Disparate macrophage responses are linked to infection outcome of Hantan virus in humans or rodents.

Hantaan virus (HTNV) is asymptomatically carried by rodents, yet causes lethal hemorrhagic fever with renal syndrome in humans, the underlying mechanisms of which remain to be elucidated. Here, we show that differential macrophage responses may determine disparate infection outcomes. In mice, late-phase inactivation of inflammatory macrophage prevents cytokine storm syndrome that usually occurs in HTNV-infected patients.

Direct regulation of FNIP1 and FNIP2 by MEF2 sustains MTORC1 activation and tumor progression in pancreatic cancer.

MTOR (mechanistic target of rapamycin kinase) complex 1 (MTORC1) orchestrates diverse environmental signals to facilitate cell growth and is frequently activated in cancer. Translocation of MTORC1 from the cytosol to the lysosomal surface by the RRAG GTPases is the key step in MTORC1 activation. Here, we demonstrated that transcription factors MEF2A and MEF2D synergistically regulated MTORC1 activation via modulating its cyto-lysosome shutting.

Regulation of TFEB nuclear localization by HSP90AA1 promotes autophagy and longevity.

TFEB (transcription factor EB) regulates multiple genes involved in the process of macroautophagy/autophagy and plays a critical role in lifespan determination. However, the detailed mechanisms that regulate TFEB activity are not fully clear. In this study, we identified a role for HSP90AA1 in modulating TFEB.

Chaperone-mediated autophagy degrades Keap1 and promotes Nrf2-mediated antioxidative response.

Accumulation of oxidative stress is highly intertwined with aging process and contributes to aging-related diseases, such as neurodegenerative diseases. Deciphering the molecular machinery that regulates oxidative stress is fundamental to further uncovering the pathogenesis of these diseases. Chaperone-mediated autophagy (CMA), a highly selective lysosome-dependent degradation process, has been proven to be an important maintainer of cellular homeostasis through multiple mechanisms, one of which is the attenuation of oxidative stress.

Several miRNAs derived from serum extracellular vesicles are potential biomarkers for early diagnosis and progression of Parkinson's disease.

Background: Blood-based test for predicting disease progression and early diagnosis of Parkinson's disease (PD) is an unmet need in the clinic. The profiles of microRNAs (miRNAs) are regarded as potential diagnostic biomarkers for human diseases, whereas miRNAs in the periphery are susceptible to the influence of various components. MiRNAs enriched in serum extracellular vesicles (EVs) have demonstrated disease-specific advantages in diagnosis due to their high abundance, stability and resistance to degradation.

The Classification and Basic Processes of Autophagy.

Autophagy is a general term for the process of the lysosomal degradation of intracellular components, a process occurring exclusively in eukaryotic cells. Based on the way that intracellular substrates are transported to lysosomes, autophagy in mammalian cells can be divided into three main types: macroautophagy, microautophagy, and chaperone-mediated autophagy (CMA). Each type has its unique molecular machinery and is tightly regulated by various cellular signals, helping cells adapt to a changing environment.

Regulation of IFN-Is by MEF2D Promotes Inflammatory Homeostasis in Microglia.

Background: Microglia play an essential role in the central nervous system immune response. The transcription factor myocyte enhancer factor-2 D (MEF2D) is known to participate in stress regulation in various cell types and is easily activated in microglia. MEF2D has been shown to transcriptionally regulate several cytokine genes in immune cells and directly regulates the inflammatory response, suggesting that MEF2D may act as a key stimulus response regulator of microglia and is involved in the regulation of brain microhomeostasis.

Chaperone-mediated autophagy controls the turnover of E3 ubiquitin ligase MARCHF5 and regulates mitochondrial dynamics.

As a highly dynamic organelle, mitochondria undergo constant fission and fusion to change their morphology and function, coping with various stress conditions. Loss of the balance between fission and fusion leads to impaired mitochondria function, which plays a critical role in the pathogenesis of Parkinson disease (PD). Yet the mechanisms behind mitochondria dynamics regulation remain to be fully illustrated.

Loss of Drosha underlies dopaminergic neuron toxicity in models of Parkinson's disease.

MiRNAs, a group of powerful modulator of gene expression, participate in multiple cellular processes under physiological and pathological conditions. Emerging evidence shows that Drosha, which controls the initial step in canonical miRNA biogenesis, is involved in modulating cell survival and death in models of several diseases. However, the role of Drosha in Parkinson's disease (PD) has not been well established.

Chaperone-mediated autophagy: Advances from bench to bedside.

Protein homeostasis or proteostasis is critical for proper cellular function and survival. It relies on the balance between protein synthesis and degradation. Lysosomes play an important role in degrading and recycling intracellular components via autophagy.

Transcription Factors: Potential Cell Death Markers in Parkinson's Disease.

Parkinson's disease (PD) is a neurodegenerative disease with a long preclinical phase. The continuous loss of dopaminergic (DA) neurons is one of the pathogenic hallmarks of PD. Diagnosis largely depends on clinical observation, but motor dysfunctions do not emerge until 70%-80% of the nigrostriatal nerve terminals have been destroyed.

In-Cell Western Assays to Evaluate Hantaan Virus Replication as a Novel Approach to Screen Antiviral Molecules and Detect Neutralizing Antibody Titers.

Hantaviruses encompass rodent-borne zoonotic pathogens that cause severe hemorrhagic fever disease with high mortality rates in humans. Detection of infectious virus titer lays a solid foundation for virology and immunology researches. Canonical methods to assess viral titers rely on visible cytopathic effects (CPE), but Hantaan virus (HTNV, the prototype hantavirus) maintains a relatively sluggish life cycle and does not produce CPE in cell culture.

Pretreatment with Sodium Phenylbutyrate Alleviates Cerebral Ischemia/Reperfusion Injury by Upregulating DJ-1 Protein.

Oxidative stress and mitochondrial dysfunction play critical roles in ischemia/reperfusion (I/R) injury. DJ-1 is an endogenous antioxidant that attenuates oxidative stress and maintains mitochondrial function, likely acting as a protector of I/R injury. In the present study, we explored the protective effect of a possible DJ-1 agonist, sodium phenylbutyrate (SPB), against I/R injury by protecting mitochondrial dysfunction the upregulation of DJ-1 protein.

Blockade of RyRs in the ER Attenuates 6-OHDA-Induced Calcium Overload, Cellular Hypo-Excitability and Apoptosis in Dopaminergic Neurons.

Calcium (Ca) dyshomeostasis induced by endoplasmic reticulum (ER) stress is an important molecular mechanism of selective dopaminergic (DA) neuron loss in Parkinson's disease (PD). Inositol 1,4,5-triphosphate receptors (IPRs) and ryanodine receptors (RyRs), which are located on the ER surface, are the main endogenous Ca release channels and play crucial roles in regulating Ca homeostasis. However, the roles of these endogenous Ca release channels in PD and their effects on the function and survival of DA neurons remain unknown.

Morphine administration induces change in anxiety-related behavior via Wnt/β-catenin signaling.

Chronic morphine administration is known to decrease anxiety-related behavior, which may lead to morphine-seeking and other social problems. Recent studies have revealed that Wnt/β-catenin signaling plays an important role in anxiety-related behavior. We used HT22 cells, which were derived from primary mouse hippocampal neuronal cultures, to explore the relationship between Wnt signaling and morphine exposure.

Regulation of ER stress-induced autophagy by GSK3β-TIP60-ULK1 pathway.

Endoplasmic reticulum (ER) stress is involved in many cellular processes. Emerging evidence suggests that ER stress can trigger autophagy; however, the mechanisms by which ER stress regulates autophagy and its role in this condition are not fully understood. HIV Tat-interactive protein, 60 kDa (TIP60) is a newly discovered acetyltransferase that can modulate autophagy flux by activating ULK1 upon growth factor deprivation.

Salidroside Protects Against 6-Hydroxydopamine-Induced Cytotoxicity by Attenuating ER Stress.

Parkinson's disease (PD) is a neurodegenerative disease characterized by a persistent decline of dopaminergic (DA) neurons in the substantia nigra pars compacta. Despite its frequency, effective therapeutic strategies that halt the neurodegenerative processes are lacking, reinforcing the need to better understand the molecular drivers of this disease. Importantly, increasing evidence suggests that the endoplasmic reticulum (ER) stress-induced unfolded protein response is likely involved in DA neuronal death.

[Clinical characteristics of pediatric hemorrhagic fever with renal syndrome].

Objective: To study the clinical characteristics of pediatric hemorrhagic fever with renal syndrome (HFRS), and to improve its understanding so as to reduce the misdiagnosis.

Methods: A retrospective analysis was performed on the clinical data of 26 children with HFRS between January 2009 and December 2012.

Results: The age of disease onset was mainly distributed between 7 and 14 years (23 cases, 88%), and the male-to-female ratio was 1.