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Recent Advances in Inflammation & Allergy Drug Discovery - Online First
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Total Anti-oxidant Capacity and Immunosuppressive Drug Blood Levels after Kidney Transplantation: A Patent Perspective
Available online: 10 December 2024More LessBackgroundIt is well known that acute or chronic kidney injury could be due to free radicals and pro-oxidants. This investigation aimed to monitor tacrolimus or cyclosporine blood trough levels and anti-oxidant capacity after kidney transplantation. Methods: There was no intervention in the routine management of transplant recipients. The sample size (n=70) included healthy individuals and kidney-transplanted recipients (n=25 on tacrolimus and n=10 on cyclosporine). The study population was matched for age. The attained information was examined by using the Statistical Package (SPSS Inc, Chicago, IL, USA). The significance level was considered as P ≤ 0.05.
ResultsIn healthy individuals, the mean ± SD for the capacity of antioxidants was 91.9 ± 16.6 (u/ml), which was significantly higher when compared to the mean value of 28.5 ± 22.6 (u/ml) versus 24.7 ± 25.5 (u/ml), kidney recipients with tacrolimus versus cyclosporine (P ≤ 0.04) as immunosuppressive drugs. The mean value of tacrolimus levels was 14.6 ± 6.4 (ng/ml). The correlation between tacrolimus and cyclosporine trough levels and anti-oxidant capacity was 0.19 (P ≤ 0.14). There were no significant differences regarding age in cases and controls (P ≤ 42).
ConclusionThis study showed that the capacity of anti-oxidants in kidney transplant recipients, those on tacrolimus or cyclosporine, might be lower than in healthy individuals. Subsequent investigations are recommended to delve into the therapeutic consequences of the influence of antioxidant therapies on the clinical outcomes of transplanted recipients.
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Transforming Wound Management: Advancement in Nanomaterials-based Therapeutics
Authors: Kanika Goyal, Shaveta Ahalwat and Vikas JogpalAvailable online: 04 December 2024More LessThe landscape of wound management has undergone a revolutionary transformation with the integration of nanomaterials-based therapeutics. This abstract explores the profound impact of nanotechnology on wound care, highlighting the unique properties of nanomaterials and their role in advancing therapeutic interventions. Nanomaterials, characterized by their dimensions at the nanoscale, have emerged as versatile tools in wound management. The review focuses on various types of nanomaterials, including nanoparticles, nanofibers, and nanocomposites, which offer tailored solutions for optimizing wound healing processes to facilitate controlled drug delivery, developing a novel approach on account of achieving controlled transport of bioactive agents, such as growth factors, antimicrobial compounds, and anti-inflammatory drugs. This precision in drug delivery enhances therapeutic efficacy, promoting optimal wound healing outcomes. One of the pivotal contributions of nanomaterials to wound management is their engineered antimicrobial properties. Nanoparticles also exhibit effective antibacterial characteristics, addressing concerns related to wound infections. Nanomaterials integrated into dressings and scaffolds enhance mechanical strength and provide a conducive environment for cellular processes, fostering tissue regeneration, angiogenesis, and extracellular matrix synthesis. Nanoparticles with anti-inflammatory and antioxidant functionalities create a balanced microenvironment, reduce chronic inflammation, and promote a pro-regenerative milieu. In conclusion, integrating nanomaterials into wound management strategies represents a paradigm shift in therapeutic approaches.
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Neutrophil-lymphocyte, Lymphocyte-monocyte, and Platelet-lymphocyte Ratios: Non-invasive Biomarkers for Assessing Inflammatory Bowel Disease Activity
Available online: 04 December 2024More LessBackgroundInflammatory bowel diseases (IBD) necessitate cost-effective biomarkers for efficient management. This study aimed to explore the potential correlations of neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and platelet-to-lymphocyte ratio (PLR) with IBD disease activity. Additionally, we assessed their associations with other inflammatory markers.
MethodsWe recruited 180 IBD patients with over 12 months of disease duration, categorized into two groups: Group 1 (active IBD) with 113 cases and Group 2 (inactive IBD) with 67 cases, alongside 200 group-matched healthy controls (Group 3). Hemogram, NLR, LMR, PLR, hs-CRP, ESR, fecal calprotectin (FC), and relevant parameters were recorded.
ResultsNLR and PLR were elevated, while LMR was decreased in active IBD patients compared to those in remission. The cutoff values for active IBD were determined as NLR > 1.98, LMR < 3.01, and PLR > 147, exhibiting sensitivity of 92%, 88%, and 91%, and specificity of 93%, 87%, and 89% respectively. Optimal cutoff values for IBD disease activity were CRP > 9.71, ESR > 24, and FC > 176. Multivariate logistic regression identified NLR, LMR, and PLR as robust parameters for discriminating IBD disease activity after adjusting for WBC, CRP, ESR, and FC markers (p < 0.05). NLR and PLR exhibited proportional increases with IBD severity, while LMR lacked such predictive capability.
ConclusionsNLR, PLR, and LMR emerge as simple, non-invasive, and cost-effective independent markers of IBD disease activity, complementing traditional markers like CRP and ESR.
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Analysis of Oral and Gut Microbiota Composition in Children with Dental Caries by NGS Approaches
Available online: 04 December 2024More LessObjectivesThis study aimed to characterize oral and gut microbiota of children with high dmft index and caries-free children at phylum, family and species levels as well as to evaluate the effect of Streptococcus salivarius M18 DSM 14685 (Carioblis) administration on microbiota composition of caries active children.
Materials and MethodsTen children with active caries and nine caries-free children have been recruited. Four samples from different oral niches and stools were collected from each patient for the NGS sequencing of 16s Microbiota rDNA by S5 Ion Torrent.
ResultsOur results revealed modifications in the microbiota composition of teeth, saliva and vestibular regions of the oral cavity and faecal samples in the presence of dental caries. These changes were evident at the family and species levels, with no significant differences found at the phylum composition level. In particular, Streptococcaceae were positively correlated to the high degree of caries in all niches, and the analysis at the species level led to the identification of 39 bacterial species significantly modulated in the analyzed groups. The use of probiotic seemed to exert beneficial effects on oral but not on faeces dysbiosis. The intestinal tract was confirmed to have a different microbiota composition compared to the oral cavity.
ConclusionsDental caries mainly lead to modifications in the oral microbiota composition. Streptococcus salivarius M18 DSM 14685 administration determines a shift in the oral microbiota composition towards a healthier state. Concerning the gastrointestinal tract, our study found for the first time that caries cause the increase of two bacterial species, related to other disorders: Bifidobacterium adolescentis and Ruminococcus torques.
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Network Pharmacology Analysis to Explore the Pharmacological Mechanism of Cang Er Zi Powder Against Allergic Rhinitis
Authors: Qisheng Cui, Ping Liu, Huifang He, Cuiyin Chen, Xuemin Hou, Tao Xie and Weijie ChenAvailable online: 06 November 2024More LessBackgroundAllergic rhinitis (AR) is a leading public health problem with high prevalence, but the therapies remain limited. Cang Er Zi Powder (CEZP), a Traditional Chinese Medicine formula, has been used for the clinical treatment of chronic rhinitis and allergic rhinitis in China for decades. However, the underlying mechanism is unclear.
ObjectiveIn this study, we aimed to clarify the pharmacological mechanism of CEZP on allergic rhinitis
MethodThe active ingredients of CEZP were screened in the TCMSP (http://tcmspw.com/tcmsp.php) database. The targets related to “allergic rhinitis” were retrieved from MALACARDS, TTD, and DisGeNET disease target databases. The active ingredients and the candidate targets for AR were constructed and visualized using Cytoscape 3.7.2 software. The underlying mechanism involved in the treatment of CP against AR was analyzed using the WEB-based GEne SeT AnaLysis Toolkit. The effects of CEZP on levels of β-hexosaminidase, histamine, interleukin (IL)-4, and tumor necrosis factor (TNF)-α on DNP-IgE/HSA-stimulated rat basophilic leukemia cells were determined by enzyme-linked immunosorbent assay (ELISA) kits.
ResultsA total of 78 active ingredients in 9 Chinese herbs of CEZP and 90 target overlap targets from CEZP and AR were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis suggested that the inflammation response and NF-κB signaling pathway were responsible for the therapeutic targets of CEZP on AR, and CEZP could suppress mast cell degranulation via Toll-like receptor (TLR) and NF-κb signaling pathway.
ConclusionNetwork pharmacology analysis and in vitro assays suggested that CEZP may exert therapeutic effects on AR by inhibiting the NF-κB signaling pathways.
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Multifaceted Role of Tiliroside in Inflammatory Pathways: Mechanisms and Prospects
Authors: Gurjeet Kaur, Jasleen Kaur, Jayant Goyal, Lavish Vaid, Thakur Gurjeet Singh, Randhir Singh and Sushma DeviAvailable online: 23 October 2024More LessTiliroside, a natural polyphenolic compound found in several plant sources, has garnered attention for its potential to mitigate inflammation and its associated diseases. The current review explores the multifaceted functions of Tiliroside in inflammation-related diseases, delving into the underlying mechanisms and prospects for therapeutic applications. Tiliroside exerts its anti-inflammatory effects through a variety of mechanisms, such as the inhibition of inflammatory mediators’ cytokines and chemokines, as well as the suppression of nuclear factor-kappa B (NF-κB) signaling pathways. Additionally, it demonstrates potent antioxidant properties, which further contribute to its anti-inflammatory activity by reducing oxidative stress. In preclinical studies, Tiliroside has shown promising results in ameliorating inflammation in conditions like rheumatoid arthritis, inflammatory bowel disease, and atherosclerosis. Furthermore, Tiliroside's ability to modulate immune responses and stimulate tissue regeneration contributes to its potential as a multimodal agent in treating inflammation-associated disorders. In conclusion, Tiliroside emerges as a promising natural compound with a multifaceted role in inflammation-related diseases with understanding the underlying mechanisms of its therapeutic prospects may pave the way for novel treatments.
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Efficacy of Eugenol Loaded Chitosan Nanoparticles on Sepsis Induced Liver Injury in Rats
Available online: 11 October 2024More LessBackgroundSepsis is a life-threatening condition responsible for high morbidity and mortality rates around the world and is characterized by a dysregulated host response to infection, resulting in multiple organ dysfunctions. Eugenol is a phenolic aromatic compound derived from clove oil. It has anti-inflammatory, antioxidant, antibacterial, antiviral, antifungal, and anticancer characteristics, which have led to its extensive use in diverse fields, including cosmetology, medicine, and pharmacology. The ongoing study aimed to evaluate the efficacy of eugenol-loaded chitosan nanoparticles (EC-NPs) on sepsis-induced liver damage using the cecal ligation and puncture (CLP) model.
MethodsThirty male albino rats were randomly divided into five groups: Sham, sepsis, and septic rats treated with chitosan, eugenol, or EC-NPs.
ResultsEC-NPs showed excellent antibacterial, antioxidant, and anti-inflammatory effects in vitro. EC-NP administration significantly improved liver function, as indicated by the decreased liver enzyme activities and C-reactive protein (CRP) level, as well as the increase of albumin content. Moreover, EC-NPs caused an increase in glutathione-reduced and antioxidant enzyme activities, as well as a reduction of malondialdehyde and nitric oxide formation. In addition, the EC-NP treatment reduced the DNA damage in septic rats; also, the EC-NP treatment repaired, to some extent, the abnormal architecture of the hepatic tissues of septic rats. Furthermore, the immunohistochemical examination showed a marked decrease in inflammation through the reduction of TNF-α and IL-1β expression.
ConclusionIn conclusion, EC-NPs attenuated liver injury in sepsis through its anti-inflammatory, anti-bacterial, and anti-oxidant activities and protection of DNA.
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Unlocking Toll-Like Receptors: Targeting Therapeutics for Respiratory Tract Infections and Inflammatory Disorders
Authors: Vishal Pandey, Debasis Sen, Sunny Rathee, Sakshi Soni, Shashank Mishra, Sanjay K. Jain and Umesh K. PatilAvailable online: 08 October 2024More LessThe Toll-like Receptors (TLRs) family has significantly enhanced the understanding of innate immune responses by identifying and responding to various microbes or host-derived organisms. TLRs contribute to these responses by increasing the levels of cytokines, interleukins, and other inflammatory mediators through multiple pathways. Located both intracellularly and on the surface of various cells and tissues, including vascular smooth muscles (VSMs) and myocardium cells, TLRs play distinct roles in innate immune activation, such as recognizing pathogen-associated molecular patterns (PAMPs) and activating downstream signaling pathways. In the context of COVID-19, TLRs are critically involved in the pathophysiology by mediating excessive inflammatory responses that exacerbate disease severity, influencing both the acute phase and long-term outcomes. It has been observed that inflammatory diseases such as atherosclerosis, viral myocarditis, and other comorbidities associated with the spread of COVID-19 have increased, although the exact mechanisms remain not fully understood. Nonetheless, there is evidence of TLR-mediated increased pro-inflammatory signaling by different mechanisms in these diseases. This review explains the role of TLRs in various inflammatory diseases related to COVID-19, including viral myocarditis, acute lung infections, and atherosclerosis. Furthermore, the review discusses various herbal drugs, such as Platycodon grandiflorum, Acanthopanax senticosus, Scutellaria baicalensis Georgi, and Engelhardia roxburghiana, and their mechanisms of action on TLRs, including NF-κB, MyD88-dependent, MyD88-independent pathways, and Plasmacytoid DCs. Enhanced clarity on TLRs' specific contributions to COVID-19 pathophysiology and stronger evidence supporting herbal interventions targeting TLRs could improve the impact and applicability of these findings in clinical settings.
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Cyclooxygenases: From Prostaglandin Synthesis to Innovative Therapies for Inflammation
Authors: Sumeet Sharma, Prerna Sharma and Nidhi RaniAvailable online: 03 October 2024More LessCyclooxygenases are enzymes involved in prostaglandin synthesis, a part of the inflammatory process. The most frequently applied anti-inflammatory drugs are NSAIDs; however, these medications exhibit very serious side effects, and often, reduce production or are withdrawn from the market. Recently, researchers were focused on finding new, safe, selective COX-2 inhibitors with safety features. This paper reviews cyclooxygenase enzyme malfunction-related diseases, current therapies and new drug discovery opportunities. Prostaglandin-endoperoxide synthases are enzymes involved in the synthesis of prostanoid peptides through the oxidation of nitric oxide and pyruvate phosphate. They are participating factors for various physiological and pathological processes, which include disorders of the oral tissues such as periodontitis, pulpitis, and oral cancer. This paper is a review of some pharmaceutical products in terms of history, efficiency, and possible side effects as inhibitors of the Cyclooxygenase enzyme. The analysis concludes that more recent Cox inhibitors, such as dietary modifications and natural supplements, hold promise for safer and more efficient treatment of diseases involving Cox enzyme function.
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A Comprehensive Review of Acanthosis Nigricans: Pathogenesis, Clinical manifestation and Management
Authors: Shiana, Shivika Parmar, Priyanka guleria, Shammy Jindal, M.S Ashawat and Pravin KumarAvailable online: 03 October 2024More LessBackgroundAcanthosis Nigricans is a dermatological condition characterized by hyperpigmented velvet plaques that can be observed in flexural areas such as the neck, axilla, and groin. AN is frequently associated with insulin resistance and obesity, however, it can also appear in non-obese people and as a paraneoplastic disease. Its prevalence varies across different populations, with higher rates observed in individuals with obesity, diabetes, and certain genetic syndromes. Classification of AN can be based on underlying etiology, distinguishing primary and secondary forms. Pathogenesis is the complex interplay of genetic, hormonal, and environmental factors, with insulin resistance playing a central role. Diagnosis relies on clinical evaluation of characteristics of skin changes, often requiring further investigation for underlying systemic disease. Topical therapies involve keratolytic agents, retinoids, and alpha hydroxyl acids to improve the cosmesis and reduce the plaque's thickness. Treatment strategies address underlying conditions by emphasizing lifestyle modifications and in some cases, pharmacological interventions.
ObjectiveThis review aims to comprehensively examine the pathogenesis, clinical manifestation, and management of acanthosis nigricans.
DiscussionAN is closely linked to insulin resistance, characterized by impaired cellular response to insulin, leading to compensatory hyperinsulinemia. Recognizing AN’s clinical presentation is paramount for early diagnosis and appropriate management.
ConclusionAcanthosis Nigricans is a skin condition characterized by dark, thickened patches of skin, typically occurring in skin folds and creases. It can be a sign of an underlying health issue such as insulin resistance, obesity, hormonal disorders, or certain medications. Proper diagnosis and management of the underlying conditions are crucial. Treatment may involve addressing the underlying causes, lifestyle changes, and topical medications to improve the appearance of the skin. Regular monitoring and follow-up with a health care professional are essential for optimal management and to prevent complications.
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Integrating Precision Medicine in Diabetes Mellitus: Enhancing Wound Healing and Shaping Future Therapies
Authors: Abhash Kumar, Avijit Mazumder, Priyanka Bansal, Pankaj Kumar Tyagi and Amrinder KaurAvailable online: 03 October 2024More LessThis extensive analysis explores the dynamic interface between precision medicine and diabetes mellitus treatment, with a specific emphasis on wound healing in diabetic populations. Beginning with an insightful introduction, the article underscores the critical importance of effective wound healing within the broader context of diabetes mellitus, while tracing the evolutionary trajectory of precision medicine in healthcare. By elucidating the pathophysiological intricacies of diabetic wound healing, the review unveils the complex molecular mechanisms that drive this multifaceted process. Subsequently, a meticulous exploration follows into the application of precision medicine paradigms in diabetic wound care, delineating fundamental principles and diverse avenues through which precision medicine strategies can optimize diabetes management. Through a nuanced discussion of targeted therapies and interventions, the review highlights burgeoning approaches tailored to individual patient needs, accentuating the transformative potential of precision medicine in reshaping treatment paradigms. Drawing upon clinical trials and compelling case studies, the article offers valuable insights into the real-world efficacy of precision treatment modalities, elucidating successful applications and their profound implications for diabetic wound healing outcomes. Moreover, the review anticipates and addresses emerging challenges and future trajectories within the field, including the pivotal roles of biomarkers and diagnostic modalities, the integration of telemedicine platforms, and the increasing influence of artificial intelligence on diabetic wound healing endeavours. By synthesizing contemporary knowledge and delineating prospective pathways, this review underscores the catalytic potential of precision medicine in heralding a new era of enhanced outcomes for diabetic patients grappling with impaired wound healing.
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Preliminary In silico Analysis of Adenylate Kinase 1 (ADK1) of Echinococcus granulosus as a Candidate for Vaccination against Cystic Echinococcosis
Available online: 19 September 2024More LessBackgroundA neglected zoonosis, Cystic Echinococcosis (CE), is most common in developing nations worldwide. Vaccination is, therefore, helpful in preventing the disease.
ObjectivePredicting the main biochemical properties of E. granulosus Adenylate Kinase 1 (ADK1) and its possible B-cell and T-cell-binding epitopes as a valuable candidate for immunization was the goal of the current study.
MethodsPredictions were made to determine biochemical, antigenic, structural, and subcellular characteristics, along with the immunogenic epitopes, using several online servers.
ResultsThe extracellular 22 KDa protein had no allergenicity, while it possessed hydrophilicity (GRAVY: -0.286), stability (instability: 17.48), tolerance to a wide range of temperatures (aliphatic: 93.45), and 17 post-translational modification sites. The secondary structure mostly comprised helices and random coils and the 3D model was generated using Robetta server (confidence: 0.88). Common B-cell epitopes were discovered by three servers and screened for antigenic, allergenic, and solubility traits. Moreover, MHC-associated epitopes for mice and humans were predicted in E. granulosus ADK1 with subsequent screening.
ConclusionThis work offers a foundation for further investigation on designing an effective vaccination against CE. Further empirical research study with the examined protein solely or combined with other antigens is needed.
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