Angiotensin-converting enzyme 2 (ACE2) was identified as a molecule that mediates the cellular entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Several membrane molecules of the host cell must cooperate in this process. While ACE2 serves in a membrane receptor-mediating interaction with the surface spike (S) glycoprotein of SARS-CoV-2 located on the virus envelope, enzyme A disintegrin and metalloproteinase 17 (ADAM17) regulates ACE2 availability on the membrane and transmembrane protease serine 2 (TMPRSS2) facilitates virus-cell membrane fusion. Interestingly, ACE2, ADAM17 and TMPRSS2 show a daily rhythm of expression in at least some mammalian tissue. The circadian system can also modulate COVID-19 progression via circadian control of the immune system (direct, as well as melatonin-mediated) and blood coagulation. Virus/ACE2 interaction causes ACE2 internalization into the cell, which is associated with suppressed activity of ACE2. As a major role of ACE2 is to form vasodilatory angiotensin 1-7 from angiotensin II (Ang II), suppressed ACE2 levels in the lung can contribute to secondary COVID-19 complications caused by up-regulated, pro-inflammatory vasoconstrictor Ang II. This is supported by the positive association of hypertension and negative COVID-19 prognosis although this relationship is dependent on numerous comorbidities. Hypertension treatment with inhibitors of renin-angiotensin system does not negatively influence prognosis of COVID-19 patients. It seems that tissue susceptibility to SARS-CoV-2 shows negative correlation to ACE2 expression. However, in lungs of infected patient, a high ACE2 expression is associated with better outcome, compared to low ACE2 expression. Manipulation of soluble ACE2 levels is a promising COVID-19 therapeutic strategy
The parasite communities of predatory fish can be species rich and diverse, making them effective models for studying the factors influencing temporal and spatial variation in these communities. Over a ten-year period an initial study was done on the metazoan parasite communities of Scomberomorus sierra (Jordan et Starks) from four locations on the south-central Pacific coast of Mexico. Twenty-four metazoan parasite taxa were identified from 674 S. sierra specimens: three species of Monogenea, eight Digenea, one Cestoda, one Acanthocephala, four Nematoda, five Copepoda, and two Isopoda. The parasite communities were characterised by high ectoparasite species richness, with monogeneans and some didymozoid species being numerically dominant. Community structure and species composition varied between locations, seasons and sampling years. Similarity between the component parasite communities was generally low, despite the occurrence of a distinctive set of host-specialist parasites. Interannual or local variations in some biotic and abiotic environmental factors are possible causes of the observed variations in the structure and species composition of the parasite community of S. sierra. Ecological factors were therefore considered to have more influence than phylogenetic aspects (host phylogeny) on parasite community structure.
Buffaloes represent an important economic resource for several regions of the world including Romania. In the present study, we examined 104 faecal samples collected from 38 buffalo calves (2-11 weeks old) from household rearing systems in Romania for gastrointestinal parasites. All samples were tested using the saturated salt flotation, McMaster and modified Ziehl-Nielsen staining methods. PCR coupled with sequencing isolates were used to identify assemblages of Giardia lamblia (Kunstler, 1882) and species of Cryptosporidium Tyzzer, 1907. Overall, 33 out of 38 examined buffalo calves were infected with different gastrointestinal parasites: 16 had single infections and 17 had mixed infections with two or three parasites. Species of Eimeria Schneider, 1875 (32/38; 84%) were the most prevalent parasites; eight species were identified according to the oocyst morphology, including the pathogenic E. bareillyi (Gill, Chhabra et Lall, 1963) which was detected for the first time in buffaloes from Romania. The nematodes Toxocara vitulorum (Goeze, 1782) (11/38; 37%) and Strongyloides papillosus (Wedl, 1856) (6/38; 16%) were also detected. Cryptosporidium spp. were found in four (11%) buffalo calves; two of them were molecularly identified as C. ryanae Fayer, Santin et Trout, 2008, and another one clustered in the same clade with C. ryanae, C. bovis Fayer, Santin et Xiao, 2005, and C. xiaoi Fayer et Santin, 2009. Giardia duodenalis assemblage E was also molecularly detected in a single (2.6%) buffalo calf. The presence of other buffaloes in the same barn was identified as a risk factor for infection with T. vitulorum. Our results indicate extensive parasitic infections in buffalo calves from northwestern Romania and underline the necessity of prophylactic treatments for T. vitulorum and E. bareillyi.
This study tested whether cell cycle inhibitor mitomycin C (MMC) prevents arthrogenic contracture progression during remobilization by inhibiting fibroblast proliferation and fibrosis in the joint capsule. Rat knees were immobilized in a flexed position to generate flexion contracture. After three weeks, the fixation device was removed and rat knees were allowed to freely move for one week. Immediately after and three days after fixator removal, rats received intra-articular injections of MMC or saline. The passive extension range of motion (ROM) was measured before and after myotomy of the knee flexors to distinguish myogenic and arthrogenic contractures. In addition, both cellularity and fibrosis in the posterior joint capsule were assessed histologically. Joint immobilization significantly decreased ROMs both before and after myotomy compared with untreated controls. In saline-injected knees, remobilization increased ROM before myotomy, but further decreased that after myotomy compared with that of knees immediately after three weeks of immobilization. Histological analysis revealed that hypercellularity, mainly due to fibroblast proliferation, and fibrosis characterized by increases in collagen density and joint capsule thickness occurred after remobilization in saline-injected knees. Conversely, MMC injections were able to prevent the remobilization-enhanced reduction of ROM after myotomy by inhibiting both hypercellularity and joint capsule fibrosis. Our results suggest that joint capsule fibrosis accompanied by fibroblast proliferation is a potential cause of arthrogenic contracture progression during remobilization, and that inhibiting fibroblast proliferation may constitute an effective remedy.
The taxonomy of myxosporeans was traditionally dependent solely upon the spore morphological and morphometric data. Intensive reports of intraspecific morphological variation, however, are increasingly challenging the taxonomic approaches for myxosporeans. In the present work, the morphological pleomorphism of myxospores of Myxobolus drjagini (Akhmerov, 1954) was observed. More interestingly, all of these pleomorphic myxospores occurred in the same plasmodium of M. drjagini, which refutes the previous hypothesis that morphological variation of M. drjagini was derived from its responses to differences in nutrition and immunological responses associated with different host tissues. Bearing the intraspecific morphometric and morphotype variation in mind, the combination of morphological, ecological and molecular data should be applied to the species identification and delimitation for myxosporeans. This is the first reported myxobolid species with high pleomorphic myxospores which are present in the same plasmodium.
Morphometric data from spores of ten myxosporean species were statistically analysed to explore myxosporean intraspecific variation in measurements when obtained from a sample from: (1) the same plasmodium, (2) different plasmodia from the same host and (3) different host individuals and localities. In some cases, significant differences in spore dimensions were found between samples from the same plasmodium, highlighting the difficulty of obtaining representative measurements of myxosporean spore. In addition, significant differences in spore dimensions were found when plasmodia from the same site of infection were compared, suggesting that measurements of spores should come from several different plasmodia of the sampling to increase the reliability of the morphology data. Moreover, significant differences in spore dimensions were observed for most spore dimensions when data were compared between localities. In all cases, there was clear overlap in ranges of dimensions even when means differed significantly. The present statistical analysis shows that intraspecific morphometric variation of myxosporean species commonly occurs, highlighting the importance of reporting ranges of measurements for a species, not just the mean dimensions, and taking into account all evidence when assigning or describing myxosporean species., Yanhua Zhai, Christopher M. Whipps, Zemao Gu, Qingxiang Guo, Zizhen Wu, Hongmei Wang, Yang Liu., and Obsahuje bibliografii
Cancer is a complex, multifactorial disease that modern medicine ultimately aims to overcome. Downstream of tyrosine kinase 2 (DOK2) is a well-known tumor suppressor gene, and a member of the downstream protein DOK family of tyrosine kinases. Through a search of original literature indexed in PubMed and other databases, the present review aims to extricate the mechanisms by which DOK2 acts on cancer, thereby identifying more reliable and effective therapeutic targets to promote enhanced methods of cancer prevention and treatment. The review focuses on the role of DOK2 in multiple tumor types in the lungs, intestines, liver, and breast. Additionally, we discuss the potential mechanisms of action of DOK2 and the downstream consequences via the Ras/MPAK/ERK or PI3K/AKT/mTOR signaling pathways., Pei Sun, Rumeng Li, Yingying Meng, Shijun Xi, Qinqi Wang, Xiulan Yang, Xiaochun Peng, Jun Cai., and Obsahuje bibliografii
Pulmonary pathology is common in HIV-infected individuals, but the possible role of the parasitic protist Toxoplasma gondii (Nicolle et Manceaux, 1908) is not completely known. The present account reports result of a retrospective cohort study. Medical cards of 907 HIV-positive people, which included 120 deceased patients, were analysed. During a three-year follow-up, the pulmonary pathology was diagnosed in 306 patients (33.7 ± 1.6%): pneumocystis pneumonia in 124 (13.7 ± 1.1%), primary pulmonary tuberculosis in 113 (12.5 ± 1.1%), bacterial pneumonia in 58 (6.4 ± 0.8%) toxoplasmosis pneumonia in two (0.2 ± 0.2%), and others. All patients were divided into two cohorts: 531 individuals seropositive for T. gondii and 376 seronegative ones. It has been found out that general lung pathology is more common in patients with seropositivity to T. gondii than in seronegative ones (43.3 ± 2.2% vs. 20.1 ± 2.0%, p < 0.001). The diagnosis of pneumocystis pneumonia was made ten times more often in the cohort of seropositive patients than in the cohort of seronegative ones (21.9 ± 1.8% vs. 2.1 ± 0.7%, respectively, p < 0.001) and in deceased patients of these cohorts it was 5.5 times more (45.1 ± 5.9% vs. 8.2 ± 3.9, respectively, p < 0.001). In patients with fatal outcome and seropositivity to T. gondii, the incidences of pneumocystis pneumonia increased by 23.2% (p < 0.001) and bacterial pneumonia by 12.4% (p < 0.05), whereas in seronegative individuals only pulmonary tuberculosis increased by 13.1% (p < 0.05) сompared with corresponding whole cohorts. Pearson's contingency coefficient showed the mean strength association between infection with T. gondii and incidence of pneumocystis pneumonia both in whole cohort (C = 0.272) and in patients with fatal outcomes (C = 0.368). In сonclusion, significantly increasing rate of pneumocystis pneumonia in patients with HIV/AIDS and T. gondii infection can be caused by certain synergism between T. gondii and Pneumocystis jirovecii and in some cases overdiagnosis pneumocystis pneumonia due to undiagnosed toxoplasmosis pneumonia.