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Topic Review
The H+ Transporter SLC4A11
Solute-linked cotransporter, SLC4A11, a member of the bicarbonate transporter family, is an electrogenic H+ transporter activated by NH3 and alkaline pH. Although SLC4A11 does not transport bicarbonate, it shares many properties with other members of the SLC4 family. SLC4A11 mutations can lead to corneal endothelial dystrophy and hearing deficits that are recapitulated in SLC4A11 knock-out mice. SLC4A11, at the inner mitochondrial membrane, facilitates glutamine catabolism and suppresses the production of mitochondrial superoxide by providing ammonia-sensitive H+ uncoupling that reduces glutamine-driven mitochondrial membrane potential hyperpolarization. Mitochondrial oxidative stress in SLC4A11 KO also triggers dysfunctional autophagy and lysosomes, as well as ER stress. SLC4A11 expression is induced by oxidative stress through the transcription factor NRF2, the master regulator of antioxidant genes.
  • 809
  • 25 Jan 2022
Topic Review
Emerging Role of ALDH1A1 in Cancer Stem Cells
The protein family of aldehyde dehydrogenases (ALDH) encompasses nineteen members. The ALDH1 subfamily consists of enzymes with similar activity, having the capacity to neutralize lipid peroxidation products and to generate retinoic acid; however, only ALDH1A1 emerges as a significant risk factor in acute myeloid leukemia. Not only is the gene ALDH1A1 on average significantly overexpressed in the poor prognosis group at the RNA level, but its protein product, ALDH1A1 protects acute myeloid leukemia cells from lipid peroxidation byproducts. This capacity to protect cells can be ascribed to the stability of the enzyme under conditions of oxidant stress. The capacity to protect cells is evident both in vitro, as well as in mouse xenografts of those cells, shielding cells effectively from a number of potent antineoplastic agents. However, the role of ALDH1A1 in acute myeloid leukemia has been unclear in the past due to evidence that normal cells often have higher aldehyde dehydrogenase activity than leukemic cells. This being true, ALDH1A1 RNA expression is significantly associated with poor prognosis. It is hence imperative that ALDH1A1 is methodically targeted, particularly for the acute myeloid leukemia patients of the poor prognosis risk group that overexpress ALDH1A1 RNA.
  • 809
  • 09 Jun 2023
Topic Review
PIM1 Inhibition Affects Glioblastoma Stem Cell Behavior
Despite comprehensive therapy and extensive research, glioblastoma (GBM) still represents the most aggressive brain tumor in adults. Glioma stem cells (GSCs) are thought to play a major role in tumor progression and resistance of GBM cells to radiochemotherapy. The PIM1 kinase has become a focus in cancer research.
  • 808
  • 11 Nov 2021
Topic Review
LncRNAs in Pulmonary Arterial Hypertension
Pulmonary arterial hypertension (PAH) is a debilitating condition of the pulmonary circulatory system that occurs in patients of all ages and if untreated, eventually leads to right heart failure and death.
  • 808
  • 02 Dec 2021
Topic Review
Circular RNAs in Metabolism
Circular RNAs (circRNAs) are an emerging group of long non-coding RNAs (lncRNAs) and have attracted attention again according to the progress in high-throughput sequencing in recent years. circRNAs are genome transcripts produced from pre-messenger (m)RNA regions in a specific process called “back-splicing,” which forms covalently closed continuous loops.
  • 808
  • 30 Jan 2022
Topic Review
Therapeutic Role of Chromatin Remodeling in Heart Failure
Cardiovascular diseases are a major cause of death globally, with no cure to date. Many interventions have been studied and suggested, of which epigenetics and chromatin remodeling have been the most promising. Major advancements have been made in the field of chromatin remodeling, particularly for the treatment of heart failure, because of innovations in bioinformatics and gene therapy. Specifically, understanding changes to the chromatin architecture have been shown to alter cardiac disease progression via variations in genomic sequencing, targeting cardiac genes, using RNA molecules, and utilizing chromatin remodeler complexes.
  • 808
  • 22 Feb 2023
Topic Review
Therapeutic Strategies for Leukemic Stem Cells
Notoriously known for their capacity to reconstitute hematological malignancies in vivo, leukemic stem cells (LSCs) represent key drivers of therapeutic resistance and disease relapse, posing as a major medical dilemma. Despite having low abundance in the bulk leukemic population, LSCs have developed unique molecular dependencies and intricate signaling networks to enable self-renewal, quiescence, and drug resistance. The abundance of molecular and phenotypical aberrations associated with LSCs offers a wealth of promising therapeutic targets. Therapeutic designs have focused on drugging surface biomarkers selectively overexpressed on LSCs, antagonizing the protective bone marrow (BM) microenvironment niche to dismantle LSC dormancy, blocking signal transduction to re-sensitize resistant LSCs to available chemotherapeutics, and even expediting the drug supply pipeline through drug repurposing. Evidently, growing insight into the biological properties and prognostic values of LSCs have prompted the implementation of many clinical trials and have laid critical groundwork for the development of more effective, personalized, scalable, and less-toxic therapeutic strategies.
  • 807
  • 08 Oct 2022
Topic Review
Endothelial Senescence on Angiogenesis in Alzheimer’s Disease
Endothelial cells are constantly exposed to environmental stress factors that, above a certain threshold, trigger cellular senescence and apoptosis. The altered vascular function affects new vessel formation and endothelial fitness, contributing to the progression of age-related diseases. 
  • 807
  • 26 Jul 2023
Topic Review
Extracellular ncRNAs
Non-coding RNAs (ncRNAs) are key regulators of post-transcriptional gene expression in prokaryotic and eukaryotic organisms. These molecules can interact with mRNAs or proteins, affecting a variety of cellular functions. Emerging evidence shows that intra/inter-species and trans-kingdom regulation can also be achieved with exogenous RNAs, which are exported to the extracellular medium, mainly through vesicles. In bacteria, membrane vesicles (MVs) seem to be the more common way of extracellular communication.
  • 805
  • 06 Jan 2021
Topic Review
Tumor Microenvironment in Glioblastoma Niches
Among gliomas, malignant gliomas and more specifically glioblastomas (GBM) are a challenge in their diagnosis and treatment. Monocytes have been proved to actively participate in tumor growth, giving rise to the support of tumor-associated macrophages (TAMs). In GBM, TAMs represent up to one-half of the tumor mass cells, including both infiltrating macrophages and resident brain microglia. Infiltrating macrophages/monocytes constituted ~ 85% of the total TAM population, they have immune functions, and they can release a wide array of growth factors and cytokines in response to those factors produced by tumor and non-tumor cells from the tumor microenvironment (TME). This cell population has been increasingly studied in GBM TME to understand its role in tumor progression and therapeutic resistance. 
  • 804
  • 07 Apr 2023
Topic Review
Intrinsic Mechanisms of Hippocampal Neural Stem Cell Aging
Since Joseph Altman's groundbreaking research revealing neurogenesis in the adult rat hippocampus, the field has witnessed an exponential growth in publications. Researchers know that the adult hippocampus harbors a pool of adult neural stem cells (NSCs) driving life-long neurogenesis and plasticity. Aging significantly influences NSC functions, leading to a diminished capacity for generating new neurons and contributing to the gradual deterioration of hippocampus-related cognitive functions. Although the mechanisms underlying this age-related decline are only partially understood, factors such as increased NSC quiescence, altered differentiation patterns and NSC exhaustion have been linked to it.
  • 804
  • 30 Nov 2023
Topic Review
T Lymphocytes in Brief
T lymphocytes, often referred to as T cells, are a crucial component of the immune system. These specialized white blood cells originate in the bone marrow and undergo maturation in the thymus gland. T cells are known for their remarkable specificity in recognizing antigens presented by other cells. This recognition is mediated by the T cell receptor (TCR) on their surface. There are two primary subsets of T lymphocytes: CD4+ T cells (helper T cells) and CD8+ T cells (cytotoxic T cells). Helper T cells assist in coordinating immune responses, while cytotoxic T cells directly target and destroy infected or abnormal cells. T cells also have memory subsets that provide long-term immunity. T lymphocytes play pivotal roles in defending the body against infections, regulating immune responses, and contributing to the immune system's ability to distinguish between self and non-self. Their diverse functions and clinical significance make T cells a subject of extensive research and therapeutic exploration in the field of immunology.
  • 803
  • 08 Oct 2023
Topic Review
Immune Checkpoint Molecules
Antibodies against inhibitory immune checkpoint molecules (ICPMs), referred to as immune checkpoint inhibitors (ICIs), have gained a prominent place in cancer therapy. Several ICIs in clinical use have been engineered to be devoid of effector functions because of the fear that ICIs with preserved effector functions could deplete immune cells, thereby curtailing antitumor immune responses. ICPM ligands (ICPMLs), however, are often overexpressed on a sizeable fraction of tumor cells of many tumor types and these tumor cells display an aggressive phenotype with changes typical of tumor cells undergoing an epithelial-mesenchymal transition. Moreover, immune cells expressing ICPMLs are often endowed with immunosuppressive or immune-deviated functionalities. Taken together, these observations suggest that compounds with the potential of depleting cells expressing ICPMLs may become useful tools for tumor therapy.
  • 802
  • 28 Apr 2021
Topic Review
NcRNA in Intracellular/Intercellular DDR
Non-coding RNA (ncRNA) has recently emerged as a vital component of the DNA damage response (DDR), which was previously believed to be solely regulated by proteins. Many species of ncRNA can directly or indirectly influence DDR and enhance DNA repair, particularly in response to double-strand DNA breaks, which may hold therapeutic potential in the context of cancer. These include long non-coding RNA (lncRNA), microRNA, damage-induced lncRNA, DNA damage response small RNA, and DNA:RNA hybrid structures, which can be categorised as cis or trans based on the location of their synthesis relative to DNA damage sites. Mechanisms of RNA-dependent DDR include the recruitment or scaffolding of repair factors at DNA break sites, the regulation of repair factor expression, and the stabilisation of repair intermediates. DDR can also be communicated intercellularly via exosomes, leading to bystander responses in healthy neighbour cells to generate a population-wide response to damage. Many microRNA species have been directly implicated in the propagation of bystander DNA damage, autophagy, and radioresistance, which may prove significant for enhancing cancer treatment via radiotherapy. 
  • 802
  • 29 Sep 2021
Topic Review
Cellular Senescence in Metabolic-Associated Kidney Disease
Metabolic syndrome (MetS), a complex of interrelated risk factors for cardiovascular disease and diabetes, is characterized by central obesity (increased waist circumference), hyperglycemia, dyslipidemia (high triglyceride blood levels and low high-density lipoprotein blood levels), and increased blood pressure. As an important metabolic organ, the kidney has a close relationship with metabolic syndrome. MetS usually aggravates kidney damage and causes or aggravates kidney pathologies, typically manifested as microalbuminuria and renal insufficiency. For example, severe obesity can lead to glomerular hypertrophy and glomerular sclerosis, leading to proteinuria. This is called obesity-related nephropathy, which was first discovered in 1974 by Weisinger. Diabetic capillary complications can lead to pathological changes to the kidney, thickening of the glomerular capillary basement membrane, and widening of the mesangium. Clinical manifestations can change from proteinuria to uremia. Similarly, hypertension-related nephropathy is a serious complication of hypertension, which is characterized by arteriosclerotic kidneys. Clinical manifestations include nocturia increasing, albuminuria, and finally, uremia. For hyperlipidemia, although there is no hyperlipidemia-related nephropathy, a large number of studies have shown that lipids have an effect on the proliferation and signal transduction of glomerular cells, and accelerate glomerulosclerosis through inflammatory reaction. These metabolic diseases often exist at the same time, and can promote each other; furthermore, they share a common pathophysiological basis: insulin resistance. It is widely believed that there exists a significant relationship between hyperglycemia, hypertension, and hyperlipemia.
  • 802
  • 18 Nov 2022
Topic Review
Early Spliceosomal Complex
Crucial for the definition of the exon–intron junctions is the early spliceosomal complex (E complex), also called commitment complex (CC) in yeast. This minimal complex consists of the U1-snRNP, SF1, and U2AFand is sufficient to recognize all intron definingciselements. Base pairing between the 5′ ss and the 5′-end of U1 snRNA defines the start of the intron.
  • 801
  • 06 Dec 2021
Topic Review
AtWAKL10
Receptor-like kinases (RLKs) constitute a large group of cell surface receptors that play crucial roles in multiple biological processes. However, the function of most RLKs in plants has not been extensively explored, and much less for the class of cell wall associated kinases (WAKs) and WAK-like kinases (WAKLs). In this study, analyses of developmental expression patterns uncovered a putative role of AtWAKL10 in modulating leaf senescence, which was further investigated at physiological and molecular levels. The expression level of AtWAKL10 increased with the developmental progression and was rapidly upregulated in senescing leaf tissues. The promoter of AtWAKL10 contains various defense and hormone responsive elements, and its expression could be significantly induced by exogenous ABA, JA and SA. Moreover, the loss-of-function atwakl10 mutant showed earlier senescence along the course of natural development and accelerated leaf senescence under darkness and hormonal stresses, while plants overexpressing AtWAKL10 showed an opposite trend.
  • 798
  • 18 May 2021
Topic Review
Extracellular Vesicles as Novel Treatments
Mesenchymal stem/stromal cells (MSCs) represent a promising therapy for musculoskeletal diseases. There is compelling evidence indicating that MSC effects are mainly mediated by paracrine mechanisms and in particular by the secretion of extracellular vesicles (EVs). Many studies have thus suggested that EVs may be an alternative to cell therapy with MSCs in tissue repair.
  • 798
  • 14 Oct 2021
Topic Review
RNF168 in Tumor Progression
RING finger protein 168 (RNF168) is an E3 ubiquitin ligase with the RING finger domain. It is an important protein contributing to the DNA double-strand damage repair pathway. 
  • 798
  • 06 Feb 2023
Topic Review
Intratumor Heterogeneity in Hepatocellular Carcinoma: Challenges and Opportunities
Hepatocellular carcinoma (HCC) represents a leading cause of cancer-related death, but it remains difficult to treat. Intratumor genetic and phenotypic heterogeneity are inherent properties of breast, skin, lung, prostate, and brain tumors, and intratumor heterogeneity (ITH) helps define prognosis and therapeutic response in these cancers. Several recent studies estimate that ITH is inherent to HCC and attribute the clinical intractability of HCC to this heterogeneity.
  • 797
  • 25 Nov 2021
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