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Background: We have reported that polydatin (PD) alleviates mitochondrial dysfunction in rat models of sepsisinduced acute kidney injury (SI-AKI), but the mechanism is not well understood. Here, we investigated the role of Parkin-mediated mitophagy in the protective effects of PD in SI-AKI in mice. Methods: Sepsis was induced in the mice by caecal ligation and puncture. Mitophagy was determined by mitochondrial mass. NLRP3 inflammasome activation was determined by NLRP3, ASC and caspase-1. Mitophagy was blocked by treatment with mitochondrial division inhibitor-1 and Parkin knockout. Key results: PD treatment increased the sepsis-induced loss of mitochondrial mass, indicating the upregulation of mitophagy. Furthermore, PD treatment mediated Parkin translocation from the cytoplasm to the mitochondria. This suggests that Parkin-mediated mitophagy is an underlying mechanism. This was confirmed by the suppression of PD-induced mitophagy in Parkin−/− mice and in mice that were treated with a mitophagy inhibitor. PD-induced Parkin translocation and mitophagy were blocked by inhibiting SIRT1; thus, activation of SIRT1 might be an important molecular mechanism that is triggered by PD. Additionally, PD treatment protected against sepsis-induced kidney injury. These effects were blocked by inhibition of Parkin-dependent mitophagy. Furthermore, PD also protected against mitochondrial dysfunction and mitochondria-dependent apoptosis, and the effect was blocked when Parkindependent mitophagy was inhibited. Finally, PD suppressed NLRP3 inflammasome activation that was also dependent on Parkin-mediated mitophagy. Conclusions: These findings indicate that Parkin-mediated mitophagy is important for the protective effect of PD in SI-AKI, and the underlying mechanisms include the inhibition of mitochondrial dysfunction and NLRP3 inflammasome activation.

Kaposiform hemangioendothelioma (KHE) is a rare infiltrative vascular tumor that is potentially life-threatening when presenting with Kasabach-Merritt phenomenon (KMP). KMP is clinically characterized as severe thrombocytopenia and hypofibrinogenemia and therefore is associated with a high mortality rate. There is no standard of cure for KHE currently. Potential medications, including corticosteroids, propranolol, and chemotherapy drugs such as sirolimus, are often used for alleviating KHE symptoms. Although some case reports of sirolimus treatment have shown promising results with recovered coagulant parameters, the off-target effects may cause severe problems. Here we describe 2 cases of infant patients with KHE and KMP who were scheduled to receive sirolimus on a long-term basis. However, both patients developed paroxysmal cough and tachypnea shortly after the onset of sirolimus treatment and succumbed to infection thereafter. This report reveals a potential risk of infection in sirolimus-treated infant patients. The fatal complication highlights the importance of antibiotic prophylaxis and serum sirolimus level monitoring to ensure the safe use of sirolimus in the treatment of infant patients with KHE.

Background The triglyceride-glucose (TyG) index is a reliable alternative biomarker of insulin resistance (IR). However, whether the TyG index has prognostic value in critically ill patients with coronary heart disease (CHD) remains unclear. Methods Participants from the Medical Information Mart for Intensive Care III (MIMIC-III) were grouped into quartiles according to the TyG index. The primary outcome was in-hospital all-cause mortality. Cox proportional hazards models were constructed to examine the association between TyG index and all-cause mortality in critically ill patients with CHD. A restricted cubic splines model was used to examine the associations between the TyG index and outcomes. Results A total of 1,618 patients (65.14% men) were included. The hospital mortality and intensive care unit (ICU) mortality rate were 9.64% and 7.60%, respectively. Multivariable Cox proportional hazards analyses indicated that the TyG index was independently associated with an elevated risk of hospital mortality (HR, 1.71 [95% CI 1.25–2.33] P = 0.001) and ICU mortality (HR, 1.50 [95% CI 1.07–2.10] P = 0.019). The restricted cubic splines regression model revealed that the risk of hospital mortality and ICU mortality increased linearly with increasing TyG index (P for non-linearity = 0.467 and P for non-linearity = 0.764). Conclusions The TyG index was a strong independent predictor of greater mortality in critically ill patients with CHD. Larger prospective studies are required to confirm these findings.

The neuroprotective effect of polydatin (PD) against hemorrhagic shock-induced mitochondrial injury has been described previously, and mitochondrial dysfunction and apoptosis were reportedly involved in ischemic stroke. In the present study the neuroprotective effect of PD in preventing apoptosis was evaluated following induction of focal cerebral ischemia by middle cerebral artery occlusion (MCAO) in rats. PD (30 mg/kg) was administered by caudal vein injection 10 min prior to ischemia/reperfusion (I/R) injury. 24 h following I/R injury, ameliorated modified neurological severity scores (mNSS) and reduced infarct volume were observed in the PD treated group. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining and Annexin V/propidium iodide assays demonstrated the anti-apoptotic effect of PD in the ischemic cortex. In addition, PD improved I/R injury-induced mitochondrial dysfunction, reflected by morphological observations and measurements of mitochondrial membrane potential and intracellular ATP measurement. Western blot analysis revealed an increase in B-cell lymphoma 2 apoptosis regulator (Bcl-2) expression, and a decrease in Bcl-2-associated protein X apoptosis regulator expression in the PD group in comparison with the vehicle treated group. PD treatment also prevented the release of cytochrome c from mitochondria into the cytoplasm, and blunted the activities of caspase-9 and caspase-3. Furthermore, PD treatment decreased the levels of reactive oxygen species in neurons isolated from the ischemic cortex. The findings of this study, therefore, suggest that PD has a dual effect, ameliorating both oxidative stress and mitochondria-dependent apoptosis, making it a promising new therapy for the treatment of ischemic stroke.

Metabolism and immune responses are two fundamental biological processes that serve to protect hosts from viral infection. As obligate intracellular pathogens, viruses have evolved diverse strategies to activate metabolism, while inactivating immune responses to achieve maximal reproduction or persistence within their hosts. The two-way virus-host interaction with metabolism and immune responses choreograph cytokine production via reprogramming metabolism of infected cells/hosts. In return, cytokines can affect the metabolism of virus-infected and bystander cells to impede viral replication processes. This review aims to summarize our current understanding of the cross-talk between metabolic reprogramming and cytokine responses, and to highlight future potential research topics. Although the focus is placed on viral pathogens, relevant findings from other microbes are integrated to provide an overall picture, particularly when corresponding information on viral infection is lacking.

Propranolol (2 mg/kg per day) may significantly reduce the size of a hemangioma. As an outpatient therapy, propranolol was found to be safe for Chinese children and to have minor side effects.

Acute kidney injury (AKI) is a common clinical complication characterized by a sudden deterioration of the kidney’s excretory function, which normally occurs secondary to another serious illness. AKI is an important risk factor for chronic kidney disease (CKD) occurrence and progression to kidney failure. It is, therefore, crucial to block the development of AKI as early as possible. To date, existing animal studies have shown that senescence occurs in the early stage of AKI and is extremely critical to prognosis. Cellular senescence is an irreversible process of cell cycle arrest that is accompanied by alterations at the transcriptional, metabolic, and secretory levels along with modified cellular morphology and chromatin organization. Acute cellular senescence tends to play an active role, whereas chronic senescence plays a dominant role in the progression of AKI to CKD. The occurrence of chronic senescence is inseparable from senescence-associated secretory phenotype (SASP) and senescence-related pathways. SASP acts on normal cells to amplify the senescence signal through senescence-related pathways. Senescence can be improved by initiating reprogramming, which plays a crucial role in blocking the progression of AKI to CKD. This review integrates the existing studies on senescence in AKI from several aspects to find meaningful research directions to improve the prognosis of AKI and prevent the progression of CKD.