To provide instructive clues for clinical practice and further research of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection, we analyzed the existing literature on viral ...neuroinvasion of SARS‐CoV‐2 in coronavirus disease 2019 (COVID‐19) patients. To date, SARS‐CoV‐2 has been detected in the cerebrospinal fluid (CSF) or brain parenchyma in quite a few patients, which provide undeniable evidence for the neuroinvasive potential of this novel coronavirus. In contrast with the cerebrum and cerebellum, the detection rate of SARS‐CoV‐2 was higher in the olfactory system and the brainstem, both of which also showed severe microgliosis and lymphocytic infiltrations. As compared with the number of patients who underwent viral testing in the central nervous system (CNS), the number of patients showing positive results seems very small. However, it seems too early to conclude that the neuroinvasion of SARS‐CoV‐2 is rare in COVID‐19 patients because the detection methods or sampling procedures in some studies may not be suitable or sufficient to reveal the CNS infection induced by neurotropic viruses. Moreover, the primary symptoms and/or causes of death were distinctly different among examined patients, which probably caused more conspicuous pathological changes than those due to the direct infection that usually localized to specific brain areas. Unfortunately, most autopsy studies did not provide sufficient details about neurological symptoms or suspected diagnoses of the examined patients, and the documentation of neuropathological changes was often incomplete. Given the complex pathophysiology of COVID‐19 and the characteristics of neurotropic viruses, it is understandable that any study of the CNS infection may inevitably have limitations.
Highlights
We analyzed the papers on CSF testing and brain autopsies in COVID‐19 patients.
SARS‐CoV‐2 has been detected in the CSF or brain parenchyma in a few patients.
The detection rate of SARS‐CoV‐2 is high in the olfactory system and the brainstem.
Some detection methods are not sufficient to reveal the CNS infection of SARS‐CoV‐2.
Symptoms or death causes of examined patients are not often provided in some papers.
It cannot be simply concluded that viral neuroinvasion is rare in COVID‐19 patients.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The outbreak of coronavirus disease 2019 (COVID‐19), caused by severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2), has become a significant and urgent threat to global health. This review ...provided strong support for central nervous system (CNS) infection with SARS‐CoV‐2 and shed light on the neurological mechanism underlying the lethality of SARS‐CoV‐2 infection. Among the published data, only 1.28% COVID‐19 patients who underwent cerebrospinal fluid (CSF) tests were positive for SARS‐CoV‐2 in CSF. However, this does not mean the absence of CNS infection in most COVID‐19 patients because postmortem studies revealed that some patients with CNS infection showed negative results in CSF tests for SARS‐CoV‐2. Among 20 neuropathological studies reported so far, SARS‐CoV‐2 was detected in the brain of 58 cases in nine studies, and three studies have provided sufficient details on the CNS infection in COVID‐19 patients. Almost all in vitro and in vivo experiments support the neuroinvasive potential of SARS‐CoV‐2. In infected animals, SARS‐CoV‐2 was found within neurons in different brain areas with a wide spectrum of neuropathology, consistent with the reported clinical symptoms in COVID‐19 patients. Several lines of evidence indicate that SARS‐CoV‐2 used the hematopoietic route to enter the CNS. But more evidence supports the trans‐neuronal hypothesis. SARS‐CoV‐2 has been found to invade the brain via the olfactory, gustatory, and trigeminal pathways, especially at the early stage of infection. Severe COVID‐19 patients with neurological deficits are at a higher risk of mortality, and only the infected animals showing neurological symptoms became dead, suggesting that neurological involvement may be one cause of death.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
As compared to many other viral pulmonary infections, there existed several peculiar manifestations in the COVID‐19 patients, including the “silence” of pneumonia in both mild and severe cases and a ...long intensive care unit stay for those requiring invasive mechanical ventilation. Similar silent pneumonia has been documented in the infectioninduced by H5N1 influenza virus HK483 and was found to result from the direct attack of the virus on the bronchopulmonary C‐fibers at the early stage and the final infection in the brainstem at the late stage. The long stay of critical patients in the intensive care unit is possibly due to the depression of central respiratory drive, which resulted in the failure to wean from the mechanic ventilation. Carotid and aortic bodies and bronchopulmonary C‐fibers are two key peripheral components responsible for the chemosensitive responses in the respiratory system, while triggering respiratory reflexes depends predominantly on the putative chemosensitive neurons located in the pontomedullary nuclei. In view of the findings for the H5N1 influenza virus, the silence of pneumonia induced by SARS‐CoV‐2 may be due to the possible impairment of peripheral chemosensitive reflexes as well as the damage to the respiratory‐related central neurons.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Poor postharvest handling, microbial infestation, and high respiration rate are some the factors are responsible for poor storage life of perishable commodities. Therefore, effective preservation of ...these commodities is needed to lower the damages and extend shelf life. Preservation is regarded as the action taken to maintain desired properties of a perishable commodity as long as possible. Persimmon (Diospyros kaki) is perishable fruit with high nutritive value; however, has very short shelf-life. Therefore, effective preservation and drying is needed to extend its storage life. Drying temperature and preservatives significantly influence the quality of perishable vegetables and fruits during drying. The current study investigated the effect of different temperatures and preservatives on drying kinetics and organoleptic quality attributes of persimmon. Persimmon fruits were treated with preservatives (25% honey, 25% aloe vera, 2% sodium benzoate, 1% potassium metabisulfite, and 2% citric acid solutions) under different drying temperatures (40, 45, and 50°C). All observed parameters were significantly affected by individual effects of temperatures and preservatives, except ash contents. Similarly, interactive effects were significant for all parameters except total soluble sugars, ash contents, and vitamin C. Generally, fruits treated with citric acid and dried under 50°C had 8.2% moisture loss hour-1, 14.9 drying hours, 0.030 g H2O g-1 hr-1, 1.23° Brix of total soluble solids, 6.71 pH, 1.35% acidity, and 6.3 mg vitamin C. These values were better than the rest of the preservatives and drying temperatures used in the study. Therefore, treating fruits with citric acid and drying at 50°C was found a promising technique to extend storage life of persimmon fruits. It is recommended that persimmon fruits dried at 50°C and preserved in citric acid can be used for longer storage period.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objective. Roux-en-Y gastric bypass (RYGB) has shown good effects in improving obesity and type II diabetes mellitus (T2DM), but the underlying mechanisms remain unclear. This study explored the ...changes of related lncRNAs, mRNAs, and signaling pathways in white adipose tissue of T2DM rats after RYGB based on RNA-Seq sequencing, with the aim to provide a theoretical basis for RYGB treatment. Methods. T2DM rat models were established by continuous feeding with a high-fat diet and injection of streptozotocin (STZ), after which they underwent RYGB or sham surgery. After the surgery, their body weight was measured weekly. Their fasting blood glucose (FBG) and fasting serum insulin (FSI) were also measured. A homeostasis model assessment of insulin resistance (HOMA-IR) was calculated at weeks 0, 8, and 12. Besides, white adipose tissue of T2DM rats was collected for RNA-Seq sequencing and validated by qRT-PCR. A series of bioinformatics analyses, such as differential expression genes (DEGs) screening, was performed. GO and KEGG functional enrichment analysis and protein-protein interaction (PPI) network construction were conducted based on the sequencing data. Results. RYGB surgery could significantly inhibit the weight growth rate and decrease the FBG, FSI, and HOMA-IR of T2DM rats. Bioinformatics analysis of RNA sequencing (RNA-Seq) results revealed that 87 DE- lncRNAs (49 upregulated and 38 downregulated) and 1,824 DEGs (896 upregulated and 928 downregulated) were present in between the RYGB group and Sham group. GO and KEGG analysis showed that the target genes of DEGs and differentially expressed lncRNAs (DE-lncRNAs) were mainly associated with amino acid metabolism, fatty acid metabolism, channel activity, and other processes. In addition, the PPI network diagram also displayed that genes such as Fasn, Grin3a, and Nog could be key genes playing a role after RYGB. qRT-PCR showed that the expression level of Grin3a in the RYGB group was significantly increased compared with the Sham group, while the expression of Fasn and Nog was significantly decreased, which was consistent with the sequencing results. Conclusion. Using RNA-Seq sequencing, this study revealed the changes of related lncRNAs, mRNAs, and signaling pathways in the white adipose tissue of T2DM rats after RYGB and identified Fasn, Grin3a, and Nog as potential key genes to function after RYGB.
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Interleukin-21 and its receptors (IL-21/IL-21R) aggravate chlamydial lung infection, while macrophages (Mφ) are one of the main cells infected by chlamydia and the main source of inflammatory ...cytokines. Therefore, it is particularly important to study whether IL-21/IL-21R aggravates chlamydia respiratory infection by regulating Mφ. Combined with bioinformatics analysis, we established an IL-21R-deficient (IL-21R−/−) mouse model of Chlamydia muridarum (C. muridarum) respiratory tract infection in vivo, studied C. muridarum-stimulated RAW264.7 by the addition of rmIL-21 in vitro, and conducted adoptive transfer experiments to clarify the association between IL-21/IL-21R and Mφ. IL-21R−/− mice showed lower infiltration of pulmonary total Mφ, alveolar macrophages, and interstitial macrophages compared with WT mice following infection. Transcriptomic analysis suggested that M1-related genes are downregulated in IL-21R−/− mice and that IL-21R deficiency affects the Mφ-mediated inflammatory response during C. muridarum infection. In vivo experiments verified that in IL-21R−/− mice, pulmonary M1-type CD80+, CD86+, MHC II+, TNFα+, and iNOS+ Mφ decreased, while there were no differences in M2-type CD206+, TGF-β+, IL-10+ and ARG1+ Mφ. In vitro, administration of rmIL-21 to C. muridarum-stimulated RAW264.7 cells promoted the levels of iNOS-NO and the expression of IL-12p40 and TNFα, but had no effect on TGFβ or IL-10. Further, adoptive transfer of M1-like bone marrow-derived macrophages derived from IL-21R−/− mice, unlike those from WT mice, effectively protected the recipients against C. muridarum infection and induced relieved pulmonary pathology. These findings help in understanding the mechanism by which IL-21/IL-21R exacerbates chlamydia respiratory infection by promoting the proinflammatory effect of Mφ.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
To date, ischemia-induced damage to dendritic spines has attracted considerable attention, while the possible effects of ischemia on presynaptic components has received relatively less attention. To ...further examine ischemia-induced changes in pre- and postsynaptic specializations in the hippocampal CA1 subfield, we modeled global cerebral ischemia with two-stage 4-vessel-occlusion in rats, and found that three postsynaptic markers, microtubule-associated protein 2 (MAP2), postsynaptic density protein 95 (PSD95), and filamentous F-actin (F-actin), were all substantially decreased in the CA1 subfield after ischemia/reperfusion (I/R). Although no significant change was detected in synapsin I, a presynaptic marker, in the CA1 subfield at the protein level, confocal microscopy revealed that the number and size of synapsin I puncta were significantly changed in the CA1 stratum radiatum after I/R. The size of synapsin I puncta became slightly, but significantly reduced on Day 1.5 after I/R. From Days 2 to 7 after I/R, the number of synapsin I puncta became moderately decreased, while the size of synapsin I puncta was significantly increased. Interestingly, some enlarged puncta of synapsin I were observed in close proximity to the dendritic shafts of CA1 pyramidal cells. Due to the more substantial decrease in the number of F-actin puncta, the ratio of synapsin I/F-actin puncta was significantly increased after I/R. The decrease in synapsin I puncta size in the early stage of I/R may be the result of excessive neurotransmitter release due to I/R-induced hyperexcitability in CA3 pyramidal cells, while the increase in synapsin I puncta in the later stage of I/R may reflect a disability of synaptic vesicle release due to the loss of postsynaptic contacts.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The incidence of Chlamydia trachomatis respiratory infection is increasing, and its pathogenesis is still unclear. Pyroptosis, as a mode of inflammatory cell death, plays a vital role in the ...occurrence and development of Chlamydia trachomatis respiratory infection. In this study, the potential pyroptosis-related genes involved in Chlamydia trachomatis respiratory infection were identified by constructing a mouse model of C. muridarum infection combined with bioinformatics analysis. Through in-depth analysis of the RNA sequencing data, 13 differentially expressed pyroptosis-related genes were screened, including 1 downregulated gene and 12 upregulated genes. Gene ontology (GO) analysis showed that these genes mainly regulate inflammatory responses and produce IL-1β. Protein–protein interaction network analysis identified eight hub genes of interest: Tnf, Tlr2, Il1b, Nlrp3, Tlr9, Mefv, Zbp1 and Tnfaip3. Through quantitative real-time PCR (qPCR) analysis, we found that the expression of these genes in the lungs of C. muridarum-infected mice was significantly reduced, consistent with the bioinformatics results. At the same time, we detected elevated levels of caspase-3, gasdermin D and gasdermin E proteins in the lungs of C. muridarum-infected mice, demonstrating that Chlamydia trachomatis infection does induce pyroptosis. We then predicted nine miRNAs targeting these hub genes and constructed a key competitive endogenous RNA (ceRNA) network. In summary, we identified six key pyroptosis-related genes involved in Chlamydia trachomatis respiratory infection and constructed a ceRNA network associated with these genes. These findings will improve understanding of the molecular mechanisms underlying pyroptosis in Chlamydia trachomatis respiratory infections.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
•F-actin becomes disrupted in the dentritic spines of CA1 neurons after ischemia.•F-actin is aggregated in CA1 stratum radiatum before complete depolymerization.•F-actin rods are located in dendritic ...shafts of CA1 neurons.•Ischemia results in a significant decrease of F-actin/G-actin ratio in area CA1.•F-actin damage proceeds concurrently with the evolution of the ischemic damage.
Transient global ischemia usually results in delayed neuronal death in selective brain regions, prior to which a rapid loss of dendritic spines has been widely reported in these regions. Dendritic spines are characterized by a highly branched meshwork of actin cytoskeleton (F-actin), which is extremely vulnerable to the ATP-depleted conditions such as hypoxia/ischemia. However, the ischemia-induced changes of F-actin are still not clarified in the vulnerable brain areas. This study was designed to examine the temporal and spatial alterations of F-actin in the CA1 subfield of rat hippocampus following reperfusion after global cerebral ischemia. Phalloidin staining and confocal microscopic examination showed that F-actin disappeared from the dentritic spines in the CA1 stratum radiatum, but aggregated into thread- or fiber-like structures on days 1.5–2 after ischemia. This was followed by a nearly complete loss of F-actin in the CA1 subfield on days 3–7 after ischemia. Colocalization analysis demonstrated that the F-actin threads or fibers were located mainly within the dentritic trunks. As revealed by Nissl and Fluoro-Jade B staining, the decrease of F-actin proceeded concurrently with the evolution of ischemic damage. Consistently, western blots detected a significant decrease of F-/G-actin ratio in the dissected CA1 subfield after ischemia. To our knowledge, this is the first report on the change of F-actin in the ischemic brain. Although the underlying mechanisms remain to be elucidated, our findings may provide an important structural clue for the neuronal dysfunction induced by ischemia.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Acute neuronal degeneration is always preceded under the light and electron microscopes by a stage called microvacuolation, which is characterized by a finely vacuolar alteration in the cytoplasm of ...the neurons destined to death. In this study, we reported a method for detecting neuronal death using two membrane-bound dyes, rhodamine R6 and DiOC6(3), which may be associated with the so-called microvacuolation. This new method produced a spatiotemporally similar staining pattern to Fluoro-Jade B in kainic acid-damaged brains in mice. Further experiments showed that increased staining of rhodamine R6 and DiOC6(3) was observed only in degenerated neurons, but not in glia, erythrocytes, or meninges. Different from Fluoro-Jade-related dyes, rhodamine R6 and DiOC6(3) staining is highly sensitive to solvent extraction and detergent exposure. Staining with Nile red for phospholipids and filipin III for non-esterified cholesterol supports that the increased staining of rhodamine R6 and DiOC6(3) might be associated with increased levels of phospholipids and free cholesterol in the perinuclear cytoplasm of damaged neurons. In addition to kainic acid-injected neuronal death, rhodamine R6 and DiOC6(3) were similarly useful for detecting neuronal death in ischemic models either in vivo or in vitro. As far as we know, the staining with rhodamine R6 or DiOC6(3) is one of a few histochemical methods for detecting neuronal death whose target molecules have been well defined and therefore may be useful for explaining experimental results as well as exploring the mechanisms of neuronal death.
•KA-injured neurons show increased staining of rhodamine R6 and DiOC6(3).•Increased staining is present only in damaged neurons but not healthy neurons or glia.•The staining is spatiotemporally consistent with that obtained by Fluoro-jade B.•The staining is sensitive to solvent extraction and detergent exposure.•The staining is associated with increased membranous components in damaged neurons.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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