Mechanics

Thyroid cancer is one of the most common malignancies of endocrine organs, and its incidence rate has increased steadily over the past several decades. Most differentiated thyroid tumors derived from thyroid epithelial cells exhibit slow-growing cancers, and patients with these tumors can achieve a good prognosis with surgical removal and radioiodine treatment. However, a small proportion of patients present with advanced thyroid cancer and are unusually resistant to current drug treatment modalities. Thyroid tumorigenesis is a complex process that is regulated by the activation of oncogenes, inactivation of tumor suppressors, and alterations in programmed cell death...

Apoptosis is important in regulating cell death turnover and is mediated by the intrinsic and death receptor-based extrinsic pathways which converge at the mitochondrial outer membrane (MOM) leading to mitochondrial outer membrane permeabilization (MOMP). MOMP results in the release of apoptotic proteins that further activate the downstream pathway of apoptosis. Thus, tight regulation of MOMP is crucial in controlling apoptosis, and a lack of control may lead to tissue and organ malformation and the development of cancers...

BACKGROUND: Bariatric surgery markedly reduces fat mass with beneficial effects on cardiometabolic health but the mechanisms involved are not fully understood. Extracellular vesicles (EVs) are secreted by a variety of cells, including adipocytes, and may mediate some of these benefits. However, the effects of bariatric surgery on circulating EVs are unclear. METHODS: Concentration of plasma EVs isolated by ultracentrifugation at baseline, 1 and 6 months post-bariatric surgery (n = 20) was established using Nanoparticle Tracking Analysis...

Traumatic brain injury (TBI) is the leading cause of death and disability for people under the age of 45 years worldwide. Neuropathology after TBI is the result of both the immediate impact injury and secondary injury mechanisms. Secondary injury is the result of cascade events, including glutamate excitotoxicity, calcium overloading, free radical generation, and neuroinflammation, ultimately leading to brain cell death. In this study, the P2X7 receptor (P2X7R) was detected predominately in microglia of the cerebral cortex and was up-regulated on microglial cells after TBI...

In this review, we show how chromaffin cells have contributed to evaluate neuroprotective compounds with diverse mechanisms of action. Chromaffin cells are considered paraneurons, as they share many common features with neurons: (i) they synthesize, store, and release neurotransmitters upon stimulation and (ii) they express voltage-dependent calcium, sodium, and potassium channels, in addition to a wide variety of receptors. All these characteristics, together with the fact that primary cultures from bovine adrenal glands or chromaffin cells from the tumor pheochromocytoma cell line PC12 are easy to culture, make them an ideal model to study neurotoxic mechanisms and neuroprotective drugs...

INTRODUCTION: Previous studies have reported that specific depletion of mammalian sterile-like kinase (MST1) in the mouse liver driven Hepatocellular carcinoma (HCC). However, how the expression of MST1 was regulated in the progression of HCC remains largely unknown. MATERIALS AND METHODS: The expression of miR-3910 in the HCC tissues and cell lines were examined using q-PCR. The functions of miR-3910 in HCC were examined using MTT assay, Boyden chamber assay and soft agar assay...

PURPOSE: Surprisingly, the activation characteristics of the neck inspiratory muscles as a function of key inspiratory mechanical parameters have yet to be demonstrated experimentally under well-controlled conditions. This study aimed to elucidate the muscle activation patterns of the neck inspiratory muscles by strictly controlling flow rate and lung volume. METHODS: Thirteen healthy subjects matched their inspiratory flow rate at approximately 20-100% of peak flow rate (PFR) as steady as possible during inspiration...

A coupled agent-based model (ABM) and finite element analysis (FEA) computational framework is developed to study the interplay of bio-chemo-mechanical factors in blood vessels and their role in maintaining homeostasis. The agent-based model implements the power of REPAST Simphony libraries and adapts its environment for biological simulations. Coupling a continuum-level model (FEA) to a cellular-level model (ABM) has enabled this computational framework to capture the response of blood vessels to increased or decreased levels of growth factors, proteases and other signaling molecules (on the micro scale) as well as altered blood pressure...

In order to regenerate the dental pulp, many strategies have been developed as phototherapy. In the pulp repair, we do not know if gallium-aluminum-arsenide (GaAlAs) laser preserves the primary odontoblasts or stimulates the formation of more dentin matrix when dental pulp is damaged. The aim of the present study was to examine the effect of laser phototherapy (λ780 nm) on vascularization, inflammation, density of the primary odontoblast layer, and formation of reactionary and reparative dentin in the dental pulp by provoking extrusion of the rat incisor...

For many practitioners, longevity of full glass ceramic crowns in the posterior area, molars and premolars, remains a real challenge. The purpose of this article is to identify and evaluate the parameters that can significantly influence their resistance when preparing a tooth. The analysis proposed in this article relies on interrelated studies conducted at three levels: in vitro (mechanical tests), in silico (finite elements simulations) and in vivo (clinical survival rates). The in vitro and the in silico studies proved that an appropriate variation of the geometric design of the preparations enables to increase up to 80% the mechanical strength of ceramic reconstructions...

Cryptic MHC I-associated peptides (MAPs) are produced via two mechanisms: translation of protein-coding genes in non-canonical reading frames and translation of allegedly non-coding sequences. In general, cryptic MAPs are coded by relatively short open reading frames whose translation can be regulated at the level of initiation, elongation or termination. In contrast to conventional MAPs, the processing of cryptic MAPs is frequently proteasome independent. The existence of cryptic MAPs derived from allegedly non-coding regions enlarges the scope of CD8 T cell immunosurveillance from a mere ~2% to as much as ~75% of the human genome...

Glioblastoma, also known as glioblastoma multiforme (GBM), is the most recurrent and malignant astrocytic glioma found in adults. Biologically, GBMs are highly aggressive tumors that often show diffuse infiltration of the brain parenchyma, making complete surgical resection difficult. GBM is not curable with surgery alone because tumor cells typically invade the surrounding brain, rendering complete resection unsafe. Consequently, present-day therapy for malignant glioma remains a great challenge. The location of the invasive tumor cells presents several barriers to therapeutic delivery...

Knee osteoarthritis (OA) is becoming more prevalent worldwide due to increases in the numbers of elderly and obese patients. Currently, pharmaceutical medicines used for the treatment of OA are for symptomatic therapy and therefore new therapeutic agents are needed. Kaempferia parviflora (KP) is a plant growing naturally in Southeast Asia and has various pharmacological effects including an anti-inflammatory effect, but no effect on OA has yet been reported. We therefore conducted a search for the effects KP and the active components of KP extract (KPE) exert on OA as well as its mechanism of action...

Electric pulses, when applied to a cell suspension, induce a reversible permeabilization of the plasma membrane. This permeabilized state is a long-lived process (minutes). The biophysical molecular mechanisms supporting the membrane reorganization associated to its permeabilization remain poorly understood. Modeling the transmembrane structures as toroidal lipidic pores cannot explain why they are long-lived and why their resealing is under the control of the ATP level. Our results describe the effect of the level of free Calcium ions...

OBJECTIVE: Osteochondromas are the most common benign bone tumors, and thus far, their spontaneous shrinkage is considered a rare phenomenon. This study was designed to investigate the exact ratio of remission to progressive or stable cases and analyze the mechanism of tumor regression on the basis of existing theories. MATERIALS AND METHODS: We retrospectively collected images of solitary osteochondromas in patients from 1992 to 2013, excluding cases involving short-term follow-up periods and follow-up periods that ended before growth plate closure...

Glucagon-like peptide 1 receptor agonists (GLP-1RAs) are relatively new pharmacological agents used to normalize glucose level in type 2 diabetes. Recently, GLP-1RAs have been approved for the treatment of obesity to reduce body weight in non-diabetic patients. The extra-pancre-atic effects of GLP-1RAs, as well as their molecular mechanism of action, are still poorly understood. Thus this study was aimed to verify the hypothesis that the mechanism of action of the GLP-1RAs involves mitochondria and that GLP-1RAs administration can improve mitochondrial functions...

Anti-cancer drug resistance is a major problem in colorectal cancer (CRC) research. Although several studies have revealed the mechanism of cancer drug resistance, molecular targets for chemotherapeutic combinations remain elusive. To address this issue, we focused on the expression of cellular prion protein (PrP(C)) in 5-FU-resistant CRC cells. In 5-FU-resistant CRC cells, PrP(C) expression is significantly increased, compared with that in normal CRC cells. In the presence of 5-FU, PrP(C) increased CRC cell survival and proliferation by maintaining the activation of the PI3K-Akt signaling pathway and the expression of cell cycle-associated proteins, including cyclin E, CDK2, cyclin D1, and CDK4...

Lepidium meyenii (Walp.), commonly called maca, is an Andean crop belonging to the Brassicaceae family. Maca hypocotils are habitually consumed as customary food as well as traditional remedies for pathological conditions such as infertility. Moreover, the characterization of maca extracts revealed the presence of compounds that are able to modulate the nervous system. Aimed to evaluate the efficacy of L. meyenii in persistent pain, the present study analyzed the effects of a commercial root extract from maca in different animal models reproducing the most common causes of chronic painful pathologies...

Activation of large conductance, calcium-activated potassium (BKCa) channels evokes cell survival programs that mitigate intestinal ischemia and reperfusion (I/R) inflammation and injury 24 hours later. The goal of the current study was to determine the role of reactive oxygen species (ROS) and heme oxygenase (HO)-1 in delayed acquisition of tolerance to I/R induced by pretreatment with the BKCa channel opener NS-1619. Superior mesentery arteries were occluded for 45 min followed by reperfusion for 70 min in wild type (WT) or HO-1 null (HO-1(-/-)) mice that were pretreated with NS-1619 or saline vehicle 24 hrs earlier...

Acute kidney injury (AKI) after acute myocardial infarction (MI) worsens the prognosis of MI patients. Although type 2 diabetes mellitus (DM) is a major risk factor of AKI after MI, the underlying mechanism remains unclear. Here, we examined roles of renal toll-like receptors (TLRs) in the impact of DM on AKI after MI. MI was induced by coronary artery ligation in OLETF, a rat DM model, and LETO, non-diabetic controls. Sham-operated rats served as no-MI controls. Renal mRNA levels of TLR2 and MyD88 were significantly higher in sham-operated OLETF than in sham-operated LETO, though levels of TLR1, TLR3, and TRL4 were similar...