American journal of clinical and experimental immunology最新文献

Bladder cancer is the most common malignancy in the urinary tract, and is biologically and clinically quite heterogeneous. Around 90% of diagnoses are made in the 6^th decade, being more prevalent in males. The programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) axis play a putative role in immune checkpoint and as a means through which cancer evades the immune system. Inhibition of the glicogênio synthase kinase (GSK) 3 leads to the downregulation of PD-1 via upregulation of the transcription factor Tbet. The use of biomarkers PD-L1 and GSK-3β and evaluation of the immune infiltrate have very promising correlations with urothelial carcinoma prognosis and treatment prediction.

Objective: To investigate the protein expression of PD-L1 and GSK-3β and the CD8-positive immune infiltrates in bladder carcinomas.

Materials and methods: This was a cross-sectional study of 140 samples of urothelial carcinomas from 2015 to 2018. Automated digitally assisted scoring and conventional analyses of the markers of GSK-3β (27C10), CD8 (7103β) and PDL-1 (22c3), were reviewed by two pathologists independently and a histologic score was calculated. The density of CD8 was also measured.

Results: The immunoexpression of GSK-3β (91%) was presented in most samples, PD-L1 in 62.9% and CD8 cells present in 46.3% of cases. When analyzed in conjunction, the levels of GSK-3β and PD-L1 (P = 0.033), and CD8 and PD-L1 (P<0.002) showed significant correlations. No significant associations were observed between GSK-3β and CD8. The positivity of GSK-3β and PD-L1 was predominant in high-grade tumors.

Conclusion: Despite the tumor microenvironment heterogeneity, the expression of CD8, GSK-3β and PDL1 could be valuable and GSK-3β could be a potential target in advanced bladder cancer, especially in the context of immunotherapy.

Objective: To explore the distribution and epidemiological characteristics of patients with syphilis in a first-class tertiary hospital and to evaluate the coincidence rate between chemiluminescence immunoassay (CLIA) and Treponema pallidum particle agglutination assay (TPPA).

Methods: The medical records of 247,501 outpatients and inpatients were retrospectively analyzed. TPPA was used to verify positive and suspected cases, and the coincidence rate between CLIA and TPPA was evaluated. Receiver operating characteristic (ROC) curve was used to determine optimal diagnostic thresholds.

Results: Of the 247,501 serum samples, 5,173 were detected positive for syphilis using CLIA, with a detection rate of 2.09% and a men-to-women ratio of 1.39. The chi-square test showed that sex and age were both factors that affected the detection rate (χ²=229.51, P < 0.0001). In addition, urology, orthopedics, cardiology, general surgery, gastroenterology, and gynecology represented the top six departments with the highest numbers of positive cases. Comparative analysis showed that the overall coincidence rate between CLIA and TPPA was 80.24%. Analysis of the ROC curve showed that the area under the curve (AUC) was 0.936 (95% confidence interval [CI]: 0.929-0.942, P < 0.0001) using sample/cut-off value (S/CO) as a diagnostic indicator. The results showed that an S/CO value of 3.945 was the best diagnostic value for the CLIA method, with a diagnostic specificity of 93.64% and a sensitivity of 81.90%.

Conclusions: Syphilis is widely distributed in various hospital departments and primarily affects middle-aged and older individuals. For cases that have been initially screened as positive or suspicious, TPPA and other tests should be used for verification to avoid misdiagnosis and missed diagnosis.

Objectives: Asthma is the most prevalent respiratory disease, caused by chronic bronchial inflammation. Cytokines are known to play an important role in the pathophysiology of asthma. This study aimed to compare interleukin-4 (IL-4) and interleukin-10 (IL-10) gene polymorphisms between Iranian pediatric asthmatic patients and healthy controls and to investigate IL4 and IL10 gene variations in children with atopic and non-atopic asthma phenotypes.

Methods: In this prospective case-control study, a total of 95 unrelated pediatric asthmatic patients were recruited according to the Global Initiative for Asthma (GINA) criteria. The control group comprised two subgroups of 538 and 491 healthy individuals, undergoing IL4 and IL10 polymorphism assessments, respectively. The IL4 -589C/T (rs2243250) and IL10 -592A/C (rs1800872) gene polymorphisms were evaluated using the tetra-primer amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) assay.

Results: The findings indicated a significant difference in IL4 gene polymorphisms at position -589 between the asthmatic and healthy control groups. However, no significant difference was found in terms of IL10 gene polymorphisms, and they were not associated with atopy in the patients.

Conclusion: The IL4 -589C/T polymorphism (rs2243250) can be a risk factor for asthma susceptibility, whereas the IL10 -592A/C polymorphism (rs1800872) is not a risk factor in the Iranian pediatric population. The results also showed that these polymorphisms are not risk factors for atopy in asthmatic children.

Telomere, the biological chronometer, and its effect on the immune system considerably varies among individuals. During pregnancy, multiple risk factors affect telomere reprogramming during fetal life which can lead to health disparities in newborns. These changes may cause a long-term impact on the telomere genetics of the newborn and become a reason for lifelong health implications and immune senescence. Therefore, telomere shortening in parents due to genetic variation may act as a hallmark of immune senescence and aging in their newborns.

Objectives: Peanut (PN) allergy is a major public health concern. Recent research has brought clarity about how individuals become sensitized to PN allergen with routes known through the skin, as well as the airway. Still unclear, however, is the role of sex hormones on the development of allergic immune responses to PN. This study examines the role of androgen receptor (AR) signaling in regulating PN-specific immune responses.

Methods: We utilized a 4-week inhalation mouse model of PN allergy that is known to drive the production of PN-specific antibodies and elicit systemic anaphylaxis following PN challenge. Wildtype (WT) male, female, and androgen receptor-deficient testicular feminization mutant (AR^Tfm) male mice were examined using this model to document sex differences in PN allergy. To determine if sex differences also existed in the cellular immune response, this study utilized a 3-day inhalation mouse model of PN to examine the response of group 2 innate lymphoid cells (ILC2s). WT male and female mice were examined using this model to document sex differences in ILC2 response within the lungs.

Results: AR use is critical in regulating PN-specific antibody levels. We found that AR^Tfm males have a higher antibody response and significantly worse anaphylactic response following PN challenge relative to WT males. WT males also exhibit a less severe anaphylactic response compared to AR^Tfm male and female mice. Lastly, we discovered that lung ILC2s from female mice respond more robustly to PN compared to ILC2s within WT male mice.

Conclusions: Taken together, this study suggests that male sex hormones, namely androgens, negatively regulate allergic immune responses to PN.

Objective: Increasing evidence demonstrates that long non-coding RNAs (lncRNAs) are closely related to multiple human autoimmune diseases, and their dysregulation is tightly linked to inflammation and disease progression. Nonetheless, little is known about the consequences of aberrant expression of lncRNAs during rheumatoid arthritis (RA) development. In this study, we screened for the expressions of lncRNAs in RA synovial fibroblasts (RA-SF) and investigated their functions in RA-SF proliferation and migration, and the relevant underlying mechanisms.

Methods: The lncRNAs expression profiles were interrogated with microarrays. The expressions of key lncRNAs were confirmed in synovial fibroblasts from RA patients and MH7A cells using qRT-PCR. Proliferations and migrations of MH7A and HFL-1 cells were evaluated using CCK-8 assay and cell migration assay kits, respectively. The expression of inflammatory cytokines (IL-6, IL-1β, and TNF-α) and cell migration related proteins (MMP-1 and MMP-3) were evaluated using qRT-PCR and western blotting. Collagen type II-induced arthritis (CIA) in mice was used as an animal model of RA.

Results: Nine lncRNAs were significantly altered in RA-SF, of which lncRNA-000239 showing the most significant upregulation. Overexpression of lncRNA-000239 significantly enhanced the proliferation and migration of human RS-SF cells (MH7A), while the opposite effect was observed with lncRNA-000239 silencing. Importantly, lncRNA-000239 enhanced annexin A1 expression by upregulating the expression of miR-146a. Moreover, locally enhanced expression of lncRNA-000239 promoted the onset of arthritis in CIA.

Conclusion: These data indicate that lncRNA-000239 upregulates annexin A1 expression via miR-146a and thus, promotes the proliferation and migration of RA-SF. This highlights a potential role of lncRNA-000239 as an inflammatory factor of RA.

The epididymis is a highly specialized tissue that plays vital roles in sperm maturation and storage. The spatio-temporal repertoire of epididymal cells and their gene expression in the epididymis remain less characterized. With the help of single-cell RNA sequencing (scRNA-seq), Shi et al., reveal a spatio- and segment-specific distribution pattern of mitochondria that adds another layer of complexity to our understanding of the epididymis. They unexpectedly find a higher abundance of mitochondria and mitochondrial transcription in the corpus and cauda compared to the caput of epididymis, which are believed to be responsible for providing the energy necessary for sperm maturation and motility.

Phthiriasis palpebrarum, also known as crab lice, is a rare eyelash infestation by Pthirus pubis that is often misdiagnosed as common blepharitis, and thus mistreated. Treatment of Phthiriasis palpebrarum is widely variable. Tea tree oil is an essential oil with broad-spectrum anti-microbial therapeutic effects. Notably, however, the role of this agent in Phthiriasis palpebrarum management is unclear. The current article reports a case of phthiriasis palpebrarum effectively treated with tea tree oil.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes Coronavirus Disease 2019 (COVID-19), one of the deadliest medical difficulties to affect people in more than a century. The virus has now spread to many countries worldwide, posing a big challenge to the health status of people in affected populations. Gaining more knowledge about the different aspects of this virus will lead us to better control and treatment methods. In this paper, we discuss the SARS-CoV-2 structure and the mechanism of this virus's entry into host cells through angiotensin-converting enzyme 2 (ACE2), the main receptor for the SARS-CoV-2 virus. The main connection between SARS-CoV-2 and ACE2 is Spike protein. Other topics are also included, like ACE2 structure, functions, and physiology. For instance, ACE2 is involved in the renin-angiotensin-aldosterone system, Angiotensin A/ACE2/Alamandine/MAS-Related GPCR D (MrgD) Axis, the Kinin-Kallikrein System. It also acts as Chaperone Protein for the Amino Acid Transporter, B0AT1, and has a connection with Apelin Peptides. Since ACE2 plays a primary role in COVID-19 pathogenesis, scientists have discovered some SARS-CoV-2 therapy methods based on ACE2 targeting. Tissue expression in different genders and ages, polymorphisms, and host epigenetics, the role of ACE2 in hypertension, and cytokine storm are explained separately.

Objectives: Headache is one of the most common neurological disorders around the world. Previous studies have proposed associations of food allergies with headaches. Therefore, this study evaluated the frequency of sensitization to food allergens in patients with migraine and tension headaches and their correlations with these disorders.

Methods: The study subjects consisted of 20 patients with migraine headache and 20 subjects with tension headache. Headache disorders were confirmed by a specialist. Food allergen sensitization was diagnosed by skin prick test (SPT) or radioallergosorbent test (RAST), clinical history, and physical examination.

Results: There was no significant difference in age and gender between patients with migraine and tension headaches. Other results showed sensitization to food allergens, such as egg, wheat, fish, banana, orange, and soybean, in patients with migraine headache was similar to those in subjects with tension headache. However, patients with migraine headache significantly differed from individuals with tension headache in allergic responses to tree nut (P=0.047), peanut (P=0.028), and cow's milk (P=0.044).

Conclusion: The results of this study showed that sensitization to food allergens may relate to migraine headache which their diagnosis can help to better control and manage the disease.