Anti-inflammatory effects of low-molecular weight chitosan oligosaccharides in IgE-antigen complex-stimulated RBL-2H3 cells and asthma model mice

The anti-inflammatory effects of low-molecular weight chitosan oligosaccharides (LM-COS) prepared from high-molecular weight chitosan by enzymatic digestion were investigated against allergic reaction and allergic asthma in vivo and in vitro. Allergic asthma is an inflammatory disease of the airways associated with enhanced degranulation and cytokine generation. The LM-COS (<1 kDa), consisting of glucosamine (GlcN)(n), n=3-5, were capable of inhibiting both antigen-stimulated degranulation and cytokine generation in rat basophilic leukemia RBL-2H3 cells. The protective effect of LM-COS against ovalbumin (OVA)-induced lung inflammation in asthma model mice was also examined. Oral administration of LM-COS (16 mg/kg body weight/day) resulted in a significant reduction in both mRNA and protein levels of interleukin (IL)-4, IL-5, IL-13, tumor necrosis factor (TNF)-α in the lung tissue and bronchoalveolar lavage fluid (BALF); The protein levels of IL-4, IL-13 and TNF-α in BALF were decreased by 5.8-fold, 3.0-fold and 9.9-fold, respectively, compared to those in the OVA-sensitized/challenged asthma control group. These results suggest that the oral administration of LM-COS is effective in alleviating the allergic inflammation in vivo and thus can be a good source material for the development of a potent therapeutic agent against mast cell-mediated allergic inflammatory responses and airway inflammation in allergic inflammatory diseases, including asthma.     

Immunotherapeutic approaches in nasopharyngeal carcinoma

ABSTRACT

Introduction: Nasopharyngeal carcinoma (NPC) is endemic in Southern China and Southeast Asia. Epstein-Barr virus (EBV) represents a unique etiological culprit in the poorly differentiated nonkeratinizing and undifferentiated subtypes. EBV antigens are expressed on tumor cells albeit in a restricted manner. Treatment options for recurrent or metastatic disease are limited. Nevertheless, emerging data from immunotherapy studies in NPC have shed light into their potential antitumor efficacy.

Areas covered: This article reviews existing clinical evidence for different immunotherapeutic approaches for NPC, including adoptive cellular therapy, therapeutic cancer vaccines, and immune checkpoint inhibitors.

Expert opinion: There is a growing understanding on EBV virology and the immune evasion mechanisms in NPC. Immunotherapeutic strategies leveraging these properties have shown encouraging efficacy and safety results in early-phase clinical studies. Moving forward, areas to be addressed include appropriate patient selection, optimal incorporation into standard treatment paradigms, biomarker identification, as well as the development of scalable and reproducible immune product generation processes.     

Clinical characteristics and risk of melanoma development from giant congenital melanocytic naevi in Korea: a nationwide retrospective study

Background Giant congenital melanocytic naevi (GCMN) are known risk factors for the development of melanoma. However, melanoma risk among Asians is rarely evaluated. Objectives To evaluate the clinical characteristics and risk of melanoma development from GCMN in Koreans, we performed a nationwide retrospective cohort study in Korea. GCMN were defined as those comprising ≥ 5% body surface area in children or measuring ≥ 20 cm in adults. Methods In total, 131 patients with GCMN were enrolled, with a mean age of 10·3 years (range: birth–70 years). Results The posterior trunk was the most common site (67, 51·1%), followed by lateral trunk, anterior trunk, legs, both anterior and posterior trunk, buttocks, and arms. Satellite naevi were present in 69 cases (52·7%), and axial areas were more commonly involved in patients with satellite naevi than in those without satellite lesions. Atypical features such as rete ridge elongation and bridges were seen, and, among these, pagetoid spread and ballooning cell changes were more common in patients < 4 years old. Proliferative nodules were found in three cases. Melanomas had developed in three of 131 patients (2·3%; a 6‐year‐old girl, a 14‐year‐old girl and a 70‐year‐old man), and the incidence rate was 990 per 100 000 person‐years. Melanomas in these three patients consisted of two cutaneous melanomas and one extracutaneous meningeal melanoma. Conclusions We should be aware of melanoma development from GCMN, and lifelong follow‐up is required due to the risk of melanoma arising in GCMN.     

Analysis of the complete genome sequence of two Korean sacbrood viruses in the Honey bee, Apis mellifera

The complete genomic RNAs of two Korean sacbrood virus (SBV) strains, which infect the honey bee, Apis mellifera, were sequenced. The two sequences (AmSBV-Kor19, AmSBV-Kor21) were distinguished by the presence or absence of a PstI restriction site. These strains comprised of 8784 bp and 8835 bp; contained a single large ORF (179-8707 and 179-8758) encoding 2843 and 2860 amino acids, respectively. Deduced amino acid sequences comparison with some insect viruses showed that regions of helicase, protease and RdRp domains; structural genes were located at the 5′ end and non-structural genes at the 3′ end. Multiple sequence alignment showed that AmSBV-Kor19 was missing a section between nucleotides 2311 and 2361 (present in SBV-UK and CSBV) but was similar to that of the Korean SBV strain that infects A. cerana (AcSBV-Kor). The differences in the AmSBV-Kor19 strain may be the result of the virus adapting to a different host.     

Evidence for novel structures (primo vessels and primo nodes) floating in the venous sinuses of rat brains

We for the first time report evidence for existence of novel structures, primo vessels (PVs) and primo nodes (PNs) floating inside the venous sinuses of rat brains. For this purpose, we applied a chromium-hematoxylin (Cr-Hx) solution to stain the PVs and the PNs floating inside the venous sinuses (superior sagittal sinus, strait sinus, and transverse sinus) of seven rats' brains preferentially compared to the blood clots that easily form during surgery. Cr-Hx-stained PVs and PNs were examined by light and transmission electron microscopies: (1) we were consistently able to visualize the PVs and the PNs in the venous sinuses of all seven rats' brains. (2) The PVs and PNs consisted of rod-shaped and some round-shaped cells, respectively, as demonstrated by using 4',6-diamidino-2-phenylindole (DAPI). (3) Cross sections of the PVs showed that the sinuses contained loose fibrous materials and clusters of nano-sized granules enveloped by the cortex. The above data imply that thrombus of the venous sinuses may be related with these novel floating structures. However, the functions of the PVs and PNs floating in the venous sinuses remain to be investigated in terms of normal or thrombus-provoked diseases.     

Blockade of Myd88 signaling induces antitumor effects by skewing the immunosuppressive function of myeloid‐derived suppressor cells

Myd88 is an important adaptor molecule for the activation of NADPH oxidase and arginase‐1, which are responsible for the suppressive function of myeloid‐derived suppressor cells (MDSCs). When wild‐type and Myd88^?/? mice were subcutaneously injected with CT26 colon cancer cells expressing human Her‐2/neu, tumor growth was retarded in Myd88^?/? mice than in wild‐type mice. Although the generation of CD11b⁺Gr‐1⁺ MDSCs was less in Myd88^?/? mice than in wild‐type mice, Myd88^?/? mice having tumor masses still had significant quantities of MDSCs, suggesting that MDSC generation might be independent of Myd88 signaling. However, MDSCs obtained from tumor‐bearing Myd88^?/? mice failed to suppress antigen‐specific proliferation of CD8⁺ T cells and CD4⁺ T cells, whereas MDSCs from wild‐type mice significantly suppressed both types of T cells. Consistent with this, we found that the levels of costimulatory molecules and MHC class II were significantly increased in MDSCs obtained from Myd88^?/? mice compared with wild‐type mice after tumor challenge. Furthermore, CD4⁺ T cells residing in tumor‐draining lymph nodes of Myd88^?/? mice secreted more TNF‐α than those of wild‐type mice. Finally, the blockade of Myd88 signaling by treatment with Myd88 inhibitory peptide, during later tumor stages, significantly inhibited the growth of immunogenic tumors. Overall, these data suggest that signaling through the Myd88 adaptor molecule is critical for the direct suppressive function of MDSCs and approaches to block Myd88‐mediated signaling in MDSCs might be effective to inhibit the immunosuppressive function of MDSCs.     

The prevalence and correlation of carotid artery calcification on panoramic radiographs and peripheral arterial disease in a population from the Republic of Korea: the Dong-gu study

Objectives:

The aim of this study was to determine the prevalence of carotid artery calcification (CAC) detected on panoramic radiographs and peripheral arterial disease (PAD), and to evaluate the difference in the prevalence of PAD between patients with CAC and patients without CAC detectable by panoramic radiograph.

Methods:

The surveyed population consisted of 4078 subjects aged 50 years and older (1410 males and 2668 females) who underwent medical and dental examination in Gwangju city, South Korea. Two oral and maxillofacial radiologists interpreted the panoramic radiographs for the presence of carotid artery calcification. A trained research technician measured the ankle–brachial index (ABI). An ABI <0.9 in either leg was considered evidence of PAD.

Results:

The prevalence of CAC on panoramic radiographs was 6.2% and that of PAD was 2.6%. Subjects with CAC had a significantly higher prevalence of PAD than those without CAC (5.5% vs 2.4%, respectively). The presence of CAC on panoramic radiographs was associated with PAD (odds ratio 1.84; 95% confidence interval 1.01–3.36) after adjusting for potential confounders.

Conclusion:

CACs detected on panoramic radiographs were positively associated with PAD in middle-aged and older Korean adults.     

Complicated mumps viral infection: An unusual presentation affecting only submandibular gland

This case is a single submandibular gland mumps viral infection patient without parotid gland involvement who developed complications of meningitis and orchitis. Since spontaneous remission is common in mumps viral infection, missing opportunities for exact diagnosis is frequent. As in this case, single submandibular glands infection without parotid gland involvement not only delays diagnosis but also increases risk of developing complications. This case instructs us that despite the atypical manifestation, the clinician should suspect mumps and conduct serologic tests for diagnosis while observing for complications such as meningoencephalitis and orchitis.