Acute Inflammatory Disorders Research Articles

The Preventive and Therapeutic Effects of Acute and Severe Inflammatory Disorders with Heparin and Heparinoid.

Systematic inflammatory response syndrome (SIRS) and the accompanying sepsis pose a huge threat to human health worldwide. Heparin is a part of the standard supportive care for the disease. However, the molecular mechanism is not fully understood yet, and the potential signaling pathways that play key roles have not yet been elucidated. In this paper, the main findings regarding the molecular mechanisms associated with the beneficial effects of heparin, including inhibiting HMGB-1-driven inflammation reactions, histone-induced toxicity, thrombo-inflammatory response control and the new emerging mechanisms are concluded. To set up the link between the preclinical research and the clinical effects, the outcomes of the clinical trials are summarized. Then, the structure and function relationship of heparin is discussed. By providing an updated analysis of the above results, the paper highlights the feasibility of heparin as a possible alternative for sepsis prophylaxis and therapy.

Anti-inflammatory peptide therapeutics and the role of sulphur containing amino acids (cysteine and methionine) in inflammation suppression: A review.

Inflammation serves as our body's immune response to combat infections, pathogens, viruses, and external stimuli. Inflammation can be classified into two types: acute inflammation and chronic inflammation. Non-steroidal anti-inflammatory medications (NSAIDs) are used to treat both acute and chronic inflammatory disorders. However, these treatments have various side effects such as reduced healing efficiency, peptic ulcers, gastrointestinal toxicities, etc. METHOD: This review assesses the potential of anti-inflammatory peptides (AIPs) derived from various natural sources, such as algae, fungi, plants, animals, and marine organisms. Focusing on peptides rich in cysteines and methionine, sulphur-containing amino acids known for their role in suppression of inflammation. Due to their varied biological activity, ability to penetrate cells, and low cytotoxicity, bioactive peptides have garnered interest as possible therapeutic agents. The utilisation of AIPs has shown great potential in the treatment of disorders associated with inflammation. AIPs can be obtained from diverse natural sources such as algae, fungi, plants, and animals. Cysteine and methionine are sulphur-containing amino acids that aid in the elimination of free radicals, hence assisting in the treatment of inflammatory diseases. This review specifically examines several sources of AIPs including peptides that contain numerous cysteines and methionine. In addition, the biological characteristics of these amino acids and advancements in peptide delivery are also discussed.

Lipid mediators in neutrophil biology: inflammation, resolution and beyond.

Acute inflammation is the body's first defense in response to pathogens or injury. Failure to efficiently resolve the inflammatory insult can severely affect tissue homeostasis, leading to chronic inflammation. Neutrophils play a pivotal role in eradicating infectious pathogens, orchestrating the initiation and resolution of acute inflammation, and maintaining physiological functions. The resolution of inflammation is a highly orchestrated biochemical process, partially modulated by a novel class of endogenous lipid mediators known as specialized pro-resolving mediators (SPMs). SPMs mediate their potent bioactions via activating specific cell-surface G protein-coupled receptors (GPCR). This review focuses on recent advances in understanding the multifaceted functions of SPMs, detailing their roles in expediting neutrophil apoptosis, promoting clearance by macrophages, regulating their excessive infiltration at inflammation sites, orchestrating bone marrow deployment, also enhances neutrophil phagocytosis and tissue repair mechanisms under both physiological and pathological conditions. We also focus on the novel role of SPMs in regulating bone marrow neutrophil functions, differentiation, and highlight open questions about SPMs' functions in neutrophil heterogeneity. SPMs play a pivotal role in mitigating excessive neutrophil infiltration and hyperactivity within pathological milieus, notably in conditions such as sepsis, cardiovascular disease, ischemic events, and cancer. This significant function highlights SPMs as promising therapeutic agents in the management of both acute and chronic inflammatory disorders.

Discovery and Characterization of a New Class of C5aR1 Antagonists Showing In Vivo Activity.

C5a is an anaphylatoxin protein produced by the cleavage of the complement system's component C5 protein. It signals through the G-protein-coupled receptor C5a receptor 1 (C5aR1) to induce the chemotaxis of primarily neutrophils and monocytes and the release of inflammatory molecules. A large body of evidence linking C5aR1 signaling to acute and chronic inflammatory disorders has triggered interest in developing potent C5aR antagonists. Herein we report the discovery of new C5aR1 antagonistic chemical classes. Many representatives showed low nanomolar IC50 values in a C5aR1 β-arrestin-2 recruitment assay, inhibiting the migration of human neutrophils toward C5a and the internalization of the receptor in human whole blood. Two leading compounds were characterized further in vivo. Target engagement of the receptor by these two C5aR1 antagonists was demonstrated in vivo. In particular, the inhibition of migration in vitro with the two compounds further translated in a dose-dependent efficacy in a rat model of C5a-induced neutrophilia.

Precision treatment of viral pneumonia through macrophage-targeted lipid nanoparticle delivery

Macrophages are integral components of the innate immune system, playing a dual role in host defense during infection and pathophysiological states. Macrophages contribute to immune responses and aid in combatting various infections, yet their production of abundant proinflammatory cytokines can lead to uncontrolled inflammation and worsened tissue damage. Therefore, reducing macrophage-derived proinflammatory cytokine release represents a promising approach for treating various acute and chronic inflammatory disorders. However, limited macrophage-specific delivery vehicles have hindered the development of macrophage-targeted therapies. In this study, we screened a pool of 112 lipid nanoparticles (LNPs) to identify an optimal LNP formulation for efficient siRNA delivery. Subsequently, by conjugating the macrophage-specific antibody F4/80 to the LNP surface, we constructed MacLNP, an enhanced LNP formulation designed for targeted macrophage delivery. In both in vitro and in vivo experiments, MacLNP demonstrated a significant enhancement in targeting macrophages. Specifically, delivery of siRNA targeting TAK1, a critical kinase upstream of multiple inflammatory pathways, effectively suppressed the phosphorylation/activation of NF-kB. LNP-mediated inhibition of NF-kB, a key upstream regulator in the classic inflammatory signaling pathway, in the murine macrophage cell line RAW264.7 significantly reduced the release of proinflammatory cytokines after stimulation with the viral RNA mimic Poly(I:C). Finally, intranasal administration of MacLNP-encapsulated TAK1 siRNA markedly ameliorated lung injury induced by influenza infection. In conclusion, our findings validate the potential of targeted macrophage interventions in attenuating inflammatory responses, reinforcing the potential of LNP-mediated macrophage targeting to treat pulmonary inflammatory disorders.

Amelioration of ovalbumin-induced lung inflammation in a mouse model by Trichinella spiralis novel cystatin.

Asthma, a chronic disease affecting humans and animals, has recently become increasingly prevalent and steadily widespread. The alternative treatment of asthma using helminth infections or helminth-derived immunomodulatory molecules (IMs) has been evaluated and demonstrated significant amelioration of disease severity index in vitro and in vivo. Trichinella spiralis, a parasitic nematode and its IMs, elicits a potential to relieve asthma and other immune-related disorders. In this study, we investigated the immunomodulatory function of recombinant T. spiralis novel cystatin (rTsCstN) in ameliorating acute inflammatory asthma disorders in a murine model. Female BALB/c mice were sensitized using intraperitoneal injection of ovalbumin (OVA)/alum and subsequently challenged with intranasal administration of OVA alone or OVA + rTsCstN for 3 consecutive days, producing OVA-induced allergic asthma models. To evaluate the therapeutic efficacy of rTsCstN, the inflammatory cells and cytokines in bronchoalveolar lavage fluid (BALF) and OVA-specific immunoglobulin E levels in serum were assessed. Histological alterations in the lung tissues were determined by hematoxylin and eosin (H&E) staining and eventually scored for the extent of inflammatory cell infiltration. The asthmatic mouse models challenged with OVA + rTsCstN demonstrated a significant reduction of eosinophils (p < 0.01), macrophages (p < 0.05), and cytokines tumor necrosis factor-α (p < 0.05) and interferon (IFN)-γ (p < 0.05) in BALF when compared with the mice challenged with OVA alone. However, the levels of interleukin (IL)-4 and IL-10 remained unchanged. Histological examination revealed that mice administered OVA + rTsCstN were less likely to have inflammatory cell infiltration in their perivascular and peribronchial lung tissues than those administered OVA alone. Recombinant T. spiralis novel cystatin demonstrated immunomodulatory effects to reduce severe pathogenic alterations in asthma mouse models, encouraging a viable alternative treatment for asthma and other immunoregulatory disorders in humans and animals in the future.

E-selectin-mediated rapid NLRP3 inflammasome activation regulates S100A8/S100A9 release from neutrophils via transient gasdermin D pore formation

S100A8/S100A9 is a proinflammatory mediator released by myeloid cells during many acute and chronic inflammatory disorders. However, the precise mechanism of its release from the cytosolic compartment of neutrophils is unclear. Here, we show that E-selectin-induced rapid S100A8/S100A9 release during inflammation occurs in an NLRP3 inflammasome-dependent fashion. Mechanistically, E-selectin engagement triggers Bruton’s tyrosine kinase-dependent tyrosine phosphorylation of NLRP3. Concomitant potassium efflux via the voltage-gated potassium channel KV1.3 mediates ASC oligomerization. This is followed by caspase 1 cleavage and downstream activation of pore-forming gasdermin D, enabling cytosolic release of S100A8/S100A9. Strikingly, E-selectin-mediated gasdermin D pore formation does not result in cell death but is a transient process involving activation of the ESCRT III membrane repair machinery. These data clarify molecular mechanisms of controlled S100A8/S100A9 release from neutrophils and identify the NLRP3/gasdermin D axis as a rapid and reversible activation system in neutrophils during inflammation.

P21 Lupus or else?

P21 Lupus or else?

7-Hydroxy Frullanolide Ameliorates Isoproterenol-Induced Myocardial Injury through Modification of iNOS and Nrf2 Genes.

Myocardial infarction (MI) is the principal cause of premature death. Protecting myocardium from ischemia is the main focus of intense research. 7-hydroxy frullanolide (7-HF) is a potent anti-inflammatory agent, showing its efficacy in different acute and chronic inflammatory disorders such as atherosclerosis, suggesting it can be a potential cardioprotective agent. For the induction of MI, Sprague-Dawley rats (n = 5) were administered isoproterenol (ISO) 85 mg/kg s.c at 24 h intervals for two days. The potential cardioprotective effect of 7-HF and its mechanisms were explored by in vivo and in vitro methods. 7-HF significantly prevented the extent of myocardial injury by decreasing the infarct size, preserving the histology of myocardial tissue, and reducing the release of cardiac biomarkers. Further, 7-HF increased the mRNA expression of cardioprotective gene Nrf2 and reduced the mRNA expression of iNOS. 7-HF also improved cardiac function by decreasing the cardiac workload through its negative chronotropic and negative ionotropic effect, as well as by reducing peripheral vascular resistance due to the inhibition of voltage-dependent calcium channels and the release of calcium from intracellular calcium stores. In conclusion, 7-HF showed cardioprotective effects in the MI model, which might be due to modulating the expression of iNOS and Nrf2 genes as well as improving cardiac functions.

MITOCHONDRIAL ROS AND LYTIC PROGRAMMED CELL DEATH IN ACUTE INFLAMMATION.

Redox signaling through mitochondrial reactive oxygen species (ROS) has a key role in several mechanisms of regulated cell death, necroptosis, ferroptosis, pyroptosis, and apoptosis, thereby decisively contributing to inflammatory disorders. The role of mitochondrial ROS in apoptosis has been extensively addressed, but their involvement in necrotic-like regulated cell death has just started to be elucidated, providing novel insights into the pathophysiology of acute inflammation. Mitochondrial ROS trigger positive feedback loops leading to lytic regulated cell death in conjunction with the necrosome, the inflammasome, glutathione depletion, and glutathione peroxidase 4 deficiency. p53 together with mitochondrial ROS drive necroptosis in acute inflammation through downregulation of sulfiredoxin and peroxiredoxin 3. Mitochondrial hydroorotate dehydrogenase is a key redox system in the regulation of ferroptosis. In addition, a non-canonical pathway, which generates mitochondrial ROS through the Ragulator-Rag complex and acts via mTORC1 to promote gasdermin D oligomerization, triggers pyroptosis. The precise mechanism of membrane rupture in ferroptosis and the contribution of mitochondrial ROS to ferroptosis in inflammatory disorders are still unclear, which will need further research. Mitochondrial antioxidants may provide promising therapeutic approaches towards acute inflammatory disorders. However, establishing doses and windows of action will be required to optimize their therapeutic potential, and to avoid potential adverse side effects linked to blockade of beneficial mitochondrial ROS adaptive signaling.

Salivary tumour necrosis factor-alpha and receptor for advanced glycation end products as prognostic and predictive markers for recurrence in oral squamous cell carcinoma – a pilot study

Introduction and aim. Tumour necrosis factor-alpha (TNF-α) belongs to the cytokine family TNF/TNFR. As a multifunctional cytokine, TNF-α plays a significant role in diverse and a variety of cellular events such as cell survival, proliferation, differentiation, and death. As a pro-inflammatory cytokine, TNF-α acts as a bridge between inflammation and carcinogenesis. Receptor for advanced glycation end products (RAGE) are cellular receptors belonging to the immunoglobulin superfamily. As one of the primary mediators of innate immunity, acute and chronic inflammatory disorders, and certain cancers, RAGE signaling plays an important role. The aim of the present study is to analyze the prognostic significance of salivary TNF-α and RAGE in oral squamous cell carcinoma. Material and methods. A study was conducted testing saliva samples collected from ten patients with well-differentiated and moderately differentiated oral squamous cell carcinomas. To determine the levels of TNF-α and RAGE in unstimulated saliva from patients, an ELISA kit from RAY BIOTECH was used for the study, and the readings were read at 450 nm. Statistical analysis was performed using SPSS software. Version 23 of SPSS was used to plot the standard curve. Statistical comparisons were done using Mann-Whitney U test and ROC analysis. Results. Salivary TNF-α and RAGE in patients were considered to be induced by radiotherapy at a higher level in moderately differentiated squamous cell carcinoma when compared to well differentiated squamous cell carcinoma. Thus, there is an increase in the induced Salivary TNF-α and RAGE levels by radiotherapy with increase in the histological stages of oral squamous cell carcinoma. The statistical analysis also proved the same. Conclusion. Hence salivary TNF-α and RAGE may be used as a biomarker for oral cancer to predict the prognosis.

Overexpression of TREM1 is Associated with the Immune-Suppressive Microenvironment and Unfavorable Prognosis in Pan-Cancer.

Triggering receptors expressed by myeloid cells-1 (TREM1) is a receptor belonging to the immunoglobulin superfamily and plays an important role in pro-inflammation in acute and chronic inflammatory disorders. However, the understanding of the immunomodulatory roles of TREM1 in the tumor microenvironment remains incomplete. The expression patterns of TREM1 mRNA in tumors and adjacent normal tissues were compared by analyzing data obtained from the Genotype-Tissue Expression and The Cancer Genome Atlas datasets. Survival analysis was performed to determine the prognostic value of TREM1. Functional enrichment analysis was applied to decipher the discrepancy in biological processes between high- and low-TREM1 groups across various cancers. The correlation between TREM1 and immune cell infiltration determined by using multiple algorithms was evaluated with the Pearson method. Four independent immunotherapy cohorts were adopted to validate the role of TREM1 as a biomarker. TREM1 was elevated in most cancers as verified with clinical samples. Overexpression of TREM1 was linked with undesirable prognosis in patients. Further analysis revealed that TREM1 was positively correlated with immune response, pro-tumor pathways, and myeloid cell infiltration, while being negatively correlated with CD8+ T cell (including infiltration level and biological processes). Concordantly, tumors with high TREM1 levels were more resistant to immunotherapy. Through connective map analysis, therapeutically potential compounds like tozasertib and TPCA-1 were identified, which can be used synergistically with immunotherapy to improve the poor prognosis of patients with high TREM1 levels. Through a systematic and comprehensive pan-cancer analysis, we demonstrated that overexpression of TREM1 in tumors correlated closely with unfavorable outcome, infiltration of immune-suppressive cells, and immune regulation, which highlights its potential use as a tumor prognostic biomarker and a novel target for immunotherapy.

CXCR2 Antagonist RIST4721 Acts as a Potent Chemotaxis Inhibitor of Mature Neutrophils Derived from Ex Vivo-Cultured Mouse Bone Marrow

Neutrophils act as critical mediators of innate immunity, which depends on their rapid responses to chemokines followed by their migration towards sites of infection during chemotaxis. Chemokine receptors expressed on the surface of neutrophils mediate chemotaxis by activating contractile machinery as the cells escape from capillary beds and then attack pathogens. Neutrophils also contribute to inflammatory responses, which support pathogen destruction but can lead to acute and chronic inflammatory disorders. CXCR2, a G-protein-coupled chemokine receptor expressed on both myeloid and epithelial cells, is well-characterized for its capacities to bind multiple chemokines, including interleukin-8 and growth-related oncogene alpha in humans or keratinocyte chemokine (KC) in mice. Here we show that a small molecule CXCR2 antagonist termed RIST4721 can effectively inhibit KC-stimulated chemotaxis by neutrophils derived from ex vivo-cultured mouse bone marrow in a potent and dose-dependent manner. Antagonistic properties of RIST4721 are thoroughly characterized, including the maximal, half-maximal and minimum concentrations required to inhibit chemotaxis. Importantly, RIST4721-treated neutrophils exhibit robust phagocytosis and reactive oxygen species production, confirming drug specificity to chemotaxis inhibition. Together our data indicate that RIST4721 acts to inhibit inflammation mediated and potentiated by neutrophils and therefore promises to facilitate treatment of a host of inflammatory conditions.

Virtual screening, molecular simulations and bioassays: Discovering novel microsomal prostaglandin E Synthase-1 (mPGES-1) inhibitors

Microsomal prostaglandin E synthase-1 (mPGES-1) is an inducible prostaglandin E synthase expressed following exposure to pro-inflammatory stimuli. The mPGES-1 enzyme represents a new target for the therapeutic treatment of acute and chronic inflammatory disorders and cancer. In the present study, compounds from the ZINC15 database with an indole scaffold were docked at the mPGES-1 binding site using Glide (high-throughput virtual screening [HTVS], standard precision [SP] and extra precision [XP]), and the stabilities of the complexes were determined by molecular simulation studies. Following HTVS, the top 10% compounds were retained and further screened by SP. Again, the top 10% of these compounds were retained. Finally, the Glide XP scores of the compounds were determined, 20% were analyzed, and the Prime MM-GBSA total free binding energies of the compounds were calculated. The molecular simulations (100 ns) of the reference ligand, LVJ, and the two best-scoring compounds were performed with the Desmond program to analyze the dynamics of the target protein-ligand complexes. In human lung cells treated with the hit compounds, cell viability by colorimetric method and PGE2 levels by immunoassay method were determined. These in vitro experiments demonstrated that the two indole-containing hit compounds are potential novel inhibitors of mPGES-1 and are, therefore, potential therapeutic agents for cancer/inflammation therapies. Moreover, the compounds are promising lead mPGES-1 inhibitors for novel molecule design.

Diffusion Weighted Imaging in Neuro-Oncology: Diagnosis, Post-Treatment Changes, and Advanced Sequences-An Updated Review.

DWI is an imaging technique commonly used for the assessment of acute ischemia, inflammatory disorders, and CNS neoplasia. It has several benefits since it is a quick, easily replicable sequence that is widely used on many standard scanners. In addition to its normal clinical purpose, DWI offers crucial functional and physiological information regarding brain neoplasia and the surrounding milieu. A narrative review of the literature was conducted based on the PubMed database with the purpose of investigating the potential role of DWI in the neuro-oncology field. A total of 179 articles were included in the study.

Review of Anti-inflammatory and Immunosuppressive Drugs Used in COVID-19 Epidemic

Introduction Immunosuppressive drugs are classified into different groups depending on the mechanism of action and are used in the control of acute and chronic inflammatory disorders. Considering the possibility of severe inflammatory complications such as acute respiratory failure and cytokine storm in the patients with COVID-19, there is a need to review the updated data on the effectiveness and side effects of administering these drugs in patients. In the present article, along with the brief introduction of different categories of immunosuppressive medications, positive and negative effects of using these drugs in corona patients have been discussed.&#x0D; Conclusion: Taken together, it seems that the administration of immunosuppressive drugs has positive effects on COVID-19 patients. Reduced need for mechanical ventilation, decreased admission to the intensive care unit, promotion of acute symptoms, and decreased mortality rate, especially in critically ill patients are some of these advantages. However, the possibility of treatment prolongation and increased risk of bacterial and fungal infections should be kept in mind. Maintaining a balance in the doses and duration of immunosuppressant drugs might diminish their adverse effects.

Alternative pre-mRNA splicing as a mechanism for terminating Toll-like Receptor signaling.

While inflammation induced by Toll-like receptor (TLR) signaling is required to combat infection, persistent inflammation can damage host tissues and contribute to a myriad of acute and chronic inflammatory disorders. Thus, it is essential not only that TLR signaling be activated in the presence of pathogens but that TLR signaling is ultimately terminated. One mechanism that limits persistent TLR signaling is alternative pre-mRNA splicing. In addition to encoding the canonical mRNAs that produce proteins that promote inflammation, many genes in the TLR signaling pathway also encode alternative mRNAs that produce proteins that are dominant negative inhibitors of signaling. Many of these negative regulators are induced by immune challenge, so production of these alternative isoforms represents a negative feedback loop that limits persistent inflammation. While these alternative splicing events have been investigated on a gene by gene basis, there has been limited systemic analysis of this mechanism that terminates TLR signaling. Here we review what is known about the production of negatively acting alternative isoforms in the TLR signaling pathway including how these inhibitors function, how they are produced, and what role they may play in inflammatory disease.

Decidua Stromal Cell (DSCs), As an Alternative Treatment for Acute Inflammatory Diseases

Introduction: Mesenchymal stromal cells (MSCs) were first explored from the bone marrow in the late 60s and further studies have shown that MSCs are present in several tissues including bone marrow, adipose tissue, umbilical cord, and placenta. Their safety and efficacy were explored in several inflammatory disorders (e.g. acute graft-versus-host disease-aGvHD, Acute respiratory distress syndrome-ARDS) and non-inflammatory diseases (Osteoarthritis and regenerative medicine). We have expanded this cell therapy approach to newer and more efficient stromal cells, derived from human placenta named decidua stroma cells (DSCs). The fetus is protected against the mother's immune system by the placenta and fetal membranes (Fig1). The DSCs play an important role in the feto-maternal tolerance and have been used in Africa for centuries to treat burns. We have cultured stromal cells from fetal membranes and found that they have a better immunosuppressive effect than stromal cells from other origins. DSCs are safe to infuse with no serious side effects. DSCs differ from BM-MSCs in several aspects; they are half the size, more immunosuppressive, need direct contact to show the immunomodulatory effect, have a better expansion capacity, but do not differentiate well to cartilage and bone. We have so far used DSCs to treat patients with ARDS following Covid-19 infection as well as aGVHD and hemorrhagic cystitis (HC) following HCT. In all treated patients we achieved fairly high positive responses in the vast majority of patients. Methods The fetal membranes are dissected from the placenta tissues and undergo enzymatic digestion. DSCs are then isolated and expanded under GMP conditions from healthy donors after caesarian section. The isolated DSCs are characterized by flow cytometry, karyotype analysis. Subsequently DSCs are frozen slowly in fetal bovine serum and stored in liquid nitrogen until use. Optimal dose of DSCs is 1 × 106 /kg body weight. To prevent allergic reactions steroids were administered intravenously before each cell infusion. All DSC infusions were administered intravenously. Results: DSCs were given to ten ARDS patients following Covid-19 infection with pulmonary infiltrate. Eight patients survived and were discharged from ICU, where the blood oxygen level dramatically increased after two DSCs infusions (Behnam et al 2021) (Fig 2). Eleven patients with HC, grade 3-4 were also treated with DSCs after HCT. In 5 patients, HC disappeared within 5 days after DSC infusion. Patients who received DSCs within 3 days after the start of HC had a duration of HC of 5 days and a shorter duration of pain than patients who were given DSCs later (p = 0.02). Nine of the 11 patients (82%) were alive 1 year after HCT (Aronsson-Kurtila et al 2018) . DSCs were also given to 21 patients with severe aGVHD. All patients responded, and one-year survival was 76%. No patient died of GVHD. Cause of death was like those observed in allogeneic HCT patients and no death related to DCS therapy. One-year survival was significantly better than 23% in 22 patients who were treated with BM-MSCs, or 3% for 32 historic controls with conventional therapy (p<0.01) (Ringdén et al 2018). There was no infusion related toxicity. Among more than 200 DSCs infusions we observed only transient reversible infusion reactions in 3 patients. In none of them cell infusion was stopped since no severe side effect was observed ( Sadeghi et al 2019) Conclusion: MSCs from tissues, like BM, adipose, umbilical cord, and placenta tissues, have taken the step from experimental animals to clinical trials. In this abstract, we have presented the use of DSCs as treatment for acute GvHD, HC and ARDS. Further improvements in clinical efficacy by stromal cells therapy may be achieved by optimizing the cell production process. In future, many different types of MSCs products may be used for specific clinical indications. Primary indications for MSCs and DSCs include among others acute GvHD and hemorrhages, e.g. hemorrhagic cystitis and ARDS, but many other indications, e.g. osteogenesis imperfecta, rheumatic inflammatory disorders, cardiovascular diseases, sepsis and septic shock, inflammatory bowel disease, multiple sclerosis, neuroinflammation and other acute inflammatory disorders may join the line of established therapies. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Chitosan Encapsulated Meloxicam Nanoparticles for Sustained Drug Delivery Applications: Preparation, Characterization, and Pharmacokinetics in Wistar Rats

Meloxicam (MLX) is currently used in the therapeutic management of both acute and chronic inflammatory disorders such as pain, injuries, osteoarthritis, and rheumatoid arthritis in both humans and animals. Gastrointestinal toxicity and occasional renal toxicity were observed in patients taking it for a long-term period. Meloxicam's late attainment of peak plasma concentration results in a slow onset of action. The goal of the current study was to prepare and characterize chitosan encapsulated meloxicam nanoparticles (CEMNPs) with high bioavailability and less gastro intestinal toxicity in order to prevent such issues. The size of the prepared CEMNPs was approximately 110-220 nm with a zetapotential of +39.9 mV and polydispersity index of 0.268, suggesting that they were uniformly dispersed nanoparticles. The FTIR and UV-Vis spectroscopy have confirmed the presence of MLX in the prepared CEMNPs. The pharmacokinetics have been studied with three groups of male Wistar rats receiving either of the treatments, viz., 4 mg·kg-1 of MLX and 1 or 4 mg·kg-1 of CEMNPs. Plasma samples were collected until 48 h post administration, and concentrations of MLX were quantified by using reverse (C18) phase HPLC. Non-compartmental analysis was applied to determine pharmacokinetic variables. Upon oral administration, the maximum concentration (Cmax) was reached in 4 h for CEMNPs and 6 h for MLX. The mean area under the plasma MLX concentration-time curve from 'zero' to infinity (AUC0-∞), half-life (t1/2β), and mean resident time (MRT) of 1 mg·kg-1 of CEMNPs was 1.4-, 2-, and 1.8-fold greater than 4 mg·kg-1 of MLX. The prepared CEMNPs demonstrated quicker absorption and prolonged release along with a significant improvement in the bioavailability of MLX, paving a prospective path for the development of drugs with enhanced bioavailability with less side effects.

Evaluation of Risk Factors of Premature Coronary Artery Disease in Patients From North India: A Rising Epidemic

Background: The incidence of premature coronary artery disease (PCAD) is on rising trend in low- and middle-income countries. Considering the limited reports, the current study was conducted to evaluate the prevalence, various predisposing factors, and coronary angiographic findings of PCAD in North India. Methods: Study design—hospital-based analytical cross-sectional study. Setting: Outpatient and inpatient units of a tertiary cardiac center in North India. Two hundred sequential patients (170 males and 30 females) with acute coronary syndrome were evaluated for history of risk factors, measurement of anthropometric parameters, biochemical blood examination, electrocardiogram, complete dental examination, and angiographic assessment of coronary artery lesion. Patients with acute infection or chronic inflammatory disorders were excluded. Patients were divided into PCAD (age ≤45 years) and mature CAD. Results: The prevalence of PCAD was 15% (N = 30). PCAD had higher rates of family history of CAD ( P &lt; 0.001), tobacco consumption ( P = 0.01), smoking ( P = 0.004), and single-vessel disease (SVD) ( P &lt; 0.001). Premature CAD group had significantly lower mean fasting blood glucose (105 ± 41 mg/dL vs 127 ± 45 mg/dL) levels. Conclusion: Family history of CAD, smoking, and tobacco consumption are important risk factors of PCAD. SVD is more common in PCAD. Screening the susceptible population at risk and controlling the cardiovascular risk factors will help reduce the epidemic and consequences of PCAD.