Pharmacotherapy guideline concordance for major depressive disorder and its link to functioning via symptom change.

Introduction: Alleviation of symptom severity for major depressive disorder (MDD) is known to be associated with a lagged improvement of functioning. Pharmacotherapy guidelines support algorithms for MDD treatment. However, it is currently unclear whether concordance with guidelines influences functional recovery.

Novel Quality Control Metric for the Pharmacotherapy of Major Depressive Disorder: Measuring Guideline Concordance and Its Impact on Symptom Severity.

Studies suggest that people with major depressive disorder (MDD) often receive treatment that is not concordant with practice guidelines. To evaluate this, we (1) developed a guideline concordance algorithm for MDD pharmacotherapy (GCA-8), (2) scored it using clinical data, and (3) compared its explanation of patient-reported symptom severity to a traditional concordance measure. This study evaluated 1,403 adults (67% female, 85% non-Hispanic/Latino White, mean age 43 years) with non-psychotic MDD (per codes), from the Penn State Psychiatry Clinical Assessment and Rating Evaluation System (PCARES) registry (visits from February 1, 2015, to April 13, 2021).

Aberrant Expression of ACO1 in Vasculatures Parallels Progression of Idiopathic Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) is characterized by mitochondrial dysfunction. However, details about the non-mitochondrial enzymes that sustain the proliferative nature of IPF are unclear. Aconitases are a family of enzymes that sustain metabolism inside and outside mitochondria.

Mitochondrial Protein 1 Deletion Exacerbates Endoplasmic Reticulum Stress in Mice Exposed to Hyperoxia.

Acute lung injury (ALI) and its severe manifestation, acute respiratory distress syndrome (ARDS), are treated with high concentrations of supplementary oxygen. However, prolonged exposure to high oxygen concentrations stimulates the production of reactive oxygen species (ROS), which damages the mitochondria and accumulates misfolded proteins in the endoplasmic reticulum (ER). The mitochondrial protein A-kinase anchoring protein 1 () is critical for mitochondrial homeostasis.

SRSF1 promotes the inclusion of exon 3 of SRA1 and the invasion of hepatocellular carcinoma cells by interacting with exon 3 of SRA1pre-mRNA.

Steroid receptor RNA activator 1 (SRA1) has been described as a novel transcriptional co-activator that affects the migration of cancer cells. Through RT-PCR, we identified that skipping exon 3 of SRA1 produces two isoforms, including the truncated short isoform, SRA1-S, and the long isoform, SRA1-L. However, the effect of these two isomers on the migration of HCC cells, as well as the specific mechanism of exon 3 skipping remain unclear.

Alda-1 Attenuates Hyperoxia-Induced Acute Lung Injury in Mice.

Acute lung injury (ALI), a milder form of acute respiratory distress syndrome (ARDS), is a leading cause of mortality in older adults with an increasing prevalence. Oxygen therapy, is a common treatment for ALI, involving exposure to a high concentration of oxygen. Unfortunately, hyperoxia induces the formation of reactive oxygen species which can cause an increase in 4-HNE (4-hydroxy 2 nonenal), a toxic byproduct of lipid peroxidation.

Coronavirus: a shift in focus away from IFN response and towards other inflammatory targets.

In the past two decades, two beta-coronaviruses, severe acute respiratory syndrome-related coronavirus (SARS-CoV-1) and the Middle East respiratory syndrome-related coronavirus (MERS-CoV), have infected approximately 8000 and 2500 across the globe, respectively (de Wit et al. 2016; Amanat and Krammer 2020). The current viral pandemic, caused by SARS-CoV-2, has already affected 4.

Coronavirus: a shift in focus away from IFN response and towards other inflammatory targets.

In the past two decades, two beta-coronaviruses, severe acute respiratory syndrome-related coronavirus (SARS-CoV-1) and the Middle East respiratory syndrome-related coronavirus (MERS-CoV), have infected approximately 8000 and 2500 across the globe, respectively (de Wit et al. 2016; Amanat and Krammer 2020). The current viral pandemic, caused by SARS-CoV-2, has already affected 4.

Skipping of exon 10 in pre-mRNA regulated by PTBP1 mediates invasion and metastasis process of liver cancer cells.

The Axl gene is known to encode for a receptor tyrosine kinase involved in the metastasis process of cancer. In this study, we investigated the underlying molecular mechanism of Axl alternative splicing. : The expression levels of PTBP1 in hepatocellular carcinoma (HCC) tissues were obtained from TCGA samples and cell lines.

PTBP1 enhances exon11a skipping in Mena pre-mRNA to promote migration and invasion in lung carcinoma cells.

Alternative splicing (AS) events occur in the majority of human genes. AS in a single gene can give rise to different functions among multiple isoforms. Human ortholog of mammalian enabled (Mena) is a conserved regulator of actin dynamics that plays an important role in metastasis.

Therapeutic effects of the rhSOD2-Hirudin fusion protein on bleomycin-induced pulmonary fibrosis in mice.

Idiopathic pulmonary fibrosis (IPF) is a disease with a poor prognosis and high mortality, posing a major threat to human health. Increased levels of inflammatory cytokines, reactive oxygen species and coagulation cascade have been extensively reported in IPF. We previously fused Hirudin and human manganese superoxide dismutase (hSOD2) to generate a dual-feature fusion protein, denoted as rhSOD2-Hirudin fusion protein.

Altered expression of p63 isoforms and expansion of p63- and club cell secretory protein-positive epithelial cells in the lung as novel features of aging.

Aging is a key contributor for subclinical progression of late-onset lung diseases. Basal, club, and type II alveolar epithelial cells (AECs) are lung epithelial progenitors whose capacities of differentiation are extensively studied. The timely transition of these cells in response to environmental changes helps maintain the intricate organization of lung structure.

Oxidative stress induces club cell proliferation and pulmonary fibrosis in Atp8b1 mutant mice.

Atp8b1 (ATPase, aminophospholipid transporter, class I, type 8B, member 1) is a cardiolipin transporter in the apical membrane of lung epithelial cells. While the role of Atp8b1 in pneumonia-induced acute lung injury (ALI) has been well studied, its potential role in oxidative stress-induced ALI is poorly understood. We herein show that Atp8b1 mice under hyperoxic conditions display exacerbated cell apoptosis at alveolar epithelium and aberrant proliferation of club cells at bronchiolar epithelium.

Thyroid hormone: a resurgent treatment for an emergent concern.

The story of thyroid hormone in human physiology is one of mixed emotions. Studying past literature on its use leads one to believe that it serves only a few functions in a handful of diseases. In reality, the pathophysiological role of thyroid hormone is an uncharted expanse.

Remission of fibrosis: rage to the rescue.

Idiopathic pulmonary fibrosis (IPF) is characterized by a progressive and permanent decline of lung function that eventually leads to expiry. A study published in 2017 performed by Kumar et al. revealed that the disease may not be as irreversible as was once believed.

miR-330-3p promotes lung cancer cells invasion, migration, and metastasis by directly targeting hSOD2b.

Lung cancer is a serious threat to human health. Studies have revealed that human manganese superoxide dismutase (hSOD2) and miRNAs play an essential role in the metastasis process of lung cancer. However, the miRNAs that associated with hSOD2 and involved in metastasis, remain elusive.

A mitochondrial delicacy: dynamin-related protein 1 and mitochondrial dynamics.

The constant physiological flux of mitochondrial fission and fusion is inextricably tied to the maintenance of cellular bioenergetics and the fluidity of mitochondrial networks. Yet, the intricacies of this dynamic duo remain unclear in diseases that encompass mitochondrial dysregulation. Particularly, the role of the GTPase fission protein dynamin-related protein 1 (Drp1) is of profound interest.

The novel truncated isoform of human manganese superoxide dismutase has a differential role in promoting metastasis of lung cancer cells.

Growing evidences have demonstrated alternative splicing makes great contribution to tumor metastasis since multiple protein isoforms from a single gene that often display different functions in the cell. Human manganese superoxide dismutase (hMnSOD) was revealed dysregulation in progress of tumor metastasis, while the effect of hMnSOD isoforms on metastasis remained unclear. In this study, we showed a novel truncated hMnSOD isoform hMnSOD183, which lacked 39 amino acids compared with hMnSOD222.

Akap1 genetic deletion increases the severity of hyperoxia-induced acute lung injury in mice.

Critically ill patients are commonly treated with high levels of oxygen, hyperoxia, for prolonged periods of time. Unfortunately, extended exposure to hyperoxia can exacerbate respiratory failure and lead to a high mortality rate. Mitochondrial A-kinase anchoring protein (Akap) has been shown to regulate mitochondrial function.

The dawn of succinylation: a posttranslational modification.

Posttranslational modifications affect almost all proteins and are critical to a well-functioning and diverse proteome; however, many modifications remain relatively unknown and unstudied. This paper will give a perspective on the rapidly developing, novel posttranslational modification called succinylation. This modification may be implicated in numerous diseases, such as hepatic, cardiac, and pulmonary diseases.

Epigenetics of Mucus Hypersecretion in Chronic Respiratory Diseases.

Asthma, chronic obstructive pulmonary disease, and cystic fibrosis are three chronic pulmonary diseases that affect an estimated 420 million individuals across the globe. A key factor contributing to each of these conditions is mucus hypersecretion. Although management of these diseases is vastly studied, researchers have only begun to scratch the surface of the mechanisms contributing to mucus hypersecretion.

The role of club cell phenoconversion and migration in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is an age-related multifactorial disease featuring non-uniform lung fibrosis. The decisive cellular events at early stages of IPF are poorly understood. While the involvement of club cells in IPF pathogenesis is unclear, their migration has been associated with lung fibrosis.