptive response of unresolved inflammation can seed chronic disease over a lifetime. We propose the concept of a molecular thumbprint: a biological signature of loss of identity as a measure of incomplete return to homeostasis after an inflammatory response. Over time, personal molecular thumbprints can measure dynamic and precise trajectories to chronic inflammatory diseases and further loss of self to cancer. Why is this important? Because the phenotypes and molecular signatures of established complex inflammatory diseases are a far cry from the root of the complex problem, let alone the initial seed. Understanding the science behind key germinating seeds of disease helps to identify molecular factors of susceptibility, resilience, and early dietary or drug intervention. We pilot this hypothesis in a rat colitis model that is well-established for understanding molecular mechanisms of colonic health, disease, and transition of colitis to cancer. [ABSTRACT FROM AUTHOR]

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In this study, a new and straightforward process for the preparation of budesonide 21-phosphate (Bud-21P) and its disodium salt (Bud-21P-Na2) is described. The method results in a yield comparable to those obtained by diphosphoryl chloride, but it is more manageable, less expensive, and safer. The new compounds are characterized by better water solubility compared to the parent compound. Moreover, they have been evaluated for their anti-inflammatory activity and the obtained results clearly evidence that Bud-21P and Bud-21P-Na2 retained anti-inflammatory activity like the parent compound budesonide (Bud) in mice with cutaneous induced edema. [ABSTRACT FROM AUTHOR]

The severity of adenovirus infection or the success of adenovirus-vectorized gene therapy largely depends on the efficiency of viral entry into cells. Various drugs can alter viral entry. This study evaluated the effects of dexamethasone, paracetamol, diclofenac, ibuprofen, and ketorolac on adenovirus entry into cells in vitro and in vivo. SiHa cell cultures pretreated with dexamethasone, paracetamol, diclofenac, ibuprofen, ketorolac, or no drug were exposed to the Ad-BGal vector. The percentage of cells showing vector entry was quantified microscopically. In vivo, BALB-C mice pretreated for 7 days with the drugs or no drug were exposed to the Ad-BGal vector intravenously (IV) or via oral (VO). Organs showing vector entry were identified by X-Gal staining and eosin counterstaining. Hepatic areas with adenovirus entry were quantified in µm2. Dexamethasone, paracetamol, and ibuprofen increased adenovirus entry both in vitro and in vivo. Diclofenac increased entry only in vitro. Ketorolac did not affect adenoviral entry. The liver exhibited the most significant changes, with dexamethasone, paracetamol, and ibuprofen increasing adenovirus entry the most. Oral administration of the vector showed that dexamethasone increased its entry into the pharynx. Some physicochemical properties of the drugs (MW (g/mol), LogP, MR [cm3/mol], tPSA, CMR, LogS, and ClogP) were analyzed, and their possible implications on cell membrane properties that could potentially influence adenovirus entry through mechanisms independent of cellular receptors were discussed. Anti-inflammatory drugs could alter adenoviral infections and adenovirus vector-based gene therapies, necessitating further research. [ABSTRACT FROM AUTHOR]

This review summarizes the impact of systemic and ocular inflammatory disorders on diabetes mellitus (DM) and diabetic retinopathy (DR). Local inflammation is a key pathology in diabetic retinopathy (DR) and is also an evolving target for clinical therapy. The legacy effects of local inflammation at the intracellular level make DR a persistent self-driven vicious process. Ocular inflammation is accompanied as well as incited by systemic inflammation due to diabetes mellitus (DM) itself. Over the years, a multitude of studies have evaluated the impact of systemic inflammatory disorders (SIDs, like rheumatoid arthritis, lupus, psoriasis, etc.) and anti-inflammatory drugs prescribed for managing them on manifestations of DM. Recent studies have indicated increased insulin resistance to be a result of chronic inflammation, and the anti-inflammatory drugs to have a protective effect towards DM. Very few studies have evaluated the impact of SIDs on DR. Furthermore, the evidence from these studies is conflicting, and while local anti-inflammatory therapy has shown a lot of clinical potential for use in DR, the results of systemic anti-inflammatory therapies have been inconsistent. The impact of local ocular inflammation due to uveitis on DR is a crucial aspect that has not been evaluated well at present. Initial pre-clinical studies and small-sized clinical reports have shown a strong and positive relationship between the presence of uveitis and the severity of DR as well as its progression, while larger cross-sectional patient surveys have refuted the same. The long term impact of ocular inflammation due to uveitis on DR needs to be studied while adjusting for confounders. [ABSTRACT FROM AUTHOR]

The severity of adenovirus infection or the success of adenovirus-vectorized gene therapy largely depends on the efficiency of viral entry into cells. Various drugs can alter viral entry. This study evaluated the effects of dexamethasone, paracetamol, diclofenac, ibuprofen, and ketorolac on adenovirus entry into cells in vitro and in vivo. SiHa cell cultures pretreated with dexamethasone, paracetamol, diclofenac, ibuprofen, ketorolac, or no drug were exposed to the Ad-BGal vector. The percentage of cells showing vector entry was quantified microscopically. In vivo, BALB-C mice pretreated for 7 days with the drugs or no drug were exposed to the Ad-BGal vector intravenously (IV) or via oral (VO). Organs showing vector entry were identified by X-Gal staining and eosin counterstaining. Hepatic areas with adenovirus entry were quantified in µm2. Dexamethasone, paracetamol, and ibuprofen increased adenovirus entry both in vitro and in vivo. Diclofenac increased entry only in vitro. Ketorolac did not affect adenoviral entry. The liver exhibited the most significant changes, with dexamethasone, paracetamol, and ibuprofen increasing adenovirus entry the most. Oral administration of the vector showed that dexamethasone increased its entry into the pharynx. Some physicochemical properties of the drugs (MW (g/mol), LogP, MR [cm3/mol], tPSA, CMR, LogS, and ClogP) were analyzed, and their possible implications on cell membrane properties that could potentially influence adenovirus entry through mechanisms independent of cellular receptors were discussed. Anti-inflammatory drugs could alter adenoviral infections and adenovirus vector-based gene therapies, necessitating further research.

Acute coronary syndrome (ACS) remains a major cause of morbidity and mortality worldwide, requiring ongoing efforts to identify novel therapeutic targets to improve patient outcomes. This manuscript reviews promising therapeutic targets for ACS identified through preclinical research, including novel antiplatelet agents, anti-inflammatory drugs, and agents targeting plaque stabilization. Preclinical studies have expounded these agents' efficacy and safety profiles in mitigating key pathophysiological processes underlying ACS, such as platelet activation, inflammation, and plaque instability. Furthermore, ongoing clinical trials are evaluating the efficacy and safety of these agents in ACS patients, with potential implications for optimizing ACS management. Challenges associated with translating preclinical findings into clinical practice, including patient heterogeneity and trial design considerations, are also discussed. Overall, the exploration of emerging therapeutic targets offers promising avenues for advancing ACS treatment strategies and improving patient outcomes. [ABSTRACT FROM AUTHOR]

Introduction: Periodontal procedures can promote prolonged intense pain, particularly in clinical situations requiring surgical procedures. In this context, preemptive analgesia has also been assessed for its utility in controlling postoperative pain and discomfort in patients undergoing periodontal invasive procedures. This study assessed the efficacy and safety of preemptive oral analgesia with steroidal and non-steroidal anti-inflammatory drugs in periodontal surgeries. Methods: This systematic review performed a search in the following electronic sources: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (via PubMed), EMBASE (via Ovid), Web of Science, Virtual Health Library and in clinical trials electronic databases for relevant randomized clinical trials (RCTs); published up to July 2023. Primary outcomes assessed were post-operative pain, edema and trismus. A narrative synthesis of the findings was carried out. Results: Six RCTs, involving a total of 250 participants, were included. The studies reviewed had a high risk of bias, particularly due to allocation concealment and blinding of participants and personnel. The RCTs reported only the outcome pain. The preemptive use of dexamethasone 8 mg, etoricoxib 90 mg or 120 mg and ketorolac 20 mg seems to be more effective for controlling post-operative pain than placebo. Discussion: The anti-inflammatory drugs evaluated proved to be effective for controlling post-operative pain. However, given the limitations regarding lack of studies, methodological biases, disparities in drugs and doses, report restricted the pain outcome; further RCTs confirming the effectiveness and safety of these drugs in periodontal surgical procedures are warranted. [ABSTRACT FROM AUTHOR]

The use of electrospun fibers as anti-inflammatory drug carriers is currently one of the most interesting approaches for the design of drug delivery systems. In recent years, biodegradable polymers blended with naturally derived ones have been extensively studied to fabricate bioinspired platforms capable of driving biological responses by releasing selected molecular/pharmaceutical signals. Here, sodium diclofenac (DicNa)-loaded electrospun fibers, consisting of polycaprolactone (PCL) or gelatin-functionalized PCL, were studied to evaluate fibroblasts' in vitro and in vivo response. In vitro studies demonstrated that cell adhesion of L929 cells (≈70%) was not affected by the presence of DicNa after 4 h. Moreover, the initial burst release of the drug from PD and PGD fibers, e.g., 80 and 48%, respectively, after 5 h—combined with its sustained release—did not produce any cytotoxic effect and did not negatively influence the biological activity of the cells. In particular, it was demonstrated that the addition of gelatin concurred to slow down the release mechanism, thus limiting the antiproliferative effect of DicNa, as confirmed by the significant increase in cell viability and collagen deposition after 7 days, with respect to PCL alone. In vivo studies in a rat subcutaneous model also confirmed the ability of DicNa-loaded fibers to moderate the inflammatory/foreign body response independently through the presence of gelatin that played a significant role in supporting the formation of small-caliber vessels after 10 days of implantation. All of these results suggest using bicomponent fibers loaded with DicNa as a valid therapeutic tool capable of supporting the wound healing process and limiting in vivo inflammation and rejection phenomena. [ABSTRACT FROM AUTHOR]

The pathophysiology of posttraumatic stress disorder (PTSD) is associated with the activation of the innate immune system, including cytokines like interleukin 6 (IL-6). However, the role of IL-6 in the etiology and treatment of PTSD still remains elusive. We conducted a prospective controlled trial to investigate the development of IL-6 during psychosomatic treatment in individuals with PTSD in comparison with individuals without PTSD. We assessed IL-6 mRNA expression before and after 2 months of psychosomatic treatment in individuals with and without PTSD. Severities of PTSD and depressive symptoms were assessed in parallel. Linear mixed regression was applied for statistical analysis, including the factors diagnosis PTSD and pre–post treatment after subgrouping for intake of anti-inflammatory drugs. The development of IL-6 mRNA expression during treatment was affected by the use of anti-inflammatory drugs. In the subgroup without intake of anti-inflammatory drugs, no significant statistical treatment effect in individuals with and without PTSD emerged. In the subgroup of individuals taking anti-inflammatory drugs, a significant interaction effect of the factors pre–post treatment and diagnosis PTSD was observed. Whereas IL-6 mRNA expression in individuals without PTSD decreased according to amelioration of symptoms, IL-6 mRNA expression in individuals with PTSD increased significantly during treatment, in opposite direction to symptom severity. Anti-inflammatory drugs might affect IL-6 mRNA expression in individuals with PTSD in a paradoxical way. This study offers a further piece of evidence that IL-6 could be involved in the pathophysiology of PTSD and PTSD-specific immunologic molecular mechanisms. [ABSTRACT FROM AUTHOR]

Anti-inflammatory enzymes have wide applications in the pharmaceutical industry. The objective of this study was to find new and efficient strains for the commercial production of serratiopeptidase enzyme. Vast number of samples were processed for the isolation of potent strains. The experimental treatment includes processing of twenty soil samples, silkworm gut, and sugarcane stem. The total protein and protease activity was estimated by Lowry's method and casein hydrolysis. The HRBC stabilization assay was performed for finding the anti-inflammatory potential of all strains. The serratiopeptidase production was confirmed by HPLC with the standard. Molecular characterization of selected potent strains was done by 16S rDNA and confirmed the taxonomy. The one step rapid purification of serratiopeptidase was performed by Ultra three phase partitioning method. The clot lysis potential of the Serratia marcescens VS56 was observed by modified Holmstorm method. The results of the study revealed that among the 60 strains, 12 strains were protease-positive on skim milk agar plates and showed significant protease activity. All 12 strains were screened for serratiopeptidase using high-performance liquid chromatography (HPLC) and VS56, VS10, VS12 and VS18 showed a similar retention time (4.66 ± 0.10 min) with standard. The selected potent strain, Serratia marcescens VS56 showed a proteolytic activity of 21.30 units/mL and produced a total protein of 102 mg/mL. The HRBC suspension results also showed a percentage of 94.6 ± 1.00 protection, which was compared to the standard diclofenac. The clot lysis potential of Serratia marcescens VS56 was 53% in 4 h. Furthermore, the molecular weight of the protein was identified to confirm the presence of serratiopeptidase. The study hence contributed successfully to isolating, screening, and identifying a potent producer for serratiopeptidase from an environmental source. This inherent advantage of the strain will undoubtedly contribute much to the coco comm commercial production of serratiopeptidase in the near future. [ABSTRACT FROM AUTHOR]

Postoperative pain is a common complication in patients undergoing major surgical operations, interfering with comfort and recovery and increasing the risk of further complications. This study aimed to evaluate the effectiveness of NSAIDs in managing postoperative pain at Manokwari Regional Hospital. Utilizing qualitative research methods, data was collected through observation and literature study and analyzed via data reduction, data presentation, and conclusion drawing. The findings indicate that NSAIDs effectively alleviate postoperative pain by inhibiting cyclooxygenase (COX) enzymes responsible for prostaglandin production. However, their use is limited by potential systemic side effects, including gastrointestinal disorders, kidney impairment, increased blood pressure, heart attack, and heart failure. Consequently, topical NSAID formulations are recommended to mitigate these risks. The study suggests that while NSAIDs are effective, clinicians should consider their side effects and prefer topical alternatives. Future research should explore the efficacy and safety of topical NSAIDs and alternative pain management strategies to enhance clinical practice. [ABSTRACT FROM AUTHOR]

Background: This study is the first to summarize the evidence on how the use of anti-inflammatory drugs during acute pain has an impact on the development of chronic pain. Methods: Randomized controlled trials retrieved from nine databases included anti-inflammatory drugs (NSAIDs or steroids) versus non-anti-inflammatory drugs in patients with acute pain and reported the incidence of chronic pain. No specified date, age, sex, or language restrictions. Subgroup analyses were performed according to pain classification, follow-up time, and medication. The GRADE method was used to evaluate quality of evidence. Results: A total of 29 trials (5220 patients) were included. Steroids or NSAIDs did not reduce the incidence of chronic nociceptive pain. Steroid use in acute phase significantly reduced the incidence of chronic neuropathic pain. In subgroup analysis, benefits were observed for methylprednisolone and dexamethasone, with some adverse effects. Steroids or NSAIDs were statistically significant in reducing pain intensity over 1 year, but the effect size was too small, and whether the long-term effect is clinically relevant needs to be further studied. Conclusion: Quality of the evidence was low to moderate. No drug can be recommended to prevent chronic nociceptive pain. Injections of steroids (methylprednisolone or dexamethasone) during the acute phase reduce the incidence of chronic neuropathic pain, but most included studies also used local anesthetics. The results are indirect and need to be interpreted with caution. The pooled data effect sizes for pain intensity were small, so the clinical relevance was unclear. Study registration PROSPERO (CRD42022367030). [ABSTRACT FROM AUTHOR]

Neurodegenerative disorders (NDs) have become increasingly common during the past three decades. Approximately 15% of the total population of the world is affected by some form of NDs, resulting in physical and cognitive disability. The most common NDs include Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease. Although NDs are caused by a complex interaction of genetic, environmental, and lifestyle variables, neuroinflammation is known to be associated with all NDs, often leading to permanent damage to neurons of the central nervous system. Furthermore, numerous emerging pieces of evidence have demonstrated that inflammation not only supports the progression of NDs but can also serve as an initiator. Hence, various medicines capable of preventing or reducing neuroinflammation have been investigated as ND treatments. While anti-inflammatory medicine has shown promising benefits in several preclinical models, clinical outcomes are often questionable. In this review, we discuss various NDs with their current treatment strategies, the role of neuroinflammation in the pathophysiology of NDs, and the use of anti-inflammatory agents as a potential therapeutic option. [ABSTRACT FROM AUTHOR]

In recent years, extensive research has delved into the pathophysiology of local reactions triggered by Bothrops snake venoms. Even though antivenom works well at reducing death and systemic effects, it is still not very effective in treating local reactions because it cannot counteract damage that has already been triggered. This limitation might be attributed to certain molecules that amplify the venom-induced innate response. While evidence suggests endogenous mediators at the venom site play a role in this envenomation, in Brazil, the concurrent use of anti-inflammatory agents or other drugs alongside antivenom remains uncommon. This study evaluated the pharmacological mediation of alterations in leukocyte–endothelium interactions following the experimental envenomation of mice with Bothrops jararaca venom, the main culprit of snake-related accidents in Southeast Brazil. We treated envenomed mice with inhibitors of different pharmacological pathways and observed the cremaster muscle microcirculation with intravital microscopy. We found that eicosanoids related to cyclooxygenase pathways and nitric oxide significantly contributed to B. jararaca venom-induced alterations in leukocyte–endothelium interactions. Conversely, lipoxygenase-mediated eicosanoids, histamine, and serotonin had minimal participation. Notably, dexamethasone and antivenom treatment diminished B. jararaca venom–induced alterations in leukocyte–endothelium interactions. The limited efficacy of the antivenom in managing Bothrops venom-induced local reactions emphasizes the critical need for supplementary treatments to enhance therapeutic outcomes. [ABSTRACT FROM AUTHOR]

Byline: Shu-Wei Zhang, Hui-Fang Shi, Yi Xi and Li Zhang Keywords:biological activity, secondary metabolite, Broussonetia papyrifera,Indigofera amblyantha,Sophora davidii INTRODUCTION Due to the rapid development of animal husbandry, the demand for [...]

Introduction: Periodontal procedures can promote prolonged intense pain, particularly in clinical situations requiring surgical procedures. In this context, preemptive analgesia has also been assessed for its utility in controlling post-operative pain and discomfort in patients undergoing periodontal invasive procedures. This study assessed the efficacy and safety of preemptive oral analgesia with steroidal and non-steroidal anti-inflammatory drugs in periodontal surgeries.Methods: This systematic review performed a search in the following electronic sources: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (via PubMed), EMBASE (via Ovid), Web of Science, Virtual Health Library and in clinical trials electronic databases for relevant randomized clinical trials (RCTs); published up to July 2023. Primary outcomes assessed were post-operative pain, edema and trismus. A narrative synthesis of the findings was carried out.Results: Six RCTs, involving a total of 250 participants, were included. The studies reviewed had a high risk of bias, particularly due to allocation concealment and blinding of participants and personnel. The RCTs reported only the outcome pain. The preemptive use of dexamethasone 8 mg, etoricoxib 90 mg or 120 mg and ketorolac 20 mg seems to be more effective for controlling post-operative pain than placebo.Discussion: The anti-inflammatory drugs evaluated proved to be effective for controlling post-operative pain. However, given the limitations regarding lack of studies, methodological biases, disparities in drugs and doses, report restricted the pain outcome; further RCTs confirming the effectiveness and safety of these drugs in periodontal surgical procedures are warranted.

Each life is challenged to adapt to an ever-changing environment with integrity—simply put, to maintain identity. We hypothesize that this mission statement of adaptive homeostasis is particularly poignant in an adaptive response, like inflammation. A maladaptive response of unresolved inflammation can seed chronic disease over a lifetime. We propose the concept of a molecular thumbprint: a biological signature of loss of identity as a measure of incomplete return to homeostasis after an inflammatory response. Over time, personal molecular thumbprints can measure dynamic and precise trajectories to chronic inflammatory diseases and further loss of self to cancer. Why is this important? Because the phenotypes and molecular signatures of established complex inflammatory diseases are a far cry from the root of the complex problem, let alone the initial seed. Understanding the science behind key germinating seeds of disease helps to identify molecular factors of susceptibility, resilience, and early dietary or drug intervention. We pilot this hypothesis in a rat colitis model that is well-established for understanding molecular mechanisms of colonic health, disease, and transition of colitis to cancer.

In this study, a new and straightforward process for the preparation of budesonide 21-phosphate (Bud-21P) and its disodium salt (Bud-21P-Na2) is described. The method results in a yield comparable to those obtained by diphosphoryl chloride, but it is more manageable, less expensive, and safer. The new compounds are characterized by better water solubility compared to the parent compound. Moreover, they have been evaluated for their anti-inflammatory activity and the obtained results clearly evidence that Bud-21P and Bud-21P-Na2 retained anti-inflammatory activity like the parent compound budesonide (Bud) in mice with cutaneous induced edema.