We present two pediatric patients who exhibited an unusual clinical presentation of cutaneous acute graft-versus-host disease (GVHD), characterized by livedo-like appearance. Such manifestations of cutaneous acute GVHD have not been previously documented.

Due to the advanced studies on stem cells in developmental biology, the roles of stem cells in the body and their phenotypes in related diseases have not been covered clearly. Meanwhile, with the intensive research on the mechanisms of stem cells in regulating various diseases, stem cell therapy is increasingly being attention because of its effectiveness and safety. As one of the most widely used stem cell in stem cell therapies, hematopoietic stem cell transplantation shows huge advantage in treatment of leukemia and other blood-malignant diseases. Besides, due to the effect of anti-inflammatory and immunomodulatory, mesenchymal stem cells could be a potential therapeutic strategy for variety infectious diseases. In this review, we summarized the effects of Staphylococcus aureus (S. aureus) and its components on different types of adult stem cells and their downstream signaling pathways. Also, we reviewed the roles of different kinds of stem cells in various disease models caused by S. aureus, providing new insights for applying stem cell therapy to treat infectious diseases.

The pivotal role of Granzyme B (GzmB) in immune responses, initially tied to cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells, has extended across diverse cell types and disease models. A number of studies have challenged conventional notions, revealing GzmB activity beyond apoptosis, impacting autoimmune diseases, inflammatory disorders, cancer, and neurotoxicity. Notably, the diverse functions of GzmB unfold through Perforin-dependent and Perforin-independent mechanisms, offering clinical implications and therapeutic insights. This review underscores the multifaceted roles of GzmB, spanning immunological and pathological contexts, which call for further investigations to pave the way for innovative targeted therapies.

Cross-disease genome-wide association studies (GWASs) unveil pleiotropic loci, mostly situated within the non-coding genome, each of which exerts pleiotropic effects across multiple diseases. However, the challenge \"W-H-W\" (namely, whether, how, and in which specific diseases pleiotropy can inform clinical therapeutics) calls for effective and integrative approaches and tools. We here introduce a pleiotropy-driven approach specifically designed for therapeutic target prioritization and evaluation from cross-disease GWAS summary data, with its validity demonstrated through applications to two systems of disorders (neuropsychiatric and inflammatory). We illustrate its improved performance in recovering clinical proof-of-concept therapeutic targets. Importantly, it identifies specific diseases where pleiotropy informs clinical therapeutics. Furthermore, we illustrate its versatility in accomplishing advanced tasks, including pathway crosstalk identification and downstream crosstalk-based analyses. To conclude, our integrated solution helps bridge the gap between pleiotropy studies and therapeutics discovery.

DPP4 (Dipeptidyl-peptidase 4) a versatile protease, emerges as a prominent player in soluble and membrane-bound forms. Its heightened expression has been intimately linked to the initiation and severity of diverse autoimmune diseases, spanning rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis (SSc), inflammatory bowel disease, autoimmune diabetes, and even SARS-CoV-2 infection. Operating as a co-stimulator of T cell activity, DPP4 propels T cell proliferation by binding adenosine deaminase (ADA), thereby augmenting the breakdown of adenosine-an influential inhibitor of T cell proliferation. However, the discovery of a wide range of DPP4 inhibitors has shown promise in alleviating these diseases\' signs, symptoms, and severity. The available DPP4 inhibitors have demonstrated significant effectiveness in blocking DPP4 activity. Based on the characterization of their binding mechanisms, three distinct groups of DPP4 inhibitors have been identified: saxagliptin, alogliptin, and sitagliptin, each representing a different class. Elevated levels of angiotensin-converting enzyme 2 (ACE2) expression are associated with producing various coronavirus peptidases. With its anti-inflammatory properties, Sitagliptin may assist COVID-19 patients in preventing and managing cytokine storms. This comprehensive review delves into the burgeoning realm of DPP4 inhibitors as therapeutic interventions for diverse autoimmune diseases. With a discerning focus on their efficacy, the investigation sheds light on their remarkable capacity to alleviate the burdensome signs and symptoms intricately linked to these conditions.

UNASSIGNED: Atopic dermatitis (AD) is a common inflammatory cutaneous disease that arises due to dysregulation of the Th2 immune response, impaired skin barrier integrity, and dysbiosis of the skin and gut microbiota. An abundance of Staphylococcus aureus biofilms in AD lesions increases the Th2 immune response, and gut bacteria release breakdown products such as Short Chain Fatty Acids that regulate the systemic immune response.
UNASSIGNED: We aim to evaluate therapies that modulate the microbiome in humans and discuss the clinical implications of these treatments. We performed a review of the literature in which 2,673 records were screened, and describe the findings of 108 studies that were included after full-text review. All included studies discussed the effects of therapies on the human microbiome and AD severity. Oral probiotics, topical probiotics, biologics, and investigational therapies were included in our analysis.
UNASSIGNED: Oral probiotics demonstrate mixed efficacy at relieving AD symptoms. Topical probiotics reduce S. aureus abundance in AD lesional skin, yet for moderate-severe disease, these therapies may not reduce AD severity scores to the standard of biologics. Dupilumab and tralokinumab target key inflammatory pathways in AD and modulate the skin microbiome, further improving disease severity.

Inflammatory diseases are conditions characterized by abnormal and often excessive immune responses, leading to tissue and organ inflammation. The complexity of these disorders arises from the intricate interplay of genetic factors and immune responses, which challenges conventional therapeutic approaches. However, the field of genetic manipulation has sparked unprecedented optimism in addressing these complex disorders. This review aims to comprehensively explore the application of gene therapy and gene editing in the context of inflammatory diseases, offering solutions that range from correcting genetic defects to precise immune modulation. These therapies have exhibited remarkable potential in ameliorating symptoms, improving quality of life, and even achieving disease remission. As we delve into recent breakthroughs and therapeutic applications, we illustrate how these advancements offer novel and transformative solutions for conditions that have traditionally eluded conventional treatments. By examining successful case studies and preclinical research, we emphasize the favorable results and substantial transformative impacts that gene-based interventions have demonstrated in patients and animal models of inflammatory diseases such as chronic granulomatous disease, cryopyrin-associated syndromes, and adenosine deaminase 2 deficiency, as well as those of multifactorial origins such as arthropathies (osteoarthritis, rheumatoid arthritis) and inflammatory bowel disease. In conclusion, gene therapy and gene editing offer transformative opportunities to address the underlying causes of inflammatory diseases, ushering in a new era of precision medicine and providing hope for personalized, targeted treatments.

Protein kinases have emerged as major contributors to various diseases. They are currently exploited as a potential target in drug discovery because they play crucial roles in cell signaling, growth, and regulation. Their dysregulation is associated with inflammatory disorders, cancer, and neurodegenerative diseases. Pyruvate dehydrogenase kinase 3 (PDK3) has become an attractive drug target in cancer therapeutics. In the present study, we investigated the effective role of thymol in PDK3 inhibition due to the high affinity predicted through molecular docking studies. Hence, to better understand this inhibition mechanism, we carried out a 100 ns molecular dynamics (MD) simulation to analyse the dynamics and stability of the PDK3-thymol complex. The PDK3-thymol complex was stable and energetically favourable, with many intramolecular hydrogen bond interactions in the PDK3-thymol complex. Enzyme inhibition assay showed significant inhibition of PDK3 by thymol, revealing potential inhibitory action of thymol towards PDK3 (IC50 = 2.66 μM). In summary, we established thymol as one of the potential inhibitors of PDK3, proposing promising therapeutic implications for severe diseases associated with PDK3 dysregulation. This study further advances our understanding of thymol\'s therapeutic capabilities and potential role in cancer treatment.

Formyl peptide receptors (FPRs) comprise a class of chemoattractant pattern recognition receptors, for which several physiological functions like host-defences, as well as the regulation of inflammatory responses, have been ascribed. With accumulating evidence that agonism of FPR1/FPR2 can confer pro-resolution of inflammation, increased attention from academia and industry has led to the discovery of new and interesting small-molecule FPR1/FPR2 agonists. Focused attention on the development of appropriate physicochemical and pharmacokinetic profiles is yielding synthesis of new compounds with promising in vivo readouts. This review presents an overview of small-molecule FPR1/FPR2 agonist medicinal chemistry developed over the past 20 years, with a particular emphasis on interrogation in the increasingly sophisticated bioassays which have been developed.

OBJECTIVE: We aim to establish the utility of a trial of low-dose systemic glucocorticoid therapy in the assessment of new clinically suspected inflammatory arthritis patients.
METHODS: We retrospectively identified patients from a private rheumatology practice in Melbourne, Australia between January 1st, 2019, and December 31st, 2021, who presented with clinically suspected inflammatory arthritis and subsequently underwent a trial of low-dose prednisolone (15 mg daily weaned over three weeks in 5 mg increments). We excluded patients with known autoimmune/ inflammatory disorders or concurrent immunosuppression at presentation. We collected basic participant demographic details and clinical details of their presentation, glucocorticoid response, investigations, and treatment.
RESULTS: We recruited 177 participants with a median age of 52, and 69.5% were female gender. The median symptom time to presentation was 12 months. Hands were the most affected joint in 63.3% and 85% had bilateral disease. Among the participants, 29.4% had synovitis on clinical review and 75.7% had imaging performed as part of the initial assessment. At presentation, the median CRP was 11 and the median ESR was 16. 79.7% of the cohort experienced significant improvement in their arthritis symptoms from low-dose glucocorticoids and 83.6% of the cohort required long-term immunosuppression for an underlying inflammatory condition. Of those who responded to glucocorticoids, 92.1% were diagnosed with an inflammatory condition. Rheumatoid arthritis was the most common overall diagnosis in 28%.
CONCLUSIONS: An initial trial of low-dose glucocorticoids in undifferentiated arthritis patients is useful in predicting the diagnosis of inflammatory arthritis. It is also a predictor of further long-term steroid-sparing therapy.