Alcohol abuse is a major health problem worldwide, resulting to extensive admissions in many general hospitals. The overall economic cost of alcohol abuse is enormous worldwide. As a small molecule, ...alcohol can easily cross membrane barriers and reach different parts of the body very quickly. Attainment of its equilibrium concentration in different cellular compartments depends on the respective water content. Alcohol can affect several parts of the brain, but, in general, contracts brain tissues, destroys brain cells, as well as depresses the central nervous system. Excessive drinking over a prolonged period of time can cause serious problems with cognition and memory. Alcohol interacts with the brain receptors, interfering with the communication between nerve cells, and suppressing excitatory nerve pathway activity. Neuro-cognitive deficits, neuronal injury, and neurodegeneration are well documented in alcoholics, yet the underlying mechanisms remain elusive. The effect can be both direct and/ or indirect. In this review we highlighted the role of alcoholism on the CNS and its impact on human health.
Cell-free DNA (cfDNA) is present in numerous body fluids and generally blood cells. It is undoubtedly the utmost promising tool among all components of liquid biopsy. Liquid biopsy is a specialized ...method investigating the non-solid biological tissue by revealing circulating cells, cell-free DNA, etc., that enter the body fluids. Since cancer cells disengage from compact tumors circulating in peripheral blood, evaluating cancer patients' blood profile is essential for the molecular level analysis of various tumor-derived constituents. Cell-free DNA samples can deliver a significant diagnosis in oncology, for instance, tumor heterogeneity, rapid tumor development, response to therapy and treatment, comprising immunotherapy, and mechanisms of cancer metastasis. Malignant growth at any phase can cause the occurrence of tumor cells in addition to fragments of neoplasticity. Liquid biopsy indicates diverse blood-based biomarkers comprising circulating tumor cells (CTCs), circulating tumor DNA (ctDNA) or cfDNA, circulating RNA (cfRNA), and exosomes. Cell-free DNAs are little DNA fragments circulating in plasma or serum, just as other fluids present in our body. Cell-free DNA involves primarily double-stranded nuclear DNA and mitochondrial DNA, present both on a surface level and in the vesicles' lumen. The probable origins of the tumor-inferred portion of cfDNA are apoptosis or tumor necrosis, lysis of CTCs or DNA release from the tumor cells into circulation. The evolution of innovations, refinement, and improvement in therapeutics to determine the fragment size of cfDNA and its distribution provide essential information related to pathological conditions of the cell, thus emerging as a promising indicator for clinical output in medical biotechnology.
Polyphenols are natural plant compounds and are the most abundant antioxidants in the human diet. As the gastrointestinal tract is the primary organ provided to diet sections, the diet may be ...regarded as one of the essential factors in the functionality, integrity, and composition of intestinal microbiota. In the gastrointestinal tract, many polyphenols remain unabsorbed and may accumulate in the large intestine, where the intestinal microbiota are most widely metabolized. When assuming primary roles for promoting host well-being, this intestinal health environment is presented to the effect of external influences, including dietary patterns. A few different methodologies have been developed to increase solvency and transport across the gastrointestinal tract and move it to targeted intestinal regions to resolve dietary polyphenols at the low bioavailability. Polyphenols form a fascinating community among the different nutritional substances, as some of them have been found to have critical biological activities that include antioxidant, antimicrobial, or anticarcinogenic activities. Besides, it affects metabolism and immunity of the intestines and has anti-inflammatory properties. The well-being status of subjects can also benefit from the development of bioactive polyphenol-determined metabolites, although the mechanisms have not been identified. Even though the incredible variety of health-advancing activities of dietary polyphenols has been widely studied, their effect on intestinal biology adaptation, and two-way relationship between polyphenols and microbiota is still poorly understood. We focused on results of polyphenols in diet with biological activities, gut ecology, and the influence of their proportional links on human well-being and disease in this study.
Triple-negative breast cancer (TNBC) is an aggressive breast cancer with a high rate of metastases, a short overall survival time, and a poor response to targeted therapy. Improving tumor hypoxia by ...lowering the oxygen consumption rate of breast tumor cells is a powerful strategy. A viable way to address this issue is to improve therapeutic efficacy by improving the effectiveness of radiation and overcoming drug resistance in TNBC treatment by controlling hypoxia in the tumor microenvironment. The failure of radiation and chemotherapy in TNBC is frequently caused by hypoxia. In TNBC therapy, novel nanomaterials are used for oxygen delivery or generation to affect the tumor microenvironment to improve the effects of ionizing radiation using nanoplatforms. One of the growing fields is novel nano-based drug delivery devices for hypoxic regions and hypoxia- inducible factor-1 (HIF1) targeted therapeutics. Biocompatible nanoparticles may be used in the treatment of TNBC patients in the clinic. Because of the rising market and competition, intellectual property rights (IPR), patents, and tactics may be critically considered. To better comprehend the current state of IPR and patents in cancer nanotechnology, this overview examines recent advances and sophisticated protection measures in this area.
PIWI-interacting RNAs (piRNAs) constitute new small non-coding RNA molecules of around 24-31 nucleotides in length, mostly performing regulatory roles for the piwi protein family members. In recent ...times, developing evidence proposes that piRNAs are expressed in a tissue-specific way in various human tissues and act as moderate vital signalling pathways at the transcriptional or post-transcriptional level in addition to mammalian germline. Recent findings, however, show that the unusual expression of piRNAs is an exclusive and discrete feature in several diseases, including many human cancers. Recently, considerable evidence indicates that piRNAs could be dysregulated thus playing critical roles in tumorigenesis. The function and underlying mechanisms of piRNAs in cancer, particularly in colorectal carcinoma, are not fully understood to date. Abnormal expression of piRNAs is emerging as a critical player in cancer cell proliferation, apoptosis, invasion, and migration in vitro and in vivo. Functionally, piRNAs preserve genomic integrity and regulate the expression of downstream target genes through transcriptional or post-transcriptional mechanisms by repressing transposable elements' mobilization. However, little research has been done to check Piwi and piRNAs' potential role in cancer and preserve genome integrity by epigenetically silencing transposons via DNA methylation, especially in germline cancer stem cells. This review reveals emerging insights into piRNA functions in colorectal carcinoma, revealing novel findings behind various piRNA-mediated gene regulation mechanisms, biogenetic piRNA processes, and possible applications of piRNAs and piwi proteins in cancer diagnosis and their potential clinical significance in the treatment of colorectal carcinoma patients.
Hypoxia is a classical function of the tumor's microenvironment with a substantial effect on the development and therapeutic response of cancer. When put in hypoxic environments, cells undergo ...several biological reactions, including activation of signaling pathways that control proliferation, angiogenesis, and death. These pathways have been adapted by cancer cells to allow tumors to survive and even develop in hypoxic conditions, and poor prognosis is associated with tumor hypoxia. The most relevant transcriptional regulator in response to hypoxia, Hypoxia-inducible factor-1 alpha (HIF-1α), has been shown to modulate hypoxic gene expression and signaling transduction networks significantly. The significance of non-coding RNAs in hypoxic tumor regions has been revealed in an increasing number of studies over the past few decades. In regulating hypoxic gene expression, these hypoxia-responsive ncRNAs play pivotal roles. Hypoxia, a general characteristic of the tumor's microenvironment, significantly affects the expression of genes and is closely associated with the development of cancer. Indeed, the number of known hypoxia-associated lncRNAs has increased dramatically, demonstrating the growing role of lncRNAs in cascades and responses to hypoxia signaling. Decades of research have helped us create an image of the shift in hypoxic cancer cells' DNA repair capabilities. Emerging evidence suggests that hypoxia can trigger genetic instability in cancer cells because of microenvironmental tumor stress. Researchers have found that critical genes' expression is coordinately repressed by hypoxia within the DNA damage and repair pathways. In this study, we include an update of current knowledge on the presentation, participation, and potential clinical effect of ncRNAs in tumor hypoxia, DNA damage reactions, and genomic instability, with a specific emphasis on their unusual cascade of molecular regulation and malignant progression induced by hypoxia.
The term Mitophagy has been newly concerned in reforming the metabolic landscape inside cancerous cells in addition to the interface between malignant cells as well as other major constituents of ...tumour microenvironment. Several profoundly interrelated systems, comprising mitochondrial dynamics and mitophagy, function in mammalian cells as vital mitochondrial regulator processes, and their consequence in neoplastic development has recently been illuminated clinically. In specific instances of cancer cells, mitochondrial-protected metabolic paths are revamped to meet expanded bioenergetics along with biosynthetic necessities of malignant cells, in addition to deal with oxidative stress. It is an exhausting task to foresee the role that mitophagy has on malignant growth cells since it relies upon various elements like cancer variability, malignant growth phase, genetic background and harmony between cell demand and accessibility. As per condition, mitophagy may have a double role as cancer suppressor for example Atg5 (autophagy related 5) or Atg7 (autophagy related 7) or execute promoter like function for instance FUNDC1 (FUN14 domain-containing protein 1), BNIP3 (BCL2/adenovirus E1B 19-kDa-interacting protein 3), PINK1 (PTEN-instigated kinase 1) etc. Tumour suppressive function of Parkin (E3 ubiquitin ligase) is likewise distinguished in mammary gland carcinoma where obstruction of mitophagy impacts tumour progression. In pancreatic cancer cells and hepatocellular carcinoma hypermethylation of the BNIP3, promoter occurs that prevent HIF-1 (Hypoxia-Inducible Factor 1) binding besides ensuing initiation of mitophagy. Since the dual role of mitophagy has in malignant growth relying upon various circumstances and cell varieties, a range of studies have been performed on mitophagy and its role in cancer progression and development is opening up a new paradigm with immense clinical importance.
The progression of metastasis, a complex systemic disease, is facilitated by interactions between tumor cells and their isolated microenvironments. Over the past few decades, researchers have ...investigated the metastatic spread of cancer extensively, identifying multiple stages in the process, such as intravasation, extravasation, tumor latency, and the development of micrometastasis and macrometastasis. The premetastatic niche is established in target organs by the accumulation of aberrant immune cells and extracellular matrix proteins. The “seed and soil” idea, which has become widely known and accepted, is being used to this day to guide cancer studies. Changes in the local and systemic immune systems have a major impact on whether an infection spreads or not. The belief that the immune response may play a role in slowing tumor growth and may be beneficial against the metastatic disease underpins the responsiveness shown in the immunological landscape of metastasis. Various hypotheses on the phylogenesis of metastases have been proposed in the past. The primary tumor’s secreting factors shape the intratumoral microenvironment and the immune landscape, allowing this progress to be made. Therefore, it is evident that among disseminated tumor cells, there are distinct phenotypes that either carry budding for metastasis or have the ability to obtain this potential or in systemic priming through contact with substantial metastatic niches that have implications for medicinal chemistry. Concurrent immunity signals that the main tumor induces an immune response that may not be strong enough to eradicate the tumor. Immunotherapy’s success with some cancer patients shows that it is possible to effectively destroy even advanced-stage tumors by modifying the microenvironment and tumor-immune cell interactions. This review focuses on the metastasome in colorectal carcinoma and the therapeutic implications of site-specific metastasis, systemic priming, tumor spread, and the relationship between the immune system and metastasis.
Hypoxia-inducible factors (HIFs) are a collection of transcriptional factors that engage in the regulation of oxygen homeostasis. They are hypoxia-responsive stress factors whose expression is linked ...to tumor growth and angiogenesis. HIF is a crucial player in the progression of breast cancer. Patients with high levels of hypoxia-inducible HIFs in their primary tumor biopsies had a higher chance of metastasis, the leading cause of breast cancer-related death. HIF polymorphisms have been shown in several epidemiological studies to influence breast cancer susceptibility. In the oxygendependent degradation domain, several short nucleotide polymorphisms (SNPs) of the HIF gene have been connected with higher HIF activity. To find SNP that make up the genetic diversity that underpins the phenotypic difference found between individuals in their susceptibility to cancer and the course of their disease, researchers used a variety of potential pathway-based approaches.
Genome editing is an addition, deletion, or replacement of a gene to remove or initiating explicit and preferred characters in the genome. Utilizing gene-editing tools like CRISPR-Cas9 technology ...could be accomplished either by gene-based methodology or protein-based technology that has been under scrutiny for the protracted time wherein physical techniques, viral and non-viral strategies have been utilized together. Transplanting ex vivo CRISPR edited cells empowers screening of single guide RNAs with high-throughput and CRISPR based screening in organoids transplantation to validate cancer cells including colorectal carcinoma in various phases of its development and treatment.CRISPR knockout screens have recognized genes that drive interest in colon cancer to develop hallmarks, especially in some cancer cell lines with single guide RNA, to disclose drug resistance mechanisms. One advantage of this method is to deal with CRISPR knockout genomic screening, which disrupts gene expression, rather than the partial knockdown that is mostly done with RNA interference and CRISPR/Cas technology. This technique is used to treat different forms of cancer because of its proficient editing of the target gene, along with the CRISPR/Cas system. Latest research has shown that the CRISPR/Cas gene-editing technique has theoretically reformed the expression in colorectal carcinoma of long non-coding RNA. For the next decade CRISPR/Cas9 technology will positively fuel the development of more in vivo gene editing clinical trials in colon cancer and will have an enormous impact on molecular medicine.
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