Role of aspirin, beta-blocker, statins, and heparin therapy in septic patients under mechanical ventilation: a narrative review.

Sepsis is the main cause of death among patients admitted to intensive care units. Management of sepsis includes fluid resuscitation, vasopressors, intravenous antimicrobials, source control, mechanical ventilation, and others. New insights into the potential benefits of non-antimicrobial drugs in sepsis have evolved based on the pathophysiology of the disease and the mechanism of action of some drugs, but the findings are still controversial. In this study, we aimed to evaluate the effect of beta-blockers, aspirin, statins, and heparin as adjunctive treatments in septic patients under mechanical ventilation with non-cardiovascular diseases and their effect on mortality. We searched PubMed with relevant keywords (beta-blockers, aspirin, statins, or heparin, and critically ill or sepsis) for the last 10 years and some personal collection of relevant articles, and then we assessed studies according to prespecified inclusion and exclusion criteria. Our results show that beta-blockers, aspirin, and heparin may have promising feedback on reducing mortality. However, new well-controlled, randomized, multicenter studies are needed to confirm that, and multiple issues regarding their usage need to be addressed. On the other hand, the feedback regarding the effectiveness of statins was not as strong as that of the other drugs studied, and we suggest that further research is needed to confirm these results.

Disturbed expression of autophagy genes in blood of Parkinson's disease patients.

Parkinson's disease (PD) is a common neurodegenerative disorder which affects dopaminergic neurons leading to alteration of numerous cellular pathways. Several reports highlight that PD disturbs also other cells than CNS neurons including PBMCs, which could lead, among other things, to dysfunctions of immune functions. Because autophagy could be altered in PD, a monocentric pilot study was performed to quantify the transcripts levels of several autophagy genes in blood cells. MAP1LC3B, GABARAP, GABARAPL1, GABARAPL2 and P62/SQSTM1 were found to be overexpressed in patients. On the contrary, transcripts for HSPA8 and GAPDH were both decreased. Expression of MAP1LC3B and GABARAP was able to successfully segregate PD patients from healthy controls. The accuracy of this segregation was substantially increased when combined expressions of MAP1LC3B and GAPDH or GABARAP and GAPDH were used as categorical variables. This pilot study suggests that autophagy genes expression is dysregulated in PD patients and may open new perspectives for the characterisation of prediction markers.

Dysregulation of apoptosis and autophagy gene expression in peripheral blood mononuclear cells of efficiently treated HIV-infected patients.

OBJECTIVE: We measure the transcript levels of the proapoptotic GALIG, antiapoptotic MCL1 genes and those of the autophagy genes BECN1, MAP1LC3B, ATG9a, P62/SQSTM1, GABARAP, GABARAPL1 and GABARAPL2 to define if mRNA alteration can characterize HIV-infected patients effectively treated with combined antiretroviral therapy (cART). DESIGN: Monocentric pilot study conducted on peripheral blood mononuclear cell (PBMC) of 40 uninfected donors and 27 HIV-positive patients effectively treated by cART for at least 8.4 years. METHODS: Transcripts of the various genes were quantified by reverse transcription (RT)-quantitative PCR (qPCR) and RT-droplet digital PCR and compared using the standard statistical Mann-Whitney U test and machine learning algorithms. RESULTS: A concomitant overexpression of GALIG and MCL1 is detected in PBMC of effectively cART-treated patients. Overexpression of MAP1LC3B and GABARAPL1 is also measured, whereas BECN1 is underexpressed. Finally, accurate classification (94.5%) of our PBMC samples as HIV-negative donors or HIV-positive cART-treated is obtained in three separate machine-learning algorithms with GABARAPL1 and ATG9a as input variables. CONCLUSION: cART-treated HIV patients display altered transcript levels for three genes of basal autophagy. Some of these alterations may appear contradictory: BECN1 and ATG9a, both key actors in the formation of mammalian autophagosome, exhibit decreased amount of transcripts, whereas mRNA from the ATG8 family increase. Given the known role of impaired basal autophagy in immune senescence and chronic inflammation, the functional significance of our findings should be explored in larger studies.

Interaction of Alpha-synuclein with Cytogaligin, a protein encoded by the proapoptotic gene GALIG.

GALIG, an internal gene to the human galectin-3 gene, encodes two distinct proteins, Mitogaligin and Cytogaligin through translation of a unique mRNA in two overlapping alternative reading frames. When overexpressed GALIG induces apoptosis. In cultured cells, Mitogaligin destabilizes mitochondria membranes through interaction with cardiolipin. Little is known regarding the role of Cytogaligin. This protein displays multiple subcellular localizations; cytosol, nucleus, and mitochondria. We illustrate here that Cytogaligin is also secreted in the extracellular medium. Cytogaligin is shown to interact with α-Synuclein, the major component of Lewy bodies in Parkinson's disease. Overexpression of Cytogaligin reduces α-Synuclein dimerization raising a possible role in the evolution of α-Synuclein aggregation, a key molecular event underlying the pathogenesis of Parkinson's disease.