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A simple method is described for the patterned deposition of Teflon on paper to create an integrated platform for parallel organic synthesis and cell-based assays. Solvent-repelling barriers made of Teflon-impregnated paper confine organic solvents to specific zones of the patterned array and allow for 96 parallel flow-through syntheses on paper. The confinement and flow-through mixing significantly improves the peptide yield and simplifies the automation of this synthesis. The synthesis of 100 peptides ranging from 7 to 14 amino acids in length gave over 60 % purity for the majority of the peptides (>95 % yield per coupling/deprotection cycle). The resulting peptide arrays were used in cell-based screening to identify 14 potent bioactive peptides that support the adhesion or proliferation of breast cancer cells in a 3D environment. In the future, this technology could be used for the screening of more complex phenotypic responses, such as cell migration or differentiation. [ABSTRACT FROM AUTHOR]

We investigated the role of the phosphatidylinositol-3 kinase (PI-3K) pathway in regulating the proliferation of primary chronic myeloid leukaemia (CML) progenitor cells by using imatinib to inhibit the activity of p210Bcr-Abl. The effect of imatinib on the expression of PI-3K pathway proteins was investigated by kinase assays and Western blotting; PI-3K was inhibited by wortmannin or LY294002, Jak2 by AG490 and farnesylation by FTI II; progenitor cell proliferation (self-renewal) was measured by growing myeloid colonies in vitro, then replating them to observe secondary colony formation. Suppression of p210Bcr-Abl with imatinib indirectly suppressed the activity of PI-3K and its downstream targets (Erk, Akt and p70S6 kinase), thereby implicating the PI-3K pathway in p210Bcr-Abl-mediated signalling in primary CML progenitor cells. The PI-3K inhibitors, wortmannin and LY294002 reproduced the differential effects of imatinib on normal and CML progenitor cell proliferation in vitro by increasing normal cell (P = 0.001) and reducing CML cell proliferation (P = 0.0003). This differential effect was attributable to dysregulated signalling by granulocyte colony-stimulating factor in CML. The responses of individual patient's cells to wortmannin correlated with their responses to imatinib (P = 0.004) but not their responses to AG490 (Jak2 kinase inhibitor) or FTI II (farnesyltransferase inhibitor). Individual responses to wortmannin also correlated with responses to interferon α (IFNα) (P = 0.016). Imatinib-resistant K562 cells were sensitive to LY294002. Inhibition of the PI-3K pathway may be common to imatinib and IFNα and reflect dysregulated cytokine signalling. As imatinib-resistant cells remained sensitive to wortmannin and LY294002, targeting the PI-3K pathway may provide an alternative therapy for imatinib-resistant patients. [ABSTRACT FROM AUTHOR]

Paroxysmal nocturnal haemoglobinuria (PNH) results from acquired mutations in the PIG-A gene of an haematopoietic stem cell, leading to defective biosynthesis of glycosylphosphatidylinositol (GPI) anchors and deficient expression of GPI-anchored proteins on the surface of the cell's progeny. Some laboratory and clinical findings have suggested genomic instability to be intrinsic in PNH; this possibility has been supported by mutation analysis of hypoxanthine-guanine phosphoribosyltransferase ( HPRT) gene abnormalities. However, the HPRT assay examines lymphocytes in peripheral blood (PB), and T cells may be related to the pathophysiology of PNH. We analysed the molecular and functional features of HPRT mutants in PB mononuclear cells from eleven PNH patients. CD8 T cells predominated in these samples; approximately half of the CD8 cells lacked GPI-anchored protein expression, while only a small proportion of CD4 cells appeared to derive from the PNH clone. The HPRT mutant frequency (Mf) in T lymphocytes from PNH patients was significantly higher than in healthy controls. The majority of the mutant T lymphocyte clones were of CD4 phenotype, and they had phenotypically normal GPI-anchored protein expression. In PNH patients, the majority of HPRT mutant clones were contained within the V β2 T cell receptor (TCR) subfamily, which was oligoclonal by complementarity-determining region three (CDR3) size analysis. Our results are more consistent with detection of uniform populations of expanded T cell clones, which presumably acquired HPRT mutations during antigen-driven cell proliferation, and not due to an increased Mf in PNH. HPRT mutant analysis does not support underlying genomic instability in PNH. [ABSTRACT FROM AUTHOR]

Disease progression in B-cell chronic lymphocytic leukaemia (B-CLL) is determined by the interplay between proliferation kinetics in the proliferating compartment and cell death in the accumulating compartment. Improving our knowledge of cell cycle regulation in B-CLL cells might therefore be important for identifying therapeutic targets. Cyclin E was detected by Western blotting in purified B-CLL cells from peripheral blood samples of all 12 patient tested but not in normal peripheral blood B cells. While cyclin-dependent kinase 2 (cdk2) expression was similar in different samples, p27 and cyclin E expression was highly variable. We further investigated the regulation of p27, cyclin E and cdk2 in an in vitro model of cycling B-CLL cells. Cyclin E and cdk2 expression was increased in B-CLL cells stimulated with a CpG-oligodeoxynucleotide and interleukin-2, while p27 expression rapidly declined. This was accompanied by the increased formation of cyclin E–cdk2 complexes, which were able to phosphorylate Histone H1 in vitro. Pharmacological inhibition of cdk2 activity with Roscovitine-inhibited thymidine incorporation and Histone H1 phosphorylation. We conclude that further evaluation of cyclin E and p27 in peripheral blood cells might help to identify prognostic subgroups. In addition, inhibition of Cyclin E–cdk2 activity by Roscovitine might be a new therapeutic strategy in B-CLL. [ABSTRACT FROM AUTHOR]

Neutrophils from patients with chronic myeloid leukaemia (CML) have an aberrant expression of leukotriene (LT)C4 synthase. In order to learn more about the regulation of this abnormality, LTC4 synthase mRNA expression was determined by reverse transcription polymerase chain reaction. A digoxigenin (DIG)-labelled LTC4 synthase RNA was synthesized and incubated in cytsolic extracts from CML neutrophils, normal neutrophils and eosinophils. LTC4 synthase mRNA was detected in total but not cytoplasmic RNA from normal neutrophils. In contrast, LTC4 synthase mRNA was found in the cytoplasm of CML neutrophils and in normal eosinophils, which also express the enzyme. The DIG-labelled LTC4 synthase RNA was, as opposed to normal neutrophils, degraded in cytosolic extracts from CML neutrophils. The degradation was time dependent and cell concentration dependent. Degradation was also seen in eosinophils, indicating that degradation of LTC4 synthase RNA was correlated to the expression of the protein. This study showed that the difference in expression of LTC4 synthase in normal and CML neutrophils was not because of a total lack of LTC4 synthase mRNA in normal neutrophils. However normal neutrophils lack, in contrast to CML neutrophils, LTC4 synthase mRNA in the cytoplasm. This discrepancy is not caused by a stabilized LTC4 synthase RNA in the cytosol of CML neutrophils. Instead an abnormal degradation of LTC4 synthase RNA was found in the cytosol of CML neutrophils. [ABSTRACT FROM AUTHOR]

Platelet microparticles (PMP) are endogenous substances generated during the coagulation process in a hypercoagulable state. This study demonstrated that PMP promote the proliferation and survival, migration, and tube formation in human umbilical vein endothelial cells (HUVEC). Heat-treated PMP did not significantly decrease the angiogenic activity in HUVEC compared with that of the untreated PMP. Meanwhile when PMP were treated with activated charcoal, a procedure known to remove the lipid growth factors, the angiogenic activity was significantly reduced. These results suggest that the lipid component(s) of the PMP may be major active factor(s) and that protein component(s) may be minor contributor(s). PMP were also shown to augment endothelial progenitor cell differentiation in peripheral blood mononuclear cells. In addition, PMP-stimulated proliferation, chemotaxis and tube formation of the HUVEC was mediated via the Pertussis toxin-sensitive G protein, extracellular signal-regulated kinase and the phosphoinositide 3-kinase pathway. Herein, a new action of PMP was demonstrated to be a potent angiogenic stimulator. It is expected that in pathological states such as a growing tumour, PMP shed from the circulating platelets may reach adequate concentrations and that the elevated levels of PMP could contribute to florid formation of new blood vessels. [ABSTRACT FROM AUTHOR]

A member of the ATPases associated with diverse cellular activities (AAA) family, the cell division cycle gene CDC48/VCP (valosin-containing protein)/p97, was cloned from zebrafish and found to be a major cold-inducible protein in fish cells. CDC48 mRNA levels increased significantly after reducing the temperature from 30 to 15°C for 25 days. CDC48 protein levels also increased 2.5-fold after 30 days at cold temperatures. When fish cells overexpressing CDC48 were exposed to a temperature of 15°C, cell proliferation was markedly enhanced in comparison with control cells. By contrast, expression of a mutant molecule with a tyrosine-805 to alanine substitution at the C-terminal phosphorylation site inhibited cell proliferation and induced apoptosis at low temperatures. Therefore, CDC48 may promote cell cycling and cell proliferation via C-terminal tyrosine phosphorylation during cold acclimation in fish cells. [Copyright &y& Elsevier]

Aim: Endometriosis is a chronic disease of reproductive age, associated with pelvic pain and infertility. Endometriotic cells adapt to changing environments such as oxidative stress and hypoxia in order to survive. However, the underlying mechanisms remain to be fully elucidated. In this review, we summarize our current understanding of the pathogenesis of endometriosis, focusing primarily on the molecular basis of energy metabolism, redox homeostasis, and mitochondrial function, and discuss perspectives on future research directions. Methods: Papers published up to March 31, 2023 in the PubMed and Google Scholar databases were included in this narrative literature review. Results: Mitochondria serve as a central hub sensing a multitude of physiological processes, including energy production and cellular redox homeostasis. Under hypoxia, endometriotic cells favor glycolysis and actively produce pyruvate, nicotinamide adenine dinucleotide phosphate (NADPH), and other metabolites for cell proliferation. Mitochondrial fission and fusion dynamics may regulate the phenotypic plasticity of cellular energy metabolism, that is, aerobic glycolysis or OXPHOS. Endometriotic cells have been reported to have reduced mitochondrial numbers, increased lamellar cristae, improved energy efficiency, and enhanced cell proliferation and survival. Increased mitochondrial fission and fusion turnover by hypoxic and normoxic conditions suggests an activation of mitochondrial quality control mechanisms. Recently, candidate molecules that influence mitochondrial dynamics have begun to be identified. Conclusion: This review suggests that unique energy metabolism and redox homeostasis driven by mitochondrial dynamics may be linked to the pathophysiology of endometriosis. However, further studies are needed to elucidate the regulatory mechanisms of mitochondrial dynamics in endometriosis. [ABSTRACT FROM AUTHOR]

An indolent T‐lymphoblastic proliferation (iT‐LBP) is a rare benign disorder characterized by an abnormal expansion of immature T‐cells, which morphologically can mimic malignancy. Since the first case was described in 1999, dozens more have been reported in the literature. However, the epidemiologic, clinical, pathologic, and biologic features of this disease have not been well described. Here, we retrospectively reviewed all known cases reported in the literature to better understand this entity. A PubMed search up to January 2022 highlighted 25 papers describing cases/case series of iT‐LBP, one of which was a case presentation in a slide workshop. Except for 9 of the cases in one of the papers, where it was evident that the number of CD3+/TdT+ cells were too few to conform with a diagnosis of iT‐LBP, all papers and all the cases reported were included in the study amounting to a total of 45 cases. Clinicopathologic characteristics were analyzed using descriptive statistics and frequencies. Our analysis highlighted the previously known association with Castleman disease and Castleman‐like features and underlined its association with dendritic cell proliferations in general, as well as uncovering high frequency of concurrence with hepatocellular carcinoma and autoimmune diseases, most notably myasthenia gravis, paraneoplastic pemphigus and paraneoplastic autoimmune multiorgan syndrome. Furthermore, the co‐expression of CD4 and CD8 and high prevalence of extranodal disease and recurrences were other less well described features that were revealed. [ABSTRACT FROM AUTHOR]

Platelet‐rich plasma (PRP) has become an accepted and general wound healing approach with an extremely wide range of applications. Despite considerable diversity in the composition of platelet‐rich plasma products that are applied in specific wound healing usage, it is widely recognised that such diverse platelet‐rich plasma complex mixtures routinely display hormetic‐like biphasic concentrations that are independent of the tissue treated and endpoints measured. The present paper is the first to place the area of platelet‐rich plasma‐biomedical research and applications within an hormetic framework. The platelet‐rich plasma area is also unique as it represents the application of the hormetic concept to the issue of complex biological mixtures. [ABSTRACT FROM AUTHOR]

Cellulase on‐site production can occur in a supplementary unit in a kraft paper mill to create additional revenue. In this study, the production of cellulase enzyme from kraft hardwood pulp by Trichoderma reesei Rut C‐30 was investigated in a 3 L fermenter. Experiments were conducted at three pH levels, 3.5, 4.0, and 5.0, to study their impact on T. reesei Rut C‐30 growth and cellulase production. It was found that higher pH values promoted cell proliferation but not cellulase production. The highest cellulase activity and productivity were obtained at a pH level of 3.5. The solid loading effect of the substrate was also investigated over the range of 2% to 5% (w/v) to determine the maximum levels of cellulase activity obtainable. The highest titer of 7.5 FPU mL–1 was achieved at 4% (w/v) of hardwood pulp. Cellulase production in this condition yielded 246.7 FPU/g‐glucan of hardwood pulp with a productivity of 56.8 FPU L–1h–1. The higher xylanase activity in the enzyme produced in‐house resulted in higher glucan and xylan digestibility than the commercial enzyme. © 2019 Society of Chemical Industry and John Wiley & Sons, Ltd [ABSTRACT FROM AUTHOR]

An increased frequency of chromosome segregation errors, known as chromosomal instability (CIN), leads to accumulation of aneuploid cells with abnormal chromosomal numbers, which impairs viability through negative effects on survival and proliferation under most conditions. Two recent papers find by independent approaches that the key to surviving high levels of CIN is reducing the instability itself, showcasing the remarkable adaptability of the chromosome segregation machinery, in particular the microtubule–kinetochore interface, and highlighting the crucial role that maintaining chromosomal stability plays in cell proliferation. [ABSTRACT FROM AUTHOR]

Background: Marijuana and alcohol are both substances that, when used during pregnancy, may have profound effects on the developing fetus. There is evidence to suggest that both drugs have the capacity to affect working memory, one function of the hippocampal formation; however, there is a paucity of data on how perinatal exposure to alcohol or cannabis impacts the process of adult neurogenesis. Methods: This systematic review examines immunohistochemical data from adult rat and mouse models that assess perinatal alcohol or perinatal marijuana exposure. A comprehensive list of search terms was designed and used to search 3 separate databases. All results were imported to Mendeley and screened by 2 authors. Consensus was reached on a set of final papers that met the inclusion criteria, and their results were summarized. Results: Twelve papers were identified as relevant, 10 of which pertained to the effects of perinatal alcohol on the adult hippocampus, and 2 pertained to the effects of perinatal marijuana on the adult hippocampus. Cellular proliferation in the dentate gyrus was not affected in adult rats and mice exposed to alcohol perinatally. In general, perinatal alcohol exposure did not have a significant and reliable effect on the maturation and survival of adult born granule neurons in the dentate gyrus. In contrast, interneuron numbers appear to be reduced in the dentate gyrus of adult rats and mice exposed perinatally to alcohol. Perinatal marijuana exposure was also found to reduce inhibitory interneuron numbers in the dentate gyrus. Conclusions: Perinatal alcohol exposure and perinatal marijuana exposure both act on inhibitory interneurons in the hippocampal formation of adult rats. These findings suggest simultaneous perinatal alcohol and marijuana exposure (SAM) may have a dramatic impact on inhibitory processes in the dentate gyrus. [ABSTRACT FROM AUTHOR]

We study a free boundary problem modeling the growth of multilayer tumors. This model describes the invasion of tumors: the tumor cells produce matrix degrading enzymes (MDEs) to degrade the extracellular matrix (ECM) which provides structural support of the surrounding tissue. As in Pan and Xing, the influence of ECM and MDE interactions is considered in this paper. The model equations include two diffusion equations for the nutrient concentration and MDE concentration and an ordinary differential equation for ECM concentration. The tumor cell proliferation is at the rate λ, which characterizes the aggressiveness of the tumor. In contrast to Pan and Xing, we consider "flat stationary solution" in this paper. We first show that there exists a unique flat stationary solution for any λ>0. Then, we prove that there are infinite branches of bifurcation solutions from the flat stationary solutions at the bifurcation points λ=λk(ρ*) (k≥1). [ABSTRACT FROM AUTHOR]

In this paper, the boron‐containing mesoporous bioactive glass (MBG) nanospheres have been successfully synthesized by modified sol‐gel method assisted by surfactant, and the effect of boron substitution on structure and bioactivity was evaluated by combining experiments and ab initio molecular dynamics (AIMD) simulations. All of the samples exhibit regularly uniform mesoporous spherical microstructure with an average size of about 60 nm, and the boron‐containing MBGs show higher specific surface area with the value up to 416.20 m2/g. The simulated body fluid (SBF) immersion test confirms that the deposited hydroxyapatite (HA) evidently increases with the increasing of boron content, indicating that the biological behavior has been significantly improved resulting from incorporation of boron. Additionally, our results also reveal that B2O3 substitution has positive impact on cell proliferation of human periodontal ligament cells (hPDLCs) at lower extracted concentration. Furthermore, AIMD simulation is employed to understand the relationship between structural changes and in vitro bioactivity in terms of structural information, especially the boron coordination number. The results illustrate that the boron‐containing MBG nanospheres with excellent bioactivity are great potential for biomedical applications. [ABSTRACT FROM AUTHOR]

Keratinocyte culture is a necessary and widely used tool in a variety of experimental dermatological and biomedical studies. Literature search has revealed a variety of different protocols of human primary keratinocyte isolation and culture. Therefore, the aim of this paper was to review and summarize current trends in human primary keratinocyte culture techniques. We present data on the most popular and effective methods of human keratinocyte isolation and cultivation obtained from screening of 945 papers published during the last 10 years. [ABSTRACT FROM AUTHOR]

The ovule and its developmental successor, the seed, together represent a highly characteristic feature of seed plants that has strongly enhanced the reproductive and dispersal potential of this diverse group of taxa. Ovules encompass multiple tissues that perform various roles within a highly constrained space, requiring a complex cascade of genes that generate localized cell proliferation and programmed cell death during different developmental stages. Many heritable morphological differences among lineages reflect relative displacement of these tissues, but others, such as the second (outer) integuments of angiosperms and Gnetales, represent novel and apparently profound and independent innovations. Recent studies, mostly on model taxa, have considerably enhanced our understanding of gene expression in the ovule. However, understanding its evolutionary history requires a comparative and phylogenetic approach that is problematic when comparing extant angiosperms not only with phylogenetically distant extant gymnosperms but also with taxa known only from fossils. This paper reviews ovule characters across a phylogenetically broad range of seed plants in a dynamic developmental context. It discusses both well‐established and recent theories of ovule and seed evolution and highlights potential gaps in comparative data that will usefully enhance our understanding of evolutionary transitions and developmental mechanisms. [ABSTRACT FROM AUTHOR]

BMP9 is a cytokine involved in the maturation phase of the angiogenic process that signals through its serine/threonine receptor ALK1 and its coreceptor endoglin. In this paper, we explain how BMP9 directs the regulation of endothelial cell proliferation blockage while in turn stimulating protein synthesis. To achieve this, BMP9 promotes SGK1 synthesis and activation through mTORC2 in order to stimulate the mTORC1/S6K/S6 axis. Moreover, BMP9 blocks proliferation also through SGK1 by reducing the activity of the MEK/ERK signalling pathway. Inhibition of SGK1 activity is sufficient to prevent BMP9‐mediated inhibition of ERK, leading to an increase in endothelial cell proliferation. Overall, our findings reveal that SGK1 is a key player during angiogenesis, mediating the pro‐quiescent and maturation effects of BMP9/ALK1. [ABSTRACT FROM AUTHOR]

Kruppel‐like factor 14 (KLF14) is a newly identified member of the KLF family. Expression of KLF14 is induced by TGF‐β in intrauterine and ectodermal tissue. Initial researches on KLF14 focused on its role in lipid and glucose metabolism. In recent years, however, the role of KLF14 in regulating cell signaling pathways, cell proliferation and differentiation has been explored. Moreover, the research has gradually extended into the field of tumorigenesis and immune regulation. This paper aims to briefly review the functions of KLF14 in physiologyical and pathological process. [ABSTRACT FROM AUTHOR]

IKBKE (inhibitor of nuclear factor kappa‐B kinase subunit epsilon), a member of the nonclassical IKK family, plays an important role in the regulation of inflammatory reactions, activation and proliferation of immune cells, and metabolic diseases. Recent studies have demonstrated that IKBKE plays a crucial regulatory role in malignant tumor development. In recent years, IKBKE, an important oncoprotein in several kinds of tumors, has been widely found to regulate a variety of cytokines and signaling pathways. IKBKE promotes the growth, proliferation, invasion, and drug resistance of various cancers. This paper makes a detailed review that focuses on the recent discoveries of IKBKE in the malignant tumors, and puts forward that IKBKE is becoming an important therapeutic target for clinical treatment, which has been more and more realized. [ABSTRACT FROM AUTHOR]

Brain‐derived neurotrophic factor (BDNF) is involved in regulating the growth of ovarian follicles, maturation of the oocyte, and development of the early embryo through its receptor, tyrosine kinase receptor B (TrkB). However, it is still unclear as to how BDNF influences proliferation and steroidogenesis of bovine granulosa cells (GCs). In this paper, we confirmed that BDNF and TrkB were expressed in bovine GCs, and that proliferation and steroidogenesis by bovine GCs were reduced by knockdown of BDNF or inhibition of TrkB. With respect to GC proliferation, BDNF enhanced cellular viability and the percentage of cells in the S phase. BDNF also activated both protein kinase B (PKB, also known as AKT) and the extracellular signal‐regulated protein kinase 1/2 (ERK1/2)‐signaling pathway. Through the AKT‐signaling pathway, BDNF increased the expression of proliferation‐related genes, including cyclin A1 (CCNA1), cyclin E2 (CCNE2), cyclin D1 (CCND1), and cyclin‐dependent kinase 1 (CDK1). However, through the ERK1/2 signaling pathway, BDNF only increased the expression of CCNA1 and CCNE2. Regarding steroidogenesis by bovine GCs, BDNF promoted progesterone (P 4) synthesis, but had no effect on estradiol; it also activated the AKT‐signaling pathway and increased the expression of steroidogenesis‐related genes, including steroidogenic acute regulatory protein (STAR) and hydroxy‐δ‐5‐steroid dehydrogenase, 3β‐ and steroid δ‐isomerase 1 (HSD3B1). In summary, our data are the first to show that BDNF promotes the proliferation of bovine GCs through TrkB–AKT and ERK1/2 signaling pathways and increases P4 synthesis by bovine GCs through the TrkB–AKT signaling pathway. We are the first to show stimulatory effects of brain‐derived neurotrophic factor (BDNF) on proliferation and progesterone (P4) synthesis by bovine granulosa cells (GCs); and that the AKT signaling pathway participates in both proliferation and P4 synthesis induced by BDNF, while the ERK1/2 signaling pathway only participates in cellular proliferation. CCNA1: cyclin A1; CCND1: cyclin D1; CCNE2: cyclin E2; CDK1: cyclin‐dependent kinase 1; STAR: steroidogenic acute regulatory protein; MAPK: mitogen‐activated protein kinases; PI3K: phosphoinositide 3‐kinase [ABSTRACT FROM AUTHOR]

Baicalin is one of the main flavonoids of the dried root of Scutellaria baicalensis Georgi and is reported to exert beneficial effects on the regulation of glucose/lipid metabolism. However, understanding its specific target and unique mechanism for improving glucose utilization is a challenge. In this paper, target fishing with a baicalin probe reveals that baicalin interacts with AKT. An immunofluorescence assay further demonstrates the colocalization of baicalin with AKT in the cytoplasm. A competitive test and virtual docking show that baicalin might bind to the pleckstrin homology domain of AKT. This specific binding hampers AKT membrane translocation, activates the phosphorylation of AKT on Ser473, induces the downstream glycogen synthase kinase 3β activation, and affects glycogen synthesis. [ABSTRACT FROM AUTHOR]

Acquired perforating calcific collagenosis (APCC), which is characterized by the calcification of dermal collagen fibers with subsequent transepidermal elimination and perforation, is an extremely rare entity. Thus far, it has only been reported in a patient with direct contact exposure to calcium chloride. Here, we report a unique case of APCC occurring in a drug addict admitted for rhabdomyolysis. The present case is a 20‐year‐old male patient hospitalized for drug‐related rhabdomyolysis and multiple organ damage. During hospitalization, he gradually developed unusual skin rashes. There were multiple confluent umbilicated and keratotic erythematous to brownish papules and plaques with scratch‐like linear plaques on his lower abdomen, inguinal areas and gluteal sulci. Also, multiple well‐demarcated flesh‐colored rough, hard and thin plaques with a "crepe paper"‐like texture were found on the bilateral popliteal fossae, olecranon fossae and axillae. The histopathology of two biopsied lesions demonstrated acquired perforating calcific collagenosis. The lesions appeared during the rhabdomyolysis‐related hypercalcemia phase and resolved spontaneously after the calcium level returned to normal. This is the first reported case of disseminated APCC occurring during transient hypercalcemia due to rhabdomyolysis. [ABSTRACT FROM AUTHOR]

The cellular cytoskeleton is involved with multiple biological processes and is tightly regulated by multiple proteins and effectors. Among these, the RhoGTPases family is one of the most important players. RhoGTPAses are, in turn, regulated by many other elements. In the past decade, one of those regulators, the RhoGAP Rho GTPase Activating Protein 21 (ARHGAP21), has been overlooked, despite being implied as having an important role on many of those processes. In this paper, we aimed to review the available literature regarding ARHGAP21 to highlight its importance and the mechanisms of action that have been found so far for this still unknown protein involved with cell adhesion, migration, Golgi regulation, cell trafficking, and even insulin secretion. [ABSTRACT FROM AUTHOR]

In the present paper, the biological effects of three different naphthalene diimides (NDIs) G‐quadruplex (G4) ligands (H‐NDI‐Tyr, H‐NDI‐NMe2, and tetra‐NDI‐NMe2) were comparatively evaluated to those exerted by RHPS4, a well‐characterized telomeric G4‐ligand, in an in vitro model of glioblastoma. Data indicated that NDIs were very effective in blocking cell proliferation at nanomolar concentrations, although displaying a lower specificity for telomere targeting compared to RHPS4. In addition, differently from RHPS4, NDIs failed to enhance the effect of ionizing radiation, thus suggesting that additional targets other than telomeres could be involved in the strong NDI‐mediated anti‐proliferative effects. In order to test telomeric off‐target action of NDIs, a panel of genes involved in tumor progression, DNA repair, telomere maintenance, and cell‐cycle regulation were evaluated at transcriptional and translational level. Specifically, the compounds were able to cause a marked reduction of TERT and BCL2 amounts as well as to favor the accumulation of proteins involved in cell cycle control. A detailed cytofluorimetric analysis of cell cycle progression by means of bromodeoxyuridine (BrdU) incorporation and staining of phospho‐histone H3 indicated that NDIs greatly reduce the progression through S‐phase and lead to G1 accumulation of BrdU‐positive cells. Taken together, these data indicated that, besides effects on telomeres and oncogenes such as Tert and Bcl2, nanomolar concentrations of NDIs determined a sustained block of cell proliferation by slowing down cell cycle progression during S‐phase. In conclusion, our data indicate that NDIs G4‐ligands are powerful antiproliferative agents, which act through mechanisms that ultimately lead to altered cell‐cycle control. The effect of different telomeric G‐quadruplex (G4) ligands (three naphthalene diimides (NDIs) derivatives and RHPS4), were comparatively evaluated in radio‐resistant U251MG glioblastoma cells. Although displaying a lower than RHPS4 specificity for telomeric G4 and absence of radio‐sensitization potential, NDIs were very effective in blocking cell proliferation through the deregulation of proteins involved in cell‐cycle control and the slow‐down of cell‐cycle progression through the S phase. [ABSTRACT FROM AUTHOR]

APJ, an orphan G protein‐coupled receptor, is first identified through homology cloning in 1993. Apelin is endogenous ligand of APJ extracted from bovine stomach tissue in 1998. Apelin/APJ system is widely expressed in many kinds of cells such as endothelial cells, cardiomyocytes, especially vascular smooth muscle cell. Vascular smooth muscle cell (VSMC), an integral part of the vascular wall, takes part in many normal physiological processes. Our experiment firstly finds that apelin/APJ system enhances VSMC proliferation by ERK1/2‐cyclin D1 signal pathway. Accumulating studies also show that apelin/APJ system plays a pivotal role in mediating the function of VSMC. In this paper, we review the exact role of apelin/APJ system in VSMC, including induction of proliferation and migration, enhance of contraction and relaxation, inhibition of calcification. Furthermore, we discuss the role of apelin/APJ system in vascular diseases, such as atherosclerosis, hypertension, and chronic kidney disease (CKD) from the point of VSMC. Above all, apelin/APJ system is a promising target for managing vascular disease. [ABSTRACT FROM AUTHOR]

Long non-coding RNAs (lncRNAs), a group of non-protein- coding RNAs with more than 200 nucleotides in length, are involved in multiple biological processes, such as the proliferation, apoptosis, migration and invasion. Moreover, numerous studies have shown that lncRNAs play important roles as oncogenes or tumour suppressor genes in human cancers. In this paper, we concentrate on actin filament-associated protein 1-antisense RNA 1 (AFAP1-AS1), a well-known long non-coding RNA that is overexpressed in various tumour tissues and cell lines, including oesophageal cancer, pancreatic ductal adenocarcinoma, nasopharyngeal carcinoma, lung cancer, hepatocellular carcinoma, ovarian cancer, colorectal cancer, biliary tract cancer and gastric cancer. Moreover, high expression of AFAP1-AS1 was associated with the clinicopathological features and cancer progression. In this review, we sum up the current studies on the characteristics of AFAP1-AS1 in the biological function and mechanism of human cancers. [ABSTRACT FROM AUTHOR]

Genetic mutation leads to anatomical variation only indirectly because many proteins involved in generating anatomical structures in embryos operate cooperatively within molecular networks. These include gene-regulatory or control networks ( CNs) for timing, signaling and patterning together with the process networks ( PNs) for proliferation, apoptosis, differentiation and morphogenesis that they control. This paper argues that anatomical variation is achieved through a two-stage process: mutation alters the outputs of CNs and perhaps the proliferation network, and such changed outputs alter the ways that PNs construct tissues. This systems-biology approach has several implications: first, because networks contain many cooperating proteins, they amplify the effects of genetic variation so enabling mutation to generate a wider range of phenotypes than a single changed protein acting alone could. Second, this amplification helps explain how novel phenotypes can be produced relatively rapidly. Third, because even organisms with novel anatomical phenotypes derive from variants in standard networks, there is no genetic barrier to their producing viable offspring. This approach also clarifies a terminological difficulty: classical evolutionary genetics views genes in terms of phenotype heritability rather than as DNA sequences. This paper suggests that the molecular phenotype of the classical concept of a gene is often a protein network, with a mutation leading to an alteration in that network's dynamics. [ABSTRACT FROM AUTHOR]

Chlamydia trachomatis is a bacterium that causes eye infection and blindness in humans. In the simplest form, it has an unusual life cycle involving two developmental forms. Within a cytoplasmic inclusion, the reticulate body (RB) repeatedly divides by binary fission and asynchronously differentiates into the infectious elementary body (EB). Upon the death of the mammalian cell that host many such inclusions, only the EB form of the bacteria survive and proceed to infect other cells. Given the bacteria's fast spreading infection, conventional wisdom would have the few initial EB turn into RB, divide and proliferate first, and then eventually start converting to maximize the terminal EB population upon host cell lysis. Several biological processes are seen as possible mechanisms for implementing such a conversion strategy. However, the optimality of an instinctual strategy with a period of proliferate without conversion prior to the onset of differentiation has never been substantiated theoretically or justified mathematically. This paper formulates three relatively simple models that capture the essential features of the Chlamydia life cycle. When the initial infection is caused by the endocytosis of a small EB population well below the carrying capacity of the host cell, the Maximum Principle in control theory requires for these models an optimal conversion strategy that confirms and rigorously justifies the prevailing view of no conversion at the early stage of the host cell infection. However, the conventional supposition is found to be inappropriate for an initial EB (-to-RB) population near or above the carrying capacity. Previously suggested and new biological mechanisms are examined for their role in implementing the different optimal conversion strategies associated with models investigated herein. [ABSTRACT FROM AUTHOR]

Summary During fluorescent live cell imaging it is critical to keep excitation light dose as low as possible, especially in the presence of photosensitizer drugs, which generate free radicals upon photobleaching. During fluorescent imaging, stress by excitation and free radicals induces serious cell damages that may arrest the cell cycle. This limits the usefulness of the technique for drug discovery, when prolonged live cell imaging is necessary. This paper presents a strategy to provide gentle experimental conditions for dynamic monitoring of the proliferation of human lung epithelial carcinoma cells (A549) in the presence of the photosensitizer Polyvinylpyrrolidone-Hypericin. The distinctive strategy of this paper is based on the stringent environmental control and optimizing the excitation light dose by (i) using a low-power pulsed blue light-emitting diode with short pulse duration of 1.29 ms and (ii) adding a nontoxic fluorescent dye called carboxyfluorescein-diacetate-succinimidyl-ester (CFSE) to improve the fluorescence signals. To demonstrate the usefulness of the strategy, fluorescence signals and proliferation of dual-marked cells, during 5-h fluorescence imaging under pulsed excitation, were compared with those kept under continuous excitation and nonmarked reference cells. The results demonstrated 3% cell division and 2% apoptosis due to pulsed excitation compared to no division and 85% apoptosis under the continuous irradiation. Therefore, our strategy allows live cell imaging to be performed over longer time scales than with conventional continuous excitation. [ABSTRACT FROM AUTHOR]

This paper is concerned with the elastodynamics of embryonic epidermal wound closing. Underlying the recovery process for this type of wounds is a mechanism of wound recognition through directed cell-to-cell signaling. The observed actin filament realignment induced by the biological signals leads to a purse-string effect and the resulting (unknown) “active stresses.” The circumferential contraction of the epidermis surrounding the wound is then determined by the laws of mechanics and propagation properties of the relevant cell–cell signaling that decays with distance. With the wound known to retract for a short period immediately after infliction, the quasi-equilibrium configuration reached during this initial phase serves as the initial condition for the dynamic wound closing phase. A small strain variation of the Murray–Sherratt model of the quasi-equilibrium problem will be formulated for speedy computation of this initial state at the inception of the wound closure phase, with the latter problem being the main concern of this paper. Some theoretical developments are found to be instrumental to an efficient algorithm for the otherwise time-consuming task of calculating the effect of the biological signals generated by the presence of a wound. Application of our elastodynamic model to the case of a circular wound suggests that the propagation range of our choice of cell–cell signaling mechanism must be above a certain minimum fraction of the wound radius for wound closure. As expected, stress concentration occurs adjacent to the edge of the remaining small wound near the end of the wound closing process. At that point, the present model is not expected to be adequate and more appropriate expressions of elastic strain and active stress induced by actin filaments may be in order. Other biological processes such as cell proliferation and differentiation may be involved. [ABSTRACT FROM AUTHOR]

The group of authors from San Francisco and Shanghai describe their investigation of wogonin, a flavonoid extracted from a naturally occurring root, which has been used in traditional Chinese medicine to treat inflammatory diseases. Here they study the mechanisms for its anti-inflammatory properties. The previous paper published in the BJU International on genital piercing proved to be of great interest to urologists in general. We do not have a history section in the Journal, but it is worth knowing more about the use of this ‘body decoration’ in historic times and up to the present. The Historical Committee of the European Association of Urology has produced much interesting material over the years and here some of that group have written another very interesting paper. To test the effect of wogonin on cellular proliferation and expression of monocyte chemoattractant protein 1 (MCP-1) in cells derived from normal and diseased tunica albuginea (TA), as related to Peyronie's disease (PD). Cells with characteristics of fibroblasts were isolated from three tissue sources. Those from the plaque of patients with PD were designated as P cells, those from the adjacent, normal-appearing tissue as C cells, and those from the TA of patients without PD as N cells. These cells were treated with wogonin at doses of 0, 10, 20 and 40 µmol/L for 24 h or treated at a fixed dose of 40 µmol/L for 1, 8 and 24 h. Cell proliferation was assayed with a commercial kit, MCP-1 mRNA expression by reverse transcription-polymerase chain reaction, and secreted MCP-1 by enzyme-linked immunosorbent assay. Wogonin suppressed cell proliferation in a dose-dependent manner; the effect was more pronounced against P cells at 8 and 24 h. Wogonin down-regulated MCP-1 mRNA expression, especially in P cells. Wogonin suppressed the level of secreted MCP-1 by 59–88%. P cells, which secreted far more MCP-1 than N and C cells at 1 h, were suppressed by 88%. C cells were the least suppressed at all three times. Wogonin suppressed the proliferation, the expression of MCP-1 mRNA, and the expression of secreted MCP-1 in TA-derived cells. In most cases, the effect of wogonin was greatest against cells derived from the plaque. Wogonin appears to be a worthy candidate for preclinical trials in men with PD. [ABSTRACT FROM AUTHOR]

The size, body conformation and skull shape of Roman dogs from the 'Vila de Madrid necropolis' site, where 1480 dog remains were recovered, are described in this paper to provide evidence of the morphometric variability of Roman dogs in Hispania Tarraconensis. The individualized and detailed morphometric analysis of 10 individuals shows that the proliferation and explosion of the morphological variability already documented in different regions of the Roman Empire (Italia, Gallia, Britannia, Pannonia) are also noted here. The presence of very different individuals in terms of their shape and size, similar to the differences that can at present be noted between Pekingese and Doberman dogs, has been documented at the site. The reasons for the appearance of this morphological variability within those territories that were part of the Roman Empire are also discussed. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Cutaneous mastocytosis is a disease characterized by the infiltration and proliferation of mast cells in the skin. In children, the most common form of presentation is urticaria pigmentosa, while the diffuse cutaneous bullous mastocytosis is one of the rarest subtypes seen. The aim of this paper is to present a case of diffuse bullous mastocytosis with detection of IgM deposits at dermo-epidermal junction using direct immunofluorescence (DIF) microscopy. The diagnosis of diffuse bullous mastocytosis is a challenge, and DIF microscopy is necessary in order to exclude an autoimmune bullous disorder. However, IgM deposits at dermo-epidermal junction can be nonspecific, being found in a variety of skin disorders. A 6-month-old girl presented with bullous lesions and erosions on the scalp and the trunk. During hospitalization, further bullous lesions appeared, along with generalized erythrodermia. Skin biopsy revealed aspects of urticaria pigmentosa. Taking into account the clinical findings, the case was enclosed as bullous mastocytosis. Treatment included the avoidance of trigger factors, and administration of antihistamines along with a short-term course of systemic steroids. The evolution was favorable, with remission of the existing lesions and without occurrence of new ones. [ABSTRACT FROM AUTHOR]

In this paper, we report the synthesis of 14 new cycloalkane-fused tricyclic coumarin sulfonate derivatives. They were examined for in vitro anticancer activity against NCI-57 cancer cell line panel of nine different cancer types. Among all the target analogs, compounds 1c, 1e, and 1n showed the highest activities. Compound 1e exerted the highest percentage growth inhibition (91.91%) against SNB-75 CNS cancer cell line at 10 μM concentration and was more active than carmustine against this cell line. Compound 1c also showed strong activity against HT29 colon, ACHN renal, and PC-3 prostate cancer cell lines. Furthermore, compound 1n was selective toward the HT29 colon cancer cell line. Compounds 1c, 1e, and 1n showed superior selectivity against cancer cell lines compared to the noncancerous RAW 264.7 macrophages. The in silico predictions estimate the oral bioavailability, which is in compliance with Lipinski's rule of five. [ABSTRACT FROM AUTHOR]

The first aim of this paper is to review recent progress in identifying genes in plants homologous to cell division cycle (cdc) genes of fission yeast. In the latter, cdc genes are well-characterised. Arguably, most is known about cdc2 which encodes a 34 kDa protein kinase (p34cdc2) that functions at the G2-M and G1-S transition points of the cell cycle. At G2-M, the p34cdc2 protein kinase is regulated by a number of gene products that function in independent regulatory pathways. The cdc2 kinase is switched on by a phosphatase encoded by cdc25, and switched off by a protein kinase encoded by wee1. p34 Must also bind with a cyclin protein to form maturation promoting factor before exhibiting protein kinase activity. In plants, homologues to p34cdc2 have been identified in pea, wheat, Arabidopsis, alfalfa, maize and Chlamydomonas. They all exhibit the PSTAIRE motif, an absolutely conserved amino acid sequence in all functional homologues sequenced so far. As in animals, some plant species contain more than one cdc2 protein kinase gene, but in contrast to animals where one functions at G2-M and the other (CDK2 in humans and Eg1 in Xenopus) at G1-S, it is still unclear whether there are functional differences between the plant p34cdc2 protein kinases. Again, whereas in animals cyclins are well characterised on the basis of sequence analysis, into class A, class B (G2-M) and CLN (G1 cyclins), cyclins isolated from several plant species cannot be so clearly characterised. The differences between plant and animal homologues to p34cdc2 and cyclins raises the possibility that some of the regulatory controls of the plant genes may be different from those of their animal counterparts. The second aim of the paper is to review how planes of cell division and cell size are regulated at the molecular level. We focus on reports showing that p34cdc2 binds to the preprophase band (ppb) in late G2 of the cell cycle. The binding of p34cdc2 to ppbs may be important in regulating changes in directional growth but, more importantly, there is a requirement to understand what controls the positioning of ppbs. Thus, we highlight work resolving proteins such as the microtubule associated proteins (MAPs) and those mitogen activated protein kinases (MAP kinases), which act on, or bind to, mitotic microtubules. Plant homologues to MAP kinases have been identified in alfalfa. Finally, some consideration is given to cell size at division and how alterations in cell size can alter plant development. Transgenic tobacco plants expressing the fission yeast gene, cdc25, exhibited various perturbations of development and a reduced cell size at division. Hence, cdc25 affected the cell cycle (and as a consequence, cell size at division) and cdc25 expression was correlated with various alterations to development including precocious flowering and altered floral morphogenesis. Our view is that the cell cycle is a growth cycle in which a cell achieves an optimal size for division and that this size control has an important bearing on differentiation and development. Understanding how cell size is controlled, and how plant cdc genes are regulated, will be essential keys to ‘the cell cycle locks’, which when ‘opened’, will provide further clues about how the cell cycle is linked to plant development. [ABSTRACT FROM AUTHOR]

This article presents information on research papers contributed for the joint meeting with phycological section of Botanical Society of America, to be held from August 28-30, 1967. Researchers G.J. Hill and L. Machlis contributed papers on cell division in oedogonium. In this paper, the ultrastructural events occurring during vegetative and sexual cell division of oedogonium is described. Researcher Norma J. Lang contributed papers in which the extraplastidic red pigment astaxanthin was investigated.

Possible hormonal interactions between soybean roots and the Rhizobium initiating nodule proliferation in this genus were studied. A cytokinin has been isolated by column and paper chromatography from an effective strain of Rhizobium japonicum grown in pure culture. The substance promotes cell proliferation in a cytokinin-requiring soybean callus tissue. The bacteria are capable of conditioning a cytokinin-free soybean culture medium so that it is able to support the cytokinin- requiring tissue. It is concluded that the substance is a product of the bacteria rather than an artifact of purification. This unidentified cytokinin or a substance moving to a similar Rf value on the paper chromatograrn produces polyploid divisions when tested on cultured pea root segments. Some of the division figures exhibit the diplochromosomes typical of the root nodule primordium in pea. [ABSTRACT FROM AUTHOR]

Chemoresistance enables cancer cells to evade apoptotic stimuli and leads to poor clinical prognosis. It arises from dysregulation of signaling factors responsible for inducing cell proliferation and death and for modulating the microenvironment. In gynecologic cancers, p53 is a pivotal determinant of cisplatin sensitivity, while BCL-2 family members are associated with taxane sensitivity. Mitochondria fusion and fission dynamics are required for many mitochondrial functions and are also involved in mitochondria-mediated apoptosis, which is closely associated with chemosensitivity. Mitochondrial dynamics are controlled by a number of intracellular proteins, including fusion (Opa1 and mitofusion 1 and 2) and fission proteins (Drp1 and Fis1), which can be proapoptotic or antiapoptotic, depending on the cell types, status, and stimuli from the microenvironment. This paper describes the role of mitochondrial dynamics in the mechanism of chemoresistance and the evidence supporting a significant contribution of a hyperfusion state to chemoresistance in gynecological cancers. Moreover, we discuss our findings showing that enforced fission induces apoptosis of cancer cells and sensitizes them to chemotherapeutic agents. Understanding the regulation of mitochondrial dynamics inchemoresistancemay provide insight intonewbiomarkers that better predict cancer chemosensitivity and may aid the development of effective therapeutic strategies for clinical management of gynecologic cancers. [ABSTRACT FROM AUTHOR]

The Yes-associated protein ( YAP) is an important transcriptional co-activator that mediates the cellular response to mechanical and cytoskeletal cues. In two recent papers published in The EMBO Journal, Dae-Sik Lim and colleagues show how YAP activity affects cancer formation and metastasis via a crosstalk with myocardin-related transcription factors (MRTFs; Kim et al, 2017) and SKP2-dependent cell cycle progression (Jang et al, 2017). [ABSTRACT FROM AUTHOR]

Objectives Regulatory mechanisms of cell proliferation have been extensively studied as they represent major challenges when dealing with pathologies such as fibrosis, tumourigenesis or tissue regeneration. Numerous in vitro studies still exploit conventional, two-dimensional cell cultures where cells are forced to adhere to unnaturally stiff and flat surfaces of culture dishes. In the living organism, however, each cell is in contact with components of the extracellular matrix and/or neighbouring cells, thus creating a complex three-dimensional (3D) tissue structure. The current paper describes a native 3D culture of cells, based on the GD25β1 fibroblast cell line, and its use for investigating cell proliferation in in vivo-like conditions. Materials and methods Four-day post-confluent culture of GD25β1 fibroblasts resulted in formation of a 3D system of cells embedded in naturally synthesized extracellular matrix. Morphological characterization of the culture was performed by histochemistry, immunohistochemistry and immunofluorescence. Viability/proliferation was assayed by MTT testing, FACS analysis and Western blotting for determination of expression levels and activation status of the relevant signalling molecules. Results GD25b1 fibroblasts, grown as 3D culture, gave rise to tissue-like structures characterized by low level of apoptosis, low senescence and development of 3D matrix adhesions, typical of living tissues. Transition to three-dimensionality led to a switch from exponential to linear culture growth, accompanied by accumulation of activated ERK1/2 into caveolin-containing raft domains. Disruption of raft domains as well as reverse transition from 3D back to monolayer culture led to release of phosphorylated ERK1/2 from rafts, activation of cyclin D1 expression and increase in proliferation levels. Conclusions These results imply that under in vivo-like conditions, cells might achieve reduction of their proliferation level by sequestering activated ERK1/2 to lipid rafts. [ABSTRACT FROM AUTHOR]

SUMMARY In this paper, we extend the 3D multispecies diffuse-interface model of the tumor growth, which was derived in Wise et al. (Three-dimensional multispecies nonlinear tumor growth-I: model and numerical method, J. Theor. Biol. 253 (2008) 524-543), and incorporate the effect of a stiff membrane to model tumor growth in a confined microenvironment. We then develop accurate and efficient numerical methods to solve the model. When the membrane is endowed with a surface energy, the model is variational, and the numerical scheme, which involves adaptive mesh refinement and a nonlinear multigrid finite difference method, is demonstrably shown to be energy stable. Namely, in the absence of cell proliferation and death, the discrete energy is a nonincreasing function of time for any time and space steps. When a simplified model of membrane elastic energy is used, the resulting model is derived analogously to the surface energy case. However, the elastic energy model is actually nonvariational because certain coupling terms are neglected. Nevertheless, a very stable numerical scheme is developed following the strategy used in the surface energy case. 2D and 3D simulations are performed that demonstrate the accuracy of the algorithm and illustrate the shape instabilities and nonlinear effects of membrane elastic forces that may resist or enhance growth of the tumor. Compared with the standard Crank-Nicholson method, the time step can be up to 25 times larger using the new approach. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

T cell proliferation and T helper (TH) cells that make IL-17 (TH17 cells) and IFN-γ (TH1 cells) have been shown to be inhibited by 1,25(OH)2D3. Previous work has shown that immune-mediated diseases, where TH1 and TH17 cells are pathogenic, are ameliorated with 1,25(OH)2D3 treatment. Paradoxically, infectious diseases that require TH1 and TH17 responses for host resistance are unaffected by 1,25(OH)2D3 treatment. Resting T cells are not responsive to vitamin D because they do not express the vitamin D receptor (VDR) until late after activation. T cells activated following an infection help clear the infection, and since the antigen is eliminated, vitaminDis not needed to dampen the immune response. Conversely, in immune-mediated disease, there is chronicTcell activation, and in this scenario, vitamin D and 1,25(OH)2D3 are critical for inhibiting T cell proliferation and cytokine production. Vitamin D is a late regulator of T cell function and acts to turn off T cells. This paper will review these data. [ABSTRACT FROM AUTHOR]

T cell proliferation and T helper (TH) cells that make IL-17 (TH17 cells) and IFN-γ (TH1 cells) have been shown to be inhibited by 1,25(OH)2D3. Previous work has shown that immune-mediated diseases, where TH1 and TH17 cells are pathogenic, are ameliorated with 1,25(OH)2D3 treatment. Paradoxically, infectious diseases that require TH1 and TH17 responses for host resistance are unaffected by 1,25(OH)2D3 treatment. Resting T cells are not responsive to vitamin D because they do not express the vitamin D receptor (VDR) until late after activation. T cells activated following an infection help clear the infection, and since the antigen is eliminated, vitamin D is not needed to dampen the immune response. Conversely, in immune-mediated disease, there is chronic T cell activation, and in this scenario, vitamin D and 1,25(OH)2D3 are critical for inhibiting T cell proliferation and cytokine production. Vitamin D is a late regulator of T cell function and acts to turn off T cells. This paper will review these data. [ABSTRACT FROM AUTHOR]

In this paper we contrast the simple role of FOXO in the seemingly non-aging Hydra with its more diversified function in multicellular eukaryotes that manifest aging and limited life spans. From this comparison we develop the concept that, whilst once devoted to life-prolonging cell-renewal (in Hydra), evolutionary accumulation of coupled functionality in FOXO has since 'distracted' it from this role. Seen in this light, aging may not be the direct cost of competing functions, such as reproduction or growth, but the result of a shift in emphasis in a protein, which is accompanied by advantages such as greater organismal complexity and adaptability, but also disadvantages such as reduced regeneration capacity. Studying the role of FOXO in non-aging organisms might, therefore, illuminate the path to extend life span in aging organisms. Editor's suggested further reading in BioEssays Stem cells and aging from a quasi-immortal point of view [ABSTRACT FROM AUTHOR]

The recent advancements in unraveling novel mechanisms that control the induction, (trans)differentiation, proliferation, and thermogenic activity and capacity of brown adipose tissue (BAT), together with the application of imaging techniques for human BAT visualization, have generated optimism that these advances will provide novel strategies for targeting BAT thermogenesis, leading to efficacious and safe obesity therapies. This paper first provides an overview of landmark events of the past few decades that have been driving the search for pharmaceutical and nutraceutical compounds that would increase BAT thermogenesis for obesity management. It then addresses issues about what could be expected from an ideal thermogenic antiobesity approach, in particular to what extent daily energy expenditure will need to increase in order to achieve long-term weight loss currently achievable only through bariatric surgery, and whether the human body will have enough thermogenic capacity to reach this target weight loss by future therapies focused on BAT. [ABSTRACT FROM AUTHOR]

Autosomal dominant polycystic kidney disease ( ADPKD) is the most common inherited kidney disease and results from mutations in PKD1 or PKD2. Cyst initiation and expansion arise from a combination of abnormal cell proliferation, fluid secretion and extracellular matrix defects and results in kidney enlargement and interstitial fibrosis. Since its first description over 200 years ago, ADPKD has been considered an untreatable condition and its management is limited to blood pressure reduction and symptomatic treatment of disease complications. Results of the recently reported TEMPO 3/4 trial thus represent a paradigm shift in demonstrating for the first time that cystic disease and loss of renal function can be slowed in humans. In this paper, we review the major therapeutic strategies currently being explored in ADPKD including a range of novel approaches in preclinical models. It is anticipated that the clinical management of ADPKD will undergo a revolution in the next decade with the translation of new treatments into routine clinical use. [ABSTRACT FROM AUTHOR]

Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disease and results from mutations in PKD1 or PKD2. Cyst initiation and expansion arise from a combination of abnormal cell proliferation, fluid secretion and extracellular matrix defects and results in kidney enlargement and interstitial fibrosis. Since its first description over 200 years ago, ADPKD has been considered an untreatable condition and its management is limited to blood pressure reduction and symptomatic treatment of disease complications. Results of the recently reported TEMPO 3/4 trial thus represent a paradigm shift in demonstrating for the first time that cystic disease and loss of renal function can be slowed in humans. In this paper, we review the major therapeutic strategies currently being explored in ADPKD including a range of novel approaches in preclinical models. It is anticipated that the clinical management of ADPKD will undergo a revolution in the next decade with the translation of new treatments into routine clinical use. [ABSTRACT FROM AUTHOR]

Retraction: "Effects of FOSL1 silencing on osteosarcoma cell proliferation, invasion and migration through the ERK/AP‐1 signaling pathway," by Yu Han, Xingyu Zhao, Yifu Sun, Yutong Sui, and Jianguo Liu, J Cell Physiol. 2019; 3598‐3612: The above article, published online on 23 November 2018 in Wiley Online Library (https://doi.org/10.1002/jcp.27048) has been retracted by agreement between the authors, the journal's Editor in Chief, Prof. Dr. Gregg Fields, and Wiley Periodicals LLC. The retraction has been agreed following an investigation based on allegations raised by a third party. A detailed investigation revealed that several image elements of the experimental data were published elsewhere in a different scientific contest. Additionally, the authors asked to retract their paper due to anomalies in the Transwell data. Thus, the conclusions of the article are considered to be invalid. [ABSTRACT FROM AUTHOR]

Thyroid cancer is not very common, accounting for 1-2% of all cancers, with a population incidence of about 0.004%. Currently, the ability to discriminate between follicular adenoma and carcinoma represents the major challenge in preclinical diagnosis of thyroid proliferative lesions. Better discrimination between the two would help avoid unnecessary thyroidectomy and save valuable resources. Over the years, galectin-3 (Gal-3) has been proposed as a diagnostic marker with varied success. In this paper, we used Environmental Scanning Electron Microscopy Immunogold Labelling (ESEM-IGL) to investigate the expression of Gal-3 on Thin-Prep fine needle aspiration cytology (FNAC). We optimized the ESEM-IGL method on thyroid cell lines (RO-82 and FTC-133) comparing our membrane Gal-3 labeling data with Western blot. We evaluated 183 thyroid FNAC from Italian patients with a uncertain pre-surgical diagnosis. ESEM-IGL method marker sensitivity is 71.2%, while specificity is 53.3% and diagnostic efficacy is 61.2%. Our results confirmed that Gal-3 expression is associated with situations of hypertrophy and/or cellular hyperproliferation, pathophysiological situations common both to adenomas and to thyroid carcinomas. The innovation of thyroid FNAC Thin-Prep ESEM-IGL shows the levels of Gal-3 immunolabeling clearly, even through the individual cells of a thyroid nodule. However, Gal-3 alone, as a molecular marker of thyroid cancer, can still have a limited application in pre-surgery diagnosis. J. Cell. Physiol. © 2012 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]