Cover: The cover image, by Chammaa et al., is based on Original Research Article, RUMI is a novel negative prognostic marker and therapeutic target in non-small-cell lung cancer, DOI: 10.1002/jcp.26858.

STAC3 has been demonstrated to establish two discrete interactions with the DHPR: its C1 domain interacts with the IQ domain in the C-terminus, and the SH3-1 domain interacts with the IPR motif in the II–III loop of the DHPR. Here, we provide evidence of a third, hitherto unidentified, interaction, which anchors STAC3 in the triad junctions independent of the DHPR. Because of the crucial role of STAC3 in excitation-contraction coupling and because no additional proteins are necessary to restore voltage-induced calcium release in heterologous cells, STAC3 may thus directly couple the DHPR with the RyR1.

Serologic profile of serum antibody reactivity to BK polyomavirus (BKPyV) mimotopes viral capsid protein 1 (VP1) L (a) and VP1 M (b) and VP1 L+M (c). Immunologic data are from serum samples from uveal melanoma (UM) and healthy subjects (HS1). Results are presented as values of optical density (OD) readings at λ = 405 nm, of serum samples diluted at 1:20, detected in indirect ELISA. In scatter–dot plotting, each plot represents the dispersion of OD values to a mean level indicated by the line inside the scatter with the standard deviation (SD) for each group of subjects analyzed. (a) The mean OD of sera (VP1 L ± std error) in UM (0.329 ± 0.024) does not differ from that of HS1 (0.327 ± 0.008), p > 0.05, and from that of HS2 (0.324 ± 0.009), p > 0.05. (b) The mean OD of sera (VP1 M ± std error) in UM (0.298 ± 0.022) is lower than that detected in HS1 (0.417 ± 0.022), ***p < 0.001, and in HS2 (0.379 ± 0.018), *p < 0.05. (c) The mean OD of sera (VP1 L + M ± std error) in UM (0.314 ± 0.016) is lower than that detected in HS1 (0.372 ± 0.012), **p < 0.005, and in HS2 (0.352 ± 0.009), *p < 0.05. Statistical analysis was performed using ANOVA and the t test.

Our results suggest that podocytes are susceptible to palmitic acid (PA)–induced oxidative damage with impaired peroxidase activity and that peroxidases have futile antioxidant effects in the podocytes in the late stages of diabetic nephropathy (DN). Given this, PA-induced podocyte injury via inadequate peroxidase response to H₂O ₂ appears to play an important role in the pathogenesis of DN.

The present work, for the first time, reports the beneficial effects of using a microplatform on development of mouse single blastomeres (SBs) to the blastocyst stage. Three chips were introduced that provide the possibility of culturing SBs separately, in groups, and in the vicinity of the intact embryo. The quality of developed blastocysts was also examined.

Hypoxia-inducible factor (HIF)-2α has been shown to regulate multiple aspects of angiogenesis, including cell proliferation, migration, maturation of blood vessels, and metastasis. In this review, we focus on recent insights into HIF-2α expression, activation, and function under hypoxic and nonhypoxic conditions. We also summarize the current knowledge on the crosstalk between HIF-2 and angiogenesis, describing reported phenotypical changes of HIF-2α genetic models and HIF-2 target genes implicated in angiogenesis. Finally, we provide a survey of recent pharmacologic strategies to specifically target HIF-2 activity.

Mesenchymal stem cells (MSCs) and fibroblast share many properties and it is possible that fibroblasts are in fact aged MSCs and that the two cells are the same.

Numerous studies have indicated that ErbB3 binding protein 1 (Ebp1), a binding partner for ErbB3, plays an important regulatory role in the expression and function of ErbB3, but there is no agreement as to whether Ebp1 also has an ErbB3-independent function in cancer and how it might contribute to tumorigenesis. In this review, we will discuss the different functions of the two Ebp1 isoforms, p48 and p42, that may be responsible for the potentially dual role of Ebp1 in cancer growth.

Cellular senescence is linked to many human diseases. In this review, we will focus on recent studies to provide a brief overview of cellular senescence, including associated signaling pathways and pathology.

Breast tumors exhibit both inter- and intratumor heterogeneity as a result of both genetic and nongenetic alterations. Intertumor heterogeneity reflects the different cells of origin. Intratumor heterogeneity can be explained by the cancer stem cell theory, which is associated with activation of epithelial-to-mesenchymal transition.

Here, we summarized morphology and function of pinopodes. Moreover, we highlighted several molecules related with pinopodes which could be used as biomarkers.

There is increasing evidence for an association between obesity and myeloma pathogenesis. Understanding the mechanisms by which an increase in adiposity can drive disease progression may reveal new diagnostic and/or therapeutic approaches.

In the first part of this review the role of platelets in cancer metastasis as well as stem cells homing is discussed. Next, we provide some lessons learned from cancer metastasis in favor of developing strategies for improvement of stem cell homing with emphasis on the role of platelets.

Nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy is an autophagic phenomenon that specifically involves ferritin to release intracellular free iron. Ferritinophagy plays a central role in maintaining efficient erythropoiesis and driving urinary tract infections. Ferritinophagy is critical to induce ferroptosis, a newly nonapoptotic form of cell death that inhibits some types of cancers and accelerates neurodegenerative diseases including Parkinson’s disease (PD) and Alzheimer’s disease (AD).

In this review, the roles of microRNAs (miRNAs) in the regulation of cells related to bone homeostasis as well as miRNAs that deregulate in human or animal are discussed. Moreover, the miRNAs that act as clusters in the biology of cells in the bone microenvironment and the difference of some important miRNAs for bone homeostasis between bone and other organs are mentioned. Overall, miRNAs that contribute to the pathogenesis of osteoporosis and their therapeutic potential are considered.

MicroRNAs (miRNAs) are uniquely regulated in healthy, inflamed, activated, and cancerous cells and tissues. Most recently, miR-326 has been explored widely and has emerged as a key regulator of different biological processes such as metabolism of glucose and lipids; cell growth and proliferation; immune cell lineage obligation; maturation, differentiation, and maintenance of immune homeostasis; TH17 differentiation; as well as dendritic cells function. In this review, we will explain the history and classification of epigenetic changes, especially miRNAs and describe the role of miR-326 in different pathologic conditions, especially autoimmune diseases.

Here, we will focus on selected molecular pathways underlying epithelial–mesenchymal transition (EMT)—in particular, the role of tumor-associated macrophages (TAMs) in the induction and maintenance of EMT—and further discuss how the targeting of TAMs through the application of nanotechnology tools allows the development of a whole new range of therapeutics.

Monocytes are a major source of proinflammatory species during atherogenesis; in atherosclerosis, modified low-density lipoproteins (LDLs) are removed by macrophages and these are recruited in the vessel wall, inducing the release of inflammatory cytokines in inflamed tissue generating inflammatory cholesterol ester-loaded plaque. High-density lipoprotein-cholesterol (HDL-C) exhibits antiatherosclerotic effects by neutralizing the proinflammatory and pro-oxidant effects of monocytes via inhibiting the migration of macrophages and LDL oxidation in addition to the efflux of cholesterol from these cells; furthermore, HDL plays a role in suppressing the activation of monocytes and proliferation–differentiation of monocyte progenitor cells. Thus, accumulation of monocytes and reduction of HDL-C may participate in atherosclerosis and cardiovascular diseases (CVD); given that the relationship between the high number of monocytes and low HDL-C levels has been reported in inflammatory disorders, this review focused on understanding whether the monocyte-to-HDL ratio could be a convenient marker to predict atherosclerosis development and progression, hallmarks of CV events, instead of the individual monocyte count or HDL-C level.

In this review, we present the available evidence on the antitumor activity of demethoxycurcumin (DMC) in different types of tumors and discuss the molecular mechanisms underlying DMC’s antitumor activity.

(a) Infections are strongly linked to gastric cancer; (b) infections induce epigenetic alterations in gastric cancer; (c) antiviral treatments in combination with epigenetic therapeutic approaches along with standard chemotherapy are potentially superior to monotherapies in gastric cancer prevention and treatment.

Cytotoxicity and inflammation-associated toxic responses could be induced by bacterial lipopolysaccharides (LPS) in vitro and in vivo, respectively. The LPS exposure also caused the production of excess ROS, which might damage the cardiac precursor cells of developing embryos.

ΔFosB suppresses PPARγ agonist rosiglitazone-induced cellular lipid-droplets accumulation and protects cells from PPARγ activated-induced apoptosis. ΔFosB also increased MMP-9 gelatinolytic activity, and inhibition of MMP-9 suppressed the expression of Bcl-2 and increased intracellular calcium levels, and these effects were improved by overexpression of ΔFosB.

HIV-associated neurocognitive disorders are caused by HIV-1 infection of the CNS and include neurotoxic effects of the HIV-1 Tat protein. In addition to increasing the risk for becoming HIV infected, cocaine abuse enhances the neuropathogenic impacts of HIV-1. We employed microelectrode arrays to investigate the effects of Tat and cocaine on the hippocampal neuronal network. Tat and cocaine differentially disturbed neuronal activity within the hippocampal neuronal network via potentiation of inhibitory neurotransmission and the presence of astrocytes co-cultured with neuronal networks diminished the effects of Tat and cocaine. This suggests a role for astrocytes in stabilizing neuronal behavior pointing to a newly discovered pathway through which ionic homeostasis is maintained by neuron-glial crosstalk in the CNS.

Exogenous recombinant human IL-6 protein upregulated autophagy related genes and induced autophagy.

In mouse brain microvascular endothelial cells, paeoniflorin (PF) induces activation of ADAM17, which participates in the PF-induced epidermal growth factor receptor (EGFR) transactivation and TNFR1 shedding, contributing to the neuroprotective effects of PF.

In present study, we found the superiority of ES-MSC and ES-MSC EVs regarding immunomodulatory potential in comparison to those from BM- and AD-MSCs through the secretion of anti-inflammatory cytokines in vitro. ES-MSCs and ES-MSC EVs also offer anti-fibrotic, anti-necrotic and immunosuppressive effects to modulate TAA-induced cirrhotic livers after successfully engraftment in recipient damaged livers. To our knowledge, this is the preliminary evidence explaining hepatoprotective effects of ES-MSCs and their EVs in chronic liver disease model.

This study was conceived to evaluate the effects of three different diets on body composition, metabolic parameters, and serum oxidative status, and growth and differentiation of cardiomyoblast cell line H9c2 treated with H2O2 (H-H9c2). We demonstrated that the vegan diets induced a decrease in muscle mass index and lean body mass. Therefore our data showed that the omnivorous sera have major antioxidant and differentiation property compared to vegetarian and vegan sera. The results obtained in this study demonstrated that restrictive vegan diet could not prevent the onset of metabolic and cardiovascular diseases nor protect by oxidative damage.

HGF induces an antioxidant response in the pancreas. HGF displays protective effects in cerulein-induced acute pancreatitis.

DEC1 was ubiquitously expressed in most tissues in bovine and down-regulated in differentiating bovine satellite cells. Either CoCl2-simulated hypoxia or ectopic expression of DEC1 blocked bovine myoblast differentiation. Over-expression of bovine DEC1 inhibited MyoG promoter activity. The present study gives new insight into the mechanisms involved in myogenic differentiation.

(1) Amino acid metabolism and Krebs cycle were the most robust altered metabolism pathways after inflammatory cytokines treatments. (2) The altered amino acid metabolism and Krebs cycle metabolism might be important mechanisms of TNF-α induced mouse pancreatic β-cells dysfuction.

Our results suggest that maternal high folate intake confers the risk of LGA birth and accelerates the development of obesity in male offspring.

Myoblast fusion is pivotal for muscle development. We found that postphosphorylation isomerization of Smad3 by Pin1 is a crucial mechanism that governs myoblast fusion and maintains muscle mass.

Nucleotide-binding domain like receptor protein 3 (NLRP3) inflammasome plays an essential role in the pathogenesis of chronic intermittent hypoxia (CIH)-induced renal injury. NLRP3 inflammasome is required for microRNA-155 (miR-155) expression. miR-155 modulates NLRP3 and interleukin-1 cytokine signaling cascade through targeting FOXO3a to form a positive feedback loop, thus enhancing inflammatory cytokines production.

In the current study, we observed that cisplatin-resistant oral squamous cell carcinoma (OSCC) cells process lower levels of fission-state mitochondria and cell apoptosis than cisplatin-sensitive cells, and autophagy was activated in cisplatin-resistant OSCC cells. Overexpression of CerS6 increases cisplatin sensitivity via enhancement of mitochondrial fission and apoptosis and attenuation of cisplatin-induced autophagy in cisplatin-resistant OSCC cells.

Exercise, hypothalamic sphingosine-1-phosphate receptor 1, interleukin 6, and hypothalamus.

We suggest that PKC412 could be further studied as a promising anti–head and neck squamous cell carcinoma strategy, alone or in combination with C6 ceramide.

microRNA-16 is downregulated in oral squamous cell carcinoma (OSCC) tissues and cell lines, it functions as a tumor suppressor microRNAs to inhibit cell proliferation and induce apoptosis in OSCC through decreasing the oncogenes AKT3 and BCL2L2.

The objective of this study was to coculture osteogenic ADSCs (os-ADSCs) and endothelial ADSCs in three types of ratios and then compare the osteogenesis and angiogenesis effects, preliminarily exploring the best cocultured proportion that will be seeded in RADA16-I. We performed the study was because there is limited research illustrating the interactions between cocultured os-ADSCs and endothelial ADSCs.

Apoptosis was elevated in a time-dependent manner when myoblasts were subjected to cyclic mechanical stretch (CMS) for 12, 24, and 36 hr. Notably, caspase-12 cleavage at Asp94, induced by endoplasmic reticulum stress under stretch stimuli, is the key molecule in initiating the CMS-triggered apoptosis of myoblasts.

Collectively, the key findings obtained from the current study define the potential role of microRNA-186 as an inhibitor to Alzheimer’s disease development by downregulation of interleukin-2 through suppression of Janus kinase/signal transducers and activators of transcription signaling pathway.

The goal of this study was to study the relationships between maternally expressed gene 3 (MEG3), microRNA-7 (miR-7), and RASL11B, and explore their influence on the progression of clear cell renal cell carcinoma (CCRCC). MEG3 could up-regulate RASL11B to inhibit cell proliferation, invasion and migration; induce G0/G1 cell cycle arrest; and promote cell apoptosis by suppressing miR-7 in CCRCC.

Nucleolin is elevated in myocardium in DOX-treated mice, and nucleolin overexpression protects against DOX-induced cardiotoxicity. Cardiomyocyte-specific nucleolin transgenic mice are resistant to DOX-induced injury. MicroRNA-21 mediated nucleolin protective effect.

Vitamin A significance in human male gamete and in the physiopathology of varicocele. Vitamin A action on metabolism and antioxidant defense systems in human sperm SOD1, SOD2, and GSTO2 expression and activities were significantly lower in varicocele with respect to healthy sperm.

Our results showed, for the first time, that Zerumbone, as a natural substance, reduced the cell viability of colorectal cancer cell lines. Zerumbone is able to reverse epithelial-mesenchymal transition (EMT) to mesenchymal-epithelial transition (MET) through the upregulation of miR-200c. In addition, Zerumbone decreased β-catenin in the WNT signaling pathway, which led to inhibiting the transcription of genes involved in EMT and cancer stem cells.

Our study defines Notch signaling regulator RUMI as a novel strong independent factor for poor prognosis and survival in non–small-cell lung cancer (NSCLC), and further evaluates its functional contribution and potential therapeutic value as novel target in NSCLC.

In this study, we investigate the impact of the circadian clock on UVB responses in human keratinocytes. We found that the two clock proteins brain and muscle ARNT-like 1 (BMAL1) and circadian locomotor output cycles kaput (CLOCK) regulate UVB induced apoptosis in both immortal and primary human keratinocytes, but likely through different molecular mechanisms.

PMLIV overexpression promotes cancer-associated epithelial-mesenchymal transition by activating transforming growth factor-β signaling, which leads to a more aggressive cancer cell phenotype and increased cell migration.

Integrin α2 (ITGA2) expression was significantly upregulated in 134 de novo acute myeloid leukemia (AML) patients compared with 33 controls (p = 0.007). Furthermore, the overall survival in high ITGA2 expression patients was significantly shorter than low ITGA2 expression patients throughout AML cohort, non–acute promyelocytic leukemia (APL), and cytogenetic normal-AML (p = 0.001, 0.002, and 0.044, respectively). Multivariate analysis confirmed that ITGA2 overexpression served as an independent prognostic factor in both whole-cohort AML patients (p = 0.018) and non-APL AML patients (p = 0.021).

Treatment of cells with ultraviolet B (UVB) irradiation results in increased reactive oxygen species (ROS) generation and decreased Nrf2 levels by a mechanism involving lipoxygenase stimulation and TRPV1 channel activation. Increased ROS results in mitochondrial dysfunction and apoptosis. DPMQ inhibits the TRPV1 channel and scavenges ROS, and hence protects cells against UVB irradiation–induced cytotoxicity, whereas disulfiram induces copper influx and increases ROS generation, and therefore causes apoptosis.

HOMEOBOX A11 antisense RNA could promote renal cancer cells growth and invasion by modulating miR-146b-5p–MMP16 axis

Upregulated P2Y12 in satellite glial cells (SGCs) of dorsal root ganglia (DRG) was involved in diabetic neuropathic pain. Targeting the P2Y12 receptor by short hairpin RNA decreased the upregulated expression of the P2Y12 receptor in DRG SGCs and relieved mechanical and thermal hyperalgesia in type 2 DM rats.

Autophagosome formation, the LC3 2/LC3 1 ratio, autophagy-related gene expression, and the autophagic flux are increased in chronic obstructive pulmonary disease (COPD) muscle cells. Treatment of COPD myotubes with an antioxidant molecule decreased the reactive oxygen species (ROS) concentration, ROS-induced protein carbonylation, the LC3 2/LC3 1 ratio, the expression of SQSTM1 and BNIP3 and increased the COPD myotube diameter. The oxidative stress level contributes to the regulation of autophagy, which is involved in the atrophy of COPD myotubes in vitro.

Our findings showed that in wild type (WT) animals, FGF-2 is expressed in germ cells of the seminiferous epithelium, in epithelial cells of the epididymis, and in the flagellum and acrosomal region of epididymal sperm. In the FGF-2 knockout (KO) mice, we found alterations in spermatogenesis kinetics and enhanced daily sperm production compared to the WT males. A significant increase in sperm concentration and in sperm head abnormalities, as well as alterations in other sperm parameters (reduced tyrosine phosphorylation and increased acrosomal loss) were observed in FGF-2 KO animals. Overall, the results suggest that FGF-2 exerts a role in mammalian spermatogenesis, and that the lack of FGF-2 leads to dysregulated sperm production and altered sperm morphology and function.

Pharmacological and nonpharmacological adjuvant strategies in chemotherapy treatment are presented. Decreased muscle performance caused by chemotherapeutic treatment can be recovered with aerobic exercise. Aerobic training is able to bring important benefits to counteract doxorubicin metabolic effects in the whole body and skeletal muscle.

The findings from this study indicate that a combination of ammonia and ethanol incubation of C2C12 myotubes exacerbated muscle atrophy and dysregulation of anabolic and catabolic signalling pathways associated with either component individually. Our findings provide novel insight into the interactions between hyperammonaemia and hyperethanolaemia in relation to their regulation of muscle catabolism in vitro.

CDP suppresses RANKL-induced ROS production, as well as NFATc1 and MAPK activation, hence inhibits osteoclastogenesis.

A rise in [Ca²⁺]_i occurs after 1 min of incubation under capacitating conditions. Intracellular [Ca²⁺] was measured by flow cytometry in sperm collected after swim-out (0 min) and incubated under noncapacitating and capacitating conditions for different time periods (1–90 min). Histograms of normalized frequency versus Fluo-4 AM fluorescence of non-propidium-iodide stained sperm are presented.

Our results primarily provided insight into the molecular mechanisms of low shear stress-induced degradation of glycocalyx and discovered the existence of p47phox/hyaluronidase2 (Hyal2) complex. The finding will likely increase their utility as therapeutic targets.

This study was carried in the Malwa region of Punjab where breast cancer was widely feared, and the levels of pro- and anti-inflammatory cytokines were analysed in female breast cancer patients. There was a significant difference in the serum levels of interleukin (IL)-6 and IL-17a between patients and controls, and the elevated levels of these two cytokines associated significantly with poor outcome in breast cancer patients and, therefore, can be used as prognostic markers.

Bone destruction or osteolysis, marked by excessive osteoclastic bone resorption, is a very common medical condition. Identification of agents that can effectively suppress excessive osteoclast formation and function is crucial for prevention and treatment of osteolytic conditions, such as osteoporosis. In the present paper, we report that RepSox inhibits osteoclast formation in vitro and in vivo, suggesting that it is potentially valuable in the treatment of osteoclast-related diseases.

The controlled differentiation of mesenchymal stem cells (MSCs) is one of the key aspects of effective clinical transplantation. Growing evidence suggests that the cell cycle plays an important role in regulating differentiation, while p130 and E2F4 are key to cell cycle checkpoints. Our data suggest that cell cycle regulation may be involved in p130/E2F4-mediated changes in the multipotential abilities of bone-marrow-derived mouse MSCs (mMSCs).

Our study indicated that protein phosphatase 2A was an essential regulator in pulmonary artery smooth muscle cells (PASMCs) and provided evidence supporting the potential of berberine in inhibiting the migration and proliferation of PASMCs.

In summary, we provided detailed protocols for bronchus isolation from piglets and in vitro expansion of primary PBECs. Furthermore, we established the immortalized hTERT-PBEC line, which retains the morphological and functional features of primary PBECs. The establishment of immortal hTERT-PBECs is of great importance as an in vitro model for pathogenicity studies of porcine respiratory pathogens.

1 We have identified key candidate genes and pathways that might play crucial roles in regulating osteogenic differentiation of ASCs 2 FOXO1 might be a positive regulator of ASC osteogenic differentiation

Our data indicate that hydrogen sulfide (H₂S) is a novel regulator of Forkhead box protein O in cardiac cells and provide evidence supporting the potential of H₂S in inhibiting the progression of diabetic cardiomyopathy.

We here demonstrated that Smoothened (SMO) silencing resulted in a reduction of CAXII expression at messenger RNA (mRNA) and protein level in breast cancer (BC) cell lines. This led to a decrease in cell migration, which was restored when cells were treated with a SMO agonist. The reduction was confirmed also within hypoxic and inflammatory microenvironment, typical of BC, indicating a key role of the Hedgehog (Hh) pathway in controlling CAXII expression. Our results indicate that the Hh pathway controls BC cell migration and cell invasion through CAXII, with important implications in identifying novel therapeutic targets.