Inflammatory Disease Research Articles

The Mechanism and Progress of Traditional Chinese Medicine in Treating Ulcerative Colitis

Ulcerative colitis (UC) is a chronic non-specific inflammatory disease of the rectum and colon with unclear etiology, characterized by abdominal pain, diarrhea, and mucopurulent bloody stools. The majority of lesions in this disease involve the mucosa and submucosa of the rectum and sigmoid colon, which can extend to the distal end and even spread throughout the entire colon. The severity of this disease varies, and it often presents a chronic course of recurrent attacks. It is difficult to cure and has the possibility of cancer transformation. It has been listed as one of the modern difficult to treat diseases by the WHO. The incidence rate and prevalence of the disease have obvious regional and ethnic differences, with North American and Nordic whites the highest. However, in recent decades, the incidence rate of the disease in China has continued to increase. Traditional Chinese medicine has certain advantages in treating UC, and its therapeutic effect is not inferior to that of Western medicine. It has fewer adverse reactions and lower costs, and has good social and economic significance. This article provides an overview of the mechanism and clinical research status of traditional Chinese medicine in treating UC, in order to provide more ideas for the treatment research of this disease.

Indole-3-Aldehyde alleviates lung inflammation in COPD through activating Aryl Hydrocarbon Receptor to inhibit HDACs/NF-κB/NLRP3 signaling pathways.

Indole-3-aldehyde (I3A) is an intestinal microbial metabolite that regulates inflammation in various inflammatory diseases; however, its role in chronic obstructive pulmonary disease (COPD) remains unclear. This study aimed to investigate the anti-inflammatory effects and molecular mechanisms of I3A in COPD. We constructed in vivo models using cigarette smoke (CS)-stimulated mice and in vitro models using cigarette smoke extract (CSE)-stimulated MH-S cells. The results demonstrated that I3A significantly alleviated bronchial obstruction in mice with COPD and reduced the expression of inflammatory factors such as TNF-α, IL-1β, and IL-6. Additionally, I3A decreased the levels of matrix metalloproteinases MMP2, MMP12, and inhibited the NF-κB p65/NLRP3 pathways. Further investigation revealed that I3A inhibited NF-κB activity by suppressing p65 phosphorylation and nuclear translocation in CSE-stimulated MH-S cells. The activation of the NF-κB and NLRP3 signaling pathways is mediated by histone deacetylase 5 (HDAC5) and HDAC6, both of which are inhibited by I3A. Subsequent experiments indicated that aryl hydrocarbon receptor (AHR) knockdown attenuated the inhibitory effect of I3A on pro-inflammatory cytokines and the HDACs/NF-κB/NLRP3 signaling pathways, highlighting the dependence of I3A's anti-inflammatory effects on the AHR receptor. KEY MESSAGES: I3A effectively reduced lung inflammation in COPD mice by inhibiting the NF-κB pathway. In CSE-stimulated MH-S cells, I3A suppressed p65 phosphorylation and nuclear translocation, thereby inhibiting NF-κB activity. The activation of the NF-κB/NLRP3 pathways by HDAC5 and HDAC6 was diminished by I3A. Through the activation of the AHR receptor, I3A suppressed the activities of HDAC5/6, leading to a decrease in inflammatory factor levels.

Role of STING Deficiency in Amelioration of Mouse Models of Lupus and Atherosclerosis.

Systemic lupus erythematosus (SLE) is a systemic autoimmune syndrome characterized by autoreactive responses to nucleic acids, dysregulation of the type I interferon (IFN-I) pathway, and accelerated atherosclerosis. The stimulator of IFN genes (STING), a cytosolic DNA sensor, has pathogenic implications in various inflammatory diseases. However, its specific role in SLE pathogenesis, particularly in tissue damage, remains unclear. This study aimed to elucidate the role of STING in murine models of Toll-like receptor 7 (TLR7)-driven lupus and atherosclerosis. A TLR7-driven lupus model was induced using imiquimod (IMQ) in wild-type (WT) and STING knockout (Sting1-/-) mice on a B6 background. Mice were assessed for organ involvement, serum autoantibodies, and innate and adaptive immune responses. Additionally, Sting1-/- mice were backcrossed to apolipoprotein E knockout (Apoe-/-) mice, and both Apoe-/- and Apoe-/-Sting1-/- mice were fed a high-fat chow diet to induce atherosclerosis. Phenotypic assessments were conducted. Compared with IMQ-treated WT mice, Sting1-/- mice exhibited reduced disease severity in the lupus-like phenotype, characterized by decreased splenomegaly, lower renal immune complex deposition and renal damage, diminished expansion of myeloid cells, and reduced activation of T and B lymphocytes. IMQ-induced DNA release associated with IFN-β production and subsequent IFN-induced responses were attenuated in Sting1-/- mice. DNase I treatment mitigated IMQ-induced proinflammatory responses in WT mice but had no effect in Sting1-/- mice. Furthermore, STING deficiency conferred protection against vascular damage and reduced atherosclerosis burden, accompanied by decreased IFN-I production. Human monocyte-derived macrophages treated with IFN-I significantly internalized more acetylated low-density lipoprotein when compared with untreated cells, whereas an association between oxidized nucleic acids and disease activity and vascular damage was found in human SLE. These findings highlight a pathogenic role of STING and downstream IFN responses in TLR7-driven autoimmunity, vascular damage and atherosclerosis, supporting a therapeutic potential for STING inhibition in SLE treatment. Further research is warranted to elucidate the mechanisms underlying STING's involvement in these processes and to explore the feasibility of targeting STING as a therapeutic strategy in SLE and related autoimmune disorders.

Isoliquiritigenin Exhibits Anti-Inflammatory Responses in Acute Lung Injury by Covalently Binding to the Myeloid Differentiation Protein-2 Domain.

Acute lung injury (ALI), a systemic inflammatory response with high morbidity, lacks effective pharmacological therapies. Myeloid differentiation protein-2 (MD2) has emerged as a promising therapeutic target for ALI. Herein, we aimed to evaluate the ability of isoliquiritigenin (ISL), a natural flavonoid found in licorice as a novel MD2 inhibitor, to inhibit lipopolysaccharide (LPS)-induced ALI. We established a mouse ALI model and a RAW 264.7 cell injury model through LPS administration. Then, lung injury was assessed through histopathological examination, and the effects of ISL were evaluated using immunofluorescence, western blotting, reverse transcription-quantitative polymerase chain reaction, flow cytometry, and enzyme-linked immunosorbent assays. In addition, the interaction between ISL and MD2 was investigated through co-immunoprecipitation and LPS displacement assays. Molecular docking and liquid chromatography/mass spectrometry analyses were employed to predict the ISL-binding domain of MD2. We found that ISL covalently bound to the Cysteine 133 residue of MD2, disrupting the formation of the LPS/MD2/toll-like receptor 4 complex, and ISL significantly suppressed proinflammatory cytokine production and reactive oxygen species generation in LPS-induced RAW264.7 cells. Moreover, ISL significantly alleviated lung injury in LPS-induced mice, reducing pulmonary microvascular permeability, inflammatory cell infiltration, and inflammatory cytokine expression. The underlying mechanism of ISL involved the inhibition of nuclear factor kappa B and the p38 mitogen-activated protein kinase pathway. Our findings supported that MD2 is the direct target of ISL in mediating its anti-inflammatory response invivo and invitro, and it holds potential as a therapeutic candidate for treating ALI and other inflammatory diseases.

An adenoviral vector encoding an inflammation-inducible antagonist, HMGB1 Box A, as a novel therapeutic approach to inflammatory diseases.

Influenza, as well as other respiratory viruses, can trigger local and systemic inflammation resulting in an overall "cytokine storm" that produces serious outcomes such as acute lung injury (ALI) or acute respiratory distress syndrome (ARDS). We hypothesized that gene therapy platforms could be useful in these cases if the production of an anti-inflammatory protein reflects the intensity and duration of the inflammatory condition. The recombinant protein would be produced and released only in the presence of the inciting stimulus, avoiding immunosuppression or other unwanted side effects that may occur when treating infectious diseases with anti-inflammatory drugs. To test this hypothesis, we developed AdV.C3-Tat/HIV-Box A, an inflammation-inducible cassette that remains innocuous in the absence of inflammation but releases HMGB1 Box A, an antagonist of high mobility group box 1 (HMGB1), in response to inflammatory stimuli such as lipopolysaccharide (LPS) or influenza virus infection. We report here that this novel inflammation-inducible HMGB1 Box A construct in a non-replicative adenovirus (AdV) vector mitigates lung and systemic inflammation therapeutically in response to influenza infection. We anticipate that this strategy will apply to the treatment of multiple diseases in which HMGB1-mediated signaling is a central driver of inflammation.IMPORTANCEMany inflammatory diseases are mediated by the action of a host-derived protein, HMGB1, on Toll-like receptor 4 (TLR4) to elicit an inflammatory response. We have engineered a non-replicative AdV vector that produces HMGB1 Box A, an antagonist of HMGB1-induced inflammation, under the control of an endogenous complement component C3 (C3) promoter sequence, that is inducible by LPS and influenza in vitro and ex vivo in macrophages (Mϕ) and protects mice and cotton rats therapeutically against infection with mouse-adapted and human non-adapted influenza strains, respectively, in vivo. We anticipate that this novel strategy will apply to the treatment of multiple infectious and non-infectious diseases in which HMGB1-mediated TLR4 signaling is a central driver of inflammation.

The role of vitamin D in treated and refractory ulcerative colitis patients: a case-control study

BackgroundUlcerative colitis is a form of chronic inflammatory bowel disease (IBD) marked by ongoing inflammation of the mucosal lining that extends from the rectum to the upper part of the colon. Vitamin D regulates immune responses in several autoimmune and inflammatory diseases, including ulcerative colitis. Therefore, the study aims to investigate the role of vitamin D in the pathogenesis and treatment of ulcerative colitis.MethodsThis case-control study included 94 participants who were divided into four groups. Group 1: people with ulcerative colitis who responded to treatment (n = 24). Group 2: family members of patients who responded to treatment and did not have the disease (n = 24). Group 3: People with ulcerative colitis who are resistant to treatment (n = 23). Group 4: family members of treatment-resistant patients who does not have the disease (n = 23). Groups 1 and 3 were considered as patient groups (n = 47) and groups 2 and 4 as control groups (n = 47). Blood samples were taken and analyzed for complete blood count (CBC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and serum vitamin D levels.ResultsThe mean age of treatment-responsive patients (group 1) was 45.88 ± 18.51 years, while treatment-resistant patients (group 3) averaged 41.30 ± 13.01 (P = 0.33) years. Serum Vitamin D levels were 24.96 ± 9.66 ng/mL in group 1 and 27.70 ± 12.28 ng/mL in group 3, showing no significant correlation with ulcerative colitis (P = 0.41). All groups had a BMI within the normal range, and mean CRP levels varied significantly across groups. Hemoglobin was significantly lower in group 3 compared to group 1 (P = 0.029), but ESR results showed no significant relationship with ulcerative colitis. Vitamin D levels were highest in patients with lower BMI, and no significant relationships were found between Vitamin D and other risk factors, although extensive colitis was associated with higher Vitamin D levels compared to distal colitis.ConclusionIn this study, there was no significant association between ulcerative colitis and serum levels of vitamin D. However, the small number of patients may limit the conclusions that can be drawn regarding the role of vitamin D in the treatment of ulcerative colitis. Future studies should aim for larger cohorts to provide more definitive insights into this important issue.

Immune modules to guide diagnosis and personalized treatment of inflammatory skin diseases

Previous advances have identified immune pathways associated with inflammatory skin diseases, leading to the development of targeted therapies. However, there is a lack of molecular approaches that delineate these pathways at the individual patient level for personalized diagnostic and therapeutic guidance. Here, we conduct a cross-comparison of expression profiles from multiple inflammatory skin diseases to identify gene modules defining relevant immune pathways. Seven modules are identified, representing key immune pathways: Th17, Th2, Th1, Type I IFNs, neutrophilic, macrophagic, and eosinophilic. These modules allow the development of a molecular map with high diagnostic efficacy for inflammatory skin diseases and clinico-pathologically undetermined cases. Aligning dominant modules with treatment targets offers a rational framework for treatment selection, improving response rates in both treatment-naïve patients and non-responders to targeted therapies. Overall, our approach offers precision medicine for inflammatory skin diseases, utilizing transcriptional modules to support diagnosis and guide personalized treatment selection.

Seawater Pools Versus Freshwater Pools to Treat Inflammatory Skin Diseases and Rheumatic Conditions: A Scoping Review

Seawater is a long-standing remedy against a number of skin or rheumatic conditions since ancient times, now popular in many countries, where spa, thalassotherapy and seawater pools have considerably boomed. Exposure to seawater and sunlight is an essential component of thalassotherapy, defined by any controlled interaction with marine environments and their natural elements, even in the absence of skin applications of algae, sands or muds. Seawater pools therefore offer the opportunity of thalassotherapy to patients unable to go the beach or during the winter months. The evidence from various studies seems to converge on combined exposure to solar radiation and seawater as a more effective approach than irradiation alone or bathing in freshwater followed by irradiation to reduce symptoms of inflammatory skin diseases or rheumatic conditions. An unwanted consequence of chlorine-based treatment of seawater is the formation of DBPs due to reactions of disinfectants with organic matter of anthropogenic origin released by bathers. Whilst chlorination of freshwater predominantly generates chlorinated DBPs, the prevailing DBPs produced by chlorination of seawater pools are brominated DBPs, reportedly more genotoxic. However, despite greater toxicity of brominated DBPs, there is evidence that DBPs concentration in freshwater pools is significantly higher (probably due to the larger number of users) compared to seawater pools. Containing the number of bathers could therefore reduce the risk of exposure to DBPs. The outdoor location of seawater pools can further contribute to reducing the risk of genotoxicity thanks to volatilization, airborne dispersion and photodegradation of some DBPs.

Research and application of intelligent diagnosis and treatment engineering bacteria

For over a century, scientists have been harnessing the therapeutic potential of bacteria in treating diseases. The advent of synthetic biology in recent years has propelled the development of genetically engineered bacteria with enhanced intelligence. These bacteria can autonomously detect environmental cues and relay them to pivotal promoters, leading to the expression of functional proteins. By utilizing modular components, they are capable of executing a range of functions, including sensing, transmitting, and outputting signals. Based on these principles, a series of intelligent diagnostic and therapeutic engineered bacteria have emerged. These bacteria are capable of targeting diseased sites, sensing disease-specific signals, and producing reporter and therapeutic drugs. Furthermore, the integration of intelligent diagnostic and therapeutic engineered bacteria with advanced technologies such as artificial intelligence, nanomaterials, and optics has paved the way for diverse clinical applications. Three critical stages are explored in this article, which include the selection of strains, the design of biosensing systems, and the planning of release strategies. The application of intelligent diagnosis and treatment engineering bacteria in metabolic diseases, inflammatory diseases, tumors and infectious diseases is reviewed.

Dietary Modulation of the Immune System

Recent insights into the influence of nutrition on immune system components have driven the development of dietary strategies targeting the prevention and management of major metabolic-inflammatory diseases. This review summarizes the bidirectional relationship between nutrition and immunocompetence, beginning with an overview of immune system components and their functions. It examines the effects of nutritional status, dietary patterns, and food bioactives on systemic inflammation, immune cell populations, and lymphoid tissues, as well as their associations with infectious and chronic disease pathogenesis. The mechanisms by which key nutrients influence immune constituents are delineated, focusing on vitamins A, D, E, C, and B, as well as minerals including zinc, iron, and selenium. Also highlighted are the immunomodulatory effects of polyunsaturated fatty acids as well as bioactive phenolic compounds and probiotics, given their expanding relevance. Each section addresses the implications of nutritional and nutraceutical interventions involving these nutrients within the broader context of major infectious, metabolic, and inflammatory diseases. This review further underscores that, while targeted nutrient supplementation can effectively restore immune function to optimal levels, caution is necessary in certain cases, as it may increase morbidity in specific diseases. In other instances, dietary counseling should be integrated to ensure that therapeutic goals are achieved safely and effectively.

Imaging of tumor-associated macrophage dynamics during immunotherapy using a CD163-specific nanobody-based immunotracer

Immunotherapies have emerged as an effective treatment option for immune-related diseases, such as cancer and inflammatory diseases. However, variations in patient responsiveness limit the broad applicability and success of these immunotherapies. Noninvasive whole-body imaging of the immune status of individual patients during immunotherapy could enable the prediction and monitoring of the patient's response, resulting in more personalized treatments. In this study, we developed a nanobody-based immunotracer targeting CD163, a receptor specifically expressed on macrophages. This anti-CD163 immunotracer bound to human and mouse CD163 with high affinity and specificity without competing for ligand binding. Furthermore, the tracer showed no unwanted immune cell activation and was nonimmunogenic. Upon radiolabeling of the anti-CD163 immunotracer, specific imaging of CD163+ macrophages using micro-single-photon emission computerized tomography/computed tomography or micro-positron emission tomography/CT was performed. The anti-CD163 immunotracer was able to stratify immunotherapy responders from nonresponders (NR) by visualizing differences in the intratumoral CD163+ TAM distribution in Lewis lung carcinoma-ovalbumin tumor-bearing mice receiving an anti-programmed cell death protein-1 (PD-1)/CSF1R combination treatment. Immunotherapy-responding mice showed a more homogeneous distribution of the PET signal in the middle of the tumor, while CD163+ TAMs were located at the tumor periphery in NR. As such, visualization of CD163+ TAM distribution in the tumor microenvironment could allow a prediction or follow-up of therapy response. Altogether, this study describes an immunotracer, specific for CD163+ macrophages, that allows same-day imaging and follow-up of these immune cells in the tumor microenvironment, providing a good basis for the prediction and follow-up of immunotherapy responses in cancer patients.

Cannabichromene as a Novel Inhibitor of Th2 Cytokine and JAK/STAT Pathway Activation in Atopic Dermatitis Models

Cannabichromene (CBC) is one of the main cannabinoids found in the cannabis plant, and although less well known than tetrahydrocannabinol (THC) and cannabidiol (CBD), it is gaining attention for its potential therapeutic benefits. To date, CBC’s known mechanisms of action include anti-inflammatory, analgesic, antidepressant, antimicrobial, neuroprotective, and anti-acne effects through TRP channel activation and the inhibition of inflammatory pathways, suggesting that it may have therapeutic potential in the treatment of inflammatory skin diseases, such as atopic dermatitis (AD), but its exact mechanism of action remains unclear. Therefore, in this study, we investigated the effects of CBC on Th2 cytokines along with the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathways involved in AD pathogenesis. We used a 2,4-Dinitrochlorobenzene (DNCB)-induced BALB/c mouse model to topically administer CBC (0.1 mg/kg or 1 mg/kg). The results showed that skin lesion severity, ear thickness, epithelial thickness of dorsal and ear skin, and mast cell infiltration were significantly reduced in the 0.1 mg/kg CBC-treated group compared with the DNCB-treated group (p < 0.001). In addition, real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis showed a significant decrease in the mRNA expression of Th2 cytokines (TSLP, IL-4, IL-13) and inflammatory mediators (IFN-γ, IL-1β, IL-6, IL-17, IL-18, and IL-33) (p < 0.05). Western blot analysis also revealed a significant decrease in JAK1, JAK2, STAT1, STAT2, STAT3, and STAT6 protein expression (p < 0.05). These results suggest that CBC is a promising candidate for the treatment of AD and demonstrates the potential to alleviate AD symptoms by suppressing the Th2 immune response.

The predictive effects of adiponectin and irisin hormones on diagnosis and clinical involvement of Sarcoidosis

BackgroundSarcoidosis is a chronic disease of unknown etiology characterised by systemic non-caseating granulomas that can affect any organ in the body, especially the lungs and in which genetic and environmental factors are thought to play a role in its pathophysiology.Adipokines and myokines secreted from adipose and muscle tissue play a role in the pathogenesis or protection against many inflammatory and autoimmune diseases in which inflammation and immunity form the basis. In our study, we aimed to investigate the role of the irisin and adiponectin in sarcoidosis.MethodsThe study included 90 sarcoidosis patients and 86 healthy subjects. Adiponectin and irisin levels were analysed in addition to standard tests for diagnosis and follow-up of patients with sarcoidosis. The sensitivity and specificity of serum irisin levels for the diagnosis of sarcoidosis were evaluate dusing ROC analysis.ResultsIrisin levels were significantly lower in the patient group than in the control group (3.28–5.25, p < 0.001). There was no association between irisin levels and extrapulmonary involvement. The cut-off irisin value for the diagnosis of sarcoidosis was ≤ 4.2662 with 95% confidence interval, and the sensitivity and specificity were calculated as 84% and 55.8%, respectively.ConclusionsTo our knowledge, this is the first study to investigate irisin in sarcoidosis patients. Based on the available evidence, anti-inflammatory, anti-oxidant and anti-apoptocic effects of irisin may play a role in the pathophysiology of sarcoidosis.Although no significant difference was found in our study, we believe that a comprehensive evaluation of adiponectin in sarcoidosis is important.

Review of atypical optic neuritis.

Optic neuritis (ON), an inflammatory optic neuropathy, is among the most common causes of visual loss. In its initial clinical appearance, ON may have unilateral or bilateral presentation, and anterior (papillitis) or retrobulbar localization. Traditionally, cases are divided into typical and atypical ON. In the Western hemisphere, most typical cases of optic nerve inflammation are associated with multiple sclerosis (MS). However, ON may also be associated with a series of disorders of known or initially undetected origin. Atypical ON has a somewhat different clinical picture from typical ON, and encompasses neuromyelitis optica spectrum disease (NMOSD), myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), idiopathic recurrent neuroretinitis (NR), chronic relapsing inflammatory ON (CRION), ON within systemic autoimmune diseases, paraneoplastic and neuritis during or after infectious diseases or vaccination. The causes should be meticulously worked up, to address the therapeutic and prognostic challenges posed by these conditions. Here, we provide a brief overview of atypical ON, as encountered in our clinical practice, and additionally discuss the possible occurrence of optic neuropathies other than inflammatory and other ocular diseases within these disorders.

Both Feed Restriction and Transition Period Suppressed Adipose Tissue MRNA Abundance of Genes Involved in Lipogenesis and Lipolysis in Fat-Tailed Ewes.

This study sought to investigate the consequences of the induced feed restriction during the transition period on the mRNA abundance of genes entangled in lipogenesis and lipolysis in the tail adipose of fat-tailed sheep. Twenty fat-tailed ewes were randomised into the control (Control; n = 10) and restriction (Restriction; n = 10) groups. Control animals were fed 100% of the balanced diet pre-(Week -5 to parturition) and post-partum (parturition to Week 5). Restriction ewes received equivalent 100%, 50%, 65%, 80%, and 100% of the balanced ration at Weeks -5, -4, -3, -2, and -1 relative to parturition, respectively. After parturition, the latter group received the equivalent of 100%, 50%, 65%, 80%, and 100% of the diet recommendation at weeks 1, 2, 3, 4, and 5, respectively. At the end of weeks -3 and 3, tail adipose were sampled under local anesthesia. Fatty acid synthase, acetyl-CoA carboxylase, carnitine palmitoyltransferase I and II, and acyl-CoA synthase long-chain family member-1 mRNA abundances were measured using the TaqMan quantity real-time PCR. A mixed model procedure of SAS software was used to evaluate the results. Feed restriction downregulated target genes' mRNA abundance during both pre- and post-partum. Parturition suppressed the mRNA abundance of measured genes in both groups. Established on the outcomes, lipogenesis, and lipolysis of the adipose tissue would be influenced by metabolite and hormone instability during the transition period and feed restriction. The lessening of adipose tissue lipogenesis and lipolysis might be a hemostatic response to cope with the energy insufficiency for fetal growth and the onset of lactation and also prevent the induction of inflammation, metabolic disorders, and infectious diseases during feed restriction or transition period.

Residual bone level as a prognostic factor in the surgical treatment of peri-implantitis

Peri-implantitis is a progressive inflammatory disease affecting the tissues surrounding dental implants and leading to bone loss. The severity of this disease is typically classified based on the depth of the bone defect or the percentage of bone loss around the implant. Marginal bone loss is a critical factor in the surgical management of peri-implantitis, as it can complicate access for implant decontamination and hinder efforts to stabilize the condition. In cases where bone loss exceeds 50% of the implant length, explantation is often recommended due to significantly reduced success rates after treatment. This narrative review seeks to examine the scientific evidence on marginal bone loss as a prognostic factor in the surgical treatment of peri-implantitis.

Efficacy and safety of azathioprine in patients with Cronkhite-Canada syndrome: a case series from Peking Union Medical College Hospital

BackgroundCronkhite-Canada syndrome (CCS) is a rare non-hereditary chronic inflammatory disease characteristic of gastrointestinal polyps and ectodermal abnormalities. Corticosteroid therapy is the mainstay medication for CCS. Few studies indicated immunosuppressants might be the choices for patients with steroid refractory, steroid dependent or intolerant.AimTo examine the efficacy and safety of azathioprine (AZA) in CCS patients.MethodWe retrospectively reviewed the records of 12 CCS patients treated with azathioprine between July 2014 and October 2023 and the clinical data including demographic characteristics, treatment regimen and adverse events were subsequently collected and analyzed. The genetic variants of TPMT and NUDT15 genes were also retrospectively assessed using sanger sequencing in 11 patients.OutcomeAll patients were in active stage at baseline and 9 patients (75%) were in combination with corticosteroid. On account of the indication, 6 patients were steroid dependent or intolerant and another 6 patients needed augmentation therapy. The target dose of AZA was 1.0 to 1.5 mg/kg per day. Ten (83.3%) patients achieved clinical response, of whom 3 cases had endoscopic remission and 5 cases had endoscopic improvement respectively. Three (25%) patients suffered from pneumocystis carinii pneumonia, liver dysfunction and leukopenia, respectively, resulting in cessation of AZA in the initial 3 months. Four heterozygous missense variants of TPMT and NUDT15 were identified in four patients. One patient who had TPMT*6 and took AZA with the dose of 2.04 mg/kg per day suffered from severe leukopenia.ConclusionAzathioprine might be a good alternative medication in CCS patients who are steroid dependent or intolerant, or need augmentation therapy. The adverse events should be closely monitored especially myelosuppression and the tests of TPMT and NUDT15 genotypes before therapy may be helpful for medication guidance.

Dynamic 18F-FDG PET to detect differences among patients with progressive and relapsing multiple sclerosis: a pilot study.

Patients with multiple sclerosis (MS) may remain in a relapsing-remitting (RRMS) course despite long-standing disease, while others will develop secondary progression (SPMS). Chronic inflammation and changes in the blood-brain barrier resulting in perturbed glucose metabolism may account for these differences. PET-MRI with kinetic analysis of 2-deoxy-2(18F)fluoro-d-glucose (18F-FDG) provides insight into glucose metabolism and has proven useful in several chronic inflammatory diseases. However, to our knowledge, it has never been studied in MS. To explore potential differences in glucose distribution kinetics among individuals with long-standing SPMS and RRMS using dynamic 18-F-FDG PET-MRI. Dynamic 18-F-FDG PET-MRI scans were obtained in 11 patients with long-standing MS: 4 with RRMS and 7 with SPMS. Kinetic analysis of PET data was performed using a three-compartment model equation that represents plasma, tissue and 18F-FDG phosphorylation. Individual rate constants of 18-F-FDG across the compartments were calculated. Patients with SPMS exhibited a trend towards an increased net influx rate of glucose (p = 0.059) and an increased rate constant representing glucose phosphorylation. Together, the data suggest increased uptake of glucose and glycolysis in these patients. Dynamic 18F-FDG PET-MRI is a feasible technique that may show information in vivo of glucose metabolism in MS. Although preliminary data suggest a potential radiological marker of progression in MS, further studies are required to confirm this hypothesis.

Continuous Biosensing to Monitor Acute Systemic Inflammation, a Diagnostic Need for Therapeutic Guidance.

Continuous monitoring of acute inflammation can become a very important next step for guiding therapeutic interventions in severely ill patients. This Perspective discusses the current medical need for patients with acute inflammatory diseases and the potential of continuous biosensing technologies. First, we discuss biomarkers that could help to monitor the state of a patient with acute systemic inflammation based on theoretical studies and empirical data. Then, based on the state of the art, we describe sensing strategies that could be applied for the continuous monitoring of acute inflammatory biomarkers, followed by challenges that must be overcome. Nanoswitch-based continuous biosensors enable suitable measurement frequencies but still lack sensitivity, while regeneration risks lower sensor reliability. Developments are still needed in bioreceptors and molecular architectures, regeneration techniques, combined with suitable sampling and sample pretreatment methods, for bringing continuous biosensing of inflammation closer to reality. Furthermore, collaborations between healthcare professionals and scientists, regulatory bodies, and biosensor engineers are needed for a successful translation of sensing technologies from the laboratory to clinical practice.

Anti-Inflammatory Properties of Novel 1,2-Benzothiazine Derivatives and Their Interaction with Phospholipid Model Membranes

The design of novel anti-inflammatory drugs remains a critical area of research in the development of effective treatments for inflammatory diseases. In this study, a series of 1,2-benzothiazine was evaluated through a multifaceted approach. In particular, we investigated the potential interactions of the potential drugs with lipid bilayers, an important consideration for membrane permeability and overall pharmacokinetics. In addition, we evaluated their ability to inhibit cyclooxygenase 1 and cyclooxygenase 2 activity and selectivity using both a cyclooxygenase inhibition assay and molecular docking simulations. To evaluate their therapeutic potential, we performed in vitro assays to measure cytokine mRNA expression in inflamed cells. The antioxidant activity was evaluated using both in vitro assays, such as 2,2-diphenyl-1-picrylhydrazyl and 2,2-azino-bis-3-ethylbenzothiazoline-6-sulphonic acid scavenging, to determine the compounds’ capacity to neutralize free radicals and reduce oxidative stress. Theoretical calculations, including density functional theory, were used to predict the reactivity profiles of the compounds.