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Cryptococcal meningitis is a central nervous system infection caused by cryptococcal invasion of meninges and (or) brain parenchyma. It is characterized by severe intracranial hypertension and brain parenchyma damage. This opportunistic infection commonly occurs among HIV infected individuals, organ transplant recipients, and other immunosuppressive situations, and otherwise immunologically normal hosts. The global burden of human immunodeficiency virus/acquired immunodeficiency syndrome has declined over the years, but cryptococcal meningitis still has a high morbidity and mortality. The risk groups, clinical presentation, imaging characteristics, diagnostic criteria and therapeutic issues were reviewed in this article.
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Hypervirulent Klebsiella pneumoniae (HvKP) is a new variant of Klebsiella pneumoniae. It is characterized by strong virulence and easy dissemination. It mainly causes liver abscess with multiple invasive infections, including eye, lung and central nervous system, with a high fatality rate. A case of severe intracranial infection caused by HvKP was reported. The patient was a 44-year-old formerly healthy man. He had acute onset of fever, headache, and disturbance of consciousness, which rapidly progressed to intracranial hypertension and respiratory failure. Cerebrospinal fluid examination suggested purulent infection, and bacterial culture suggested Klebsiella pneumoniae, which was sensitive to other commonly used antibiotics except ampicillin. Brain magnetic resonance imaging showed multiple abnormal signals in bilateral frontal, parietal and temporal lobes, right centrum semiovale, bilateral corona radiata, basal ganglia, thalamus and insula, as well as enhancement of meningeal and ependymal membrane, and swelling of brain tissue. During hospitalization, the patient developed a blood stream infection of pan-drug-resistant Klebsiella pneumoniae and was in critical condition. After aggressive treatment, the patient was cured and discharged from the hospital. After half a year follow-up, his prognosis was good and his social function was restored. The clinical data, diagnosis and treatment of the patient were reported and the literature was reviewed to provide clinical reference for the disease.
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SARS-CoV-2 is the causative agent for the COVID-19 pandemic and there is an urgent need to understand the cellular response to SARS-CoV-2 infection. Beclin-1 is an essential scaffold autophagy protein that forms two distinct subcomplexes with modulators Atg14 and UVRAG, responsible for autophagosome formation and maturation, respectively. In the present study, we found that SARS-CoV-2 infection triggers an incomplete autophagy response, elevated autophagosome formation but impaired autophagosome maturation, and declined autophagy by genetic knockout of essential autophagic genes reduces SARS-CoV-2 replication efficiency. By screening 28 viral proteins of SARS-CoV-2, we demonstrated that expression of ORF3a alone is sufficient to induce incomplete autophagy. Mechanistically, SARS-CoV-2 ORF3a interacts with autophagy regulator UVRAG to facilitate Beclin-1-Vps34-Atg14 complex but selectively inhibit Beclin-1-Vps34-UVRAG complex. Interestingly, although SARS-CoV ORF3a shares 72.7% amino acid identity with the SARS-CoV-2 ORF3a, the former had no effect on cellular autophagy response. Thus, our findings provide the mechanistic evidence of possible takeover of host autophagy machinery by ORF3a to facilitate SARS-CoV-2 replication and raises the possibility of targeting the autophagic pathway for the treatment of COVID-19.
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The ongoing coronavirus disease (COVID-19) pandemic caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is a global public health concern due to relatively easy person-to-person transmission and the current lack of effective antiviral therapy. However, the exact molecular mechanisms of SARS-CoV-2 pathogenesis remain largely unknown. We exploited an integrated proteomics approach to systematically investigate intra-viral and virus-host interactomes for the identification of unrealized SARS-CoV-2 host targets and participation of cellular proteins in the response to viral infection using peripheral blood mononuclear cells (PBMCs) isolated from COVID-19 patients. Using this approach, we elucidated 251 host proteins targeted by SARS-CoV-2 and more than 200 host proteins that are significantly perturbed in COVID-19 derived PBMCs. From the interactome, we further identified that non-structural protein nsp9 and nsp10 interact with NKRF, a NF-[Kcy]B repressor, and may precipitate the strong IL-8/IL-6 mediated chemotaxis of neutrophils and overexuberant host inflammatory response observed in COVID-19 patients. Our integrative study not only presents a systematic examination of SARS-CoV-2-induced perturbation of host targets and cellular networks to reflect disease etiology, but also reveals insights into the mechanisms by which SARS-CoV-2 triggers cytokine storms and represents a powerful resource in the quest for therapeutic intervention.
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<p><b>OBJECTIVE</b>To investigate the effect of Acanthopanax senticosus saponins (ASS) on oxidative damage induced by hydrogen peroxide (H2O2 ) in cardiomyocytes.</p><p><b>METHOD</b>The cardiomyocytes were induced to oxidative damaged by exposed to H2O2. We evaluated the level of oxidative injury through morphology change, the survival rate, the activity of lactate dehydrogenase (LDH) and the content of cellular malondialdehyde (MDA). The activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT) and the content of reductive glutathione (GSH) of cardiomyocytes were also determined.</p><p><b>RESULT</b>When the cardiomyocytes were exposed to H2O, (50, 100, 200 micromol x L(-1)) for deigned time, the percentage of survival cells was down significantly (P < 0.01 or P < 0.001), and the activity of LDH and the content of MDA were increased markedly (P < 0.05, P < 0.01 or P < 0.001). These results show that the cells were subjected to oxidative damage. Treatment with ASS (600 mg x L(-1)) prior to H2O2 exposure could increase cell viability significantly, lessen cardiomyocyte morphological damaged change, and decrease LDH activity (1687.40 +/- 97.51) U x mL(-1) in media and cellular MDA content (16.50 +/- 2.66) nmol x mg(-1) markedly (P < 0.01 and P < 0.05). Furthermore, the activities of SOD (89.55 +/- 6.93) U x mg(-1), GSH-Px (845.87 +/- 63.76) mU x mg(-1), CAT (93.07 +/- 10.40) U x mg(-1) and the content of GSH (8.91 +/- 1.06) micromol x mg(-1) of cardiomyocytes were also raised by 600 mg x L(-1) l ASS (P < 0.05).</p><p><b>CONCLUSION</b>Taken together, the study implicate that ASS protects cardiomyocytes against oxidative-stress injury induced by H2O2 through reduction of lipid peroxidation and enhancement of the activity of antioxidant defense.</p>
