Tonsillitis exacerbates renal injury in IgA nephropathy through promoting Th22 cells chemotaxis

Background

Tonsillitis can promote the progression of IgA nephropathy (IgAN) by aggravating immunopathologic response. Th22 cell disorder is involved in the pathogenesis of IgAN with tonsillitis. This study was determined to explore the possible mechanism of IgAN with tonsillitis underlying Th22 cell chemotaxis response to the effect of CCL20, CCL22, and CCL27.

Methods

This research was conducted on 65 subjects including 16 healthy controls (HC group), 5 patients with  renal carcinoma (HTC group) and 44 patients with IgAN between 2015 and 2016. According to clinical symptoms and results of throat swab culture, patients with IgAN were divided into two groups: IgAN with tonsillitis (IgAN + tonsillitis, n = 14) and IgAN patients without tonsillitis (IgAN, n = 30). Distribution of Th22 cells in IgAN patients was determined. The expression of CCL20, CCL22, and CCL27 in both peripheral blood and kidneys of IgAN patients was investigated. Severity of pathological lesions in IgAN patients was analyzed. Coculture assay and transwell assay were performed to explore the impacts of human mesangial cells (HMC) on Th22 cell chemotaxis and Th22 cell local accumulation under hemolytic streptococcus (HS) infection.

Results

Th22 cell percentages in IgAN patients increased compared with healthy controls. This increased Th22 cell percentage was positively correlated with the renal lesions of IgAN patients. Correspondingly, the expression of CCL20, CCL22, and CCL27 in renal tissue increased in IgAN patients. Tonsillitis exacerbated these overrepresentations of Th22 cells and chemokines. It was found that HMC could produce CCL20, CCL22, and CCL27. The supernatant of HMC was chemotactic for Th22 cells. This activity of HMC was stimulated by HS infection, whereas treatment of anti-CCL20, anti-CCL22, and anti-CCL27 antibodies partly blocked this chemoattractant effect of HMC.

Conclusions

Tonsil infection may aggravate the renal pathological lesions of IgAN by exacerbating Th22 cell accumulation. Our data suggested a collaboration between HMC and Th22 cells in IgAN with tonsillitis underlying the effects of CCL20, CCL22, and CCL27.

     

Steroidogenesis decline accompanied with reduced antioxidation and endoplasmic reticulum stress in mice testes during ageing

To gain an understanding of the mechanisms by which Leydig cell steroidogenic function degenerates with ageing, we explored steroidogenic gene expression in relation to antioxidation status and endoplasmic reticulum (ER) stress during the ageing of mice. Expression of StAR, P450scc and other steroidogenic enzymes decreased starting at middle age (12‐month‐old) compared to that of the young control (3‐month‐old) mice. The immunohistochemical staining intensity of 3β‐HSD for Leydig cells was significantly weaker in the aged (24‐month‐old) group than that in the young control group. The number of Leydig cells showed no significant difference between the groups. A progressive reduction in antioxidants MnSOD and GPx4 was observed in the testicular tissue with down‐regulated SIRT1 protein level in the middle‐aged and aged (24‐month‐old) mice. The number of testicular macrophages was significantly higher in the aged group than that in the middle‐aged and young mice. Age‐associated up‐regulation of ER stress markers such as GRP78 and Chop was observed. These results suggested that oxidative stress and ER stress might play a role in the deficit of Leydig cell steroidogenic function during ageing.     

Preparation and observation methods can produce misleading artefacts in human sperm ultrastructural morphology

The aim of this study was to evaluate the production of artefacts during preparation and observation of human sperm for ultrastructural morphology and analyse the possible reasons of causing these artefacts. Under the scanning electron microscopy, damaged sperm heads (crack or/and rupture), necks (head‐neck or head‐midpiece separation) and midpiece (disassembled and denuded axoneme ultrastructures, bent midpiece) were analysed to be the consequence of exogenous effects. Thirty infertile men with teratozoospermia revealed more spermatozoa with damage to head, neck and midpiece than did thirty fertile males (p < .01). After the samples from fertile males underwent five repeated observations, most sperm heads and necks in the samples were destroyed when compared with the single observation (p < .01). Destroyed sperm heads were full of cracks and peelings, even sperm tails were broken and fragmented, and separations of the sperm head‐neck or head‐midpiece became common. Spermatozoa from fertile males with centrifugation of 600 g for washing sperm exhibited more damage to the midpiece than those with the 300 g (p < .01). These results demonstrate that preparation and observation methods can damage sperm ultrastructures, leading to producing artefacts of ultrastructural morphology. The artefacts of sperm ultrastructural morphology may be associated with sperm structural fragility, preparation conditions and electron beam damage.     

Reduction in Peyronie's‐like plaque size using a vacuum erection device in a rat model of Peyronie's disease via the TGF‐β/SMAD signalling pathway

Peyronie's disease (PD) is a fibrotic disorder of the tunica albuginea (TA). This study aimed to determine the therapeutic effects of a vacuum erection device (VED) in an animal model of PD and explore the possible mechanisms. Twenty‐seven male Sprague‐Dawley rats were used. The sham group (group A) (N = 9) received a 50‐μl‐saline vehicle injection into the TA, while the remaining 18 rats (groups B and C) received a TGF‐β1 injection into the TA. The treatment group (group C) underwent VED therapy for 10 days after the TGF‐β1 injection. Erectile function was then assessed at day 42. Rats injected with TGF‐β1 showed significantly lower intracavernous pressures than those in the sham group (p < 0.0001). After VED therapy, erectile function was significantly better in the treatment group than in the PD group (group B) (p < 0.0147). Masson's trichrome staining confirmed Peyronie's‐like plaques at the TGF‐β1 injection site in the PD group. Furthermore, the treatment group showed markedly smaller fibrotic plaque sizes than the PD group. A significant increase in TGF‐β1, SMAD2, SMAD3 and p‐SMAD2/3 protein expression was observed 6 weeks after the TGF‐β1 injection. However, the expression of the same proteins decreased after VED therapy. Protein expression trends were confirmed using immunohistochemistry analysis. The findings of this study demonstrate that VED therapy can reduce Peyronie's‐like plaque size in a rat model of PD while simultaneously improving erectile function.     

Mesenteric Lymphatic Vessel Density Is Associated with Disease Behavior and Postoperative Recurrence in Crohn’s Disease

Purpose

The aims of the present study were to examine the density of lymphatic vessels in the mesentery and to assess the predictive value of the mesenteric lymphatic vessel density for postoperative clinical recurrence.

Methods

Ileocolonic resection specimens were obtained from 53 patients with Crohn’s disease and 10 non-inflammatory bowel disease control subjects. Mesentery adipose tissues adjacent to the bowel wall were used for the histological quantification of lymphatic vessels using immunohistochemistry with the D2-40 antibody. The relationships between lymphatic vessel density and disease behavior, the presence of granulomas, the presence of creeping fat, and postoperative clinical recurrence were assessed.

Results

Median lymphatic vessel density in the mesentery adjacent to inflamed or non-inflamed intestine was lower in control subjects than in Crohn’s disease patients (2.13‰; interquartile range [IQR], 1.83–2.61; 8.34‰; IQR, 6.39–10.22; 4.43‰; IQR, 3.32–5.78; P ? 0.001). Increased mesenteric lymphatic vessel density was significantly associated with stricturing behavior, the presence of intestinal granulomas, the presence of creeping fat, and bowel thickness. Interestingly, patients with disease recurrence had an increased mesenteric lymphatic vessel density of the proximal mesenteric margin at the time of resection compared with those who did not have disease recurrence (6.23‰; IQR, 5.43–6.75 vs. 3.28‰; IQR, 2.93–4.29; P ? 0.001).

Conclusions

In addition to its correlation with disease behavior, bowel thickness, and the presence of intestinal granulomas and creeping fat, increased mesenteric lymphatic vessel density in the proximal margin is predictive of early clinical recurrence after surgery in patients with Crohn’s disease.

     

The family Amanitaceae: molecular phylogeny,higher-rank taxonomy and the species in China

Mushrooms in the basidiomycete family Amanitaceae are very important both economically and ecologically. However, the delimitation of the family is still controversial, in part due to limited taxon sampling and in part because of insufficient gene fragment employed for molecular phylogenetic analyses. Furthermore, species diversity in the family is likely to have been largely underestimated, due to morphological similarity between taxa and phenotypic plasticity. In this study, we examined 1190 collections, including 1008 Chinese and 182 external ones, and performed the first comprehensive phylogenetic analyses of Amanitaceae using multi-locus sequence data. To test the monophyly of the Amanitaceae, a concatenated (nrLSU, rpb1, and rpb2) dataset of 200 taxa of the order Agaricales was analyzed. To infer the phylogeny of Amanitaceae, a concatenated nrLSU, tef1-α, rpb2 and β-tubulin dataset (3010 sequences from ca. 890 samples with 2309 newly generated sequences) was used. In this dataset, 252 sequences from the types of 77 species were provided. Our results indicate that Amanitaceae is a monophyletic group, and consists of five genera, namely Amanita, Catatrama, Limacella, Limacellopsis and Myxoderma. It is clear that Catatrama is closely related to Limacella, however, the phylogenetic relationships among these genera remain largely unresolved. Amanita contains 95% of the species in the family, and is here divided into three subgenera and eleven sections (subgen. Amanita, containing: sect. Amanita, sect. Amarrendiae, sect. Caesareae and sect. Vaginatae; subgen. Amanitina, containing: sect. Amidella, sect. Arenariae, sect. Phalloideae, sect. Roanokenses, sect. Strobiliformes and sect. Validae; and subgen. Lepidella, containing sect. Lepidella). Subgen. Lepidella occupies the basal position in the genus. One-hundred and sixty-two species of Amanitaceae known from China are treated in this study, including 50 novel species and 112 known taxa. Amanita gleocystidiosa, A. pyriformis, A. atrofusca, A. subjunquillea var. alba and A. areolata are treated as synonyms of A. sychnopyramis f. subannulata, A. orientigemmata, A. umbrinolutea, A. subjunquillea and A. zangii, respectively. 26 extralimital taxa including a novel species, namely Catatrama indica, were included in our study to allow us to make comparisons between these and the Chinese taxa. DNA sequence data for all the species of Amanitaceae in China and keys for identification of the species are provided.     

Acteoside relieves mesangial cell injury by regulating Th22 cell chemotaxis and proliferation in IgA nephropathy

The existing therapies of IgA nephropathy are unsatisfying. Acteoside, the main component of Rehmannia glutinosa with anti-inflammatory and anti-immune effects, can improve urinary protein excretion and immune disorder. Th22 cell is involved in IgA nephropathy progression. This study was determined to explore the effect of acteoside on mesangial injury underlying Th22 cell disorder in IgA nephropathy. Serum Th22 cells and urine total protein of patients with IgA nephropathy were measured before and after six months treatment of Rehmannia glutinosa acteoside or valsartan. Chemotactic assay and co-culture assay were performed to investigate the effect of acteoside on Th22 cell chemotaxis and differentiation. The expression of CCL20, CCL22 and CCL27 were analyzed. To explore the effect of acteoside on mesangial cell injury induced by inflammation, IL-1, IL-6, TNF-α and TGF-β1 were tested. Results showed that the proteinuria and Th22 lymphocytosis of patients with IgA nephropathy significantly improved after combination treatment of Rehmannia glutinosa acteoside and valsartan, compared with valsartan monotherapy. In vitro study further demonstrated that acteoside inhibit Th22 cell chemotaxis by suppressing the production of Th22 cell attractive chemokines, i.e., CCL20, CCL22 and CCL27. In addition, acteoside inhibited the Th22 cell proliferation. Co-culture assay proved that acteoside could relieve the overexpression of pro-inflammatory cytokines, and prevent the synthesis of TGF-β1. TGF-β1 level in mesangial cells was positively correlated with the Th22 cell. This research demonstrated that acteoside can alleviate mesangial cell inflammatory injury by modulating Th22 lymphocytes chemotaxis and proliferation.