Pharmacogenomic and epigenomic approaches to untangle the enigma of IL-10 blockade in oncology

© 2024 The Author(s). Published by Cambridge University Press. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY), https://creativecommons.org/licenses/by/4.0/The host immune system status remains an unresolved mystery among several malignancies. An immune-compromised state or smart immune-surveillance tactics orchestrated by cancer cells are the primary cause of cancer invasion and metastasis. Taking a closer look at the tumour-immune microenvironment, a complex network and crosstalk between infiltrating immune cells and cancer cells mediated by cytokines, chemokines, exosomal mediators and shed ligands are present. Cytokines such as interleukins can influence all components of the tumour microenvironment (TME), consequently promoting or suppressing tumour invasion based on their secreting source. Interleukin-10 (IL-10) is an interlocked cytokine that has been associated with several types of malignancies and proved to have paradoxical effects. IL-10 has multiple functions on cellular and non-cellular components within the TME. In this review, the authors shed the light on the regulatory role of IL-10 in the TME of several malignant contexts. Moreover, detailed epigenomic and pharmacogenomic approaches for the regulation of IL-10 were presented and discussed.Peer reviewe

Effect of Gabapentin-Fluoxetine Derivative GBP1F in a murine model of depression, anxiety and cognition

Background and Objective: Gabapentin is a commonly prescribed antiepileptic agent for seizures, which is also used for pain and addiction management. Due to growing evidence of its abuse liability, there has been an incentive to synthesise potentially useful gabapentin derivatives devoid of adverse effects. A gabapentin adduct with a fluoxetine moiety, GBP1F, was assessed for any sedative, cognitive, anxiolytic, or antidepressant-like actions in murine behavioral models. Materials and Methods: Selected groups of mice were used for each behavioral paradigm, and the effect of GBP1F (5, 10, and 15 mg/kg) was assessed using spontaneous locomotor activity, the tail suspension test, elevated plus maze test, and the Y maze test models. Immediately following behavioral experiments, postmortem striatal and hippocampal tissues were evaluated for the effect of GBP1F on concentrations of dopamine, DOPAC, HVA, serotonin, 5-HIAA, vitamin C, and noradrenaline using high performance liquid chromatography with electrochemical detection. Results: GBP1F induced a mild suppression of locomotor activity, ameliorated anxiety and depression-like behavior, did not alter cognitive behavior, and raised serotonin and 5-HIAA concentrations in the hippocampus and striatum. GBP1F also positively enhanced dopamine and vitamin C tissue levels in the striatum. Thus, GBP1F represents a compound with anxiolytic- and antidepressant-like effects though further studies are warranted at the molecular level to focus on the precise mechanism(s) of action

Unraveling the relationship between the renin–angiotensin system and endometrial cancer: a comprehensive review

Endometrial cancer (EC), the most common adenocarcinoma, represents 90% of uterine cancer in women with an increased incidence of occurrence attributed to age, obesity, hypertension, and hypoestrogenism. Being the most common gynecological malignancy in women, it shows a relation with the activation of different components of the renin–angiotensin system (RAS), which is predominantly involved in maintaining blood pressure, salt, water, and aldosterone secretion, thereby playing a significant role in the etiology of hypertension. The components of the RAS, i.e., ACE-I, ACE-II, AT1R, AT2R, and Pro(renin) receptor, are widely expressed in both glandular and stromal cells of the endometrium, with varying levels throughout the different phases of the menstrual cycle. This causes the endometrial RAS to implicate angiogenesis, neovascularization, and cell proliferation. Thus, dysfunctioning of the endometrial RAS could predispose the growth and spread of EC. Interestingly, the increased expression of AngII, AGTR1, and AGTR2 showed advancement in the stages and progression of EC via the prorenin/ATP6AP2 and AngII/AGTR1 pathway. Therefore, this review corresponds to unraveling the relationship between the progression and development of endometrial cancer with the dysfunction in the expression of various components associated with RAS in maintaining blood pressure

Mechanistic evaluation of a novel cyclohexenone derivative?s functionality against nociception and inflammation: An in-vitro, in-vivo and in-silico approach

The synthesis of a novel cyclohexanone derivative (CHD; Ethyl 6-(4-metohxyphenyl)-2-oxo-4-phenylcyclohexe-3-enecarboxylate) was described and the subsequent aim was to perform an in vitro, in vivo and in silico pharmacological evaluation as a putative anti-nociceptive and anti-inflammatory agent in mice. Initial in vitro studies revealed that CHD inhibited both cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) enzymes and it also reduced mRNA expression of COX-2 and the pro-inflammatory cytokines TNF-α and IL-1β. It was then shown that CHD dose dependently inhibited chemically induced tonic nociception in the abdominal constriction assay and also phasic thermal nociception (i.e. anti-nociception) in the hot plate and tail immersion tests in comparison with aspirin and tramadol respectively. The thermal test outcomes indicated a possible moderate centrally mediated anti-nociception which, in the case of the hot plate test, was pentylenetetrazole (PTZ) and naloxone reversible, implicating GABAergic and opioidergic mechanisms. CHD was also effective against both the neurogenic and inflammatory mediator phases induced in the formalin test and it also disclosed anti-inflammatory activity against the phlogistic agents, carrageenan, serotonin, histamine and xylene compared with standard drugs in edema volume tests. In silico studies indicated that CHD possessed preferential affinity for GABAA, opioid and COX-2 target sites and this was supported by molecular dynamic simulations where computation of free energy of binding also favored the formation of stable complexes with these sites. These findings suggest that CHD has prospective anti-nociceptive and anti-inflammatory properties, probably mediated through GABAergic and opioidergic interactions supplemented by COX-2 and 5-LOX enzyme inhibition in addition to reducing pro-inflammatory cytokine expression. CHD may therefore possess potentially beneficial therapeutic effectiveness in the management of inflammation and pain

Nanotube breakthroughs: unveiling the potential of carbon nanotubes as a dual therapeutic arsenal for Alzheimer’s disease and brain tumors

Alzheimer’s disease (AD) and brain tumors are debilitating neurological conditions that pose significant challenges in current medical practices. Existing treatment options for AD primarily focus on symptom management, and brain tumors often require aggressive therapeutic approaches. Novel disease-modifying strategies and therapeutic agents are urgently needed to address the underlying causes of AD pathogenesis and improve brain tumor management. In recent years, nanoparticles (NPs) have shown promise as valuable tools in diagnosing and managing various brain disorders, including AD. Among these, carbon nanotubes (CNTs) have garnered attention for their unique properties and biomedical potential. Their ability to cross the blood-brain barrier (BBB) with ease opens up new possibilities for targeted drug delivery and neuroprotection. This literature review aims to explore the versatile nature of CNTs, which can be functionalized with various biomolecules or substances due to their sp2 hybridization. This adaptability enables them to specifically target cells and deliver medications under specific environmental conditions. Moreover, CNTs possess an exceptional capacity to penetrate cell membranes, making them valuable tools in the treatment of AD and brain tumors. By delving into the role of CNTs in biomedicine, this review sheds light on their potential in managing AD, offering a glimpse of hope for effective disease-modifying options. Understanding the mechanisms of CNTs’ action and their capabilities in targeting and delivering medication to affected cells will pave the way for innovative therapeutic strategies that can improve the lives of those afflicted with these devastating neurological conditions. The exploration of CNTs as a dual therapeutic arsenal for both brain tumors and Alzheimer’s disease holds great promise and may usher in a new era of effective treatment strategies for these challenging conditions

ADA Levels in Body Fluids as the Preferred Test to Rule Out Tuberculosis in Limited-resource Settings: Data from a Tertiary Care Hospital in Northern India

In clinical practice, the diagnosis of tuberculosis (TB) continues to be a challenge. The goal of this study was to evaluate the reliability and impact of adenosine deaminase (ADA) enzyme testing as a biochemical marker in the continued management of suspected tuberculosis in a limited resource setting hospital. The retrospective data were collected from 2018 to 2021 and comprised the results of all ADA test assays done in the laboratory. All types of body fluids received for ADA testing were analyzed. Over the course of two years, 1461 samples for ADA assay testing were received. The average age of the study population was 56.69±11.7 years, with males accounting for the majority of the subjects (55.72%). Pleural fluid (N=817, 55.92%) was the most common type of sample received for the ADA assay. 114 (13.95%) of the 817 pleural fluid samples were found to be positive. A survey was conducted to obtain physician’s response regarding reliability on ADA testing. 100% of them reported the supportive role of ADA levels in the workup of patients with suspected tuberculosis. In a limited resource setting, the ADA test, in conjunction with clinical and other laboratory findings, can help physicians to initiate early treatment in hospitals for the benefit of patients

Image_4_Viral metatranscriptomic approach to study the diversity of virus(es) associated with Common Bean (Phaseolus vulgaris L.) in the North-Western Himalayan region of India.JPEG

Plant viruses are a major threat to legume production worldwide. In recent years, new virus strains have emerged with increasing frequencies in various legume cropping systems, which demands the development of cutting-edge virus surveillance techniques. In this study, we surveyed the common bean fields of Kashmir valley for virus infection using a total of 140 symptomatic and non-symptomatic leaf samples collected from different locations. The genetic diversity of viruses was examined by high-throughput sequencing (HTS) with three viruses being identified, namely, Bean Common Mosaic Virus (BCMV), Bean Common Mosaic Necrosis Virus (BCMNV), and Clover Yellow Vein Virus (ClYVV). BCMNV and ClYVV are new reports from India. De novo assembly of transcriptome constructed near-complete genomes of these viruses. RT-PCR results confirmed the presence of these viruses with an emerge incidence of 56. 4% for BCMV, 27.1% for BCMNV and 16.4 for ClYVV in the valley. Several samples were found to contain multiple virus infections with BCMV being the most predominant. Recombination events were detected in the genomes of BCMV and ClYVV, but not BCMNV. Phylogenetic and pairwise identity matrix evidence suggests viral import from multiple countries. Our results demonstrate that HTS followed by multiplex PCR assay is a simple, rapid, and reliable approach for simultaneous diagnosis of plant viruses.</p

Table_1_Viral metatranscriptomic approach to study the diversity of virus(es) associated with Common Bean (Phaseolus vulgaris L.) in the North-Western Himalayan region of India.DOCX

Plant viruses are a major threat to legume production worldwide. In recent years, new virus strains have emerged with increasing frequencies in various legume cropping systems, which demands the development of cutting-edge virus surveillance techniques. In this study, we surveyed the common bean fields of Kashmir valley for virus infection using a total of 140 symptomatic and non-symptomatic leaf samples collected from different locations. The genetic diversity of viruses was examined by high-throughput sequencing (HTS) with three viruses being identified, namely, Bean Common Mosaic Virus (BCMV), Bean Common Mosaic Necrosis Virus (BCMNV), and Clover Yellow Vein Virus (ClYVV). BCMNV and ClYVV are new reports from India. De novo assembly of transcriptome constructed near-complete genomes of these viruses. RT-PCR results confirmed the presence of these viruses with an emerge incidence of 56. 4% for BCMV, 27.1% for BCMNV and 16.4 for ClYVV in the valley. Several samples were found to contain multiple virus infections with BCMV being the most predominant. Recombination events were detected in the genomes of BCMV and ClYVV, but not BCMNV. Phylogenetic and pairwise identity matrix evidence suggests viral import from multiple countries. Our results demonstrate that HTS followed by multiplex PCR assay is a simple, rapid, and reliable approach for simultaneous diagnosis of plant viruses.</p

Image_1_Viral metatranscriptomic approach to study the diversity of virus(es) associated with Common Bean (Phaseolus vulgaris L.) in the North-Western Himalayan region of India.JPEG

Plant viruses are a major threat to legume production worldwide. In recent years, new virus strains have emerged with increasing frequencies in various legume cropping systems, which demands the development of cutting-edge virus surveillance techniques. In this study, we surveyed the common bean fields of Kashmir valley for virus infection using a total of 140 symptomatic and non-symptomatic leaf samples collected from different locations. The genetic diversity of viruses was examined by high-throughput sequencing (HTS) with three viruses being identified, namely, Bean Common Mosaic Virus (BCMV), Bean Common Mosaic Necrosis Virus (BCMNV), and Clover Yellow Vein Virus (ClYVV). BCMNV and ClYVV are new reports from India. De novo assembly of transcriptome constructed near-complete genomes of these viruses. RT-PCR results confirmed the presence of these viruses with an emerge incidence of 56. 4% for BCMV, 27.1% for BCMNV and 16.4 for ClYVV in the valley. Several samples were found to contain multiple virus infections with BCMV being the most predominant. Recombination events were detected in the genomes of BCMV and ClYVV, but not BCMNV. Phylogenetic and pairwise identity matrix evidence suggests viral import from multiple countries. Our results demonstrate that HTS followed by multiplex PCR assay is a simple, rapid, and reliable approach for simultaneous diagnosis of plant viruses.</p