Small Groups Of Cells Research Articles

Separable mechanisms drive local and global polarity establishment in the Caenorhabditiselegans intestinal epithelium.

Apico-basolateral polarization is essential for epithelial cells to function as selective barriers and transporters, and to provide mechanical resilience to organs. Epithelial polarity is established locally, within individual cells to establish distinct apical, junctional and basolateral domains, and globally, within a tissue where cells coordinately orient their apico-basolateral axes. Using live imaging of endogenously tagged proteins and tissue-specific protein depletion in the Caenorhabditiselegans embryonic intestine, we found that local and global polarity establishment are temporally and genetically separable. Local polarity is initiated prior to global polarity and is robust to perturbation. PAR-3 is required for global polarization across the intestine but local polarity can arise in its absence, as small groups of cells eventually established polarized domains in PAR-3-depleted intestines in a HMR-1 (E-cadherin)-dependent manner. Despite the role of PAR-3 in localizing PKC-3 to the apical surface, we additionally found that PAR-3 and PKC-3/aPKC have distinct roles in the establishment and maintenance of local and global polarity. Taken together, our results indicate that different mechanisms are required for local and global polarity establishment in vivo.

Clinical Significance and Properties of IFN-γ+IL-17+ Th17 Cells in Liver Injury Associated with Chronic Hepatitis B Virus Infection

Introduction: Our previous study demonstrated that intrahepatic Th17 cells exacerbated the progression of chronic hepatitis B virus (HBV) infection. Meanwhile, we found a small group of IFN-γ and IL-17 double-positive Th17 cells (IFN-γ⁺IL-17⁺ Th17 cells) in liver tissues. This study aimed to investigate the clinical significance and properties of IFN-γ⁺IL-17⁺ Th17 cells in liver injury associated with chronic HBV infection. Methods: The frequencies of CD4⁺ Th cells, Tregs, and CD4⁺ T cells expressing specific chemokine receptors in the blood and liver tissues were detected using flow cytometry. The chemotaxis of C C chemokine receptor 5 (CCR5) and C-X-C chemokine receptor 3 (CXCR3) toward IFN-γ⁺IL-17⁺ Th17 cells and Tregs was evaluated by transwell chemotactic assay. Analyses of different variables were performed using GraphPad Prism v 5.01 and IBM SPSS Statistics 23.0. HBV-specific IFN-γ⁺IL-17⁺ Th17 cells were investigated using a cell stimulation assay with HBV antigens in vitro. Results: The frequencies of IFN-γ⁺IL-17⁺ Th17, Th17 cells, and Tregs in the blood were increased from normal controls to chronic hepatitis B (CHB) and acute-on-chronic liver failure (ACLF). The same trend could also be observed in CHB liver tissues compared to those in CHB blood specimens. Furthermore, the frequencies of IFN-γ⁺IL-17⁺ Th17 cells were positively associated with Th17 cells, Th17 cell-related cytokines (IL-17 and IL-6), HBV DNA load, and the levels of HBsAg, HBeAg, and ALT. The ratios of IFN-γ⁺IL-17⁺ Th17 cells to Tregs extremely decreased in ACLF blood specimens compared with those in CHB blood specimens. Additionally, CCR5 and CXCR3 were conducive to the recruitment of IFN-γ⁺IL-17⁺ Th17 cells and Tregs to liver tissue. Conclusions: IFN-γ⁺IL-17⁺ Th17 cells have Th17 cell-like properties in the progression of chronic HBV infection. CCR5 and CXCR3 facilitated the recruitment of IFN-γ⁺IL-17⁺ Th17 cells and Tregs to the liver. Importantly, the ratio of IFN-γ⁺IL-17⁺ Th17 cells to Tregs might be an effective assessment indicator of the severity of liver injury.

Thermal Runaway Reactions Modeling in Lithium-Ion Batteries

Lithium-ion batteries are ubiquitously used as power source in a variety of applications due to their superior performance and reliability. However, thermal runaway of Li-ion batteries is a serious concern due to risks associated with such catastrophic event, and hence elucidating the different chemical reactions involved in the thermal runaway phenomenon is a highly active area of research. It is both cost and time prohibitive to experimentally assess the different battery pack designs for the possibility of thermal runaway event, and hence mathematical models play critical role in the battery safety research. Thermal runaway of battery pack is usually initiated by one or a small group of cells which are affected by abuse conditions such as internal short circuit, nail penetration, overcharging, etc., and then depending on the battery pack design and thermal management, thermal runaway can propagate to neighboring cells resulting in fires that can sustain for long time. Since understanding chemistry leading to thermal runaway at cell level is crucial, many studies, both experimental and modeling, have focused on this topic.Some of the important reactions involved in the onset of thermal runaway are primary SEI decomposition, secondary SEI formation due to reaction between electrolyte and intercalated lithium ions, electrolyte decomposition, separator melting, and cathode decomposition. Since it is difficult to directly measure the different species involved in these reactions, calorimetric based approaches are used to determine the reaction parameters; DSC and ARC are widely used for this purpose. The model consists of system of differential equations which can be solved as a function of time for species fractions and cell temperature. In this work, we have developed flexible and easy to use framework for solving thermal runaway model equations. Both the electrochemical reactions and thermal runaway reactions are solved together with the aim of tighter two-way coupling between these two different processes. Using this model, we analyze the different reaction mechanisms proposed in the literature. We discuss the models for pressure build up in the cell, venting, and combustion of the vented gases.

The origin of gastric cancer stem cells and their effects on gastric cancer: Novel therapeutic targets for gastric cancer.

Gastric cancer (GC) is one of the most prevalent malignancies and the most common causes of cancer-related mortality worldwide. Furthermore, the prognosis of advanced GC remains poor even after surgery combined with chemoradiotherapy. As a small group of cells with unlimited differentiation and self-renewal ability in GC, accumulating evidence shows that GC stem cells (GCSCs) are closely associated with the refractory characteristics of GC, such as drug resistance, recurrence, and metastasis. With the extensive development of research on GCSCs, GCSCs seem to be promising therapeutic targets for GC. However, the relationship between GCSCs and GC is profound and intricate, and its mechanism of action is still under exploration. In this review, we elaborate on the source and key concepts of GCSCs, systematically summarize the role of GCSCs in GC and their underlying mechanisms. Finally, we review the latest information available on the treatment of GC by targeting GCSCs. Thus, this article may provide a theoretical basis for the future development of the novel targets based on GCSCs for the treatment of GC.

Early patterning followed by tissue growth establishes distal identity in Drosophila Malpighian tubules.

Specification and elaboration of proximo-distal (P-D) axes for structures or tissues within a body occurs secondarily from that of the main axes of the body. Our understanding of the mechanism(s) that pattern P-D axes is limited to a few examples such as vertebrate and invertebrate limbs. Drosophila Malpighian/renal tubules (MpTs) are simple epithelial tubules, with a defined P-D axis. How this axis is patterned is not known, and provides an ideal context to understand patterning mechanisms of a secondary axis. Furthermore, epithelial tubules are widespread, and their patterning is not well understood. Here, we describe the mechanism that establishes distal tubule and show this is a radically different mechanism to that patterning the proximal MpT. The distal domain is patterned in two steps: distal identity is specified in a small group of cells very early in MpT development through Wingless/Wnt signalling. Subsequently, this population is expanded by proliferation to generate the distal MpT domain. This mechanism enables distal identity to be established in the tubule in a domain of cells much greater than the effective range of Wingless.

Evaluation of prognostic role of tumour budding in breast carcinoma and its correlation with known clinicopathological parameters

Tumour budding (TB) consists of a small group of cells (upto 5) which have detached from the tumour bulk. TB has been studied in many malignancies including head and neck, colorectum, oesophagus, etc. However there are very few studies to determine its role in Breast cancer. This study was designed to study the role of tumour budding as a prognostic factor in Breast cancer. To study the grade of TB in Invasive Breast Carcinoma and correlate it with known clinicopathological parameters to determine its usefulness as a prognostic factor. In this retrospective observational study, 40 cases of modified radical mastectomy from July 2019 to December 2020 were evaluated for the tumour budding. Ethical clearance was not required as it was a secondary data collection study which did not relate to patient’s privacy, clinical examination or treatment. Significance and correlation was studied between the grade of TB and known clinicopathological parameters using Chi-square test. Out of the 40 cases evaluated, 20 cases (50%) were of High grade TB (>/=10/10HPF), while 20 cases (50%) were of Low grade TB (<10/10HPF). Majority patients were of age group 40-60 years (60%), with primary carcinoma (52.5%) and invasive ductal type (72.5%). Higher TB was observed with Lymphnode positive cases (p=0.002), in higher TNM stage (p=0.006) and with lymphovascular invasion (p=0.000). As higher grade tumour budding was associated with positive lymphnode status, higher tumour stage and presence of lymphovascular invasion, it can be considered as an indicator of poor prognosis in cases of breast carcinoma especially in resource poor institutes which are not equipped with sophisticated IHC and Molecular markers.

Insights Into Platelet-Derived MicroRNAs in Cardiovascular and Oncologic Diseases: Potential Predictor and Therapeutic Target.

Non-communicable diseases (NCDs), represented by cardiovascular diseases and cancer, have been the leading cause of death globally. Improvements in mortality from cardiovascular (CV) diseases (decrease of 14%/100,000, United States) or cancers (increase 7.5%/100,000, United States) seem unsatisfactory during the past two decades, and so the search for innovative and accurate biomarkers of early diagnosis and prevention, and novel treatment strategies is a valuable clinical and economic endeavor. Both tumors and cardiovascular system are rich in angiological systems that maintain material exchange, signal transduction and distant regulation. This pattern determines that they are strongly influenced by circulating substances, such as glycolipid metabolism, inflammatory homeostasis and cyclic non-coding RNA and so forth. Platelets, a group of small anucleated cells, inherit many mature proteins, mRNAs, and non-coding RNAs from their parent megakaryocytes during gradual formation and manifest important roles in inflammation, angiogenesis, atherosclerosis, stroke, myocardial infarction, diabetes, cancer, and many other diseases apart from its classical function in hemostasis. MicroRNAs (miRNAs) are a class of non-coding RNAs containing ∼22 nucleotides that participate in many key cellular processes by pairing with mRNAs at partially complementary binding sites for post-transcriptional regulation of gene expression. Platelets contain fully functional miRNA processors in their microvesicles and are able to transport their miRNAs to neighboring cells and regulate their gene expression. Therefore, the importance of platelet-derived miRNAs for the human health is of increasing interest. Here, we will elaborate systematically the roles of platelet-derived miRNAs in cardiovascular disease and cancer in the hope of providing clinicians with new ideas for early diagnosis and therapeutic strategies.

Lung Cancer Stem Cell Markers as Therapeutic Targets: An Update on Signaling Pathways and Therapies.

Cancer stem cells, a relatively small group of self-renewing cancer cells, were first isolated from acute myeloid leukemia. These cells can play a crucial role in tumor metastasis, relapse, and therapy resistance. The cancer stem cell theory may be applied to lung cancer and explain the inefficiency of traditional treatments and eventual recurrence. However, because of the unclear accuracy and illusive biological function of cancer stem cells, some researchers remain cautious about this theory. Despite the ongoing controversy, cancer stem cells are still being investigated, and their biomarkers are being discovered for application in cancer diagnosis, targeted therapy, and prognosis prediction. Potential lung cancer stem cell markers mainly include surface biomarkers such as CD44, CD133, epithelial cell adhesion molecule, and ATP-binding cassette subfamily G member 2, along with intracellular biomarkers such as aldehyde dehydrogenase, sex-determining region Y-box 2, NANOG, and octamer-binding transcription factor 4. These markers have different structures and functions but are closely associated with the stem potential and uncontrollable proliferation of tumor cells. The aberrant activation of major signaling pathways, such as Notch, Hedgehog, and Wnt, may be associated with the expression and regulation of certain lung cancer stem cell markers, thus leading to lung cancer stem cell maintenance, chemotherapy resistance, and cancer promotion. Treatments targeting lung cancer stem cell markers, including antibody drugs, nanoparticle drugs, chimeric antigen receptor T-cell therapy, and other natural or synthetic specific inhibitors, may provide new hope for patients who are resistant to conventional lung cancer therapies. This review provides comprehensive and updated data on lung cancer stem cell markers with regard to their structures, functions, signaling pathways, and promising therapeutic target approaches, aiming to elucidate potential new therapies for lung cancer.

Multimodal Optical Coherence Tomography for Intraoperative Evaluation of Tumor Margins and Surgical Margins in Breast-Conserving Surgery.

We compare the effectiveness of multimodal optical coherence tomography (MM OCT) in the traditional structural OCT mode and the OCT elastography (OCE) mode in addressing two clinically important tasks: (1) detecting groups of tumor cells at surgical margins during breast-сonserving surgery (BСS) in breast cancer (BC) and (2) identifying breast tumor margins. The obtained results were correlated with corresponding histological sections. The study was performed on 100 surgical margin samples (top, bottom, medial, and lateral - four samples from each patient in total) obtained from 25 patients with BC who underwent BCS (lumpectomy), and on 25 postoperative tumor samples (to determine tumor margins). With MM OCT method, we visually and numerically assessed the scattering (level and depth of OCT signal penetration) and elastic (stiffness values, or Young's modulus (kPa)) properties of the tumor and non-tumor breast tissue and the obtained values were compared with the results of postoperative histological examination. In 4 surgical margin samples (out of 100), with the OCE method we identified groups of histologically confirmed tumor cells ("positive" resection margins) at the distance of about 5 mm from the visible tumor margin. The identified zones were larger than 0.5 mm with stiffness of more than 400 kPa in all these cases. However, the structural OCT could not identify these groups of tumors and they were not distinguishable from the surrounding fibrous tissue.In the areas of tumor into non-tumor tissue transition, structural OCT images detected tumor margins only if they were adjacent to adipose tissue and did not detect them if there were adjacent to non-tumor fibrous tissue. OCE images with high stiffness values (more than 400 kPa) and high contrast showed a clear tumor margin with both adipose and fibrous tissue. The study demonstarets the potential of MM OCT, particularly its OCE mode, as a real-time method for intraoperative tumor margin and surgical margin assessment in BCS. OCE images compared to structural OCT images visualize higher contrast between different types of breast tissue (adipose tissue, fibrous stroma, hyalinized stroma, tumor cell clusters), as well as more accurate identification of the tumor border and detection of small groups of tumor cells at surgical margins. An algorithm for intraoperative MM OCT examination of the state of the resection margin is proposed in accordance with standard clinical guidelines for achieving clean surgical margins in breast cancer patients.

Metacell-2: a divide-and-conquer metacell algorithm for scalable scRNA-seq analysis

Scaling scRNA-seq to profile millions of cells is crucial for constructing high-resolution maps of transcriptional manifolds. Current analysis strategies, in particular dimensionality reduction and two-phase clustering, offer only limited scaling and sensitivity to define such manifolds. We introduce Metacell-2, a recursive divide-and-conquer algorithm allowing efficient decomposition of scRNA-seq datasets of any size into small and cohesive groups of cells called metacells. Metacell-2 improves outlier cell detection and rare cell type identification, as shown with human bone marrow cell atlas and mouse embryonic data. Metacell-2 is implemented over the scanpy framework for easy integration in any analysis pipeline.

Mathematical Modeling of Tumor and Cancer Stem Cells Treated with CAR-T Therapy and Inhibition of TGF-[Formula: see text

The stem cell hypothesis suggests that there is a small group of malignant cells, the cancer stem cells, that initiate the development of tumors, encourage its growth, and may even be the cause of metastases. Traditional treatments, such as chemotherapy and radiation, primarily target the tumor cells leaving the stem cells to potentially cause a recurrence. Chimeric antigen receptor (CAR) T-cell therapy is a form of immunotherapy where the immune cells are genetically modified to fight the tumor cells. Traditionally, the CAR T-cell therapy has been used to treat blood cancers and only recently has shown promising results against solid tumors. We create an ordinary differential equations model which allows for the infusion of trained CAR-T cells to specifically attack the cancer stem cells that are present in the solid tumor microenvironment. Additionally, we incorporate the influence of TGF-[Formula: see text] which inhibits the CAR-T cells and thus promotes the growth of the tumor. We verify the model by comparing it to available data and then examine combinations of CAR-T cell treatment targeting both non-stem and stem cancer cells and a treatment that reduces the effectiveness of TGF-[Formula: see text] to determine the scenarios that eliminate the tumor.

Metastatic germ cell tumour in effusion cytology

Germ cell tumours infrequently metastasise to body cavities, where early detection on fluid samples is possible and can spearhead early treatment and survival. A total of seven cases of metastatic germ cell tumours were retrieved out of 7500 effusion samples received for cytopathological examination from 2015 to 2021. Detailed cytological features of metastatic germ cell tumours in effusion samples were studied, along with a correlation between clinical, radiological, and histopathological features. A total of seven cases of metastatic germ cell tumours were analysed in effusion samples which included dysgerminoma (2), immature teratoma (2), yolk sac tumour (1), embryonal carcinoma (1), and mixed germ cell tumour (1). The smears showed predominantly discrete or loose clusters of cells. The cells with round nuclei and prominent nucleoli were helpful in detecting dysgerminoma and yolk sac tumours. Immature teratoma showed tiny groups of small cells and mature squamous cells. Serum tumour markers were raised in the majority of cases. Metastatic germ cell tumours in effusion are uncommon, but detailed clinical history, including serum markers and characteristic cytological features, are helpful in their diagnosis.

Illuminating the molecular mechanisms underlying shoot apical meristem homeostasis in plants.

Unlike animals, terrestrial plants are sessile and able to give rise to new organs throughout their lifetime. In the most extreme cases, they can survive for over a thousand years. With such protracted life cycles, plants have evolved sophisticated strategies to adapt to variable environments by coordinating their morphology as well as their growth, and have consequently acquired a high degree of developmental plasticity, which is supported by small groups of long-lived stem cells found in proliferative centers called meristems. Shoot apical meristems (SAMs) contain multipotent stem cells and provide a microenvironment that ensures both a self-renewable reservoir, to produce primordia and sustain growth, and a differentiating population that develops into all of the above-ground organs of land plants. The homeodomain transcription factor WUSCHEL (WUS) is expressed in the organizing center and acts as a master regulator to govern shoot stem cell homeostasis. In this review, I highlight recent advances in our understanding of the molecular mechanisms and signaling networks that underlie SAM maintenance, and discuss how plants utilize WUS to integrate intrinsic and extrinsic cues.

Tumour budding in colorectal carcinoma: Association with other histopathological prognostic parameters

Colorectal carcinoma (CRC) is the third leading cancer in India. Pathologists play a crucial role in assessing stage, analyzing surgical margins and documenting the histopathologic prognostic parameters. Tumour budding is one such prognostic parameter, defined as single cells or small groups of tumour cells (up to 4 cell clusters) at the invasive front of the tumour. The aim of this study is to examine the association of tumour budding with other histopathological prognostic parameters in patients with colorectal carcinoma.TheHematoxylin & Eosin (H &E) stained slides of 52 histopathologically diagnosed CRC resection specimens were reviewed and tumour budding (BD) was assessed into four grades under 200x power. Other histopathological prognostic parameters like tumour size, site, grade, laterality, lymphovascular invasion, perineural invasion, T and N stage were analyzed using descriptive statistics and Chi-square test with Software SPSS version 23.A higher BD score is seen to be more often associated with grade 3 tumour morphology, presence of perineural invasion, tumour size of 5cm or more and tumours located in the sigmoid colon or rectum. No association of tumour budding is seen with TIL’s or tumour of size < 5cm.Tumour budding is a practical and significant histological index for identification of high malignant potential and poor outcome in CRC patients with rectal or sigmoid colon location, size more than 5cm, perineural invasion and higher histological grade. Tumour budding may help identify patients who need a more intensive postoperative follow up and the possibility of adjuvant therapy.

Somatic Embryogenesis in Sugarcane (Saccharum spp.).

Somatic embryogenesis is the process by which embryos are formed from a single or small group of somatic cells in response to specific stimuli. Somatic embryogenesis has been applied to achieve mass clonal propagation on an industrial scale and to increase the agronomic performance of species of economic interest, including sugarcane. The use of somatic embryogenesis in sugarcane stands out as a biotechnological tool with a high potential for application in the clonal propagation of disease-free elite varieties, as an essential part of genetic transformation protocols, and in the production of synthetic seeds. A better understanding of each phase of somatic embryogenesis can help to optimize the process to enhance yields and produce high-quality emblings. In this chapter, we describe a detailed protocol for somatic embryogenesis in sugarcane (Saccharum sp.) to be used in research projects for small-scale production. This protocol comprises all steps from explant preparation to the establishment of sugarcane emblings.

Capturing Pluripotency and Beyond.

During the development of a multicellular organism, the specification of different cell lineages originates in a small group of pluripotent cells, the epiblasts, formed in the preimplantation embryo. The pluripotent epiblast is protected from premature differentiation until exposure to inductive cues in strictly controlled spatially and temporally organized patterns guiding fetus formation. Epiblasts cultured in vitro are embryonic stem cells (ESCs), which recapitulate the self-renewal and lineage specification properties of their endogenous counterparts. The characteristics of totipotency, although less understood than pluripotency, are becoming clearer. Recent studies have shown that a minor ESC subpopulation exhibits expanded developmental potential beyond pluripotency, displaying a characteristic reminiscent of two-cell embryo blastomeres (2CLCs). In addition, reprogramming both mouse and human ESCs in defined media can produce expanded/extended pluripotent stem cells (EPSCs) similar to but different from 2CLCs. Further, the molecular roadmaps driving the transition of various potency states have been clarified. These recent key findings will allow us to understand eutherian mammalian development by comparing the underlying differences between potency network components during development. Using the mouse as a paradigm and recent progress in human PSCs, we review the epiblast’s identity acquisition during embryogenesis and their ESC counterparts regarding their pluripotent fates and beyond.

Imaginal Disc Regeneration: Something Old, Something New.

Imaginal discs are simple epithelial sacs found in Drosophila larvae, which generate adult structures including wings and legs. The first studies of imaginal disc regeneration involved technically challenging transplantation experiments. Yet despite the difficulty, many aspects of regeneration including wound healing, blastema formation, and the repatterning of regenerated tissue were characterized. An important discovery was the phenomenon of transdetermination, where a small group of cells in regenerating tissue collectively switch fate ("collective cell reprogramming"). The development of genetic tissue-ablation systems over the last 12 years has energized this field, by making experiments less technically challenging, more reproducible, and by incorporating additional genetic analysis. Recent progress includes defining mechanistic links between early responses to wounding and the signaling pathways that drive proliferation, uncovering a role for localized silencing of damage-responsive enhancers to limit regenerative capacity as tissues mature, and identifying genes that maintain cellular plasticity within acceptable limits during regeneration.

Large cell morphology, CMYC+ tumour cells, and PD-1+ tumour cell/intense PD-L1+ cell reactions are important prognostic factors in nodal peripheral T-cell lymphomas with T follicular helper markers

BackgroundThe clinicopathological characteristics and prognostic factors in nodal peripheral T-cell lymphomas (PTCLs) with two or more T follicular helper markers (TFH+) are not adequately investigated.MethodsImmunohistologically, we selected 22 patients with TFH+ lymphoma (PTCL-TFH) in 47 of PTCL-not otherwise specified (NOS), and subclassified into large and small cell groups. We compared the two groups with 39 angioimmunoblastic T-cell lymphoma (AITL) and seven follicular T-cell lymphoma (F-TCL) patients. Prognostic factors were analysed by overall survival in patients with three types of TFH+ PTCLs.ResultsThirteen large cell and nine small cell PTCL-TFH patients had more than two TFH markers including programmed cell death-1 (PD-1). Large cell PTCL-TFH showed frequent CMYC expression in 10 patients (77%), and four of 11 large cell group (36%) had somatic RHOA G17V gene mutation by Sanger sequencing. Large cell PTCL-TFH patients showed significantly worse prognosis than those of the small cell group, AITL, and F-TCL (p < 0.05). In TFH+ PTCLs, CMYC+ tumour cells, and combined PD-1 ligand 1 (PD-L1) + tumour cells and intense reaction of PD-L1+ non-neoplastic cells (high PD-L1+ cell group) were significantly poor prognostic factors (p < 0.05). Combinations of CMYC+ or PD-1+ tumour cells and high PD-L1+ cell group indicated significantly poor prognosis (p < 0.01).ConclusionLarge cell PTCL-TFH indicated poor prognosis in TFH+ PTCLs. These data suggested that CMYC+ tumour cells and intense PD-L1+ cell reaction influenced tumour cell progression in TFH+ PTCLs, and PD-1+ tumour cell/intense PD-L1+ cell reactions may play a role in immune evasion.

El sistema especializado de conducción eléctrico del corazón. Los nodos del corazón y el sistema His-Purkinje. Sustrato anatómico de las vías accesorias

The specialized electrical conduction system of the heart. The heart nodes and the His-Purkinje system. Anatomical underpinnings of the accessory pathwaysThe muscular architecture of the heart myocardium is mainly composed of muscle cells, or cardiomyocytes, that are responsible for myocardial contraction as well as an interstitial space with a component of collagen-producing cells, or fibroblasts, surrounded by an extracellular matrix of connective tissue. Small cell groups predominantly located in the atria have neuroendocrine characteristics. In order to activate of the striated myocardium and excitation-contraction coupling through transmembrane action potential, the presence of specialized cells of the specific conduction system is necessary. The process and sequence of activation of the heart chambers occurs through the specific conduction system and is modulated by sympathetic and parasympathetic fibers of the neurovegetative system, which exercise autonomous control of it.The atrioventricular conduction system is composed of specialized myocytes and has an atrial component: the sinoatrial node and atrioventricular node, which are in contact with the atrial myocardium. Next, the bundle of His crosses the central fibrous body and divides into two bundles or branches—the left and the right—which branch into the ventricles, forming what is known as Purkinje fibers. The bundle of His and its branches are surrounded by a layer of connective tissue that is lost in the Purkinje fibers, allowing them to establish direct contact with the ventricular myocardium. Detailed knowledge of the specific conduction tissue is necessary to understand normal heart rhythm and the anatomical and electrical underpinnings that constitute heart arrhythmias.

Targeting Inflammatory Signaling in Prostate Cancer Castration Resistance.

Although castration-resistant prostate cancer (CRPC) as a whole, by its name, refers to the tumors that relapse and/or regrow independently of androgen after androgen deprivation therapy (ADT), untreated tumor, even in early-stage primary prostate cancer (PCa), contains androgen-independent (AI) PCa cells. The transformation of androgen-dependent (AD) PCa to AI PCa under ADT is a forced evolutionary process, in which the small group of AI PCa cells that exist in primary tumors has the unique opportunity to proliferate and expand selectively and dominantly, while some AD PCa cells that have escaped from ADT-induced death acquire the capability to survive in an androgen-depleted environment. The adaptation and reprogramming of both PCa cells and the tumor microenvironment (TME) under ADT make PCa much stronger than primary tumors so that, currently, there are no effective therapeutic methods available for the treatment of CRPC. Many mechanisms have been found to be related to the emergence and maintenance of PCa castration resistance; in this review, we focus on the role of inflammatory signaling in both PCa cells and the TME for the emergence and maintenance of CRPC and summarize the recent advances of therapeutic strategies that target inflammatory signaling for the treatment of CRPC.