Regimen on Dnaja3 haploinsufficiency mediated sarcopenic obesity with imbalanced mitochondrial homeostasis and lipid metabolism.

Background: Sarcopenic obesity is characterized by excess fat mass and diminished muscular mass/function. DNAJA3, a mitochondrial co-chaperone protein, plays a crucial role in skeletal muscle development. GMI, an immunomodulatory protein, promotes myogenic differentiation through DNAJA3 activation.

A genetic basis of mitochondrial DNAJA3 in nonalcoholic steatohepatitis-related hepatocellular carcinoma.

Background And Aims: NAFLD is the most common form of liver disease worldwide, but only a subset of individuals with NAFLD may progress to NASH. While NASH is an important etiology of HCC, the underlying mechanisms responsible for the conversion of NAFLD to NASH and then to HCC are poorly understood. We aimed to identify genetic risk genes that drive NASH and NASH-related HCC.

DNAJA3 regulates B cell development and immune function.

Background: DnaJ homolog subfamily A member 3 (DNAJA3), also known as the tumorous imaginal disc (Tid1), is shown to be crucial in T cell development. DNAJA3 functions as a tumor suppressor implicated in lymphocyte development and survival. However, the role of DNAJA3 in B cell development and immune function remains unknown.

IFIT2 Depletion Promotes Cancer Stem Cell-like Phenotypes in Oral Cancer.

(1) Background: Cancer stem cells (CSCs) are a small cell population associated with chemoresistance, metastasis and increased mortality rate in oral cancer. Interferon-induced proteins with tetratricopeptide repeats 2 (IFIT2) depletion results in epithelial to mesenchymal transition, invasion, metastasis, and chemoresistance in oral cancer. To date, no study has demonstrated the effect of IFIT2 depletion on the CSC-like phenotype in oral cancer cells.

Identification of plasma hsa_circ_0000190 and 0001649 as biomarkers for predicting the recurrence and treatment response of patients with oral squamous cell carcinoma.

Background: Oral squamous cell carcinoma (OSCC) is a type of malignancy characterized by high relapse and recurrence rates in the late stage despite optimal surgical intervention and postoperative chemoradiotherapy. Because the management of relapse following definitive treatment is challenging, accurate risk stratification is of clinical significance to improve treatment outcomes. Circular RNAs (circRNAs) are noncoding RNAs featured with cell-type specificity and high stability, owing to their circular structure, making these molecules excellent biomarkers for a variety of diseases.

Carboxyl terminus of HSP70-interacting protein attenuates advanced glycation end products-induced cardiac injuries by promoting NFκB proteasomal degradation.

Advanced glycation end products (AGEs), which are highly reactive molecules resulting from persistent high-glucose levels, can lead to the generation of oxidative stress and cardiac complications. The carboxyl terminus of HSP70 interacting protein (CHIP) has been demonstrated to have a protective role in several diseases, including cardiac complications; however, the role in preventing AGE-induced cardiac damages remains poorly understood. Here, we found that elevated AGE levels impaired cardiac CHIP expression in streptozotocin-induced diabetes and high-fat diet-administered animals, representing AGE exposure models.

E3 ligase activity of Carboxyl terminus of Hsc70 interacting protein (CHIP) in Wharton's jelly derived mesenchymal stem cells improves their persistence under hyperglycemic stress and promotes the prophylactic effects against diabetic cardiac damages.

Recent studies indicate that umbilical cord stem cells are cytoprotective against several disorders. One critical limitation in using stem cells is reduction in their viability under stressful conditions, such as diabetes. However, the molecular intricacies responsible for diabetic conditions are not fully elucidated.

Salubrinal Enhances Cancer Cell Death during Glucose Deprivation through the Upregulation of xCT and Mitochondrial Oxidative Stress.

Cancer cells have the metabolic flexibility to adapt to heterogeneous tumor microenvironments. The integrated stress response (ISR) regulates the cellular adaptation response during nutrient stress. However, the issue of how the ISR regulates metabolic flexibility is still poorly understood.

Loss of Tid1/DNAJA3 Co-Chaperone Promotes Progression and Recurrence of Hepatocellular Carcinoma after Surgical Resection: A Novel Model to Stratify Risk of Recurrence.

Tid1, a mitochondrial co-chaperone protein, acts as a tumor suppressor in various cancer types. However, the role of Tid1 in hepatocellular carcinoma (HCC) remains unclear. First, we found that a low endogenous Tid1 protein level was observed in poorly differentiated HCC cell lines.

Adaptation to Endoplasmic Reticulum Stress Enhances Resistance of Oral Cancer Cells to Cisplatin by Up-Regulating Polymerase η and Increasing DNA Repair Efficiency.

Endoplasmic reticulum (ER) stress response is an adaptive program to cope with cellular stress that disturbs the function and homeostasis of ER, which commonly occurs during cancer progression to late stage. Late-stage cancers, mostly requiring chemotherapy, often develop treatment resistance. Chemoresistance has been linked to ER stress response; however, most of the evidence has come from studies that correlate the expression of stress markers with poor prognosis or demonstrate proapoptosis by the knockdown of stress-responsive genes.

Ganoderma microsporum immunomodulatory protein, GMI, promotes C2C12 myoblast differentiation in vitro via upregulation of Tid1 and STAT3 acetylation.

Ageing and chronic diseases lead to muscle loss and impair the regeneration of skeletal muscle. Thus, it's crucial to seek for effective intervention to improve the muscle regeneration. Tid1, a mitochondrial co-chaperone, is important to maintain mitochondrial membrane potential and ATP synthesis.

DNAJA3/Tid1 Is Required for Mitochondrial DNA Maintenance and Regulates Migration and Invasion of Human Gastric Cancer Cells.

Background: Gastric cancer is a common health issue. Deregulated cellular energetics is regarded as a cancer hallmark and mitochondrial dysfunction might contribute to cancer progression. Tid1, a mitochondrial co-chaperone, may play a role as a tumor suppressor in various cancers, but the role of Tid1 in gastric cancers remains under investigated.

New COVID-19 saliva-based test: How good is it compared with the current nasopharyngeal or throat swab test?

As of April 15, 2020, the US Food and Drug Administration has granted emergency use authorization to a first saliva test for diagnosis of severe acute respiratory syndrome coronavirus 2 infection, the device developed by RUCDR Infinite Biologics laboratory, Rutgers University. A key feature that distinguishes the saliva-based test from nasopharyngeal or oropharyngeal (throat) swabs is that this kit allows self-collection and can spare healthcare professionals to be at risk during collecting nasopharyngeal or oropharyngeal samples, thereby preserving personal protective equipment for use in patient care rather than sampling and testing. Consequently, broader testing than the current methods of nasal or throat swabs will significantly increase the number of people screening, leading to more effective control of the spread of COVID-19.

Combinatorial Low Dose Arsenic Trioxide and Cisplatin Exacerbates Autophagy via AMPK/STAT3 Signaling on Targeting Head and Neck Cancer Initiating Cells.

Head and neck squamous cell carcinoma (HNSCC) is a highly lethal disease with high-level of epidemic both in the world and Taiwan. Previous studies support that head and neck cancer-initiating cells (HN-CICs), a subpopulation of cancer cells with enhanced stemness properties, contribute to therapy resistance and tumor recurrence. Arsenic trioxide (AsO; ATO) has shown to be an effective anti-cancer drug targeting acute promyelocytic leukemia (APL).

Corrigendum: Regulatory Role of Hexokinase 2 in Modulating Head and Neck Tumorigenesis.

[This corrects the article DOI: 10.3389/fonc.2020.

ASB6 Promotes the Stemness Properties and Sustains Metastatic Potential of Oral Squamous Cell Carcinoma Cells by Attenuating ER Stress.

Up-regulation of ASB6 has been previously associated with late-stage and poor prognosis of oral squamous cell carcinoma (OSCC) patients. To explore the cellular and molecular basis of how ASB6 enhances the malignancy of OSCC, we employed the clonogenicity and migration assays, murine pulmonary metastasis model, Western blot, and immunofluorescence microscopy to characterize the phenotypes of OSCC cells with lentiviral-based stable overexpression or knockdown of ASB6. We found that ASB6 overexpression increases, whereas ASB6 knockdown decreases, the potential of tumor-sphere formation, colony formation, and expression of Oct-4 and Nanog.

Roles of mitochondria in liver cancer stem cells.

Primary liver cancer (PLC) is heterogeneous and it is an aggressive malignancy with a poor prognostic outcome. Current evidence suggests that PLC tumorigenesis is driven by rare subpopulations of cancer stem cells (CSCs), which contribute to tumor initiation, progression, and therapy resistance through particular molecular mechanisms. Energy metabolism and mitochondrial function play an important role in the regulation of cancer stemness and stem cell specifications.

Determination of Pyruvate Metabolic Fates Modulates Head and Neck Tumorigenesis.

Even with increasing evidence for roles of glycolytic enzymes in controlling cancerous characteristics, the best target of candidate metabolic enzymes for lessening malignancy remains under debate. Pyruvate is a main glycolytic metabolite that could be mainly converted into either lactate by Lactate Dehydrogenase A (LDHA) or acetyl-CoA by Pyruvate Dehydrogenase E1 component α subunit (PDHA1) catalytic complex. In tumor cells, accumulating lactate is produced whereas the conversion of pyruvate into mitochondrial acetyl-CoA is less active compared with their normal counterparts.

Tid1-S attenuates LPS-induced cardiac hypertrophy and apoptosis through ER-a mediated modulation of p-PI3K/p-Akt signaling cascade.

Myocardial dysfunction is clinically relevant? repercussion that follows sepsis. Tid 1 protein has been implicated in many biological process. However, the role of Tid 1 in lipopolysaccharide (LPS)-induced cardiomyocyte hypertrophy and apoptosis remains elusive.

CHIP attenuates lipopolysaccharide-induced cardiac hypertrophy and apoptosis by promoting NFATc3 proteasomal degradation.

Carboxyl-terminus of Hsc70 interacting protein (CHIP) is a chaperone-dependent E3-ubiquitin ligase with important function in protein quality control system. In the current research endeavor, we have investigated the putative role of CHIP in lipopolysaccharides (LPS)-induced cardiomyopathies. Basically, H9c2 cardiomyoblasts were transfected with CHIP for 24 hr, and thereafter, treated with LPS for 12 hr.

Tumorous imaginal disc 1 (TID1) inhibits isoproterenol-induced cardiac hypertrophy and apoptosis by regulating c-terminus of hsc70-interacting protein (CHIP) mediated degradation of Gαs.

Dilated cardiomyopathy (DCM) is the most common form of non-ischemic cardiomyopathy. It is characterized by ventricular chamber dilation, and myocyte hypertrophy. Human tumorous imaginal disc 1 (Tid1), a chaperone protein and response to regulate number of signaling molecules in the mitochondria or cytosol.

HSP40 co-chaperone protein Tid1 suppresses metastasis of head and neck cancer by inhibiting Galectin-7-TCF3-MMP9 axis signaling.

Human tumorous imaginal disc (Tid1), a DnaJ co-chaperone protein, is classified as a tumor suppressor. Previously, we demonstrated that Tid1 reduces head and neck squamous cell carcinoma (HNSCC) malignancy. However, the molecular details of Tid1-mediated anti-metastasis remain elusive.

ROS-independent ER stress-mediated NRF2 activation promotes warburg effect to maintain stemness-associated properties of cancer-initiating cells.

Cancer-initiating cells (CICs) are responsible for tumor initiation, progression, and therapeutic resistance; moreover, redox homeostasis is important in regulating cancer stemness. Previously, we have identified that cancer cells containing low intracellular reactive oxygen species levels (ROS cells) display enhanced features of CICs. However, the specific metabolic signatures of CICs remain unclear and are required for further characterization by systemic screenings.

Mitochondrial co-chaperone protein Tid1 is required for energy homeostasis during skeletal myogenesis.

Background: Tid1 is a mitochondrial co-chaperone protein and its transcript is abundantly expressed in skeletal muscle tissues. However, the physiological function of Tid1 during skeletal myogenesis remains unclear.

Methods: In vitro induced differentiation assay of mouse myoblast C2C12 cells was applied to examine the physiological role of Tid1 during skeletal myogenesis.