CIP2A induces PKM2 tetramer formation and oxidative phosphorylation in non-small cell lung cancer.

Tumor cells are usually considered defective in mitochondrial respiration, but human non-small cell lung cancer (NSCLC) tumor tissues are shown to have enhanced glucose oxidation relative to adjacent benign lung. Here, we reported that oncoprotein cancerous inhibitor of protein phosphatase 2A (CIP2A) inhibited glycolysis and promoted oxidative metabolism in NSCLC cells. CIP2A bound to pyruvate kinase M2 (PKM2) and induced the formation of PKM2 tetramer, with serine 287 as a novel phosphorylation site essential for PKM2 dimer-tetramer switching.

Mechanisms of change in posttraumatic headache-related disability: A mediation model.

Objective: To explore whether the association between change in headache management self-efficacy and posttraumatic headache-related disability is partially mediated by a change in anxiety symptom severity.

Background: Many cognitive-behavioral therapy treatments for headache emphasize stress management, which includes anxiety management strategies; however, little is currently known about mechanisms of change in posttraumatic headache-related disability. Increasing our understanding of mechanisms could lead to improvements in treatments for these debilitating headaches.

Pancreatic Stones and Extracorporeal Shockwave Lithotripsy: A Review of the Literature.

Pancreatic stones are sequelae of chronic pancreatitis, resulting in poor quality of life, frequent hospitalizations, and a significant economic burden. Extracorporeal shock wave lithotripsy (ESWL) can be used to treat pancreatic stones and is less invasive when compared to other modalities. In this review article, we have discussed the role of ESWL in the treatment of pancreatic stones and how it differs from other modalities.

Design and Characterization of a Cell-Penetrating Peptide Derived from the SOX2 Transcription Factor.

SOX2 is an oncogenic transcription factor overexpressed in nearly half of the basal-like triple-negative breast cancers associated with very poor outcomes. Targeting and inhibiting SOX2 is clinically relevant as high SOX2 mRNA levels are positively correlated with decreased overall survival and progression-free survival in patients affected with breast cancer. Given its key role as a master regulator of cell proliferation, SOX2 represents an important scaffold for the engineering of dominant-negative synthetic DNA-binding domains (DBDs) that act by blocking or interfering with the oncogenic activity of the endogenous transcription factor in cancer cells.

In vivo imaging of mGlu5 receptor expression in humans with Fragile X Syndrome towards development of a potential biomarker.

Fragile X Syndrome (FXS) is a neurodevelopmental disorder caused by silencing of the Fragile X Mental Retardation (FMR1) gene. The resulting loss of Fragile X Mental Retardation Protein (FMRP) leads to excessive glutamate signaling via metabotropic glutamate subtype 5 receptors (mGluR5) which has been implicated in the pathogenesis of the disorder. In the present study we used the radioligand 3-[18F]fluoro-5-(2-pyridinylethynyl)benzonitrile ([F]FPEB) in simultaneous PET-MR imaging of males with FXS and age- and gender-matched controls to assess the availability of mGlu5 receptors in relevant brain areas.

Oropharyngeal 3-dimensional changes after maxillary expansion with 2 different orthodontic approaches.

Introduction: The objective of this research was to compare the oropharyngeal volume and minimal cross-sectional area (MCA) changes after maxillary expansion using either the Damon system or Hyrax appliances as assessed through cone-beam computed tomography (CBCT) imaging.

Methods: Patients aged between 11 and 17 years with skeletal maxillary transverse discrepancy in need of maxillary expansion were included and allocated randomly into 1 of the 2 treatment groups, Damon or Hyrax. Patients underwent CBCT imaging at 2 time points: T1, after initial clinical evaluation before treatment, and T2, after completion of full orthodontic treatment.

Melatonin Improves Mitochondrial Dynamics and Function in the Kidney of Zücker Diabetic Fatty Rats.

Obesity and associated diabetes (diabesity) impair kidney mitochondrial dynamics by augmenting fission and diminishing fusion, which results in mitochondrial and renal dysfunction. Based on available evidence, the antioxidant activities of melatonin may improve impaired renal mitochondrial function in obese diabetic animals by restoring the imbalanced dynamics through inhibiting fission and promoting fusion. Male Zücker diabetic fatty (ZDF) rats and lean littermates (ZL) were orally treated either with melatonin (10 mg/kg BW/day) (M-ZDF and M-ZL) or vehicle (C-ZDF and C-ZL) for 17 weeks.

Coronavirus Disease 2019 (COVID-19) and Its Neuroinvasive Capacity: Is It Time for Melatonin?

The world faces an exceptional new public health concern caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), subsequently termed the coronavirus disease 2019 (COVID-19) by the World Health Organization (WHO). Although the clinical symptoms mostly have been characterized, the scientific community still doesn´t know how SARS-CoV-2 successfully reaches and spreads throughout the central nervous system (CNS) inducing brain damage. The recent detection of SARS-CoV-2 in the cerebrospinal fluid (CSF) and in frontal lobe sections from postmortem examination has confirmed the presence of the virus in neural tissue.

Melatonin Induces Melanogenesis in Human SK-MEL-1 Melanoma Cells Involving Glycogen Synthase Kinase-3 and Reactive Oxygen Species.

Melatonin is present in all living organisms where it displays a diversity of physiological functions. Attenuation of melanogenesis by melatonin has been reported in some mammals and also in rodent melanoma cells. However, melatonin may also stimulate melanogenesis in human melanoma cells through mechanisms that have not yet been revealed.

Dedifferentiated liposarcoma of the spermatic cord: Case report and review of literature.

Introduction: Malignant spermatic cord tumors have an annual incidence of 0.3 cases/million. The vast majority of tumors in this region are benign.

Lungs as target of COVID-19 infection: Protective common molecular mechanisms of vitamin D and melatonin as a new potential synergistic treatment.

COVID-19 pandemic has a high mortality rate and is affecting practically the entire world population. The leading cause of death is severe acute respiratory syndrome as a consequence of exacerbated inflammatory response accompanied by uncontrolled oxidative stress as well as the inflammatory reaction at the lung level. Until now, there is not a specific and definitive treatment for this pathology that worries the world population, especially the older adults who constitute the main risk group.

Melatonin: Roles in influenza, Covid-19, and other viral infections.

There is a growing appreciation that the regulation of the melatonergic pathways, both pineal and systemic, may be an important aspect in how viruses drive the cellular changes that underpin their control of cellular function. We review the melatonergic pathway role in viral infections, emphasizing influenza and covid-19 infections. Viral, or preexistent, suppression of pineal melatonin disinhibits neutrophil attraction, thereby contributing to an initial "cytokine storm", as well as the regulation of other immune cells.

Assessing the personal impact of epilepsy in a population-based cohort of Veterans.

Purpose: Epilepsy impacts patient lives in multidimensional ways. Although previous work has investigated epilepsy impact on health status, little is known about the overall quantified impact of epilepsy in Veterans. Our goal was to describe the impact of epilepsy on Veterans' lives using the Personal Impact of Epilepsy Scale (PIES) and determine the patient and clinical characteristics most strongly correlated with epilepsy impact.

Melatonin and cannabinoids: mitochondrial-targeted molecules that may reduce inflammaging in neurodegenerative diseases.

Generally, the development and progression of neurodegenerative diseases are associated with advancing age, so they are usually diagnosed in late adulthood. A primary mechanism underlying the onset of neurodegenerative diseases is neuroinflammation. Based on this background, the concept of "neuroinflammaging" has emerged.

Daily and seasonal mitochondrial protection: Unraveling common possible mechanisms involving vitamin D and melatonin.

From an evolutionary point of view, vitamin D and melatonin appeared very early and share functions related to defense mechanisms. In the current clinical setting, vitamin D is exclusively associated with phosphocalcic metabolism. Meanwhile, melatonin has chronobiological effects and influences the sleep-wake cycle.

Establishment of an Immortalized Mouse Bmp2 Knockout Dental Papilla Mesenchymal Cell Line.

Bone morphogenetic protein 2 (Bmp2) is essential for dentin formation. Bmp2 cKO mice exhibited similar phenotype to dentinogenesis imperfecta (DGI), showing dental pulp exposure, hypomineralized dentin, and delayed odontoblast differentiation. As it is relatively difficult to obtain primary Bmp2 cKO dental papilla mesenchymal cells and to maintain a long-term culture of these primary cells, availability of immortalized deleted Bmp2 dental papilla mesenchymal cells is critical for studying the underlying mechanism of Bmp2 signal in odontogenesis.

All aboard!: Involvement of medical and pharmacy trainees in antimicrobial stewardship.

Antimicrobial stewardship (AS) involves the appropriate selection of antimicrobials. Antimicrobial stewardship programs are mandated in hospitals and are expanding to involve outpatient arenas. Multiple articles have been published describing the need for AS education for medical and pharmacy students, beginning early in the students' career to develop into competent AS practitioners.

Melatonin increases brown adipose tissue mass and function in Zücker diabetic fatty rats: implications for obesity control.

Melatonin limits obesity in rodents without affecting food intake and activity, suggesting a thermogenic effect. Previously we demonstrated that melatonin browns subcutaneous fat in Zücker diabetic fatty (ZDF) rats. Other works pointed to melatonin as a signal that increases brown adipose tissue (BAT) mass and function in rodents.

Association of Pharmacologic Treatment of Urgency Urinary Incontinence With Sleep Quality and Daytime Sleepiness.

Objective: To evaluate the association between pharmacologic therapy for urgency urinary incontinence (UUI) and sleep quality.

Methods: We conducted a planned secondary data analysis of sleep outcomes in a previously conducted multicenter, double-blind, 12-week randomized trial of pharmacologic therapy for urgency-predominant incontinence among community-dwelling women self-diagnosed using the 3-Incontinence Questions questionnaire. Participants (N=645) were assigned randomly to 4-8 mg antimuscarinic therapy daily or placebo.

Melatonin enhances hyperthermia-induced apoptotic cell death in human leukemia cells.

Melatonin is an endogenous indoleamine with a wide range of biological functions. In addition to modulating circadian rhythms, it plays important roles in the health as an antioxidant. Melatonin has also the ability to induce apoptosis in cancer cells and to enhance the antitumoral activity of chemotherapeutic agents.

Melatonin reduces hepatic mitochondrial dysfunction in diabetic obese rats.

Hepatic mitochondrial dysfunction is thought to play a role in the development of liver steatosis and insulin resistance, which are both common characteristics of obesity and type 2 diabetes mellitus (T2DM). It was hypothesized that the antioxidant properties of melatonin could potentially improve the impaired functions of hepatic mitochondria in diabetic obese animals. Male Zucker diabetic fatty (ZDF) rats and lean littermates (ZL) were given either melatonin (10 mg/kg BW/day) orally for 6 wk (M-ZDF and M-ZL) or vehicle as control groups (C-ZDF and C-ZL).

Optimization of a therapeutic electromagnetic field (EMF) to retard breast cancer tumor growth and vascularity.

Background: This study provided additional data on the effects of a therapeutic electromagnetic field (EMF) device on growth and vascularization of murine 16/C mammary adenocarcinoma cells implanted in C3H/HeJ mice.

Methods: The therapeutic EMF device generated a defined 120 Hz semi sine wave pulse signal of variable intensity. Murine 16/C mammary adenocarcinoma tumor fragments were implanted subcutaneously between the scapulae of syngeneic C3H mice.

Metabolomics tools for identifying biomarkers for neuropsychiatric diseases.

The repertoire of biochemicals (or small molecules) present in cells, tissue, and body fluids is known as the metabolome. Today, clinicians utilize only a very small part of the information contained in the metabolome, as revealed by the quantification of a limited set of analytes to gain information on human health. Examples include measuring glucose or cholesterol to monitor diabetes and cardiovascular health, respectively.

Coelomycetous fungi in human disease. A review: Clinical entities, pathogenesis, identification and therapy.

Coelomycetes are being recovered with increasing frequency in human disease. They are frequently acquired by traumatic implantation and are of concern in profoundly immunosuppressed individuals. A definition of this group of organisms is provided, along with their clinical manifestations, methods for laboratory diagnosis, criteria for identification, in vitro susceptibility data, and guidelines for antifungal therapy and management.

Caloric restriction and aging: controversial issues.

It has long been held that food restriction extends the life span of rodents and other species by decreasing caloric intake and slowing the rate of aging. Recent findings challenge these concepts. This review assesses these controversial issues.