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Topic Review
Apoptosis and (in) Pain—Potential Clinical Implications
The deregulation of apoptosis is involved in the development of several pathologies, and recent evidence suggests that apoptosis may be involved in chronic pain, namely in neuropathic pain. Neuropathic pain is a chronic pain state caused by primary damage or dysfunction of the nervous system. Recently, it was found that nerve endings contain transient receptor potential (TRP) channels that sense and detect signals released by injured tissues and respond to these damage signals. TRP channels are similar to the voltage-gated potassium channels or nucleotide-gated channels that participate in calcium and magnesium homeostasis. TRP channels allowing calcium to penetrate into nerve terminals can activate apoptosis, leading to nerve terminal destruction. Further, some TRPs are activated by acid and reactive oxygen species (ROS). ROS are mainly produced in the mitochondrial respiratory chain, and an increase in ROS production and/or a decrease in the antioxidant network may induce oxidative stress (OS). Depending on the OS levels, they can promote cellular proliferation and/or cell degeneration or death. Previous studies have indicated that proinflammatory cytokines, such as tumor necrosis factor-α (TNF-α), play an important role in the peripheral mediation of neuropathic pain. 
  • 1.3K
  • 29 Aug 2022
Topic Review
MEG3 in Carcinogenesis of Heavy Metals
Maternally expressed gene 3 (MEG3), a long non-coding RNAs (lncRNA), functions as a tumor suppressor. MEG3 regulates cell proliferation, cell cycle, apoptosis, hypoxia, autophagy, and many other processes involved in tumor development. MEG3 is downregulated in various cancer cell lines and primary human cancers. Heavy metals, such as hexavalent chromium (Cr(VI)), arsenic, nickel, and cadmium, are confirmed human carcinogens. The exposure of cells to these metals causes a variety of cancers. Most heavy metals are toxic and carcinogenic to humans. Heavy metals are widely utilized in various industrial and agricultural products, such as paints, batteries, pigments, electronic waste, and insecticides/pesticides. Contaminated heavy metals in the environment flow into soil, lake, river, and ocean through rain and groundwater, where the metals accumulate via the circulating bio-system, resulting in high concentrations in humans. Chromium (Cr(VI)), arsenic (As), nickel (Ni), and cadmium (Cd) are listed as Group 1 human carcinogens by the International Agency for Research on Cancer (IARC). Studies have indicated that exposure to these metals disrupts cellular signaling pathways, such as damaged repair processes, reduced gene expression of tumor suppressors, and aberrant metabolism, leading to carcinogenesis.
  • 1.3K
  • 27 Feb 2023
Topic Review
Clinical Trial
Clinical trials are experiments or observations done in clinical research. Such prospective biomedical or behavioral research studies on human participants are designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines, drugs, dietary choices, dietary supplements, and medical devices) and known interventions that warrant further study and comparison. Clinical trials generate data on safety and efficacy. They are conducted only after they have received health authority/ethics committee approval in the country where approval of the therapy is sought. These authorities are responsible for vetting the risk/benefit ratio of the trial – their approval does not mean that the therapy is 'safe' or effective, only that the trial may be conducted. Depending on product type and development stage, investigators initially enroll volunteers or patients into small pilot studies, and subsequently conduct progressively larger scale comparative studies. Clinical trials can vary in size and cost, and they can involve a single research center or multiple centers, in one country or in multiple countries. Clinical study design aims to ensure the scientific validity and reproducibility of the results. Costs for clinical trials can range into the billions of dollars per approved drug. The sponsor may be a governmental organization or a pharmaceutical, biotechnology or medical device company. Certain functions necessary to the trial, such as monitoring and lab work, may be managed by an outsourced partner, such as a contract research organization or a central laboratory. Only 10 percent of all drugs started in human clinical trials become an approved drug.
  • 1.3K
  • 29 Sep 2022
Topic Review
Thrombospondin-1 CD47 Signalling
Recent advances provide evidence that the cellular signalling pathway comprising the ligand-receptor duo of thrombospondin-1 (TSP1) and CD47 is involved in mediating a range of diseases affecting renal, vascular, and metabolic function, as well as cancer. In several instances, research has barely progressed past pre-clinical animal models of disease and early phase 1 clinical trials, while for cancers, anti-CD47 therapy has emerged from phase 2 clinical trials in humans as a crucial adjuvant therapeutic agent. This has important implications for interventions that seek to capitalize on targeting this pathway in diseases where TSP1 and/or CD47 play a role. Despite substantial progress made in our understanding of this pathway in malignant and cardiovascular disease, knowledge and translational gaps remain regarding the role of this pathway in kidney and metabolic diseases, limiting identification of putative drug targets and development of effective treatments. This review considers recent advances reported in the field of TSP1-CD47 signalling, focusing on several aspects including enzymatic production, receptor function, interacting partners, localization of signalling, matrix-cellular and cell-to-cell cross talk. The potential impact that these newly described mechanisms have on health, with a particular focus on renal and metabolic disease, is also discussed.
  • 1.2K
  • 02 Jul 2021
Topic Review
Immunotherapy in ACC
Adrenocortical carcinoma (ACC) is a rare cancer of the adrenal gland that is frequently associated with excess production of adrenal hormones. Although surgical resection may be curative in early-stage disease, few effective therapeutic options exist in the inoperable advanced or metastatic setting. Immunotherapies, inclusive of a broad array of immune-activating and immune-modulating antineoplastic agents, have demonstrated clinical benefit in a wide range of solid and hematologic malignancies. Immunotherapies that have been evaluated in clinical trials for ACC include the immune checkpoint inhibitors pembrolizumab, nivolumab, and avelumab. Other immunotherapies that have been evaluated include the monoclonal antibodies figitumumab and cixutumumab directed against the ACC-expressed insulin-like growth factor 1 (IGF-1) receptor, the recombinant cytotoxin interleukin-13-pseudomonas exotoxin A, and autologous tumor lysate dendritic cell vaccine.
  • 1.2K
  • 08 Jun 2021
Topic Review
Ginger Polysaccharides
Zingiber officinale Roscoe. (ginger) is a widely distributed plant with a long history of cultivation and consumption. Ginger can be used as a spice, condiment, food, nutrition, and as an herb. Significantly, the polysaccharides extracted from ginger show surprising and satisfactory biological activity, which explains the various benefits of ginger on human health, including anti-influenza, anti-colitis, anti-tussive, anti-oxidant, anti-tumor effects. 
  • 1.2K
  • 11 May 2023
Topic Review
Biological and Physiological Role of Oxidative Stress
Antioxidants are a class of molecules with an innate affinity to neutralize reactive oxygen species (ROS), which are known to cause oxidative stress. Oxidative stress has been associated with a wide range of diseases mediated by physiological damage to the cells.
  • 1.2K
  • 06 Jan 2022
Topic Review
Therapeutic Potential of Certain Terpenoids as Anticancer Agents
Cancer is a life-threatening disease and is considered to be among the leading causes of death worldwide. Chemoresistance, severe toxicity, relapse and metastasis are the major obstacles in cancer therapy. Therefore, introducing new therapeutic agents for cancer remains a priority to increase the range of effective treatments. Terpenoids, a large group of secondary metabolites, are derived from plant sources and are composed of several isoprene units. The high diversity of terpenoids has drawn attention to their potential anticancer and pharmacological activities. Some terpenoids exhibit an anticancer effect by triggering various stages of cancer progression, for example, suppressing the early stage of tumorigenesis via induction of cell cycle arrest, inhibiting cancer cell differentiation and activating apoptosis. At the late stage of cancer development, certain terpenoids are able to inhibit angiogenesis and metastasis via modulation of different intracellular signaling pathways. Significant progress in the identification of the mechanism of action and signaling pathways through which terpenoids exert their anticancer effects has been highlighted. 
  • 1.2K
  • 07 Mar 2022
Topic Review
The Genus Tulbaghia
Amaryllidaceae is a significant source of bioactive phytochemicals with a strong propensity to develop new drugs. The genera Allium, Tulbaghia, Cyrtanthus and Crinum biosynthesize novel alkaloids and other phytochemicals with traditional and pharmacological uses. Amaryllidaceae biomolecules exhibit multiple pharmacological activities such as antioxidant, antimicrobial, and immunomodulatory effects.
  • 1.2K
  • 29 Jul 2022
Topic Review
Adipose Cells and Myocytes in Sarcopenic Obesity
As a result of aging, body composition changes, with a decline in muscle mass and an increase in adipose tissue (AT), which reallocates from subcutaneous to visceral depots and stores ectopically in the liver, heart and muscles. Furthermore, with aging, muscle and AT, both of which have recognized endocrine activity, become dysfunctional and contribute, in the case of positive energy balance, to the development of sarcopenic obesity (SO). SO is defined as the co-existence of excess adiposity and low muscle mass and function, and its prevalence increases with age. SO is strongly associated with greater morbidity and mortality. The pathogenesis of SO is complex and multifactorial. 
  • 1.2K
  • 16 Nov 2022
Topic Review
Nanoparticle Features That Impact Liver-Targeting and Tolerogenic Effects
Liver-targeting nanoparticles have emerged as a promising platform for the induction of immune tolerance by taking advantage of the liver’s unique tolerogenic properties and nanoparticles’ physicochemical flexibility. Such an approach provides a versatile solution to the treatment of a diversity of immunologic diseases.
  • 1.2K
  • 05 Jan 2024
Topic Review
Stem Cell Niche Microenvironment
Limbal epithelial stem cells (LESCs), which live in a specialized stem cell niche (SCN), are crucial for the survival of the human corneal epithelium. They live at the bottom of the limbal crypts, in a physically enclosed microenvironment with a number of neighboring niche cells. Scientists also simplified features of these diverse microenvironments for more analysis in situ by designing and recreating features of different SCNs. 
  • 1.2K
  • 22 Sep 2021
Topic Review
Obesity and Wound Healing
Chronic wounds represent nowadays a major challenge for both clinicians and researchers in the regenerative setting. Obesity represents one of the major comorbidities in patients affected by chronic ulcers and therefore diverse studies aimed at assessing possible links between these two morbid conditions are currently ongoing. In particular, adipose tissue has recently been described as having metabolic and endocrine functions rather than serving as a mere fat storage deposit. In this setting, adipose-derived stem cells, a peculiar subset of mesenchymal stromal/stem cells (MSCs) located in adipose tissue, have been demonstrated to possess regenerative and immunological functions with a key role in regulating both adipocyte function and skin regeneration.
  • 1.2K
  • 24 Mar 2023
Topic Review
CXCL1 in Noncancer Diseases of the Cardiovascular System
CXC motif chemokine ligand 1 (CXCL1), a cytokine belonging to the CXC sub-family of chemokines with CXC motif chemokine receptor 2 (CXCR2) as its main receptor, causes the migration and infiltration of neutrophils to the sites of high expression. This implicates CXCL1 in many adverse conditions associated with inflammation and the accumulation of neutrophils. Herein, the significance of CXCL1 in selected diseases of the cardiovascular system is described.
  • 1.2K
  • 29 Dec 2022
Topic Review
Lipoxygenases and Arachidonic Acid in Glioblastoma Multiforme
Glioblastoma multiforme is a brain tumor with a very unfavorable prognosis, where the vast majority of patients do not survive a year after diagnosis. Arachidonic acid ARA C20:4n-6 in humans is not synthesized de novo but from linoleic acid C18:2n-6 in the polyunsaturated fatty acid (PUFA) biosynthesis pathway. In addition to the cyclooxygenases (COX) pathway, PUFA can be transformed with lipoxygenases (LOX). These enzymes exhibit dioxygenase activity, catalyzing the insertion of a hydroperoxyl group into a PUFA, most commonly ARA 20:4n-6.
  • 1.2K
  • 10 Feb 2023
Topic Review
Carcinogens in Areca Nut
A large body of literature found that habitual areca nut (AN) chewing was tightly associated with the occurrence and development of oral, esophageal, and pharyngeal cancers. In addition, many studies revealed that long-term AN usage increased the risk of hepatocellular carcinoma (HCC).
  • 1.2K
  • 15 Dec 2022
Topic Review
Ursolic Acid Pharmacodynamics towards Nuclear Receptor
Nuclear receptors (NRs) form a family of druggable transcription factors that are regulated by ligand binding to orchestrate multifaceted physiological functions, including reproduction, immunity, metabolism, and growth. NRs represent attractive and valid targets for the management and treatment of a vast array of ailments. Pentacyclic triterpenes (PTs) are ubiquitously distributed natural products in medicinal and aromatic plants, of which ursolic acid (UA) is an extensively studied member, due to its diverse bio-pertinent activities against different cancers, inflammation, aging, obesity, diabetes, dyslipidemia, and liver injury.
  • 1.2K
  • 23 Oct 2023
Topic Review
Intercellular Communication with Endothelial cells
As a cellular interface between the blood and tissues, the endothelial cell (EC) monolayer is involved in the control of key functions including vascular tone, permeability and homeostasis, leucocyte trafficking and hemostasis. EC regulatory functions require long-distance communications between ECs, circulating hematopoietic cells and other vascular cells for efficient adjusting thrombosis, angiogenesis, inflammation, infection and immunity. This intercellular crosstalk operates through the extracellular space and is orchestrated in part by the secretory pathway and the exocytosis of Weibel Palade Bodies (WPBs), secretory granules and extracellular vesicles (EVs).
  • 1.2K
  • 20 Aug 2021
Topic Review
miRNA Dysregulation in Cancer
miRNAs are a subset of non-coding RNAs that regulate the expression of a multitude of genes post-transcriptionally and thus are potential diagnostic, prognostic, and predictive biomarkers and have also emerged as potential therapeutics. Because miRNAs are involved in the post-transcriptional regulation of their target mRNAs via repressing gene expression, defects in miRNA biogenesis pathway and miRNA expression perturb the expression of a multitude of oncogenic or tumor-suppressive genes that are involved in the pathogenesis of various cancers. As such, numerous miRNAs have been identified to be downregulated or upregulated in many cancers, functioning as either oncomes or oncosuppressor miRs. Moreover, dysregulation of miRNA biogenesis pathways can also change miRNA expression and function in cancer.
  • 1.2K
  • 07 Sep 2023
Topic Review
Macrocyclic Receptors
An important direction in the design of tetrapyrrole macrocyclic receptors for a certain substrate type is modification of the macrocycle periphery with bulky substituents or molecular fragments of different natures. Bulky highly-branched lateral substituents are capable of forming additional complexing cavities that can be used for identification and selective binding of substrates of a certain type.
  • 1.2K
  • 14 Sep 2021
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