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A number of conditions and factors can cause the transformation of normal cells in the body into malignant tissue by changing the normal functions of a wide range of regulatory, apoptotic, and signal transduction pathways. Despite the current deficiency in fully understanding the mechanism of cancer action accurately and clearly, numerous genes and proteins that are causally involved in the initiation, progression, and metastasis of cancer have been identified. But due to the lack of space and the abundance of details on this complex topic, we have emphasized here more recent advances in our understanding of the principles implied tumor cell transformation, development, invasion, angiogenesis, and metastasis. Inhibition of angiogenesis is a significant strategy for the treatment of various solid tumors, that essentially depend on cutting or at least limiting the supply of blood to micro-regions of tumors, leading to pan-hypoxia and pan-necrosis inside solid tumor tissues. Researchers have continued to enhance the efficiency of anti-angiogenic drugs over the past two decades, to identify their potential in the drug interaction, and to discover reasonable interpretations for possible resistance to treatment. In this review, we have discussed an overview of cancer history and recent methods use in cancer therapy, focusing on anti-angiogenic inhibitors targeting angiogenesis formation. Further, this review has explained the molecular mechanism of action of these anti-angiogenic inhibitors in various tumor types and their limitations use. In addition, we described the synergistic mechanisms of immunotherapy and anti-angiogenic therapy and summarizes current clinical trials of these combinations. Many phase III trials found that combining immunotherapy and anti-angiogenic therapy improved survival. Therefore, targeting the source supply of cancer cells to grow and spread with new anti-angiogenic agents in combination with different conventional therapy is a novel method to reduce cancer progression. The aim of this paper is to overview the varying concepts of cancer focusing on mechanisms involved in tumor angiogenesis and provide an overview of the recent trends in anti-angiogenic strategies for cancer therapy. [ABSTRACT FROM AUTHOR]

Thermoplastic polyurethane (TPU) membrane has super physical-mechanical properties and biocompatibility, but the surface is inert and lack of active groups which limit its application in cell culture. Silk sericin (SS) can improve cell adhesion, proliferation, growth and metabolism. In this paper, SS was grafted onto the surface of TPU membrane by -NH2 bridge to build a high efficiency cell culture membrane. The FT-IR spectrum results indicated SS was grafted by chemical bond. According to the SEM and AFM results, we found that the grafting of SS reduced the water contact angle by 43.31% and increased the surface roughness by about four times. When TPU-SS was used for HepG2 cell culture, the cell adhesion rate of TPU-SS was significantly higher than that of the general TCPS cell culture plate, and the cell proliferation rate was close to that of TCPS. FDA/EB staining showed that HepG2 cells remained a better cellular growth behavior. HepG2 cells had higher cell vitality including the albumin secretion and the intracellular total protein synthesis. Grafting SS maintained the stability of cell and significantly decreased the cytotoxicity by decreased LDH release. In conclusion, SS grafting is beneficial to cell culture in vitro, and provides a key material for bioartificial liver culture system. [ABSTRACT FROM AUTHOR]

Nanoarchitectonics has emerged as a post-nanotechnology concept. As one of the applications of nanoarchitectonics, this review paper discusses the control of stem cell fate and function as an important issue. For hybrid nanoarchitectonics involving living cells, it is crucial to understand how biomaterials and their nanoarchitected structures regulate behaviours and fates of stem cells. In this review, biomaterials for the regulation of stem cell fate are firstly discussed. Besides multipotent differentiation, immunomodulation is an important biological function of mesenchymal stem cells (MSCs). MSCs can modulate immune cells to treat multiple immune- and inflammation-mediated diseases. The following sections summarize the recent advances of the regulation of the immunomodulatory functions of MSCs by biophysical signals. In the third part, we discussed how biomaterials direct the self-organization of pluripotent stem cells for organoid. Bioactive materials are constructed which mimic the biophysical cues of in vivo microenvironment such as elasticity, viscoelasticity, biodegradation, fluidity, topography, cell geometry, and etc. Stem cells interpret these biophysical cues by different cytoskeletal forces. The different cytoskeletal forces lead to substantial transcription and protein expression, which affect stem cell fate and function. Regulations of stem cells could not be utilized only for tissue repair and regenerative medicine but also potentially for production of advanced materials systems. Materials nanoarchitectonics with integration of stem cells and related biological substances would have high impacts in science and technology of advanced materials. [ABSTRACT FROM AUTHOR]

Exosomes are a class of extracellular vesicles with a diameter of 50–100 nm secreted by various cells. They are generated through complex intracellular production mechanisms before being secreted to the extracellular environment. Due to their inclusion of proteins, lipids, and nucleic acids, exosomes play an important role in intercellular communication. Pancreatic β-cells play an irreplaceable role in the body's glucose metabolism. Their dysfunction is one of the causes of diabetes. Exosomes of various cells regulate the function of β-cells by regulating autoimmunity, delivering non-coding RNAs, or directly regulating intracellular signal pathways. This communication between β-cells and other cells plays an important role in the pathogenesis and development of diabetes, and has potential for clinical application. This paper reviews the biological sources and functions of exosomes, as well as intercellular crosstalk between β-cells and other cells that is involved in β-cell failure and regeneration. [ABSTRACT FROM AUTHOR]

In the human body, maintaining the core body temperature (CBT) is vital to ensure proper cellular and body functions. The temperature of 37°C (98°F) is the well-established baseline for CBT, but significant deviations to under 35°C (95°F) or over 40°C (104°F) can result in several health complications. If unnoticed in spaceflight, astronauts CBT could reach dangerously high levels when doing physically challenging tasks such as spacewalking or exercise. Therefore, a real-time multi-physiological parameter sensing system is needed to noninvasively monitor the status of crew members in space. The purpose of this paper is to test a novel temperature sensor developed by integrating thin sheets of polyvinylidene fluoride (PVDF), a temperature dependent dielectric material, into the sensor system designed as a substrate. This substrate interacts with the electromagnetic field created by the spiral sensor to result in a quantitative temperature monitoring sensor with a resolution of 1°C. [ABSTRACT FROM AUTHOR]

Carbon nanomaterials are an inventive class of materials with wide applications in state-of-the-art bioimaging and therapeutics. They allow a broad range of tunable and integrated advantages of structural flexibility, chemical and thermal stability, upright electrical conductivity, and the option of scale-up and mass production. In the context of nanomedicine, carbon nanomaterials have been used extensively to mitigate the serious side effects of conventional chemotherapy and also to enable early cancer diagnostics, given their wide range of tunable properties. A class of carbon nanomaterials, called carbon dots (CDs) are small carbon-based nanoparticles and have been a valued discovery due to their photoluminescence, low photobleaching, and high surface area to mass ratio. The process of producing these CDs had so far been a high energy demanding process involving wet chemistry for purification. A one-step tunable production of luminescent CDs from fuel rich combustion reactors was recently presented by our group. In this paper, we explore the effects of these yellow luminescent combustion-generated CDs in MCF7 adenocarcinoma and MCF10a normal breast epithelial cells. We observed that these CDs, also at nontoxic doses, can affect basic cellular functions, such as cell cycle and proliferation; induce substantial changes on the physical parameters of the plasma membrane; and change the overall appearance of a cell in terms of morphology. [ABSTRACT FROM AUTHOR]

Nanofibrous biomaterials, because of their structural similarity to the extracellular matrix, can be employed as a scaffold in tissue engineering. The use of biopolymers to nanofibers fabrication attracts a great deal of attention. However, sometimes these nanofibers do not support specific cell behaviors. To address this drawback, surface modification of these structures has been actively investigated. Just a while ago, nanofibrous scaffolds have been modified employing various techniques to provide an appropriate microenvironment for protecting cell functions. Modification of bulk or surfaces of the nanofibrous scaffolds via different methods can promote cell adhesion, growth, proliferation, migration, and differentiation. In this paper, we are going to discuss the different and new approaches to surface modification of polymeric nanofibers that can influence scaffolds characteristics. Surface modification of nanofibrous scaffolds can improve physical & chemical properties especially cellular behaviors. [ABSTRACT FROM AUTHOR]

A protein complex is a collection of two or more associated proteins that interact with each other in a stable long-term interaction. Protein complexes have essential roles in regulatory processes, cellular functions and signaling cascades. This paper examines how well-known collections of protein complexes are supported in protein–protein interaction (PPI) networks, i.e. whether they form connected subnetworks in a particular PPI network. For that purpose, we apply a variable neighbourhood search (VNS) metaheuristic algorithm for adding the minimum number of interactions in order to support protein complexes. Experimental results obtained on several PPI networks (BioGRID, WI-PHI and String) and four protein complex standards (MIPS, TAP06, SGD and CYC2008) show that considered networks do not include enough PPIs to support all complexes from complex standards. Deeper analysis indicates that there exists common PPIs which are probably missing in the considered networks. These findings can be useful for further biological interpretation and developing of PPI prediction models. [ABSTRACT FROM AUTHOR]

Tanshinone IIa (TSA) has been approved to treat cardiovascular diseases by the China State Food and Drug Administration. TSA has exhibited a variety of pharmacological effects, including vasodilator, antioxidant, anti-inflammatory, and anti-tumor properties. Endothelial cells play an important physiological role in vascular homeostasis and control inflammation, coagulation, and thrombosis. Accumulating studies have shown that TSA can improve endothelial function through various pathways. The PubMed database was reviewed for relevant papers published up to 2020. This review summarizes the current clinical and pharmaceutical studies to provide a systemic overview of the pharmacological and therapeutic effects of TSA on endothelial cells. TSA is a representative monomeric compound extracted from Danshen and it exhibits significant pharmacological and therapeutic properties to improve endothelial cell function, including alleviating oxidative stress, attenuating inflammatory injury, modulating ion channels and so on. TSA represents a spectrum of agents that are extracted from plants and can restore the endothelial function to establish the beneficial and harmless molecular therapeutics. This also suggests the possible detection of endothelial cells for very early diagnosis of diseases. In future, precise therapeutic methods will be developed to repair endothelial cells injury and recover endothelial dysfunction. [ABSTRACT FROM AUTHOR]

Objectives: The discovery of alternative and well-tolerated anti-arthritic drugs, especially from natural products, is becoming an area of active research. Pedunculoside (PE) is a novel triterpene saponin extracted from the dried bark of Ilex rotunda Thunb. Limited published papers have reported its pharmacological properties, including anti-inflammatory, anti-myocardial ischaemia, anti-liver injury, and hypocholesterolaemic activities. However, the effect of PE on rheumatoid arthritis (RA) remains unknown. Here, we investigated the anti-arthritic effect of PE in both in vitro and in vivo models. Method: The inhibitory effects of PE on proliferation, migration, and production of inflammatory mediators in primary fibroblast-like synoviocytes (FLSs) were examined by a 5-ethynyl-2'-deoxyuridine incorporation assay, wound-healing assay, and real-time polymerase chain reaction, respectively. Cellular signalling mechanisms were analysed by Western blot. The in vivo studies were performed using a collagen-induced arthritis (CIA) rat model. Multiple methods, including arthritis scoring, enzyme-linked immunoassay, radiography, and histopathological assessment, were used to evaluate the therapeutic effects of PE on CIA rats. Results: The in vitro studies revealed that PE significantly inhibited proliferation and migration of FLSs. PE also decreased the production of pro-inflammatory cytokines, including interleukin-1β (IL-1β), IL-6, IL-8, and tumour necrosis factor-α (TNF-α). Western blot results suggested that PE suppressed TNF-α-stimulated activation of p38 and extracellular signal-regulated kinase. The in vivo studies showed that PE treatment significantly inhibited synovial inflammation and bone destruction in CIA rats. Conclusion: These results demonstrate that PE exerts an inhibitory role in FLSs and CIA rats, and therefore may have therapeutic value for the treatment of RA. [ABSTRACT FROM AUTHOR]

There are growing interests in the health benefits associated with consumption of fruits and vegetables, especially for the prevention of cancer, cardiovascular, or other chronic diseases. Epidemiological studies and clinical trials suggest that these health benefits are strongly associated with phytochemicals found in fruits and vegetables. Ursolic acid is a naturally synthesized pentacyclic triterpenoid, widely distributed in different fruits and vegetables. Current research suggested that ursolic acid and its derivatives exhibited anticancer activity, anti-inflammatory effects, and induction of apoptosis in several human cancer cells. In particular, ursolic acid inhibited breast cancer proliferation by inducing cell G1/G2 arrest and regulating the expression of key proteins in signal transduction pathways. In addition, ursolic acid induced apoptosis in human breast cancer cells through intrinsic and extrinsic apoptotic pathways. Ursolic acid was also determined to scavenge free radicals and have potent anti-inflammation activity. The purpose of this paper is to review recent literature on anticancer activity of ursolic acid and focus on its mechanisms of action. [ABSTRACT FROM AUTHOR]

Introduction: Pancreatic ductal adenocarcinoma (PDAC) is projected to be the second leading cause of cancer related mortality in the United States in 2030, with a 5-year overall survival of less than 10% despite decades of extensive research. Pancreatic cancer is marked by the accumulation of complex molecular changes, complex tumor-stroma interaction, and an immunosuppressive tumor microenvironment. PDAC has proven to be resistant to many cytotoxic, targeted and immunologic treatment approaches. Areas covered: In this paper, we review the major areas of research in PDAC, with highlights on the challenges and areas of opportunity for personalized treatment approaches. Expert commentary: The focus of research in pancreatic cancer has moved away from developing conventional cytotoxic combinations. The marked advances in understanding the molecular biology of this disease especially in the areas of the microenvironment, metabolism, and DNA repair have opened new opportunities for developing novel treatment strategies. Improved understanding of molecular abnormalities allows the development of personalized treatment approaches. [ABSTRACT FROM AUTHOR]

Although individuals with obesity and Type 2 diabetes are insulin resistant, pancreatic b-cell failure is the core defect that distinguishes individuals who eventually develop diabetes. This process is known to occur well before the onset of hyperglycemia. Although clinical trial data support the effectiveness of intensive lifestyle modification in delaying the onset of diabetes in obese subjects, less is known about the effects of, and mechanisms underlying, bariatric surgery, particularly gastric bypass surgery, on diabetes. The paper under evaluation clarifies the role of both lifestyle intervention and gastric bypass surgery on pancreatic b-cell function and raises questions regarding the role of weight loss versus incretin-related mechanisms on recovery of b-cell failure. INSET: Key issues. [ABSTRACT FROM AUTHOR]

Chaperonin containing TCP1 subunit 6A (CCT6A) was recently discovered to be involved in cancer pathogenesis and stemness; however, its role in oral squamous cell carcinoma (OSCC) has not been reported. The current study aimed to investigate the impact of CCT6A on OSCC cell malignant behaviors and stemness and to explore its potentially interreacted pathways. SCC-15 and HSC-3 cells were transfected with the plasmid loading control overexpression, CCT6A overexpression, control knockout, or CCT6A knockout. Wnt4 overexpression or Notch1 overexpression plasmids were transfected into CCT6A-knockout SCC-15 cells. Cell proliferation, apoptosis, invasion, stemness, Notch, and Wnt pathways were detected in both cell lines, whereas RNA sequencing was only performed in SCC-15 cells. CCT6A was upregulated in five OSCC cell lines, including SCC-15, HSC-3, SAT, SCC-9, and KON, compared to that in the control cell line. In SCC-15 and HSC-3 cells, CCT6A overexpression increased cell proliferation, invasion, sphere formation, CD133, and Sox2 expression, but decreased cell apoptosis; on the contrary, CCT6A knockout exhibited an opposite effect on the above indexes. RNA-sequencing data revealed that the Wnt and Notch pathways were involved in the CCT6A'effect on SCC-15 cell functions. CCT6A positively regulates the Wnt and Notch pathways in SCC-15 and HSC-3 cells. Importantly, it was shown that activation of the Wnt or Notch pathways attenuated the effect of CCT6A knockout on SCC-15 cell survival, invasion, and stemness. CCT6A may promote OSCC malignant behavior and stemness by activating the Wnt and Notch pathways. [ABSTRACT FROM AUTHOR]

In the classical "mind-body" wording, "body" is usually associated with the "mass aspect" of living entities and "mind" with the "immaterial" one. Thoughts, consciousness and soul are classified as immaterial. A most challenging question emerges: Can something that is truly immaterial, thus that in the wording of physics has no mass, exist at all? Many will answer: "No, impossible." My answer is that it is very well possible, that no esoteric mechanisms need to be invoked, but that this possibility is inherent to 2 well established but undervalued physiological mechanisms. The first one is electrical in nature. In analogy with "genome," "proteome" etc. "electrome" (a novel term) stands for the totality of all ionic currents of any living entity, from the cellular to the organismal level. Cellular electricity is truly vital. Death of any cell ensues at the very moment that it irreversibly (excluding regeneration) loses its ability to realize its electrical dimension. The second mechanism involves communication activity that is invariably executed by sender-receiver entities that incessantly handle information. Information itself is immaterial (D no mass). Both mechanisms are instrumental to the functioning of all cells, in particular to their still enigmatic cognitive memory system. Ionic/electrical currents associated with the cytoskeleton likely play a key role but have been largely overlooked. This paper aims at initiating a discussion platform from which students with different backgrounds but all interested in the immaterial dimension of life could engage in elaborating an integrating vocabulary and in initiating experimental approaches. [ABSTRACT FROM AUTHOR]

This paper serves as an overview of various aspects of thermal processing. Heat processing of foods has a long history and is still one of the most important preservation methods. To guarantee microbiological safety and stability, large safety margins are often applied in traditional heat processes. Because of the need for more fresh like foods, there is a need for milder preservation methods without compromising on safety and stability. The review deals with heat resistance data and mathematical models that describe heat inactivation. The effects of food composition are not yet fully clear and more knowledge of the cell physiology of the target microorganism could be of help in predicting the effects of food constituents. Finally, special attention has been paid to biological time temperature indicators to enable proper process calculations. [ABSTRACT FROM AUTHOR]

Most animal cells are surrounded by a thin layer of actin meshwork below their membrane, commonly known as the actin cortex (or cortical membrane). An increasing number of studies have highlighted the role of this structure in many cell functions including contraction and locomotion, but modelling has been limited by the fact that the membrane thickness (about 1 μm) is usually much smaller than the typical size of a cell (10-100 μm). To overcome theoretical and numerical issues resulting from this observation, we introduce in this paper a continuum formulation, based on surface elasticity, that views the cortex as an infinitely thin membrane that can resists tangential deformation. To accurately model the large deformations of cells, we introduced equilibrium equations and constitutive relations within the Eulerian viewpoint such that all quantities (stress, rate of deformation) lie in the current configuration. A solution procedure is then introduced based on a coupled extended finite element approach that enables a continuum solution to the boundary value problem in which discontinuities in both strain and displacement (due to cortical elasticity) are easily handled. We validate the approach by studying the effect of cortical elasticity on the deformation of a cell adhering on a stiff substrate and undergoing internal contraction. Results show very good prediction of the proposed method when compared with experimental observations and analytical solutions for simple cases. In particular, the model can be used to study how cell properties such as stiffness and contraction of both cytoskeleton and cortical membrane lead to variations in cell's surface curvature. These numerical results show that the proposed method can be used to gain critical insights into how the cortical membrane affects cell deformation and how it may be used as a means to determine a cell's mechanical properties by measuring curvatures of its membrane. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the effects of the topical application of nondiluted autologous serum on epithelial healing as an adjuvant therapy in rabbit corneal alkali wounds. Methods: Central corneal alkali wounds were produced on the right eye of 16 rabbits, by a 60-second application of a 6-mm round filter paper soaked in 1 N sodium hydroxide (NaOH). One group of rabbits (n=8) was treated with non-diluted autologous serum, the other control group (n=8) was treated with physiologic saline, topically 4 times a day. The epithelial healing of the wounds was followed on a slit lamp with and without fluorescein staining daily for 1 week. On day 7, both corneas of each rabbit were excised and assessed histopathologically. Results: A significant increase in the epithelial healing rate was observed in the autologous serum–treated corneas compared with the controls. Epithelial hyperplasia was noticed in specimens with thickened surface cells with multilayers, revealing disorganization in both groups. The autologous serum–treated epithelium showed a relatively well-organized appearance. Conclusion: Nondiluted autologous serum eye drops could be used as an adjuvant therapy for promoting the epithelial healing process during the repair stage of corneal alkali wounds. [ABSTRACT FROM AUTHOR]

This paper describes fabrication schemes to create multidimensional polymeric platforms to study cell function. A key feature of these constructs is the replication of in vivo geometry and dimensional size scales that will aid in the understanding of fundamental cell-environment interactions. Advantages of these microtextured membranes include the high degree of reproducibility, optical clarity, and the ability to create multiple features on the micron and sub-micron size scale. We have demonstrated the creation of controlled microscale features on hydrogels as well as biodegradable materials such as poly(lactic-glycolic acid). These microtopographies selectively degrade under physiological conditions. Because of the flexibility of substrate material and the ease of creating micron size structures, this technique can be applied to a multitude of physiological and biological systems. [ABSTRACT FROM AUTHOR]

A novel method for predicting effective stiffnesses of composite plates with in-plane periodicity is proposed according to two-scale strain energy equivalence. The macroscale energy is reached with the Reissner-Mindlin plate theory, while the microscale energy is obtained through the newly constructed displacement functions of a unit cell within the framework of the three-dimensional elasticity theory. The new displacement functions consist of homogenized displacements, two decoupled expansion terms, and a higher-order perturbed displacement term. The elaborate finite element formulations are presented for realizing the present method in Comsol Multiphysics. Several numerical experiments demonstrate the effectiveness of the new stiffness prediction method. [ABSTRACT FROM AUTHOR]

The moisture content of wood is changed during manufacturing processes, such as drying and impregnation. Understanding the water transport in wood is helpful for optimizing the manufacturing technology and improving the durability of wood products. Herein, the one-side imbibition tests of Chinese fir and poplar were carried out via direct contact with a water-saturated sponge. Imbibition amounts and orthotropic kinetics were evaluated by X-ray densitometry, where wood exhibited non-uniform and directional behaviors for water imbibition and there were variations in behavior between Chinese fir and poplar. More water uptake and faster migration were observed for poplar, while water preferentially accumulated at the wetting front for Chinese fir. The effective imbibition height of poplar was significantly higher than Chinese fir, regardless of orientation direction. Within the growth rings, Chinese fir showed heterogeneous water uptake, and faster water migration in latewood was observed. Imbibition height in a single fiber was simulated as a function of cell wall ratio, and the influences of anatomical factors on water movement were explored. These simulation assessments were consistent with the results of the one-side imbibition tests. These findings help to explain the water transport mechanism at the mesoscale and interactions between wood and water. [ABSTRACT FROM AUTHOR]

Targeted monoclonal antibody therapy has emerged as a powerful therapeutic strategy for cancer. However, only a minority of patients have durable responses and the development of resistance remains a major clinical obstacle. Antibody-dependent cell-mediated cytotoxicity (ADCC) represents a crucial therapeutic mechanism of action; however, few studies have explored ADCC resistance. Using multiple in vitro models of ADCC selection pressure, we have uncovered both shared and distinct resistance mechanisms. Persistent ADCC selection pressure yielded ADCC-resistant cells that are characterized by a loss of NK cell conjugation and this shared resistance phenotype is associated with cell-line dependent modulation of cell surface proteins that contribute to immune synapse formation and NK cell function. We employed single-cell RNA sequencing and proteomic screens to interrogate molecular mechanisms of resistance. We demonstrate that ADCC resistance involves upregulation of interferon/STAT1 and DNA damage response signaling as well as activation of the immunoproteasome. Here, we identify pathways that modulate ADCC sensitivity and report strategies to enhance ADCC-mediated elimination of cancer cells. ADCC resistance could not be reversed with combinatorial treatment approaches. Hence, our findings indicate that tumor cells utilize multiple strategies to inhibit NK cell mediated-ADCC. Future research and development of NK cell-based immunotherapies must incorporate plans to address or potentially prevent the induction of resistance. [ABSTRACT FROM AUTHOR]

Circular RNA (circRNA) forms closed loops via back-splicing in precursor mRNA, resisting exonuclease degradation. In higher eukaryotes, protein-coding genes create circRNAs through exon back-splicing. Unlike mRNAs, circRNAs possess unique production and structural traits, bestowing distinct cellular functions and biomedical potential. In this review, we explore the pivotal roles of viral circRNAs and associated RNA in various biological processes. Analysing the interactions between viral circRNA and host cellular machinery yields fresh insights into antiviral immunity, catalysing the development of potential therapeutics. Furthermore, circRNAs serve as enduring biomarkers in viral diseases due to their stable translation within specific tissues. Additionally, a deeper understanding of translational circRNA could expedite the establishment of circRNA-based expression platforms, meeting the rising demand for broad-spectrum viral vaccines. We also highlight the applications of circular RNA in biomarker studies as well as circRNA-based therapeutics. Prospectively, we expect a technological revolution in combating viral infections using circRNA. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is one of the most common cancers and has continued to increase in incidence worldwide. Moreover, the involvement of microRNAs (miRs) has been reported in the development and progression of HCC. Here, we investigated the role of miR-206 in HCC growth and metastasis. HCC-related microarray datasets were harvested to screen differentially expressed miRNAs in HCC samples followed by prediction of downstream target genes. The dual-luciferase reporter assay verified the target-binding relationship between miR-206 and CREB5. The human HCC cell line MHCC97-H was cultured in vitro and transfected with miR-206 mimic/inhibitor or sh-/oe-CREB5 for analyzing MHCC97-H cell biological functions. The orthotopic xenograft model of HCC mice was constructed to observe the tumorigenic ability of HCC cells in vivo. Bioinformatics analysis found that miR-206 may be involved in HCC growth and metastasis by targeting CREB5 and regulating PI3K/AKT signaling pathway. In vivo animal experiments found that CREB5 was significantly overexpressed in mouse HCC tissues. In HCC cells, miR-206 can target down-regulate the expression of CREB5, thereby inhibiting the activation of PI3K/AKT signaling pathway. Furthermore, in vitro cell experiments confirmed that overexpression of miR-206 could inhibit the PI3K/AKT signaling pathway by down-regulating CREB5 expression, thereby inhibiting the proliferation, migration and invasion of HCC cells. In conclusion, our results revealed that miR-206 could down-regulate the expression of CREB5 and inhibit the activation of PI3K/AKT signaling pathway, thereby preventing HCC growth and metastasis. Abbreviations: HCC: hepatocellular carcinoma; HBV or HCV: hepatitis B or C virus; miRNAs: microRNAs; CREB: cAMP response element-binding protein; CRE: cAMP response elements [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (T2DM) is associated with increased atherogenicity and inflammatory responses, which may be related to high mobility group box 1 (HMGB1) and Dickkopf-related protein 1 (DKK1). The role of HMGB1 and DKK1 in T2DM is examined in association with lipid and insulin profiles. Serum HMGB1 and DKK1 were measured in T2DM with and without hypertension and compared with controls. The results showed that HMGB1 and DKK1 are higher in T2DM irrespective of hypertension. A large part of the variance in the β-cell index and glucose toxicity was explained by the combined effects of HMGB1 and DKK1. In conclusion, both HMGB1 and DKK1 may contribute to increased atherogenicity in T2DM. Moreover, both biomarkers may cause more deficits in β-cell function and increase glucose toxicity leading to the development of more inflammation and diabetic complications. HMGB1 and the Wnt pathways are other drug targets in treating T2DM. [ABSTRACT FROM AUTHOR]

We aimed to determine the effects of exercise training on the function of vascular smooth muscle cells. PubMed and Web of Science about the effects of exercise training on vascular smooth muscle cells were searched up to August 2020. The effect sizes were estimated in terms of the standardized mean difference. The number of studies included was thirty-five overall. Exercise training had positive effects on vascular smooth muscle cells function in participants older than 40. Effect sizes for HIGH intensity and MIX were positive but small, and also when training duration was longer than 12 weeks. We concluded that vascular smooth muscle cells response can be promoted by exercise training. Vigorous aerobic exercise and mixture training modality were the best ways to promote the dilation response of vascular smooth muscle cells. Additionally, the significant improvement induced by exercise training only occurred when training lasted for longer than 12 weeks. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) are small, non-coding RNAs, able to regulate cellular functions by induction of mRNA degradation and post-transcriptional repression of gene expression. Platelets are the major source of circulating miRNAs, with significant regulatory potential on cardiovascular pathophysiology and other diseases. MiRNAs have been shown to modify the expression of platelet proteins, which influence the platelets reactivity. Circulating miRNAs can be determined from plasma, serum, or whole blood, and they can be used as diagnostic and prognostic biomarkers as well as therapeutic targets including cardiovascular diseases (CVDs). Herein, we present original results from bioinformatic analyses, which identified top 22 platelet-related miRNAs including hsa-miR-320a, hsa-miR-16-5p, hsa-miR-106a-5p, hsa-miR-320b, hsa-miR-15a-5p, hsa-miR-15b-5p, hsa-miR-195-5p, hsa-miR-92a-3p as widely involved in platelet reactivity and associated diseases, including CVDs, Alzheimer's and cerebrovascular diseases, cancer and hypertension. Analysis focused on the identification of the highly regulatory targets shared between those miRNAs identified 43 of them. Best ranked genes associated with overall platelet activity and most susceptible for noncoding regulation were PTEN, PIK3R1, CREB1, APP, and MAPK1. Top targets also strongly associated with CVDs were VEGFA, IGF1, ESR1, BDNF, and PPARG. Top targets associated with other platelet-related diseases including cancer identified in our study were TP53, KRAS, and CCND1. The most affected pathways by top miRNAs and top targets included diseases of signal transduction by Growth Factor Receptors (GDFRs) and second messengers, platelet activation, signaling, and aggregation, signaling by VEGF, MAPK family signaling cascades, and signaling by Interleukins. Terms specific only for platelet-related miRNAs included coronary artery disease, platelet degranulation, and neutrophil degranulation, while for the top platelet-related genes it was Estrogen Signaling Receptor (ESR) mediated signaling, extra-nuclear estrogen signaling, and endometriosis. Our results show the novel features of platelet physiology and may provide a basis for further clinical studies focused on platelet reactivity. They also show in which aspects miRNAs can be promising biomarkers of platelet-related pathological processes. [ABSTRACT FROM AUTHOR]

Scientific research looks for answers to broaden our knowledge, and the specific questions addressed in each study are those that distinguish the type of scientific investigation pursued. In the field of ecophysiology biological functions are addressed, cell strategies of adaptation and acclimation to environmental changes are explored, the roles of biotic and abiotic factors on evolutionary trajectories of organisms are investigated. In line with the ecophysiological approach, the papers included in this issue explore the taxonomic and functional diversity of algae, reflecting and following the deep interest of professor Mario Giordano in aquatic autotrophic organisms. [ABSTRACT FROM AUTHOR]

Like other cancers, considerable effort has been made in acute myeloid leukemia (AML) to identify prognostic genes and long noncoding RNAs (lncRNAs) with their potential clinical applications. However, to date, no integrated prognostic model has been developed that combines both gene expression and lncRNAs as a singular approach in AML. Comprehensive bioinformatic approaches (Weighted gene co-expression network analysis, Univariate Cox regression analyses, Pearson correlation, LASSO-Cox regression, Wilcoxon test) were used to construct the signature and to define high- and low-risk groups in AML datasets. ESTIMATE and CIBERSORT algorithms were applied to investigate the potential impact of infiltrating immune cells based on the obtained signature in tumor microenvironment. In addition, gene ontology (GO) and KEGG enrichment were applied to explore the potential function of the signature. Herein, we focused on immune-related genes (IRGs) and immune-related long noncoding RNAs (IRlncRNAs) and constructed an integrated prognostic immunorelevant signature in AML. The obtained signature exhibit five IRGs (DAXX, PSMB8, CSRP1, RAC2 and PTPN6) and one IRlncRNA (AC080037.2) and is strictly associated with age and FAB (French–American–British classification). Importantly, the high-risk AML group (defined by the signature) correlated positively with three types of scores (immune score, stroma score, and ESTIMATE score). We also identified a few immune cells (resting mast cells and monocytes) potentially involved in the correlation between signature and survival of AML patients. The prognostic ability of the obtained signature was tested in the training cohort and then validated in both test and total cohorts. The pathway enrichment analysis confirmed the possible immune- related role of the signature. We constructed an integrated prognostic signature comprising five immune-related protein-coding genes (IRPCG) (DAXX, PSMB8, CSRP1, RAC2, and PTPN6) and one immune-related lncRNA (AC080037.2) that may serve as potential biomarkers for predicting survival and further stratifying AML patients. [ABSTRACT FROM AUTHOR]

Cervical cancer (CC) is a severe malignant tumor. Recently, more and more evidence has shown that abnormal expression of fatty acid synthase (FASN) occurs in varying tumors. Therefore, this investigation devoted to FASN in CC along with its upstream regulatory miRNA. Their expression levels were tested by qRT-PCR. Cell function experiments were undertaken to test tumor-related cell behaviors. Identification of their interplay was conducted by western blot and dual-luciferase methods. As analyzed, miR-497-5p was at low level in human CC cell lines, while FASN was overexpressed and demonstrated as a target of miR-497-5p. Cell function experiments demonstrated the targeting of miR-497-5p to FASN 3′-UTR, thus restraining CC development. To sum up, this investigation primarily revealed miR-497-5p/FASN axis in CC, by which potential CC biomarkers, could be developed. However, the mechanism of the axis was not determined in vivo, as one of the study limitations. [ABSTRACT FROM AUTHOR]

The first order derivatives of a Digital Elevation Model (DEM) defined over a regular grid are usually computed without an uncertainty estimate. The standard procedure involves a compact 3 × 3 window. Using a Taylor expansion, an uncertainty interval for each partial derivative as a function of the cell size was devised using two estimates, either of different resolution or of different order. The intervals for slope and aspect can be derived afterwards. We carried out an experiment comparing some different estimates of the slope and aspect over a synthetic surface representative of a real topography and amenable to offer an exact derivative. The partial derivatives were numerically estimated with four different procedures: the Simple procedure defined by Jones over a 2 × 2 window, the Evans–Young procedure using a centered difference over a 3 × 3 window, and using a 5 × 5 window both with an extrapolated Evans–Young procedure and the expression due to Florinsky. The results confirm that intervals for both slope and aspect always included the exact value even after drastically increasing the cell size. Finally, a real case with an integer-valued DEM was considered, illustrating the combined effect of Representation and Truncation error. [ABSTRACT FROM AUTHOR]

First discovered on macrophages by Goldstein and Brown in 1979, Scavenger Receptors have since been shown to participate in a diverse number of cell functions; equally diverse are their structures and the ligands they bind. Macrophage activation is crucial in the outcome of an immune response. SR-A1 is highly abundant on macrophages and recognizes both host- and microorganism-derived molecules that impact processes that are initiated, perpetuated, or modified. This review summarizes the involvement of SR-A1 in both inflammatory and anti-inflammatory responses, the multiple-ligand internalization mechanisms and the diversity of signaling pathways that impact macrophage function and activation. Engagement of SR-A1 results in the stimulation of differential signaling pathways and patterns of cytokine expression, kinetics, magnitude of response and activation status. SR-A1 plays essential roles in phagocytosis and efferocytosis, interacting with other receptors and promoting tolerance in response to apoptotic cell uptake. In cell adhesion, tissue remodeling, and cell migration, SR-A1 signals through different pathways engaging different cytoplasmic motifs. We describe the role of SR-A1 during innate and adaptive immune responses, such as participation in macrophage polarization and interaction with other innate receptors, as well as in antigen uptake, processing, and presentation, regulating T and B cell activation. The dichotomous contribution of SR-A1 on macrophage functions is discussed. A better understanding of the role SR-A1 plays through molecular mechanisms and crosstalk with other receptors may provide insights into developing novel therapeutic strategies to modulate immune responses and immunopathologies. [ABSTRACT FROM AUTHOR]

For cell and tissue physiology research, drug discovery, and growing replacement tissues for regenerative medicine, accurate and cost-efficient in vitro techniques are increasingly demanded. The conventional model for in vitro cell culture is the two-dimensional (2D) culture. Yet, cells have been found to be more native when they are grown in 3D conditions. We present here the development and evaluation of biological properties of bacterial cellulose/hydroxyapatite (BC/HA) nanocomposite hydrogel as a potential 3D cell-culture platform. The synthesized composites were characterized using Scanning Electron Microscopy (SEM), Atomic Force Microscopy (AFM), Swelling measurements and Celltiter 96® Aqueous One Solution Cell Proliferation Assay (MTS) using mouse fibroblast cell line (L – 929). The arrangement of composites shown in SEM and AFM images closely resembles the native extracellular matrices (ECM) showing the potential to act as a viable substrate for cell culture. The composites exhibited high swelling ratio (5.31–5.81), indicating enhanced moisture absorption and potential for nutrient exchange. The in vitro biocompatibility results indicated significantly high percentage cell proliferation (85.20%-88.30%). These findings indicate that the BC/HA composites are potential candidates for 3D cell-culture applications. [ABSTRACT FROM AUTHOR]

Germline-encoded pattern recognition receptors [PRRs] in mammalian cells function in the detection of molecular patterns associated with pathogen invasion or cellular damage. A PRR subset is activated by the atypical presence and location of double-stranded RNA [dsRNA] or its synthetic analogue polyinosinic-polycytidylic acid [poly(I:C)], triggering pro-inflammatory signalling and death in many cell types. Poly(I:C) has been tested as a sole or combination cancer therapy in preclinical studies and clinical trials. The purpose of this study was to evaluate the effects of poly(I:C) transfection via electroporation on cell lines from a cancer of epithelial origin, 4T1 mammary carcinoma, and a cancer of mesenchymal origin, WEHI 164 fibrosarcoma. The effects of the poly(I:C) delivery on cell metabolism implicate the induction of cell death. A pro-inflammatory response was demonstrated by mRNA upregulation and the secretion of Type I interferon and several cytokines and chemokines. The mRNAs of dsRNA sensor DExD/H-box helicase 58/retinoic acid-inducible gene I protein [Ddx58/RIG-I] and sensor/co-sensor DEAH-box helicase 9 [Dhx9] were not regulated, but the mRNAs of RNA sensors toll-like receptor 3 [TLR3], interferoninduced with helicase C domain 1/melanoma differentiation-associated protein 5 [Ifih1/MDA5] and Z-DNA binding protein 1 [Zbp1] and co-sensors DEAD (Asp-Glu-Ala-Asp) box polypeptide 60 [Ddx60] and interferon-inducible protein 204 [Ifi204] were upregulated in both cell lines. The mRNAs encoding signalling pathways components were present or upregulated in both cell types. These data demonstrate that RNA sensing effects can be amplified by electroporation delivery, potentially expanding the practicality of this immunotherapeutic approach. [ABSTRACT FROM AUTHOR]

It has recently been shown that CFIm25, a canonical mRNA 3' processing factor, could play a variety of physiological roles through its molecular function in the regulation of mRNA alternative polyadenylation (APA). Here, we used CRISPR/Cas9-mediated gene editing approach in human embryonic stem cells (hESCs) for CFIm25, and obtained three gene knockdown/mutant cell lines. CFIm25 gene editing resulted in higher proliferation rate and impaired differentiation potential for hESCs, with these effects likely to be directly regulated by the target genes, including the pluripotency factor rex1. Mechanistically, we unexpected found that perturbation in CFIm25 gene expression did not significantly affect cellular mRNA 3' processing efficiency and APA profile. Rather, we provided evidences that CFIm25 may impact RNA polymerase II (RNAPII) occupancy at the body of transcribed genes, and promote the expression level of a group of transcripts associated with cellular proliferation and/or differentiation. Taken together, these results reveal novel mechanisms underlying CFIm25's modulation in determination of cell fate, and provide evidence that the process of mammalian gene transcription may be regulated by an mRNA 3' processing factor. [ABSTRACT FROM AUTHOR]

Latent 5' splice sites, not normally used, are highly abundant in human introns, but are activated under stress and in cancer, generating thousands of nonsense mRNAs. A previously proposed mechanism to suppress latent splicing was shown to be independent of NMD, with a pivotal role for initiator-tRNA independent of protein translation. To further elucidate this mechanism, we searched for nuclear proteins directly bound to initiator-tRNA. Starting with UV-crosslinking, we identified nucleolin (NCL) interacting directly and specifically with initiator-tRNA in the nucleus, but not in the cytoplasm. Next, we show the association of initiator-tRNA and NCL with pre-mRNA. We further show that recovery of suppression of latent splicing by initiator-tRNA complementation is NCL dependent. Finally, upon nucleolin knockdown we show activation of latent splicing in hundreds of coding transcripts having important cellular functions. We thus propose nucleolin, a component of the endogenous spliceosome, through its direct binding to initiator-tRNA and its effect on latent splicing, as the first protein of a nuclear quality control mechanism regulating splice site selection to protect cells from latent splicing that can generate defective mRNAs. [ABSTRACT FROM AUTHOR]

Simultaneous measurement of multiple modalities in single-cell analysis, represented by CITE-seq, is a promising approach to link transcriptional changes to cellular phenotype and function, requiring new computational methods to define cellular subtypes and states based on multiple data types. Here, we design a flexible single-cell multimodal analysis framework, called CITEMO, to integrate the transcriptome and antibody-derived tags (ADT) data to capture cell heterogeneity from the multi omics perspective. CITEMO uses Principal Component Analysis (PCA) to obtain a low-dimensional representation of the transcriptome and ADT, respectively, and then employs PCA again to integrate these low-dimensional multimodal data for downstream analysis. To investigate the effectiveness of the CITEMO framework, we apply CITEMO to analyse the cell subtypes of Cord Blood Mononuclear Cells (CBMC) samples. Results show that the CITEMO framework can comprehensively analyse singlecell multimodal samples and accurately identify cell subtypes. Besides, we find some specific immune cells that co-express multiple ADT markers. To better describe the co-expression phenomenon, we introduce the co-expression entropy to measure the heterogeneous distribution of the ADT combinations. To further validate the robustness of the CITEMO framework, we analyse Human Bone Marrow Cell (HBMC) samples and identify different states of the same cell type. CITEMO has an excellent performance in identifying cell subtypes and states for multimodal omics data. We suggest that the flexible design idea of CITEMO can be an inspiration for other single-cell multimodal tasks. The complete source code and dataset of the CITEMO framework can be obtained from https://github. com/studentiz/CITEMO. [ABSTRACT FROM AUTHOR]

Candida albicans is a common commensal on human mucosal surfaces, but can become pathogenic, e.g. if the host is immunocompromised. While neutrophils, macrophages and T cells are regarded as major players in the defense against pathogenic C. albicans, the role of B cells and the protective function of their antibodies are less well characterized. In this study, we show that human serum antibodies are able to enhance the association of human THP-1 monocyte-like cells with C. albicans cells. Human serum antibodies are also capable of inhibiting the adherence and damage dealt to epithelial cells. Furthermore, human serum antibodies impair C. albicans invasion of human oral epithelial cells by blocking induced endocytosis and consequently host cell damage. While aspartic proteases secreted by C. albicans are able to cleave human IgG, this process does not appear to affect the protective function of human antibodies. Thus, humans are equipped with a robust antibody response to C. albicans, which can enhance antifungal activities and prevent fungal-mediated epithelial damage. [ABSTRACT FROM AUTHOR]

Mitochondria are organelles that play a crucial role in cell physiology, cell death, and aging. They are among the first responders to different stressors that originate from the environment. Cadmium as a heavy metal affects different levels of body organization: from organs through tissues and cells to organelles. Based on our previous research results, we decided to check how the exposure to cadmium affects the functioning of mitochondria in different organs of soil living centipede Lithobius forficatus. The activity of mitochondria in somatic and germ cells has been analyzed using transmission electron microscopy (TEM), confocal microscopy, and flow cytometry. Changes in the mitochondrial membrane potential and mitochondrial dismutase (MnSOD) activity in relation to the accumulation of reactive oxygen species (ROS) caused by cadmium exposure have been studied. Individuals were divided into 3 experimental groups depending on cadmium concentration in soil. Changes in mitochondrial ultrastructure caused by cadmium are tissue-dependent and associated with an increase of ROS levels. The system of ROS and MnSOD activation works more efficiently in the case of gonads than in the digestive system. While the short-term cadmium exposure alters the fine structure of both the somatic and germ-line cells in gonads, the long-term cadmium exposure causes mitochondrial ultrastructure regeneration. [ABSTRACT FROM AUTHOR]

The small non-coding vault RNA (vtRNA) is a component of the vault complex, a ribonucleoprotein complex found in most eukaryotes. vtRNAs regulate a variety of cellular functions when unassociated with the vault complex. Human has four vtRNA paralogs (hvtRNA1-1, hvtRNA1-2, hvtRNA1-3, hvtRNA2-1), which are highly similar and differ only slightly in primary and secondary structure. Despite the increasing research on vtRNAs, a feature that distinguishes one hvtRNA from the others has not been recognized. Recently, we demonstrated that murine vtRNA (mvtRNA) promotes synapse formation by modulating the MAPK signaling pathway. Here we showed that expression ofhvtRNA1-1, but not hvtRNA2-1 increases the expression of synaptic marker proteins, ERK phosphorylation and the number of PSD95 and Synapsin I double positive puncta to an extent similar to that of mvtRNA, suggesting that hvtRNA1-1 may enhance synapse formation. This finding opens new perspectives to uncover the function of the different vtRNA paralogs. [ABSTRACT FROM AUTHOR]

RASAL2 (RAS protein activator like 2), a RASGTPase activating protein, can catalyze the hydrolysis of RAS-GTP into RAS-GDP to inactivate the RAS pathway in various types of cancer cells. However, the cellular function of RASAL2 remains elusive. Here we showed that RASAL2 can attenuate PRKAA/AMPKα phosphorylation by recruiting phosphatase PPM1B/pp2cβ, thus inhibiting the initiation of basal autophagy under normal conditions. In addition, we found that glucose starvation could induce dissociation of PPM1B from RASAL2 and then RASAL2 at S351 be phosphorylated by PRKAA, followed by the binding of phosphorylated-RASAL2 with to PIK3C3/VPS34-ATG14-BECN1/Beclin1 complex to increase PIK3C3 activity and autophagy. Furthermore, RASAL2 S351 phosphorylation facilitated breast tumor growth and correlated to poor clinical outcomes in breast cancer patients. Our study demonstrated that the phosphorylation status of RASAL2 S351 can function as a molecular switch to either suppress or promote AMPK-mediated autophagy. Inhibition of RASAL2 S351 phosphorylation might be a potential therapeutic strategy to overcome the resistance of AMPK-activation agents. Abbreviations: AICAR: aminoimidazole carboxamide ribonucleotide; AMPK: adenosine 5'-monophosphate (AMP)-activated protein kinase; ATG14: autophagy related 14; C.C: compound C; CQ: chloroquine; DKO: double-knockout; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MTOR: mechanistic target of rapamycin kinase; PIK3C3/VPS34: phosphatidylinositol 3-kinase catalytic subunit type 3; PIK3R4/VPS15: phosphoinositide-3-kinase regulatory subunit 4; PPM1B/pp2cβ: protein phosphatase, Mg2+/Mn2+ dependent 1B; PRKAA/AMPKα: protein kinase AMP-activated catalytic subunit alpha; PtdIns: phosphatidylinositol; PtdIns3P: phosphatidylinositol-3-phosphate; RASAL2: RAS protein activator like 2; RasGAPs: RasGTPase activating proteins; SQSTM1/p62: sequestosome 1; TNBC: triple-negative breast cancer. [ABSTRACT FROM AUTHOR]

RNA modifications are dynamic chemical entities that expand the RNA lexicon and regulate RNA fate. The most abundant modification present in mRNAs, N6-methyladenosine (m6A), has been implicated in neurogenesis and memory formation. However, whether additional RNA modifications may be playing a role in neuronal functions and in response to environmental queues is largely unknown. Here we characterize the biochemical function and cellular dynamics of two human RNA methyltransferases previously associated with neurological dysfunction, TRMT1 and its homolog, TRMT1-like (TRMT1L). Using a combination of next-generation sequencing, LC-MS/MS, patient-derived cell lines and knockout mouse models, we confirm the previously reported dimethylguanosine (m2,2G) activity of TRMT1 in tRNAs, as well as reveal that TRMT1L, whose activity was unknown, is responsible for methylating a subset of cytosolic tRNAAla(AGC) isodecoders at position 26. Using a cellular in vitro model that mimics neuronal activation and long term potentiation, we find that both TRMT1 and TRMT1L change their subcellular localization upon neuronal activation. Specifically, we observe a major subcellular relocalization from mitochondria and other cytoplasmic domains (TRMT1) and nucleoli (TRMT1L) to different small punctate compartments in the nucleus, which are as yet uncharacterized. This phenomenon does not occur upon heat shock, suggesting that the relocalization of TRMT1 and TRMT1L is not a general reaction to stress, but rather a specific response to neuronal activation. Our results suggest that subcellular relocalization of RNA modification enzymes may play a role in neuronal plasticity and transmission of information, presumably by addressing new targets. [ABSTRACT FROM AUTHOR]

Cervical cancer (CC) is a common gynecological malignancy and represents a major global health challenge. Chemotherapeutic agents are commonly applied in treatment of CC, while along various adverse effects and chemotherapy resistance. As an iridoid glycoside compound, gentiopicroside (GPS) possesses the characteristic of the better availability and lower toxicity effect on cancer treatment. In the present study, we investigated that GPS exhibited the anticancer effect on HeLa cells through the inhibition of cell growth, induced apoptosis, cycle arrest, and suppressed migration. Furthermore, the possible mechanism or the targets of GPS was also clarified. The results revealed that GPS exerted an anti-proliferation effect in a dose- and time-dependent manner in HeLa cells, in contrast, with the less inhibiting proliferation effects on normal cell line (HUVEC). Moreover, GPS arrested cells at G2/M phase and induced apoptosis through mitochondrial apoptotic pathway. More significantly, GPS dramatically inhibited the migration of HeLa cells and regulated the matrix metalloproteinase expression through the MAPK and Akt signaling pathways, of which MAPK1 was an underlying target in GPS against HeLa cells. [ABSTRACT FROM AUTHOR]

Introduction: Interleukin-25 is a Th2 interleukin and has been shown to influence cell behavior. This study aims to illustrate its affection on extravillous trophoblasts function and association with PE. Methods qPCR and immunohistochemistry demonstrate IL-25 and IL-17RB expression. CCK-8 test and transwell were to access the behavior of HTR8 in the presence or absence of IL-25, IL-25 neutralization antibody. Results EVTs and HTR8 express IL-25 and IL-17RB. IL-25 promotes proliferation and invasion (p< 0.05),which was abolished in the presence of IL-25Ab (p< 0.05). Conclusion: IL-25 may contribute to promote trophoblast invasion and proliferation and abnormal decline of IL-25 might be associated with PE.Methods: qPCR and immunohistochemistry (IHC) were used to demonstrate IL-25 and its receptor IL-17RB expression in primary human trophoblasts of normal first- and third- trimester, as well as third-trimester of PE. CCK-8 test and transwell invasion system in vitro were applied separately to access the behavior of trophoblast cell line (HTR8) in the presence or absence of IL-25, IL-25 neutralization antibody (IL-25 Ab).Results: EVTs and HTR8 express IL-25 and IL-17RB. The expressions increase in third-trimester during normal pregnancy. In PE, both of IL-25 and IL-17RB expressions decrease (p< 0.05). IL-25 for 24 h promoted HTR8 proliferation and invasion (p< 0.05). The effect was abolished in the presence of IL-25Ab (p< 0.05).Conclusion: This study demonstrates that IL-25 may contribute to promote trophoblast invasion and proliferation and abnormal decline of IL-25 might be associated with PE. [ABSTRACT FROM AUTHOR]

Mitochondria are organelles present in most eukaryotic cells, where they play major and multifaceted roles. The classical notion of the main mitochondrial function as the powerhouse of the cell per se has been complemented by recent discoveries pointing to mitochondria as organelles affecting a number of other auxiliary processes. They go beyond the classical energy provision via acting as a relay point of many catabolic and anabolic processes, to signaling pathways critically affecting cell growth by their implication in de novo pyrimidine synthesis. These additional roles further underscore the importance of mitochondrial homeostasis in various tissues, where its deregulation promotes a number of pathologies. While it has long been known that mitochondria can move within a cell to sites where they are needed, recent research has uncovered that mitochondria can also move between cells. While this intriguing field of research is only emerging, it is clear that mobilization of mitochondria requires a complex apparatus that critically involves mitochondrial proteins of the Miro family, whose role goes beyond the mitochondrial transfer, as will be covered in this review. [ABSTRACT FROM AUTHOR]

Oogenesis is a fundamental biological process observed in most animals. Animals employ many different mechanisms to make their eggs and oogenesis cannot be completed without the support of other intraovarian and/or extraovarian cells and tissues. Invertebrates account for 99% of all animal life on earth and their complex life histories are a reflection of the structural heterogeneity of their ovaries and the diversity of their vitellogenic mechanisms. The process of oogenesis in different invertebrates differs because it is constrained by limits imposed by their respective body design, the architecture of their ovaries and their collective phylogenetic history. Oogenesis in the majority of invertebrates has yet to be investigated and current knowledge is limited to relatively superficial descriptions of a fraction of 1% of described species in each of the major animal phyla. It has been over 30 years since the last published review of invertebrate oogenesis and during the intervening years considerable progress has been made in our understanding of the ultrastructural, biochemical and molecular aspects of the process. This review aims to identify some unifying themes by collating and synthesizing the widely dispersed literature on invertebrate oogenesis covering 30 metazoan phyla for which basic information is available. [ABSTRACT FROM AUTHOR]

Omega-3 polyunsaturated fatty acid (ω-3 PUFA) supplements for chemoprevention of different types of cancer including lung cancer has been investigated in recent years. ω-3 PUFAs are considered immunonutrients, commonly used in the nutritional therapy of cancer patients. ω-3 PUFAs play essential roles in cell signaling and in cell structure and fluidity of membranes. They participate in the resolution of inflammation and have anti-inflammatory effects. Lung cancer patients suffer complications, such as anorexia-cachexia syndrome, pain and depression. The European Society for Clinical Nutrition and Metabolism (ESPEN) 2017 guidelines for cancer patients only discuss the use of ω-3 PUFAs for cancer-cachexia treatment, leaving aside other cancer-related complications that could potentially be managed by ω-3 PUFAs. This review aims to elucidate whether the effects of ω-3 PUFAs in lung cancer is supplementary, pharmacological or both. In addition, clinical studies, evidence in cell lines and animal models suggest how ω-3 PUFAs induce anticancer effects. ω-3 PUFAs and their metabolites are suggested to modulate pivotal pathways underlying the progression or complications of lung cancer, indicating that this is a promising field to be explored. Further investigation is still required to analyze the benefits of ω-3 PUFAs as supplementation or pharmacological treatment in lung cancer. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate genomic instability and cytotoxicity in buccal mucosa cells of children living in abnormal conditions from Santos Sao Vicente estuary. The study area is located between coordinates 23°58ʹ11.8"S and 46°24ʹ26.3"W, in the southwestern zone of the Sao Paulo State, Brazil. A total of 40 children was distributed into two groups: exposed and non-exposed groups. The frequency of micronuclei increased to buccal mucosa cells of children living in Santos Sao Vicente estuary when compared to the non-exposed group (p < 0.05). No remarkable differences on buccal cells were found inpyknosis, karyorrhexis and karyolysi between groups. Taken together, our results suggest that children living in contaminated areas comprise a high group for genomic instability on buccal mucosa cells. Given that the current investigation is a preliminary study, further analysis with a larger sample of children is interesting as a future perspective. [ABSTRACT FROM AUTHOR]

Accumulating evidence has reported the role of microRNA (miR) in retinoblastoma (RB). Therefore, the objective was to discuss how miR-362-3p exerted its function in RB cell progression via regulating ubiquitin-specific protease 2 (USP22) and lysine-specific histone demethylase 1 (LSD1). MiR-362-3p, USP22 and LSD1 expression in RB cells and tissues were tested. The biological functions of RB cells were detected via over-expressing miR-362-3p and down-regulating USP22. The target relationship of USP22 and miR-362-3p as well as the interaction of USP22 and LSD1 in RB was verified. Down-regulated miR-362-3p and up-regulated USP22 and LSD1 were demonstrated in RB tissues and cells. Restoring miR-362-3p and depleting USP22 attenuated invasion, proliferation and migration, and facilitated apoptosis of RB cells. USP22 was a target gene of miR-362-3p. USP22 deubiquitinated LSD1 in RB. It is revealed that miR-362-3p targets USP22 and then restrains invasion, proliferation and migration while promotes apoptosis of RB via reducing LSD1 modified by deubiquitination. [ABSTRACT FROM AUTHOR]

In the past, various species of the unicellular algal genus Micrasterias (Zygnematophyceae) have been used for research in the fields of cell biology and physiology. Relatively large cell size, highly differentiated cell shape and a remarkable evolutionary position make Micrasterias interesting, especially for cytomorphogenetic studies. However, within this genus a model organism enabling molecular research has not yet been established. Micrasterias radians var. evoluta (W.B.Turner) Krieger allows easy culturing under axenic conditions and performs its whole life cycle in vitro thus fulfilling two important prerequisites for a model organism. In this work resources allowing transient expression of transgenes were developed. First, axenic lines were obtained by the treatment of zygospores with a cocktail of antibiotics followed by germination and regeneration. In order to allow transgene expression we isolated the 5′ -flanking region of the M. radians var. evoluta Actin1 gene (MrACT1) and fused it to the green fluorescent protein (GFP). A higher promoter activity compared with various heterologous promoters regarding GFP expression was observed. Transient transgene expression was achieved by polyethylene glycol (PEG)-mediated protoplast transformation, yielding a rate of 3.9% transformed cells per surviving protoplasts. Transgene expression was also achieved by particle bombardment of vegetative cells. Employing the established protocol, a Lifeact-GFP fusion protein for labelling F-actin was expressed, allowing visualization of the actin cytoskeleton in M. radians var. evoluta. [ABSTRACT FROM AUTHOR]