Triggering Receptor Expressed on Myeloid Cells in Cutaneous Melanoma

The tumor microenvironment plays an important role in the progression of melanoma, the prototypical immunologic cutaneous malignancy. The triggering receptor expressed on myeloid cells (TREM) family of innate immune receptors modulates inflammatory and innate immune signaling. It has been investigated in various neoplastic diseases, but not in melanoma. This study examines the expression of TREM‐1 (a proinflammatory amplifier) and TREM‐2 (an anti‐inflammatory modulator and phagocytic promoter) in human cutaneous melanoma and surrounding tissue. Indirect immunofluorescence staining was performed on skin biopsies from 10 melanoma patients and staining intensity was semiquantitatively scored. Expression of TREM‐1 and TREM‐2 was higher in keratinocytes than melanoma tissue (TREM‐1: p < 0.01; TREM‐2: p < 0.01). Whereas TREM‐2 was the dominant isoform expressed in normal keratinocytes, TREM‐1 expression predominated in melanoma tissue (TREM‐1 to TREM‐2 ratio: keratinocytes = 0.78; melanoma = 2.08; p < 0.01). The increased TREM ratio in melanoma tissue could give rise to a proinflammatory and protumor state of the microenvironment. This evidence may be suggestive of a TREM‐1/TREM‐2 paradigm in which relative levels dictate inflammatory and immune states, rather than absolute expression of one or the other. Further investigation regarding this paradigm is warranted and could carry prognostic or therapeutic value in treatment for melanoma.     

Cutaneous angiosarcoma presenting as band‐shaped erythematous plaques on the neck

Band‐shaped presentation of cutaneous angiosarcoma has not been reported. Cutaneous angiosarcoma should be included in the differential diagnosis when a persistent erythematous lesion is observed in the head and neck region of an elderly patient without a clear explanation, but skin biopsy is required for an accurate diagnosis.     

Tumor‐to‐tumor metastasis to Warthin tumor presenting as an initial sign of breast carcinoma: A case report

Metastases of distant primary tumors on the parotid gland are very rare. Tumor‐to‐tumor metastasis to salivary gland tumors is extremely rare. A case of a 69‐year‐old woman with a large left parotid gland mass with no previous salivary gland problems or cancer. Fine‐needle aspiration (FNA) showed evidence of a Warthin tumor. A total left parotidectomy was performed. The final pathology report showed a Warthin tumor containing two metastases of adenocarcinoma. The immunohistochemistry of the metastases led to the diagnosis of primary breast cancer. A negative FNA does not rule out the possibility of a malignant parotid tumor or metastasis, and a parotid lump should be presumed to be a secondary tumor until proven otherwise if the patient has a history of any distant primary cancer. Our patient case serves as a reminder that a new distant primary cancer might be the cause of a parotid lump.     

Dynamic changes of IgM and IgG antibodies in asymptomatic patients as an effective way to detect SARS‐CoV‐2 infection

BackgroundCOVID‐19 has become a global pandemic, and close contacts and asymptomatic patients are worthy of attention.MethodsA total of 1844 people in close contacts with 76 COVID‐19 patients were investigated, and nasopharyngeal swabs and venous blood were collected for centralized medical quarantine observation. Real‐time fluorescence was used to detect SARS‐CoV‐2 nucleic acid in nasopharyngeal swabs of all close contacts, and the colloidal gold method was used to detect serum‐specific antibodies. Levels of IgM‐ and IgG‐specific antibodies were detected quantitatively through chemiluminescence from the first nucleic acid turned negative date (0 week) and on weekly intervals of ≤1 week, 1–2 weeks, 2–3 weeks, 3–4 weeks, 4–5 weeks, 5–6 weeks, and 6–7 weeks.ResultsThe total positive rate of the colloidal gold method (88.5%, 23/26) was significantly higher (χ² = 59.182, p < 0.001) than that of the healthy control group (2.0%, 1/50). There was significant difference in IgG concentration at different time points (0–7 weeks) after negative nucleic acid conversion (χ² = 14.034, p = 0.029). Serum IgG levels were significantly higher at weekly time points of 4–5 weeks (Z = −2.399, p = 0.016), 5–6 weeks (Z = −2.049, p = 0.040), and 6–7 weeks (Z = −2.197, p = 0.028) compared with 1–2 weeks after negative nucleic acid conversion. However, there was no significant difference (χ² = 4.936, p = 0.552) in IgM concentration between time points tested (0–7 weeks) after negative nucleic acid conversion. The positive rates of IgM and IgG in asymptomatic patients (χ² = 84.660, p < 0.001) were significantly higher than those in the healthy control group (χ² = 9.201, p = 0.002) within 7 weeks of negative nucleic acid conversion.ConclusionsThe IgG concentration in asymptomatic cases remained at a high level after nucleic acid turned negative. Nucleic acid detection combined with IgM and IgG antibody detection is an effective way to screen asymptomatic infections.     

Budesonide repairs decreased barrier integrity of eosinophilic nasal polyp epithelial cells caused by PM2.5

BackgroundEosinophilic chronic rhinitis with nasal polyps (eos‐CRSwNP) is a subtype of nasal polyps (NPs) characterized by severe type‐2 inflammation and defective epithelial barrier function. The epithelial barrier plays important roles in the pathogenesis of NPs and type‐2 inflammation. Particular matter 2.5 (PM_2.5) are fine particles with a diameter less than 2.5 μm, containing a mixture of different components. Here, we investigated the impact of PM_2.5 on the barrier function of the eos‐CRSwNP epithelium and explored the reparative function of budesonide.MethodsSamples from noninflammatory nasal mucosa and eos‐CRSwNP were collected to establish an in vitro air–liquid interface cultured model. The cells were exposed to PM_2.5 at 50 or 100 µg/ml intermittently for 72 h, with or without budesonide pretreatment. Barrier function and tight junction (TJ) expression were reflected by measuring transepithelial resistance (TER), paracellular flux permeability of fluorescein isothiocyanate‐labeled 4‐kDa dextran, quantitative real‐time polymerase chain reaction (qPCR), and immunofluorescence staining of TJ proteins. Cytokine expression was measured by qPCR and enzyme‐linked immunosorbent assay or Luminex.ResultsPM_2.5 increased paracellular flux and downregulated TJ protein expression (zona occuldens‐1, occludin, and claudin‐1), but did not change TER. These changes could be partially restored by budesonide treatment. Interleukin (IL)‐8, IL‐10, IL‐1α, and tissue inhibitor of metalloproteinase (TIMP)‐1 concentrations were significantly increased in the culture medium of cells exposed to PM_2.5, and budesonide significantly reduced the changes in IL‐8, IL‐1α, and TIMP‐1.ConclusionPM_2.5 impaired the barrier function of eos‐CRSwNP epithelial cells and increased the permeability of large molecules. PM_2.5 also increased the secretion of pro‐inflammatory cytokines by nasal epithelial cells. Budesonide could partially repair the damage, suggesting potential applications in clinical practice.     

Viral Immune Evasion Due to Persistence of Activated T Cells Without Effector Function

We examined the regulation of virus-specific CD8 T cell responses during chronic lymphocytic choriomeningitis virus (LCMV) infection of mice. Our study shows that within the same persistently infected host, different mechanisms can operate to silence antiviral T cell responses; CD8 T cells specific to one dominant viral epitope were deleted, whereas CD8 T cells responding to another dominant epitope persisted indefinitely. These virus-specific CD8 T cells expressed activation markers (CD69^hi, CD44^hi, CD62L^lo) and proliferated in vivo but were unable to elaborate any antiviral effector functions. This unresponsive phenotype was more pronounced under conditions of CD4 T cell deficiency, highlighting the importance of CD8– CD4 T cell collaboration in controlling persistent infections. Importantly, in the presence of CD4 T cell help, adequate CD8 effector activity was maintained and the chronic viral infection eventually resolved. The persistence of activated virus-specific CD8 T cells without effector function reveals a novel mechanism for silencing antiviral immune responses and also offers new possibilities for enhancing CD8 T cell immunity in chronically infected hosts.     

The sensitivity and specificity of COVID‐19 rapid anti‐gene test in comparison to RT‐PCR test as a gold standard test

BackgroundCoronavirus disease 2019 (COVID‐19) is a modern infectious disease, first identified in December 2019 in Wuhan, China. The etiology is via severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), in a pandemic manner. The study aimed to compare between RT‐PCR and rapid anti‐gene tests for COVID‐19 with regard to sensitivity and specificity.MethodsThis is a cohort hospital‐based study done during the period of July to September 2020. Both rapid anti‐gene test kit (SARS‐CoV‐2) and RT‐qPCR were used for the detection of COVID‐19 in suspected cases.ResultsA total of 148 cases were tested using both the RT‐qPCR and rapid test. Twenty‐nine (19.6%) of these cases had positive results for RT‐qPCR and 119 (80.4%) were negative, whereas 52 (35.1%) patients were positive to rapid anti‐gene test and 96 (64.9%) of them negative. The sensitivity of the rapid test was 37.9%, the specificity was 65.5% and the accuracy was 64.44%. Rapid IgG test was positive in 47 (31.8) of cases. Although, rapid IgM test was positive in 18 (12.2%). The rapid IgG test was more sensitive than rapid IgM (Sensitivity 34.48% vs. 3.45%), but it was less specific than rapid IgM test (Specificity 68.91% vs. 85.71%).ConclusionWe cannot consider rapid anti‐gene test alone as a diagnostic method for COVID‐19. We should also conduct RT‐PCR test and other investigations like imaging CT scan of chest to confirm the diagnosis. The rapid IgG test is more sensitive than rapid IgM, but it was less specific.     

COVID‐19 infection presenting as paroxysmal nocturnal hemoglobinuria

A diagnosis of paroxysmal nocturnal hemoglobinuria (PNH) was elicited during acute COVID‐19 infection. COVID‐19 spike proteins trigger the alternative pathway of complement. Acute SARS‐CoV‐2 infection possibly expanded an existing PIG‐A mutation.     

糖尿病大鼠肾小管上皮细胞-肌成纤维细胞转分化及氯沙坦对其的影响

【目的】观察糖尿病大鼠肾小管上皮细胞-肌成纤维细胞转分化(TEMT)及氯沙坦干预对其的影响。【方法】雄性Wistar大鼠随机分为正常对照组和糖尿病模型组;后者经STZ诱导糖尿病模型成功后再随机分为糖尿病组和氯沙坦干预组[氯沙坦20mg/(kg·d)]。分别于第8周和第16周时每组各处死5只大鼠。测定24h尿蛋白排泄量、血肌酐;留取肾组织作HE和Masson染色,观察肾小管间质损伤指数、肾间质胶原面积;免疫组织化学法检测肾小管上皮细胞α-平滑肌肌动蛋白(α-SMA)、波形蛋白(Vimentin)和转化生长因子-β1(TGF-β1)表达,并作半定量分析。【结果】①与对照组相比,糖尿病模型组大鼠肾小管间质损伤指数和肾间质胶原面积明显增加(P<0.01);②糖尿病组大鼠肾小管上皮细胞α-SMA、Vimentin和TGF-β1阳性表达均显著高于对照组,α-SMA表达和TGF-β1表达呈正相关(rs=0.810,P<0.01)。③氯沙坦组尿蛋白排泄量、肾小管间质损伤和间质纤维化程度较糖尿病组减轻,肾小管上皮细胞α-SMA、Vimentin与TGF-β1表达强度较糖尿病组显著下调(P<0.01)。【结论】①糖尿病大鼠肾脏病理进程中存在TEMT;②氯沙坦可下调糖尿病大鼠肾小管上皮细胞TGF-β1、Vimentin、α-SMA表达,阻抑糖尿病肾小管上皮细胞发生TEMT而发挥肾脏保护作用。     

LncRNA MIR4435‐2HG functions as a ceRNA against miR‐125a‐5p and promotes neuroglioma development by upregulating TAZ

BackgroundExpression of the TAZ gene is closely related to the prognosis of glioma patients. We hoped to find long noncoding RNAs (lncRNAs) related to TAZ and a new target for glioma treatment.MethodsTAZ‐related genes were found by dual‐luciferase reporter gene assay, and the correlation of each gene was analyzed by the Pearson method. Human glioma cell lines U87 MG and U251 and glioma rats were used for cytology assays, and the related genes were transfected. We conducted immunohistochemistry, RT‐qPCR, Western blotting, CCK8 test, flow cytometry, transwell assays, clone formation analysis, and tumor weight measurements to verify the above relationship.ResultsWe found that miR‐125a‐5p was closely related to the TAZ gene, and the lncRNA MIR4435‐2HG was closely related to miR‐125a‐5p. Both MIR4435‐2HG‐OE and TAZ increased the expression of the TAZ gene, activated the Wnt signaling pathway, inhibited apoptosis, and promoted migration and proliferation in glioma cells. Besides, it also increased the tumor volume of gliomas in a rat model subcutaneously inoculated with glioma cells. We also found miR‐125a‐5p could block the effect of MIR4435‐2HG‐OE and TAZ.ConclusionsLncRNA MIR4435‐2HG obstructs the functions of miR‐125a‐5p and promotes neuroglioma development by upregulating the TAZ gene.     

Recombinant subunits of SARS‐CoV‐2 spike protein as vaccine candidates to elicit neutralizing antibodies

ObjectivesThe spike protein has been reported as one of the most critical targets for vaccine design strategies against the SARS‐CoV‐2 infection. Hence, we have designed, produced, and evaluated the potential use of three truncated recombinant proteins derived from spike protein as vaccine candidates capable of neutralizing SARS‐CoV‐2 virus.MethodsIn silico tools were used to design spike‐based subunit recombinant proteins (RBD (P₁), fusion peptide (P₂), and S1/S2 cleavage site (P₃)). These proteins were checked for their ability to be identified by the anti‐SARS‐CoV‐2 antibodies by exposing them to COVID‐19 serum samples. The proteins were also injected into mice and rabbit, and the antibody titers were measured for 390 days to assess their neutralization efficiency.ResultsThe antibodies that existed in the serum of COVID‐19 patients were identified by designed proteins. The anti‐spike antibody titer was increased in the animals injected with recombinant proteins. The VNT results revealed that the produced antibodies could neutralize the cultured live virus.ConclusionTruncated subunit vaccines could also be considered as robust tools for effective vaccination against COVID‐19. Using a combination of in silico, in vitro, and in vivo experiments, it was shown that the injection of spike‐based truncated recombinant proteins could stimulate long‐lasting and neutralizing antibody responses.     

Acute macular neuroretinopathy as a manifestation of coronavirus disease 2019: A case report

The current findings is important in raising clinicians'' awareness of the possibility of coincident acute macular neuroretinopathy (AMN) and COVID‐19 as a potential cause of retinal vascular damage and ischemia.     

Urticarial rash as the initial presentation of COVID‐19 infection: A case report

During the COVID‐19 pandemic, various skin manifestations have been described. These include an urticarial rash, morbilliform rash, maculopapular rash, vascular lesions, and varicella‐like eruptions. A 30‐year‐old woman presented with a mild cough, then hives and pruritic rash for 3 days, followed by fever, dyspepsia, and throat pain for one day.     

Association between serum inflammatory parameters and the disease severity in COVID‐19 patients

ObjectiveMost patients infected with the novel coronavirus (SARS‐CoV‐2), as the causative agent of COVID‐19 disease, show mild symptoms, but some of them develop severe illness. The purpose of this study was to analyze the blood markers of COVID‐19 patients and to investigate the correlation between serum inflammatory cytokines and the disease severity.MethodsIn this prospective cross‐sectional study, 50 patients with COVID‐19 and 20 patients without COVID‐19 were enrolled. According to ICU admission criteria, patients were divided into two groups of non‐severe and severe. Differences in the serum levels of C‐reactive protein (CRP), IL‐6, and TNF‐α, as well as erythrocyte sedimentation rate (ESR), lymphocytes (LYM) count, and neutrophils (NEU) count between the two groups were determined and analyzed.ResultsOut of the 50 patients with COVID‐19, 14 were diagnosed as severe cases. There was no significant difference between the two groups of COVID‐19 patients in terms of gender and age. Blood tests of COVID‐19 patients showed a significant decrease and increase in NEU and LYM counts, respectively. There were significant differences in the serum levels of IL‐6, TNF‐α, and CRP between the severe and non‐severe groups, which were higher in the severe group.Also, there was a significant correlation between the disease severity and CRP with ESR (r = 0.79), CRP with IL‐6 (r = 0.74), LYM with NEU (r = −0.97), and ESR with TNF‐α (r = 0.7).ConclusionThe findings of this study, as the first study in Iran, suggest that the levels of IL‐6, TNF‐α, ESR, and CRP could be used to predict the severity of COVID‐19 disease.     

Serum IL‐36 cytokines levels in type 2 diabetes mellitus patients and their association with obesity,insulin resistance,and inflammation

BackgroundThe interleukin (IL)‐36 cytokines include IL‐36α, IL‐36β, IL‐36γ, and IL‐36Ra. Little was known about their roles in type 2 diabetes mellitus (T2DM).MethodsThe study included 40 T2DM patients and 42 healthy control subjects. The anthropometric and biochemical measurements were performed using automatic biochemical analyzer, high‐performance liquid chromatography, and electrochemiluminescence immunoassay. Circulating IL‐36α, IL‐36γ, IL‐36Ra, and IL‐17 levels were determined by enzyme‐linked immunosorbent assay.ResultsSerum IL‐36α, IL‐36γ, and IL‐17 levels in T2DM patients were significantly higher than those in controls, whereas serum IL‐36Ra levels in T2DM patients were lower. Correlation analysis showed that serum IL‐36α was positively correlated with high sensitivity C‐reactive protein. Serum IL‐36α was negatively correlated with IL‐36Ra. Serum IL‐17 was negatively correlated with low‐density lipoprotein cholesterol.ConclusionsThis study demonstrated that T2DM patients displayed increased IL‐36α and IL‐36γ expression and decreased IL‐36Ra expression. Moreover, the inflammatory cytokine levels were directly proportional to the inflammation and blood lipid levels. Our results suggest that IL‐36 cytokines may be a new target for the diagnosis or treatment of T2DM.     

Cutaneous ulcers in association with sprue‐like enteropathy secondary to Losartan

Losartan is an angiotensin II receptor blocker (ARB) which may cause severe sprue‐like enteropathy (SLE) with skin manifestation. Clinicians should be informed of this side effect and its reversibility after cessation of the drug.