Recent Advances in Inflammation & Allergy Drug Discovery最新文献

Background: Gastrointestinal (GI) cancer is associated with a group of cancers affecting the organs in the GI tract, with a high incidence and mortality rate. This type of cancer development involves a series of molecular events that arise by the dysregulation of gene expressions and microRNAs (miRNAs).

Objectives: This mini-review focuses on elucidating the mechanism of tumor suppressor miRNA-mediated oncogenic gene silencing, which may contribute to a better understanding of miRNA-mediated gene expression regulation of cell cycle, proliferation, invasion, and apoptosis in GI cancers. In this review, the biological significance of tumor suppressor miRNAs involved in gastrointestinal cancers is briefly explained.

Methods: The articles were searched with the keywords 'miRNA', 'gastrointestinal cancers', 'esophageal cancer', 'gastric cancer', 'colorectal cancer', 'pancreatic cancer', 'liver cancer', and 'gall bladder cancer' from the Google Scholar and PubMed databases. A total of 71 research and review articles have been collected and referred for this study.

Results: This review summarises recent research enhancing the effectiveness of miRNAs as novel prognostic, diagnostic, and therapeutic markers for GI cancer treatment strategies. The expression pattern of various miRNAs has been dysregulated in GI cancers, which are associated with proliferation, cell cycle regulation, apoptosis, migration, and invasion.

Conclusion: The role of tumor suppressor miRNAs in the negative regulation of oncogenic gene expression was thoroughly explained in this review. Its potential role as a microRNA therapeutic candidate is also discussed. Profiling and regulating tumor suppressor miRNA expression in gastrointestinal cancers using miRNA mimics could be used as a prognostic, diagnostic, and therapeutic marker, as well as an elucidating molecular therapeutic approach to tumor suppression.

Background and aim: Chronic Urticaria is an allergic disorder that affects about 0.5 to 5% of the population in different communities. The disease's chronic course and long-term onset impose high economic and psychological costs on communities, adversely affecting individual and social life. Platelets play a role in various pathophysiological processes, including inflammation and immunology. Growing evidence suggests that platelets are actively involved in the pathogenesis of various inflammatory disorders, including inflammatory skin diseases. This study investigated the relationship between platelet and immunoglobulin-E markers and chronic idiopathic urticaria.

Materials and methods: In the present case-control study, for the study population, patients with chronic idiopathic urticaria were referred to the Asthma and Allergy Clinic, and their caregivers were selected as the case and control groups, respectively. In this study, the mean platelet count (PLT), mean platelet volume (MPV), platelet distribution width (PDW), and Total IgE values were simultaneously measured in the case and control groups. After taking 5CCs of venous blood, a blood sample was sent to the laboratory for platelet and IgE marker measurements.

Results: 100 patients and 100 healthy persons were evaluated in this study. The mean age in the case group was 34.95, and in the control group was 35.78 years. The results showed that the mean values of PLT, MPV, PDW, and Total IgE in the case group were 12.86, 9.83, 252190, and 147.05, respectively. The mean values of PLT, MPV, PDW, and Total IgE in the control group were 16.93, 7.53, 231410, and 15.29, respectively, which was statistically significant (P = 0.001). Moreover, total IgE in the Autologous Serum Skin Test (ASST) positive group was higher than ASST negative group and was statistically significant (P = 0.001).

Conclusion: The study results indicate the possible role of platelets in urticaria and inflammation. MPV in patients with chronic urticaria was higher than in the control group. The present study showed no significant relationship between the severity of urticaria and platelet markers, but there was a significant relationship between the severity of urticaria and ASST. Moreover, the severity of urticaria was higher in the positive skin test group.

Osteoarthritis (OA) is the most common joint disease worldwide, and its rising prevalence is supported by factors such as obesity and sedentariness. At the molecular level, it is considered an inflammatory disease that leads to the destruction of articular cartilage. Effective therapy to end the degenerative process of arthritis remains elusive, and most therapeutic tools prevent the progress or alleviate the symptoms. By now, medicines for OA are available for oral, topical, or intra-articular (IA) therapy and include analgesics, nonsteroidal anti-inflammatory drugs, corticosteroids, and hyaluronic acid. Compared with conventional oral administration, IA therapy has multiple advantages in terms of bioavailability, efficacy, and toxicity. This review aims to study the underlying beneficial effects of herbal medicine in OA therapy and to open new research perspectives. Herbal medicine administered orally or topically exhibits pharmacological properties that could be relevant for their beneficial effect in OA, mainly anti-inflammatory and antioxidant effects. There are few studies regarding IA injections of plant extracts/ compounds and none related to any combination with agents already used in the clinic. Designing natural pharmaceutical formulations with increased bioavailability that are safe, lack side effects, and are specifically tested, would be a plus for research on medicinal plants and a novelty for the clinic.

Background: Growth-differentiation factor-15 (GDF-15) is a biomarker belonging to the transforming growth factor-beta cytokine superfamily, which is linked to many pathological conditions, including inflammation and myocardial injury. Pulse wave velocity (cfPWV) and augmentation index (AIx) are indices of arterial stiffness, which are associated with the severity of coronary artery disease (CAD). Flow-mediated dilatation (FMD) is a well-studied surrogate marker of endothelial-dependent dysfunction and systemic inflammation.

Objective: In this proof-of-concept study, we aimed to investigate the relationship between circulating GDF-15, endothelial dysfunction, and indices of arterial stiffness in different settings of coronary artery disease and myocardial injury.

Methods: In this cross-sectional single-center study, we enrolled patients (n = 22) after interventional treatment for acute myocardial infarction (AMI), patients (n = 11) admitted with chest pain and elevated cardiac enzymes but without evidence of obstructing CAD (MI-NOCAD) in percutaneous coronary angiography (CAG), and patients (n = 20) who underwent CAG according to indications without evident obstructive CAD in CAG (NOCAD). FMD was assessed at the brachial artery. AIx of the central aortic pressure and cfPWV were estimated by applanation tonometry at the radial and carotid-femoral site, respectively, with a validated acquisition system (Sphygmo- Cor, AtCor Medical, Sydney (NSW), Australia). ELISA was used to determine circulating GDF- 15 serum levels (R&D Systems, Minneapolis, MN). Clinical and demographic data and values of routine biochemical biomarkers were obtained. The highest high-sensitive cardiac Troponin I (hsTpnI) value during hospitalization was also recorded. Left ventricular ejection fraction (LVEF) was assessed with a transthoracic echocardiogram.

Results: Patients with AMI were older, had worse LVEF, higher values of hsTpnI and increased circulating GDF-15 levels. Importantly, AMI patients had increased cfPWV values, deteriorated AIx values, blunted FMD and worse serum creatinine levels compared to MI-NOCAD and NOCAD patients, respectively, whereas MI-NOCAD and NOCAD did not differ from each other significantly on these biomarkers. Both AMI and MI-NOCAD patients presented a higher but comparable white blood cell count than NOCAD patients. A strong linear correlation between GDF-15 and cfPWV, hsTpnI, AIx, white blood cell count and creatinine but not with FMD was demonstrated in the general study population.

Conclusion: This proof-of-concept study showed that higher circulating levels of GDF-15, an inflammatory biomarker, were associated significantly with increased arterial stiffness only in AMI patients, whereas elevated GDF-15 demonstrated a linear relationship with the severity of the myocardial injury.

Background: The characterization of new biomarkers that could help externally validate the diagnosis of COVID-19 and optimize treatments is extremely important. Many studies have established changes in immune-inflammatory and antibody levels, but few studies measured the soluble receptor for the advanced glycation end product (sRAGE), angiotensin-converting enzyme 2 (ACE2), calcium, and magnesium in COVID-19.

Objective: To evaluate serum advanced glycation end-product receptor (sRAGE) and angiotensin converting enzyme (ACE)2 and peripheral oxygen saturation (SpO2) and chest CT scan abnormalities (CCTA) in COVID-19.

Methods: sRAGE, ACE2, interleukin (IL)-6, IL-10, C-reactive protein (CRP), calcium, magnesium, and albumin were measured in 60 COVID-19 patients and 30 healthy controls.

Results: COVID-19 is characterized by significantly increased IL-6, CRP, IL-10, sRAGE, ACE2, and lowered SpO2, albumin, magnesium, and calcium. COVID-19 with CCTAs showed lower SpO₂ and albumin. SpO2 was significantly inversely correlated with IL-6, IL-10, CRP, sRAGE, and ACE2, and positively with albumin, magnesium, and calcium. Neural networks showed that a combination of calcium, IL-6, CRP, and sRAGE yielded an accuracy of 100% in detecting COVID-19 patients, with calcium being the most important predictor followed by IL-6 and CRP. Patients with positive IgG results showed a significant elevation in the serum level of IL-6, sRAGE, and ACE2 compared to the negatively IgG patient subgroup.

Conclusion: The results show that immune-inflammatory and RAGE pathways biomarkers may be used as an external validating criterion for the diagnosis of COVID-19. Those pathways coupled with lowered SpO2, calcium, and magnesium are drug targets that may help reduce the consequences of COVID-19.

Background: Many investigations have expanded this concept that liver chronic inflammation has an essential role in persistent cell damages along with altering the liver microenvironment leading to fibrosis, cirrhosis, and finally, hepatocellular carcinoma (HCC). To reduce inflammation and relieve symptoms, Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) are commonly used; however, their long-term usage can lead to severe adverse events on vital organs like the liver. Interestingly, the α-L-Guluronic Acid (G2013), as a novel NSAID with immunomodulatory properties, has shown the inhibitory effects on inflammation and metastasis in experimental models.

Objective: This study was conducted to determine the effects of G2013 on cytotoxicity and induction of apoptosis, as a new therapeutic target for cancer therapy, in the HepG2 cell line and the mouse fibroblast cell line L929, as a control.

Methods: MTT assay and flow cytometry method were carried out using the different concentrations of G2013 (5, 15, 25, 50, 100, 200 and 400 μg/ml) in 3 distinct incubation times.

Results: Our data showed that treatment of HepG2 cells with high concentration (400μg/mL) of G2013 could effectively cause a decrease in cell viability, so that they were statistically different after 72 hours compared to other concentrations (5 to 200 μg/ml) (p<0.05 and p<0.01, respectively). Moreover, the proportion of apoptosis of HepG2 cells at the dose of 200μg/mL considerably increased, suggesting that the induction of apoptosis by G2013 in HepG2 cells is dose- and time-dependent, which could promote its anticancer properties.

Conclusion: The present study revealed that G2013 could induce apoptosis in the liver cancer model. Therefore, based on these findings, G2013 might be considered as a therapeutic option in cancer therapy.

Introduction: Lactic acidosis is a rare but life-threatening complication associated with prolonged linezolid therapy. No specific treatment is suggested, except for antibiotic therapy interruption.

Case report: A 70-years-old woman faced severe linezolid intoxication after antibiotics therapy initiation for infection of a surgical sternal wound. The patient suffered from a severe increment of blood lactate and thrombocytopenia. She was admitted to ICU twice, and due to dialytic treatment, linezolid and lactate serum levels came back to normality.

Conclusion: More studies should be conducted to evaluate the human tissue storage sites of linezolid and the influence of various factors on its clearance and plasma concentrations in critically ill patients.

Background: Preliminary evidence has pointed an association of the gene HLA-DRB1 with fibromyalgia. HLA-DRB1 alleles carrying the shared or susceptibility epitope encoding the five-amino acid motif QKRAA, QRRAA or RRRAA in positions 70 to 74 of the major histocompatibility complex class II DRβ chain are associated with several autoimmune diseases.

Objective: The objective of this study was to test the hypothesis that susceptibility epitope-encoding HLA-DRB1 alleles are associated with fibromyalgia.

Methods: Using a case-control design, the prevalence of susceptibility epitope-encoding HLADRB1 alleles in 27 white Caucasian patients fulfilling the revised diagnostic criteria for fibromyalgia of the American College of Rheumatology was compared with that in 27 white Caucasian ageand sex-matched healthy controls.

Results: 13 (48%) of the fibromyalgia patients had susceptibility epitope-coding HLA-DRB1 alleles compared with 15 (56%) of the controls (P = 0.785). The DRB1*01 allele encoding the protective epitope 70-DERAA-74 motif was found in one of the control subjects; none of the fibromyalgia patients had such a protective epitope.

Conclusion: While the present study does not provide evidence supporting the potential role of HLA-DRB1 in the etiology of fibromyalgia, it does not exclude the possibility that there is a polygenic component to a putative genetic causative role.