Showing papers in "Molecular Biology Reports in 2021"
TL;DR: The plasmid-mediated mobile colistin resistance (mcr) genes raised global public health concerns as they can spread by horizontal transfer and have chances of global dissemination.
Abstract: At the present time, the polymyxin antibiotic colistin is considered a last-line treatment option for severe human infections caused by multi-drug and carbapenem-resistant Gram-negative bacteria. Lately, the vast spread of colistin resistance among bacteria has got great attention worldwide due to its significant role as the last refuge in treating diseases caused by the resistant infectious agents. Therefore, the discovery of plasmid-mediated mobile colistin resistance (mcr) genes raised global public health concerns as they can spread by horizontal transfer and have chances of global dissemination. To date, ten slightly different variants of the mcr-1 gene (mcr-1 to mcr-10) have been identified in different bacteria isolated from animals, foods, farms, humans, and the environment. Therefore, the issue of mcr spread is growing and worsening day after day. In this backdrop, the current article presents an overview of mcr variants, their spread, and the resistance mechanisms they confer. Hence, this paper will advance our knowledge about colistin resistance while supporting the efforts toward better stewardship and proper usage of antimicrobials.
82 citations
TL;DR: In this article, the authors aim to provide comprehensive insights into the underlying symptoms, mechanism, and possible factors behind the occurrence of silent hypoxia among COVID-19 patients by using a 6-min walking test.
Abstract: The novel coronavirus disease 2019 (COVID-19) has become a severe health issue, especially to the patients who develop silent hypoxia condition after SARS-CoV-2 infection. Due to the lack of dyspnoea and extremely low oxygen saturation level, these patients are at exceptionally higher risk. Although the prevalence of silent hypoxia in COVID-19 patients has been evident in several cases, the underlying pathomechanism behind this condition is still unclear. Silent hypoxia in SARS-CoV-2 infected patients can be diagnosed with the help of a pulse oximeter, blood gas levels, and a 6-min walking test. While the clinicians and researchers figure out the exact reason for this phenomenon, the patients must be under strict day-to-day monitoring. In this article, we aim to provide comprehensive insights into the underlying symptoms, mechanism, and possible factors behind the occurrence of silent hypoxia among COVID-19 patients.
67 citations
TL;DR: A. baumannii has become a major concern for scientific attention due to extensive antimicrobial resistance as mentioned in this paper due to the acquirement of mobile genetic elements such as transposons, plasmids, and integrons and causes the prevalence of multidrug resistance strains (MDR).
Abstract: Acinetobacter baumannii has become a major concern for scientific attention due to extensive antimicrobial resistance. This resistance causes an increase in mortality rate because strains resistant to antimicrobial agents are a major challenge for physicians and healthcare workers regarding the eradication of either hospital or community-based infections. These strains with emerging resistance are a serious issue for patients in the intensive care unit (ICU). Antibiotic resistance has increased because of the acquirement of mobile genetic elements such as transposons, plasmids, and integrons and causes the prevalence of multidrug resistance strains (MDR). In addition, an increase in carbapenem resistance, which is used as last line antibiotic treatment to eliminate infections with multidrug-resistant Gram-negative bacteria, is a major concern. Carbapenems resistant A. baumannii (CR-Ab) is a worldwide problem. Because these strains are often resistant to all other commonly used antibiotics. Therefore, pathogenic multi-drug resistance A. baumannii (MDR-Ab) associated infections become hard to eradicate. Plasmid-mediated resistance causes outbreaks of extensive drug-resistant. A. baumannii (XDR-Ab). In addition, recent outbreaks relating to livestock and community settings illustrate the existence of large MDR-Ab strain reservoirs within and outside hospital settings. The purpose of this review, proper monitoring, prevention, and treatment are required to control (XDR-Ab) infections. Attachment, the formation of biofilms and the secretion of toxins, and low activation of inflammatory responses are mechanisms used by pathogenic A. baumannii strain. This review will discuss some aspects associated with antibiotics resistance in A. baumannii as well as cover briefly phage therapy as an alternative therapeutic treatment.
67 citations
TL;DR: In this article, the authors used silica-based nanoparticles obtained from diatoms (a microalgae group) as drug delivery carriers owing to their biodegradability, easy functionalization, low cost, and simple features.
Abstract: Recently, special attention has been paid to marine origin compounds such as carbohydrates, peptides, lipids, and carotenoids, which are extracted from microalgae and have anticancer, anti-inflammatory, antimicrobial (e.g., anti-COVID-19 activity), and antioxidant properties in biomedicine and pharmaceutical biotechnology. In addition, these photosynthetic marine microorganisms have several applications in biotechnology and are suitable hosts for the production of recombinant proteins/peptides, such as monoclonal antibodies and vaccines. Silica-based nanoparticles obtained from diatoms (a microalgae group) are used as drug delivery carriers owing to their biodegradability, easy functionalization, low cost, and simple features compared to synthetics, which make these agents proper alternatives for synthetic silica nanoparticles. Therefore, diatom-based nanoparticles are a viable option for the delivery of anti-cancer drugs and reducing the side-effects of cancer chemotherapy.
59 citations
TL;DR: A brief review article is intended to cover the recent advances in drug development and emerging therapeutic agents for Alzheimer's disease acting at different targets as discussed by the authors, which is concluded that novel therapeutic strategies are required to discover and develop therapeutic agents to fight against the century old AD.
Abstract: Alzheimer’s disease (AD) is a neurodegenerative old age disease that is complex, multifactorial, unalterable, and progressive in nature. The currently approved therapy includes cholinesterase inhibitors, NMDA-receptor antagonists and their combination therapy provides only temporary symptomatic relief. Sincere efforts have been made by the researchers globally to identify new targets, discover, and develop novel therapeutic agents for the treatment of AD. This brief review article is intended to cover the recent advances in drug development and emerging therapeutic agents for AD acting at different targets. The article is compiled using various scientific online databases and by referring to clinicaltrials.gov and ALZFORUM (alzforum.org) websites. The upcoming therapies act on one or more targets including amyloids (secretases, Aβ42 production, amyloid deposition, and immunotherapy), tau proteins (tau phosphorylation/aggregation and immunotherapy) and neuroinflammation in addition to other miscellaneous targets. Despite the tremendous improvement in our understanding of the underlying pathophysiology of AD, only aducanumab was approved by FDA for the treatment of AD in 18 years i.e., since 2003. Hence, it is concluded that novel therapeutic strategies are required to discover and develop therapeutic agents to fight against the century old AD.
55 citations
TL;DR: In this article, the authors used polyphenolic compounds derived from plants to inhibit glycation and formation of advanced glycation end products (AGEs) at multiple levels, which is a potential risk for pathogenesis of various chronic diseases.
Abstract: Advanced glycation end products (AGEs) are naturally occurring biomolecules formed by interaction of reducing sugars with biomolecules such as protein and lipids etc., Long term high blood sugar level and glycation accelerate the formation of AGEs. Unchecked continuous formation and accumulation of AGEs are potential risks for pathogenesis of various chronic diseases. Current mode of antidiabetic therapy is based on synthetic drugs that are often linked with severe adverse effects. Polyphenolic compounds derived from plants are supposed to inhibit glycation and formation of AGEs at multiple levels. Some polyphenolic compounds regulate the blood glucose metabolism by amplification of cell insulin resistance and activation of insulin like growth factor binding protein signaling pathway. Their antioxidant nature and metal chelating activity, ability to trap intermediate dicarbonyl compounds could be possible mechanisms against glycation and AGEs formation and hence, against AGEs induced health complications. Although, few species of polyphenolic compounds are being used in in vitro trials and their in vivo study is still in progress, increasing the area of research in this field may produce a fruitful approach in management of overall diabetic complications.
52 citations
[...]
TL;DR: In this paper, a review gives an overview of deviations of genetic code, factors influencing codon usage or bias, and computational methods to determine codon use and the significance as well as applications of codon analysis in biological research, with emphasis on plants.
Abstract: Codon usage bias is the preferential or non-random use of synonymous codons, a ubiquitous phenomenon observed in bacteria, plants and animals. Different species have consistent and characteristic codon biases. Codon bias varies not only with species, family or group within kingdom, but also between the genes within an organism. Codon usage bias has evolved through mutation, natural selection, and genetic drift in various organisms. Genome composition, GC content, expression level and length of genes, position and context of codons in the genes, recombination rates, mRNA folding, and tRNA abundance and interactions are some factors influencing codon bias. The factors shaping codon bias may also be involved in evolution of the universal genetic code. Codon-usage bias is critical factor determining gene expression and cellular function by influencing diverse processes such as RNA processing, protein translation and protein folding. Codon usage bias reflects the origin, mutation patterns and evolution of the species or genes. Investigations of codon bias patterns in genomes can reveal phylogenetic relationships between organisms, horizontal gene transfers, molecular evolution of genes and identify selective forces that drive their evolution. Most important application of codon bias analysis is in the design of transgenes, to increase gene expression levels through codon optimization, for development of transgenic crops. The review gives an overview of deviations of genetic code, factors influencing codon usage or bias, codon usage bias of nuclear and organellar genes, computational methods to determine codon usage and the significance as well as applications of codon usage analysis in biological research, with emphasis on plants.
49 citations
TL;DR: The cellular mechanism of 3T3-L1 fibroblast cells on potential anti-adipogenic herbal bioactive compounds is described.
Abstract: Obesity is growing at an alarming rate, which is characterized by increased adipose tissue. It increases the probability of many health complications, such as diabetes, arthritis, cardiac disease, and cancer. In modern society, with a growing population of obese patients, several individuals have increased insulin resistance. Herbal medicines are known as the oldest method of health care treatment for obesity-related secondary health issues. Several traditional medicinal plants and their effective phytoconstituents have shown anti-diabetic and anti-adipogenic activity. Adipose tissue is a major site for lipid accumulation as well as the whole-body insulin sensitivity region. 3T3-L1 cell line model can achieve adipogenesis. Adipocyte characteristics features such as expression of adipocyte markers and aggregation of lipids are chemically induced in the 3T3-L1 fibroblast cell line. Differentiation of 3T3-L1 is an efficient and convenient way to obtain adipocyte like cells in experimental studies. Peroxisome proliferation activated receptor γ (PPARγ) and Cytosine-Cytosine-Adenosine-Adenosine-Thymidine/Enhancer-binding protein α (CCAAT/Enhancer-binding protein α or C/EBPα) are considered to be regulating adipogenesis at the early stage, while adiponectin and fatty acid synthase (FAS) is responsible for the mature adipocyte formation. Excess accumulation of these adipose tissues and lipids leads to obesity. Thus, investigating adipose tissue development and the underlying molecular mechanism is important in the therapeutical approach. This review describes the cellular mechanism of 3T3-L1 fibroblast cells on potential anti-adipogenic herbal bioactive compounds.
46 citations
TL;DR: The potential pharmacological and therapeutic effects of Sinapic acid in various models have been summarized in this paper, where the authors present a review of the potential pharmacologic and therapeutic properties of the compound.
Abstract: Phenolic compounds, present in plants, are considered to be indispensable parts of human dietary sources. Sinapic acid, is a natural herbal compound containing phenolic acid. It is found in oranges, grapefruits, and cranberries and in herbs like canola, mustard seed and rapeseed. Sinapic acid is chemically studied as a cinnamic acid derivative that contains 3, 5-dimethoxyl and 4-hydroxyl substitutions in the phenyl group of cinnamic acid. Sinapic acid has been pharmacologically evaluated for its potent antioxidant, anti-inflammatory, anti-cancer, hepatoprotective, cardioprotective, renoprotective, neuroprotective, anti-diabetic, anxiolytic and anti-bacterial activities. In this review we have summarized the potential pharmacological and therapeutic effects of Sinapic acid in various models.
35 citations
TL;DR: In this paper, the authors reviewed and highlighted the protective role of NCL therapy in Covid-19 infection and showed that NCL has anti-SARS-CoV-2 effect via interruption of viral life-cycle and induction of cytopathic effect.
Abstract: Niclosamide (NCL) is an anthelminthic drug, which is widely used to treat various diseases due to its pleiotropic anti-inflammatory and antiviral activities. NCL modulates of uncoupling oxidative phosphorylation and different signaling pathways in human biological processes. The wide-spectrum antiviral effect of NCL makes it a possible candidate for recent pandemic SARS-CoV-2 infection and may reduce Covid-19 severity. Therefore, the aim of the present study was to review and clarify the potential role of NCL in Covid-19. This study reviewed and highlighted the protective role of NCL therapy in Covid-19. A related literature search in PubMed, Scopus, Web of Science, Google Scholar, and Science Direct was done. NCL has noteworthy anti-inflammatory and antiviral effects. The primary antiviral mechanism of NCL is through neutralization of endosomal PH and inhibition of viral protein maturation. NCL acts as a proton carrier, inhibits homeostasis of endosomal PH, which limiting of viral proliferation and release. The anti-inflammatory effects of NCL are mediated by suppression of inflammatory signaling pathways and release of pro-inflammatory cytokines. However, the major limitation in using NCL is low aqueous solubility, which reduces oral bioavailability and therapeutic serum concentration that reducing the in vivo effect of NCL against SARS-CoV-2. NCL has anti-inflammatory and immune regulatory effects by modulating the release of pro-inflammatory cytokines, inhibition of NF-κB /NLRP3 inflammasome and mTOR signaling pathway. NCL has an anti-SARS-CoV-2 effect via interruption of viral life-cycle and/or induction of cytopathic effect. Prospective clinical studies and clinical trials are mandatory to confirm the potential role of NCL in patients with Covid-19 concerning the severity and clinical outcomes.
35 citations
TL;DR: There is lack of any significant preventive measures for calcifications and hence this review explores further possibilities for drug development and treatment modalities.
Abstract: Pathological calcification is a major cause of cardiovascular morbidities primarily in population with chronic kidney disease (CKD), end stage renal diseases (ERSD) and metabolic disorders. Investigators have accepted the fact that vascular calcification is not a passive process but a highly complex, cell mediated, active process in patients with cardiovascular disease (CVD) resulting from, metabolic insults of bone fragility, diabetes, hypertension, dyslipidemia and atherosclerosis. Over the years, studies have revealed various mechanisms of vascular calcification like induction of bone formation, apoptosis, alteration in Ca-P balance and loss of inhibition. Novel clinical studies targeting cellular mechanisms of calcification provide promising and potential avenues for drug development. The interventions include phosphate binders, sodium thiosulphate, vitamin K, calcimimetics, vitamin D, bisphosphonates, Myoinositol hexaphosphate (IP6), Denosumab and TNAP inhibitors. Concurrently investigators are also working towards reversing or curing pathological calcification. This review focuses on the relationship of vascular calcification to clinical diseases, regulators and factors causing calcification including genetics which have been identified. At present, there is lack of any significant preventive measures for calcifications and hence this review explores further possibilities for drug development and treatment modalities.
TL;DR: In this article, the authors reviewed the aspects of tissue culture-induced variations with respect to DNA methylation and its effect on crop improvement programs, and it is anticipated that a precise and comprehensive knowledge of molecular basis of in vitro-derived DNA methylations will help to design strategies to overcome the bottlenecks of micropropagation system and maintain the clonal fidelity of the regenerants.
Abstract: Plant tissue culture techniques have been extensively employed in commercial micropropagation to provide year-round production. Tissue culture regenerants are not always genotypically and phenotypically similar. Due to the changes in the tissue culture microenvironment, plant cells are exposed to additional stress which induces genetic and epigenetic instabilities in the regenerants. These changes lead to tissue culture-induced variations (TCIV) which are also known as somaclonal variations to categorically specify the inducing environment. TCIV includes molecular and phenotypic changes persuaded in the in vitro culture due to continuous sub-culturing and tissue culture-derived stress. Epigenetic variations such as altered DNA methylation pattern are induced due to the above-mentioned factors. Reportedly, alteration in DNA methylation pattern is much more frequent in the plant genome during the tissue culture process. DNA methylation plays an important role in gene expression and regulation of plant development. Variants originated in tissue culture process due to heritable methylation changes, can contribute to intra-species phenotypic variation. Several molecular techniques are available to detect DNA methylation at different stages of in vitro culture. Here, we review the aspects of TCIV with respect to DNA methylation and its effect on crop improvement programs. It is anticipated that a precise and comprehensive knowledge of molecular basis of in vitro-derived DNA methylation will help to design strategies to overcome the bottlenecks of micropropagation system and maintain the clonal fidelity of the regenerants.
TL;DR: The ATP binding-cassette superfamily corresponds the mostly transmembrane transporters family found in humans as discussed by the authors, and it has an important role in many physiological functions necessary for human homeostasis, as well as in response regulation to several pharmacological substrates.
Abstract: The ATP binding-cassette superfamily corresponds the mostly transmembrane transporters family found in humans. These proteins actively transport endogenous and exogenous substrates through biological membranes in body tissues, so they have an important role in the regulation of many physiological functions necessary for human homeostasis, as well as in response regulation to several pharmacological substrates. The development of multidrug resistance has become one of the main troubles in conventional chemotherapy in different illnesses including cancer, being the increased efflux of antineoplastic drugs the main reason for this multidrug resistance, with a key role of the ABC superfamily. Likely, the interindividual variability in the pharmacological response among patients is well known, and may be due to intrinsically factors of the disease, genetic and environmental ones. Thus, the understanding of this variability, especially the genetic variability associated with the efficacy and toxicity of drugs, can provide a safer and more effective pharmacological treatment, so ABC genes are considered as important regulators due to their relationship with the reduction in pharmacological response. In this review, updated information about transporters belonging to this superfamily was collected, the possible role of these transporters in cancer, the role of genetic variability in their genes, as well as some therapeutic tools that have been tried to raise against main transporters associated with chemoresistance in cancer.
TL;DR: In this article, a review of single, dual and multiple growth factor release systems and their effects on promoting angiogenesis is presented. And the authors conclude that multiple GF release systems offer superior results compared to single and dual systems with more stable, mature and larger vessels produced.
Abstract: Tissue engineering is a rapidly developing field with many potential clinical applications in tissue and organ regeneration. The development of a mature and stable vasculature within these engineered tissues (ET) remains a significant obstacle. Currently, several growth factors (GFs) have been identified to play key roles within in vivo angiogenesis, including vascular endothelial growth factor (VEGF), platelet derived growth factor (PDGF), FGF and angiopoietins. In this article we attempt to build on in vivo principles to review the single, dual and multiple GF release systems and their effects on promoting angiogenesis. We conclude that multiple GF release systems offer superior results compared to single and dual systems with more stable, mature and larger vessels produced. However, with more complex release systems this raises other problems such as increased cost and significant GF-GF interactions. Upstream regulators and pericyte-coated scaffolds could provide viable alternative to circumnavigate these issues.
TL;DR: It is shown that TdPR1.2 gene exhibits an antibacterial effect as revealed by the in vitro tests against 8 different bacteria and against the fungi Septoria tritici, and it is demonstrated for the first time that PR1 proteins are able to bind to CaM in a Ca2+-dependent manner via a GST-Pull down assay.
Abstract: In plants, pathogenesis-related 1 protein (PR1) is considered as important defense protein. The production and accumulation of PR proteins in plants are one of the important responses to several biotic and abiotic stresses. In this regard, PR1 gene was isolated from Triticum turgidum ssp durum and was named as TdPR1.2. The amino acid sequence of TdPR1.2 protein showed 100%, 97.13%, and 44.41% with known PR1 proteins isolated from Triticum aestivum TdPR1-18, PRB1.2 of Aegilops tauschii subsp. tauschii and Arabidopsis thaliana respectively. qRT-PCR showed that TdPR1.2 was induced specially in leaves of durum wheat treated with Salicylic acid for 48 h. Besides, bioinformatic analysis showed that the durum wheat TdPR1.2 harbors a calmodulin binding domain located in it’s C-terminal part and that this domain is conserved among different PR1 proteins isolated so far. However, no information is available about the regulation of PR genes by calmodulin and Ca2+ complex (CaM/Ca2+). Here, we showed that TdPR1.2 gene exhibits an antibacterial effect as revealed by the in vitro tests against 8 different bacteria and against the fungi Septoria tritici. In addition, we demonstrate for the first time that PR1 proteins are able to bind to CaM in a Ca2+-dependent manner via a GST-Pull down assay. Finally, in presence of Mn2+ cations, CaM/Ca2+ complex stimulated the antimicrobial effect of TdPR1.2. Such effects were not reported so far, and raise a possible role for CaM/Ca2+ complex in the regulation of plant PRs during cellular response to external signals.
TL;DR: In this paper, the role of the splice variants generated by AS of these gene transcripts in modulating the metastatic potential and stem-like/chemoresistant behavior of cancer cells has also been highlighted.
Abstract: Enhanced metastasis and disease recurrence accounts for the high mortality rates associated with cancer. The process of Epithelial-Mesenchymal Transition (EMT) contributes towards the augmentation of cancer invasiveness along with the gain of stem-like and the subsequent drug-resistant behavior. Apart from the well-established transcriptional regulation, EMT is also controlled post-transcriptionally by virtue of alternative splicing (AS). Numerous genes including Fibroblast Growth Factor receptor (FGFR) as well as CD44 are differentially spliced during this trans-differentiation process which, in turn, governs cancer progression. These splicing alterations are controlled by various splicing factors including ESRP, RBFOX2 as well as hnRNPs. Here, we have depicted the mechanisms governing the splice isoform switching of FGFR and CD44. Moreover, the role of the splice variants generated by AS of these gene transcripts in modulating the metastatic potential and stem-like/chemoresistant behavior of cancer cells has also been highlighted. Additionally, the involvement of splicing factors in regulating EMT/invasiveness along with drug-resistance as well as the metabolic properties of the cells has been emphasized. Tumorigenesis is accompanied by a remodeling of the cellular splicing profile generating diverse protein isoforms which, in turn, control the cancer-associated hallmarks. Therefore, we have also briefly discussed about a wide variety of genes which are differentially spliced in the tumor cells and promote cancer progression. We have also outlined different strategies for targeting the tumor-associated splicing events which have shown promising results and therefore this approach might be useful in developing therapies to reduce cancer aggressiveness in a more specific manner.
TL;DR: In this paper, a review of the consequences of physical exercise (aerobic and resistance exercise) on major depressive disorder among elderly, and presenting its potential biological mechanisms was conducted according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines.
Abstract: Depressive disorders are common among the elderly. Major depressive disorder will be one of the highest healthcare costs in middle and higher income countries by 2030. It is known that physical inactivity leads to negative effects on mental health in the elderly.The purpose of this review was to explore investigate the consequences of physical exercise (aerobic and resistance exercise) on major depressive disorder among elderly, and presenting its potential biological mechanisms. This study was designed according to Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Clinical trials or randomized clinical trials or cohort studies participated of the study design. Ten studies were evaluated and the main outcomes of each were reported. Aerobic and resistance training revealed to be effective in fighting the symptoms of depression. The most common physical exercise protocol adopted to reduce the consequences of major depressive disorder in humans was the prescription of aerobic exercise at moderate-intensity lasting 60 min per session, 3 times per week, for 24 weeks. Physical exercise enhances IGF-I and activates PGC-1α/FNDC5/Irisin pathway. Physical exercise also increases expression of BDNF and its receptor, TrkB, in the hippocampus and prefrontal cortex leading to upstream of ERK and inhibiting depressive-like behavior. Physical exercise brings mental health benefits and plays a crucial role in avoiding the development of major depressive disorder.
TL;DR: A systematic review of human trials examining the effects of dietary phytochemicals on Nrf2 activation was conducted by as mentioned in this paper, where the authors used the Cochrane Collaboration Risk of Bias Assessment tool.
Abstract: We conducted a systematic review of human trials examining the effects of dietary phytochemicals on Nrf2 activation. In accordance with the PRISMA guidelines, Medline, Embase and CAB abstracts were searched for articles from inception until March 2020. Studies in adult humans that measured Nrf2 activation (gene or protein expression changes) following ingestion of a phytochemical, either alone or in combination were included. The study was pre-registered on the Prospero database (Registration Number: CRD42020176121). Twenty-nine full-texts were retrieved and reviewed for analysis; of these, eighteen were included in the systematic review. Most of the included participants were healthy, obese or type 2 diabetics. Study quality was assessed using the Cochrane Collaboration Risk of Bias Assessment tool. Twelve different compounds were examined in the included studies: curcumin, resveratrol and sulforaphane were the most common (n = 3 each). Approximately half of the studies reported increases in Nrf2 activation (n = 10); however, many were of poor quality and had an unclear or high risk of bias. There is currently limited evidence that phytochemicals activate Nrf2 in humans. Well controlled human intervention trials are needed to corroborate the findings from in vitro and animal studies.
TL;DR: In this paper, the anti-oxidative properties of morin were evaluated using in vitro methods such as cell viability by MTT assay, estimation of SOD and CAT activity and NO scavenging activity.
Abstract: Plant-derived phytochemicals such as flavonoids have been explored to be powerful antioxidants that protect against oxidative stress-related diseases. In the present study, Morin, a flavonoid compound was studied for its antioxidant and antidiabetic properties in relation to oxidative stress in insulin resistant models conducted in rat skeletal muscle L6 cell line model. Evaluation of antioxidant property of morin was assayed using in vitro methods such as cell viability by MTT assay, estimation of SOD and CAT activity and NO scavenging activity. The anti-oxidative nature of morin on L6 cell line was conducted by the DCF-DA fluorescent activity. Glucose uptake in morin treated L6 myotubes are accessed by 2-NBDG assay in the presence or absence of IRTK and PI3K inhibitors. Further glycogen content estimation due to the morin treatment in L6 myotubes was performed. Antioxidant and insulin signaling pathway gene expression was examined over RT-PCR analysis. Morin has a negligible cytotoxic effect at doses of 20, 40, 60, 80, and 100 µM concentration according to cell viability assay. Morin revealed that the levels of the antioxidant enzymes SOD and CAT in L6 myotubes had increased. When the cells were subjected to the nitro blue tetrazolium assay, morin lowered reactive oxygen species (ROS) formation at 60 µM concentration displaying 39% ROS generation in oxidative stress condition. Lesser NO activity and a drop in green fluorescence emission in the DCFDA assay, demonstrating its anti-oxidative nature by reducing ROS formation in vitro. Glucose uptake by the L6 myotube cells using 2-NBDG, and with IRTK and PI3K inhibitors (genistein and wortmannin) showed a significant increase in glucose uptake by the cells which shows the up regulated GLUT-4 movement from intracellular pool to the plasma membrane. Morin (60 µM) significantly enhanced the expression of antioxidant genes GPx, GST and GCS as well as insulin signalling genes IRTK, IRS-1, PI3K, GLUT-4, GSK-3β and GS in L6 myotubes treated cells. Morin has the ability to act as an anti-oxidant by lowering ROS levels and demonstrating insulin mimetic activity by reversing insulin resistance associated with oxidative stress.
TL;DR: A comprehensive review of cancer immunotherapy can be found in this article, where the authors highlight and summarize the different categories of emerging cancer immunotherapies along with the immunologically recognized tumor antigens involved in the tumor microenvironment.
Abstract: Cancer immunotherapy is a rapidly evolving concept that has been given the tag "fifth pillar" of cancer therapy while radiation therapy, chemotherapy, surgery and targeted therapy remain the other four pillars. This involves the stimulation of the immune system to control tumor growth and it specifically targets the neoplastic cells rather than the normal cells. Conventional chemotherapy has many limitations which include drug resistance, recurrence of cancer and severe adverse effects. Immunology has made major treatment breakthroughs for several cancers such as colorectal cancer, prostate cancer, breast cancer, lung cancer, liver cancer, kidney cancer, stomach cancer, acute lymphoblastic leukaemia etc. Currently, therapeutic strategies harnessing the immune system involve Checkpoint inhibitors, Chimeric antigen receptor T cells (CAR T cells), Monoclonal antibodies, Cancer vaccines, Cytokines, Radio-immunotherapy and Oncolytic virus therapy. The molecular characterization of several tumor antigens (TA) indicates that these TA can be utilized as promising candidates in cancer immunotherapy strategies. Here in this review, we highlight and summarize the different categories of emerging cancer immunotherapies along with the immunologically recognized tumor antigens involved in the tumor microenvironment.
TL;DR: MiR-96 and miR-183 in urine are promising diagnostic tumor markers for BC; particularly, when they combined with each other or with urinary cytology.
Abstract: Because of low sensitivity and specificity of the currently available urine biomarkers of bladder cancer (BC) detection and painful cystoscopy procedure. Our study aimed to evaluate expression of urinary exosomal miR-96-5p and miR-183-5p as probable non-invasive and accurate biomarkers for the diagnosis and follow up of BC. Using quantitative real-time polymerase chain reaction; expression of exosomal microRNA (miR)-96-5p and miR- 183-5p in the urine samples of 51 patients with BC, 21 patients with benign urinary bladder lesions and in 24 normal individuals as control group was done. Our study results showed higher expressions of both miR-96-5p and miR-183-5p in urine of BC patients in comparison with control group (P < 0.001 for each). Receiver operating characteristic curve (ROC) analysis showed that each microRNA had good sensitivity and specificity to differentiate BC from non-BC patients miR-96-5p 80.4% and 91.8% and miR-183-5p 78.4% and 81.6% respectively compared to cytology (37.3% and 100%). In addition, it was obvious that the sensitivity of combined miR-96-5p and miR-183-5p for the diagnosis of BC reached 88.2%% and specificity reached 87.8%, which were higher than each one alone. We also found that expression of miR-96-5p and miR-183-5p with high grade, and pathological stage was significantly increased. After surgery, collected urine samples showed significantly lower expression of miR-96-5p-: P < 0.001; and miR-183-5p: P = 0.002. In conclusion, urine miR-96-5p and miR-183-5p are promising tumor biomarkers of BC diagnosis; particularly, when they combined with each other or with urinary cytology.
TL;DR: In this article, the authors examined the possible activity and molecular function of miR-424-5p and Taxol combination in the human BC cell line, and showed that miR4245p repressed BC cell proliferation and sensitized these cells to Taxol treatment through the induction of apoptosis.
Abstract: Combination therapy has been considered as a potential method to overcome the BC chemoresistance. MicroRNAs (miRs) have been suggested as a therapeutic factor in the combination therapy of BC. This project aimed at examining the possible activity and molecular function of miR-424-5p and Taxol combination in the human BC cell line. MDA-MB-231 cells were treated with miR-424-5p mimics and Taxol, in a combined manner or separately. We used the MTT test for assessing the cell proliferation. In addition, flow-cytometry was used for evaluating apoptosis and cell-cycle. Expression levels of underlying molecular factors of miR-424-5p were assessed using western-blotting and qRT-PCR. The obtained results demonstrated that miR-424-5p repressed BC cell proliferation and sensitized these cells to Taxol treatment through the induction of apoptosis. Further investigations showed that miR-424-5p might increase BC chemosensitivity through the regulation of apoptosis-related factors including P53, Caspase-3, Bcl-2, and Bax as well as the proliferation-related gene c-Myc. Moreover, miR-424-5p restoration in combination with Taxol treatment decreased the colony formation by regulating Oct-4 and led to G2 arrest via modulating Cdk-2 expression. Western-blotting demonstrated that miR-424-5p may perform its anti-chemoresistance role by regulating the PD-L1 expression and controlling PTEN/PI3K/AKT/mTOR. Overall, the upregulation of miR-424-5p was indicated to upregulate the sensitivity of BC cells to treatment with Taxol. MiR-424-5p might regulate the chemosensitivity of the BC cell line by modulating PD-L1 and controlling the PTEN/mTOR axis. Therefore, the combination of miR-424-5p with Taxol would represent a novel procedure to treat against BC.
TL;DR: In this article, the in-depth anticancer activity of acacetin and apigenin on glioblastoma cells (U87) was evaluated and the results showed a significant effect (P < 0.05) on U87 cells.
Abstract: Brain and CNS-related cancers are rare; however, 0.3 million incidences and 0.24 million deaths in 2018 demonstrates the unrelenting associated dangers. Glioblastoma is a brain cancer of star-shaped glial cells. It is almost universally fatal within 2 years of diagnosis despite maximal medical therapies. This study aims to evaluate the in-depth anticancer activity of acacetin and apigenin on glioblastoma cells (U87). In the present report, we have isolated two flavonoids, acacetin and apigenin; and studied the in-depth anticancer activity on U87 cells. Selective cytotoxicity of acacetin and apigenin was observed towards the U87 cells (IC50: 43.73 ± 1.19 and 48.18 ± 1.37 μM, respectively). The flow cytometer-based result revealed the induction of G2/M phase arrest along with the increase in sub G1 population upon compound treatment. Annexin-V-FLUOS and DAPI staining also confirmed the apoptosis-inducing effects of compounds. Flow cytometer and confocal microscopy-based DCFH-DA staining showed ROS-inducing effect of the compounds. The up-regulation of p21 and down-regulation of Cyclin-A1, Cyclin-B1, and Cdk-1 revealed the G2/M phase arrest mechanism of acacetin and apigenin. Furthermore, western blotting result confirmed the activation of intrinsic pathway of apoptosis upon acacetin treatment and activation of both extrinsic and intrinsic pathways of apoptosis upon apigenin treatment through the regulation of Bax, t-Bid, caspase 8, caspase 9, caspase 3, and PARP. The obtained result showed a significant effect (P < 0.05) of acacetin and apigenin on U87 cells. Acacetin and apigenin-induced ROS is responsible for the induction of cell cycle arrest and activation of caspase-cascade pathways in U87 cells.
TL;DR: A review of both types of MMPs and current inhibitors, which target them in different aspects, including, biosynthesis, activation, secretion and catalytic activity, can be found in this article.
Abstract: Matrix metalloproteinases (MMPs) or matrixins, are members of a zinc-dependent endopeptidase family. They cause remodeling of the extracellular matrix (ECM) leading to numerous diseases. MMPs subfamilies possess: collagenases, gelatinases, stromelysins and membrane-type MMPs (MT-MMP). They consist of several domains; pro-peptide, catalytic, linker peptide and the hemopexin (Hpx) domains. MMPs are involved in initiation, proliferation and metastasis of cancer through the breakdown of ECM physical barriers. Overexpression of MMPs is associated with poor prognosis of cancer. This review will discuss both types of MMPs and current inhibitors, which target them in different aspects, including, biosynthesis, activation, secretion and catalytic activity. Several synthetic and natural inhibitors of MMPs (MMPIs) that can bind the catalytic domain of MMPs have been designed including; peptidomimetic, non-peptidomimetic, tetracycline derivatives, off-target MMPI, natural products, microRNAs and monoclonal antibodies.
TL;DR: In this paper, the role of osteoblast dysregulation in rheumatoid arthritis was investigated in a mouse model and it was shown that complete resolution of inflammation (with maximal reduction in the expression of pro-inflammatory factors) is crucial for bone healing.
Abstract: In the pathogenesis of several rheumatic diseases, such as rheumatoid arthritis, spondyloarthritis, osteoarthritis, osteoporosis, alterations in osteoblast growth, differentiation and activity play a role. In particular, in rheumatoid arthritis bone homeostasis is perturbed: in addition to stimulating the pathologic bone resorption process performed by osteoclasts in course of rheumatoid arthritis, proinflammatory cytokines (such as Tumor Necrosis factor-α, Interleukin-1) can also inhibit osteoblast differentiation and function, resulting in net bone loss. Mouse models of rheumatoid arthritis showed that complete resolution of inflammation (with maximal reduction in the expression of pro-inflammatory factors) is crucial for bone healing, performed by osteoblasts activity. In fact, abnormal activity of factors and systems involved in osteoblast function in these patients has been described. A better understanding of the pathogenic mechanisms involved in osteoblast dysregulation could contribute to explain the generalized and focal articular bone loss found in rheumatoid arthritis. Nevertheless, these aspects have not been frequently and directly evaluated in studies. This review article is focused on analysis of the current knowledge about the role of osteoblast dysregulation occurring in rheumatoid arthritis: a better knowledge of these mechanisms could contribute to the realization of new therapeutic strategies.
TL;DR: It was found that the levels of Bax, Caspase-3, and cytochrome c increased by Cd were decreased by the application of CRV and CRV showed an anti-apoptotic effect by increasing Bcl-2 levels.
Abstract: The potential protective properties of carvacrol (CRV), which possesses various biological and pharmacological properties, against lung toxicity caused by cadmium (Cd), a major environmental pollutant, were investigated in the present study. In the study, rats were given 25 or 50 mg/kg CRV orally 30 min after administrating 25 mg/kg cadmium chloride for seven days. Subsequently, the levels of 8-OHdG, MMP-2, and MMP-9, as well as markers of oxidative stress, inflammation, and apoptosis, were analyzed in the lung tissue of the animals. The results revealed that CRV exhibited antioxidant characteristics and raised SOD, CAT, GPx, and CAT levels and decreased the MDA levels induced by Cd. It also suppressed proinflammatory cytokines by lowering the levels of CRV NF-κB and p38 MAPK, thus exerting an anti-inflammatory effect against Cd. It was found that the levels of Bax, Caspase-3, and cytochrome c increased by Cd were decreased by the application of CRV. CRV also showed an anti-apoptotic effect by increasing Bcl-2 levels. The levels of 8-OHdG, MMP2, and MMP9, which increased with Cd administration, were observed to reduce after treatment with CRV. The results indicate that CRV has protective properties against Cd-induced lung toxicity.
TL;DR: In this paper, a comprehensive expression analysis of two widely used plant transgenes, neomycin phosphotransferase II (NPTII) and enhanced green fluorescent protein (EGFP), regulated by a double CaMV 35S promoter was performed using quantitative real-time PCR (qRT-PCR) analysis.
Abstract: The cauliflower mosaic virus (CaMV) 35S promoter is known as the most frequently used promoter in plant biotechnology. Although it is widely considered to be a strong constitutive promoter exhibiting high transcriptional activity, the transcriptional stability of CaMV 35S has not been extensively studied. Using the model plant species Arabidopsis thaliana, this study aimed for a comprehensive expression analysis of two widely used plant transgenes, neomycin phosphotransferase II (NPTII) and enhanced green fluorescent protein (EGFP), regulated by a double CaMV 35S promoter depending on the organ type, time of day, plant age, and in response to abiotic stress conditions. Quantitative real-time PCR (qRT-PCR) analysis revealed that the NPTII and EGFP transcript levels were markedly higher in the cotyledons, young leaves, and roots than in the inflorescences, stems, and adult leaves of three independent transgenic A. thaliana lines. The expression of NPTII and EGFP varied during the day and was elevated with the plant age. Drought and cold stress considerably affected the expression of the transgenes, while heat, high salinity, and wounding had no significant effect. This study shows that transgenes driven by a common constitutive promoter can exhibit marked variations in transcriptional activity depending on plant organ, physiological conditions, and in response to abiotic stress. Therefore, to ensure high and stable transgene activity, considerable attention should be given to the transgenic plant material and incubation conditions before harvesting the plant material.
TL;DR: In this paper, the role of key glycolytic enzymes in triple negative breast cancer (TNBC) was summarized and possible therapeutic options for TNBC treatment were presented, where the authors attempted to summarize the role and potential therapeutic options presently available.
Abstract: Among breast cancer subtypes, the triple negative breast cancer (TNBC) has the worst prognosis. In absence of any permitted targeted therapy, standard chemotherapy is the mainstay for TNBC treatment. Hence, there is a crucial need to identify potential druggable targets in TNBCs for its effective treatment. In recent times, metabolic reprogramming has emerged as cancer cells hallmark, wherein cancer cells display discrete metabolic phenotypes to fuel cell progression and metastasis. Altered glycolysis is one such phenotype, in which even in oxygen abundance majority of cancer cells harvest considerable amount of energy through elevated glycolytic-flux. In the present review, we attempt to summarize the role of key glycolytic enzymes i.e. HK, Hexokinase; PFK, Phosphofructokinase; PKM2, Pyruvate kinase isozyme type 2; and LDH, Lactate dehydrogenase in TNBCs, and possible therapeutic options presently available.
TL;DR: In this article, eight heat stress responsive factors, proteins and genes (HSFA2, GHSP26, GHPP2A, HSP101, HSC70-1,HSP3, APX1 and ANNAT8) were evaluated morphologically and physiologically for their role in heat stress tolerance.
Abstract: Pakistan ranked highest with reference to average temperatures in cotton growing areas of the world. The heat waves are becoming more intense and unpredictable due to climate change. Identification of heat tolerant genotypes requires comprehensive screening using molecular, physiological and morphological analysis. Heat shock proteins play an important role in tolerance against heat stress. In the current study, eight heat stress responsive factors, proteins and genes (HSFA2, GHSP26, GHPP2A, HSP101, HSC70-1, HSP3, APX1 and ANNAT8) were evaluated morphologically and physiologically for their role in heat stress tolerance. For this purpose, cotton crop was grown at two temperature conditions i.e. normal weather and heat stress at 45 °C. For molecular analysis, genotypes were screened for the presence or absence of heat shock protein genes. Physiological analysis of genotypes was conducted to assess net photosynthesis, stomatal conductance, transpiration rate, leaf-air temperature and cell membrane stability under control as well as high temperature. The traits photosynthesis, cell membrane stability, leaf-air temperature and number of heat stress responsive factors in each genotypes showed a strong correlation with boll retention percentage under heat stress. The genotypes with maximum heat shock protein genes such as Cyto-177, MNH-886, VH-305 and Cyto-515 showed increased photosynthesis, stomatal conductance, negative leaf-air temperature and high boll retention percentage under heat stress condition. These varieties may be used as heat tolerant breeding material.
TL;DR: In this paper, the authors highlight the role of long non-coding RNA in glucose metabolism and dissect the feasibility and limitations of this clinical development, which may provide potential targets for cancer therapy.
Abstract: Metabolism reprogramming is one of the hallmarks of cancer cells, especially glucose metabolism, to promote their proliferation, metastasis and drug resistance. Cancer cells tend to depend on glycolysis for glucose utilization rather than oxidative phosphorylation, which is called the Warburg effect. Genome instability of oncogenes and tumor-inhibiting factors is the culprits for this anomalous glycolytic fueling, which results in dysregulating metabolism-related enzymes and metabolic signaling pathways. It has been extensively demonstrated that protein-coding genes are involved in this process; therefore, glycolysis-targeted therapy has been widely used in anti-tumor combined therapy via small molecular inhibitors of key enzymes and regulatory molecular. The long non-coding RNA, which is a large class of regulatory RNA with longer than 200 nucleotides, is the novel and significant regulator of various biological processes, including metabolic reprogramming. RNA interference and synthetic antisense oligonucleotide for RNA reduction have developed rapidly these years, which presents potent anti-tumor effects both in vitro and in vivo. However, lncRNA-based glycolysis-targeted cancer therapy, as the highly specific and less toxic approach, is still under the preclinical phase. In this review, we highlight the role of lncRNA in glucose metabolism and dissect the feasibility and limitations of this clinical development, which may provide potential targets for cancer therapy.