Triggering receptor expressed on myeloid cells 2 (TREM2) is a single-pass transmembrane immune receptor that is mainly expressed on microglia in the brain and macrophages in the periphery. Recent ...studies have identified TREM2 as a risk factor for Alzheimer's disease (AD). Increasing evidence has shown that TREM2 can affect lipid metabolism both in the central nervous system (CNS) and in the periphery. In the CNS, TREM2 affects the metabolism of cholesterol, myelin, and phospholipids and promotes the transition of microglia into a disease-associated phenotype. In the periphery, TREM2 influences lipid metabolism by regulating the onset and progression of obesity and its complications, such as hypercholesterolemia, atherosclerosis, and nonalcoholic fatty liver disease. All these altered lipid metabolism processes could influence the pathogenesis of AD through several means, including affecting inflammation, insulin resistance, and AD pathologies. Herein, we will discuss a potential pathway that TREM2 mediates lipid metabolism to influence the pathogenesis of AD in both the CNS and periphery. Moreover, we discuss the possibility that TREM2 may be a key factor that links central and peripheral lipid metabolism under disease conditions, including AD. This link may be due to impacts on the integrity of the blood-brain barrier, and we introduce potential pathways by which TREM2 affects the blood-brain barrier. Moreover, we discuss the role of lipids in TREM2-associated treatments for AD. We propose some potential therapies targeting TREM2 and discuss the prospect and limitations of these therapies.
Hydrogen Sulfide Biology and Its Role in Cancer Khattak, Saadullah; Rauf, Mohd Ahmar; Khan, Nazeer Hussain ...
Molecules (Basel, Switzerland),
05/2022, Letnik:
27, Številka:
11
Journal Article
Recenzirano
Odprti dostop
Hydrogen sulfide (H
S) is an endogenous biologically active gas produced in mammalian tissues. It plays a very critical role in many pathophysiological processes in the body. It can be endogenously ...produced through many enzymes analogous to the cysteine family, while the exogenous source may involve inorganic sulfide salts. H
S has recently been well investigated with regard to the onset of various carcinogenic diseases such as lung, breast, ovaries, colon cancer, and neurodegenerative disorders. H
S is considered an oncogenic gas, and a potential therapeutic target for treating and diagnosing cancers, due to its role in mediating the development of tumorigenesis. Here in this review, an in-detail up-to-date explanation of the potential role of H
S in different malignancies has been reported. The study summarizes the synthesis of H
S, its roles, signaling routes, expressions, and H
S release in various malignancies. Considering the critical importance of this active biological molecule, we believe this review in this esteemed journal will highlight the oncogenic role of H
S in the scientific community.
The neutrophil is the major phagocyte and the final effector cell of the innate immunity, with a primary role in the clearance of extracellular pathogens. Using the broad array of cytokines, ...extracellular traps, and effector molecules as the humoral arm, neutrophils play a crucial role in the host defense against pathogen infections. On the other hand, the pathogen has the capacity to overcome neutrophil-mediated host defense to establish infection causing human disease. Pathogens, such as S. aureus, have the potential to thwart neutrophil chemotaxis and phagocytosis and thereby succeed in evading killing by neutrophils. Furthermore, S. aureus surviving within neutrophils promotes neutrophil cytolysis, resulting in the release of host-derived molecules that promote local inflammation. Here, we provide a detailed overview of the mechanisms by which neutrophils kill the extracellular pathogens and how pathogens evade neutrophils degradation. This review will provide insights that might be useful for the development of novel therapies against infections caused by antibiotic resistant pathogens.
Radiation‐induced myocardial fibrosis (RIMF) is a potentially lethal clinical complication of chest radiotherapy (RT) and a final stage of radiation‐induced heart disease (RIHD). RIMF is ...characterized by decreased ventricular elasticity and distensibility, which can result in decreased ejection fraction, heart failure and even sudden cardiac death. Together, these conditions impair the long‐term health of post‐RT survivors and limit the dose and intensity of RT required to effectively kill tumour cells. Although the exact mechanisms involving in RIMF are unclear, increasing evidence indicates that the occurrence of RIMF is related to various cells, regulatory molecules and cytokines. However, accurately diagnosing and identifying patients who may progress to RIMF has been challenging. Despite the urgent need for an effective treatment, there is currently no medical therapy for RIMF approved for routine clinical application. In this review, we investigated the underlying pathophysiology involved in the initiation and progression of RIMF before outlining potential preventative and therapeutic strategies to counter this toxicity.
Obesity is considered as a risk factor for chronic health diseases such as heart diseases, cancer and diabetes 2. Reduced physical activities, lifestyle, poor nutritional diet and genetics are among ...the risk factors associated with the development of obesity. In recent years, several studies have explored the link between the gut microbiome and the progression of diseases including obesity, with the shift in microbiome abundance and composition being the main focus. The alteration of gut microbiome composition affects both nutrients metabolism and specific gene expressions, thereby disturbing body physiology. Specifically, the abundance of fibre‐metabolizing microbes is associated with weight loss and that of protein and fat‐metabolizing bacteria with weight gain. Various internal and external factors such as genetics, maternal obesity, mode of delivery, breastfeeding, nutrition, antibiotic use and the chemical compounds present in the environment are known to interfere with the richness of the gut microbiota (GM), thus influencing weight gain/loss and ultimately the development of obesity. However, the effectiveness of each factor in potentiating the shift in microbes’ abundance to result in significant changes that can lead to obesity is not yet clear. In this review, we will highlight the factors involved in shaping GM, their influence on obesity and possible interventions. Understanding the influence of these factors on the diversity of the GM and how to improve their effectiveness on disease conditions could be keys in the treatment of metabolic diseases.
In recent years, a vast number of potential cancer therapeutic targets have emerged. However, developing efficient and effective drugs for the targets is of major concern. Hydrogen sulfide (H
S), one ...of the three known gasotransmitters, is involved in the regulation of various cellular activities such as autophagy, apoptosis, migration, and proliferation. Low production of H
S has been identified in numerous cancer types. Treating cancer cells with H
S donors is the common experimental technique used to improve H
S levels; however, the outcome depends on the concentration/dose, time, cell type, and sometimes the drug used. Both natural and synthesized donors are available for this purpose, although their effects vary independently ranging from strong cancer suppressors to promoters. Nonetheless, numerous signaling pathways have been reported to be altered following the treatments with H
S donors which suggest their potential in cancer treatment. This review will analyze the potential of H
S donors in cancer therapy by summarizing key cellular processes and mechanisms involved.
Aberrant variations in angiogenesis have been observed in tumor tissues with abnormal stiffness of extracellular matrix (ECM). However, it remains largely unclear how ECM stiffness influences tumor ...angiogenesis. Numerous studies have reported that vascular endothelial growth factor-A (VEGF-A) released from tumor cells plays crucial roles in angiogenesis. Hence, we demonstrated the role of ECM stiffness in VEGF-A release from neuroblastoma (NB) cells and the underlying mechanisms. Based on 17 NB clinical samples, a negative correlation was observed between the length of blood vessels and stiffness of NB tissues. In vitro, an ECM stiffness of 30 kPa repressed the secretion of VEGF
165
from NB cells which subsequently inhibited the tube formation of human umbilical vein endothelial cells (HUVECs). Knocked down VEGF
165
in NB cells or blocked VEGF
165
with neutralizing antibodies both repressed the tube formation of HUVECs. Specifically, 30 kPa ECM stiffness repressed the expression and nuclear accumulation of Yes-associated protein (YAP) to regulate the expression of Serine/Arginine Splicing Factor 1 (SRSF1) via Runt-related transcription factor 2 (RUNX2), which may then subsequently induce the expression and secretion of VEGF
165
in NB tumor cells. Through implantation of 3D col-Tgels with different stiffness into nude mice, the inhibitory effect of 30 kPa on NB angiogenesis was confirmed in vivo. Furthermore, we found that the inhibitory effect of 30 kPa stiffness on NB angiogenesis was reversed by YAP overexpression, suggesting the important role of YAP in NB angiogenesis regulated by ECM stiffness. Overall, our work not only showed a regulatory effect of ECM stiffness on NB angiogenesis, but also revealed a new signaling axis, YAP-RUNX2-SRSF1, that mediates angiogenesis by regulating the expression and secretion of VEGF
165
from NB cells. ECM stiffness and the potential molecules revealed in the present study may be new therapeutic targets for NB angiogenesis.
Abnormal migration and proliferation of vascular smooth muscle cells (VSMCs) are the pathological basis of hyperplasia during vein graft disease. It remains unknown if circular RNAs (circRNAs) are ...involved in vein graft disease. In the present study, a rat vein graft model was constructed by the “cuff” technique, and whole transcriptome deep sequencing was applied to identify differential circRNAs in the grafted vein compared to the control. We identified a novel circRNA, named circTET3, whose structure was verified by Sanger sequencing and RNase R digestion. CircTET3 was increased in the grafted vein and stably located in the cytoplasm as detected by fluorescence in situ hybridization. Knockdown of circTET3 suppressed VSMC migration by acting as an endogenous miR‐351‐5p sponge detected by RNA pull‐down and dual‐luciferase reporter assays. PTPN1 was the targeted gene due to the competitive binding of circTET3 to miR‐351‐5p. This regulatory pathway may serve as a potential therapeutic avenue against intimal hyperplasia in vein graft disease.
CircTET3, which was transcribed from the 4th exon of tet3 and stably located in the cytoplasm, was increased in the grafted vein compared to the control vein. CircTET3 suppressed vascular smooth muscle cells migration by acting as an endogenous miR‐351‐5p sponge. PTPN1 was the targeted gene due to the competitive binding of circTET3 to miR‐351‐5p.
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•Skin cancer is a fatal public health concern rising continuously all over the world.•Several environmental and genetic risk factors are associated with cutaneous carcinogenesis.•Use ...of nanocarriers for targeted delivery of anticancer agents is the most advanced approach.•Polymeric structures are suitable for tumor selective delivery of drugs, genes and imaging agents.•Polymeric micro/nanostructures have successfully used for combination anticancer therapies.
Skin cancer has been the leading type of cancer worldwide. Melanoma and non-melanoma skin cancers are now the most common types of skin cancer that have been reached to epidemic proportion. Based on the rapid prevalence of skin cancers, and lack of efficient drug delivery systems, it is essential to surge the possible ways to prevent or cure the disease.
Although surgical modalities and therapies have been made great progress in recent years, however, there is still an urgent need to alleviate its increased burden. Hence, understanding the precise pathophysiological signaling mechanisms and all other factors of such skin insults will be beneficial for the development of more efficient therapies.
In this review, we explained new understandings about onset and development of skin cancer and described its management via polymeric micro/nano carriers-based therapies, highlighting the current key bottlenecks and future prospective in this field. In therapeutic drug/gene delivery approaches, polymeric carriers-based system is the most promising strategy. This review discusses that how polymers have successfully been exploited for development of micro/nanosized systems for efficient delivery of anticancer genes and drugs overcoming all the barriers and limitations associated with available conventional therapies. In addition to drug/gene delivery, intelligent polymeric nanocarriers platforms have also been established for combination anticancer therapies including photodynamic and photothermal, and for theranostic applications. This portfolio of latest approaches could promote the blooming growth of research and their clinical availability.
Central nervous system disorders, especially neurodegenerative diseases, are a public health priority and demand a strong scientific response. Various therapy procedures have been used in the past, ...but their therapeutic value has been insufficient. The blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier is two of the barriers that protect the central nervous system (CNS), but are the main barriers to medicine delivery into the CNS for treating CNS disorders, such as brain tumors, Parkinson's disease, Alzheimer's disease, and Huntington's disease. Nanotechnology-based medicinal approaches deliver valuable cargos targeting molecular and cellular processes with greater safety, efficacy, and specificity than traditional approaches. CNS diseases include a wide range of brain ailments connected to short- and long-term disability. They affect millions of people worldwide and are anticipated to become more common in the coming years. Nanotechnology-based brain therapy could solve the BBB problem. This review analyzes nanomedicine's role in medication delivery; immunotherapy, chemotherapy, and gene therapy are combined with nanomedicines to treat CNS disorders. We also evaluated nanotechnology-based approaches for CNS disease amelioration, with the intention of stimulating the immune system by delivering medications across the BBB.
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