Glioma nanotherapy: Unleashing the synergy of dual-loaded DIM and TMZ.

Glioblastoma multiforme (GBM) is a highly aggressive form of primary brain tumor in adults, which unfortunately has an abysmal prognosis and poor survival rates. The reason behind the poor success rate of several FDA-approved drug is mainly attributed to insufficient drug distribution to the tumor site across the blood-brain barrier (BBB) and induction of resistance. In this study, we have developed a novel nanotherapeutic approach to achieve our goal.

GBM immunotherapy: Exploring molecular and clinical frontiers.

GBM is the most common, aggressive, and intracranial primary brain tumor; it originates from the glial progenitor cells, has poor overall survival (OS), and has limited treatment options. In this decade, GBM immunotherapy is in trend and preferred over several conventional therapies, due to their better patient survival outcome. This review explores the clinical trials of several immunotherapeutic approaches (immune checkpoint blockers (ICBs), CAR T-cell therapy, cancer vaccines, and adoptive cell therapy) with their efficacy and safety.

E3 ubiquitin ligases and deubiquitinases in colorectal cancer: Emerging molecular insights and therapeutic opportunities.

Colorectal cancer (CRC) presents ongoing challenges due to limited treatment effectiveness and a discouraging prognosis, underscoring the need for ground-breaking therapeutic approaches. This review delves into the pivotal role of E3 ubiquitin ligases and deubiquitinases (DUBs), underscoring their role as crucial regulators for tumor suppression and oncogenesis in CRC. We spotlight the diverse impact of E3 ligases and DUBs on CRC's biological processes and their remarkable versatility.

Chrysin-functionalized gold nanoparticles and paclitaxel exhibit synergistic impact on lung cancer cell lines via regulating the AKT/PPAR-ϒ/β-catenin pathway.

Lung cancer has become progressively widespread, posing a challenge to traditional chemotherapeutic drugs such as platinum compounds and paclitaxel (PTX) owing to growing resistance. Along with that, the chemotherapeutic drugs infer major side effects. The usage of natural compounds as chemosensitizers to boost the efficacy of these chemotherapeutic drugs and minimizing their toxicity is a plausible approach.

Crystal to Hydrogel Transformation in S-Benzyl-L-Cysteine-Containing Cyclic Dipeptides - Nanostructure Elucidation and Applications.

Cyclic dipeptides (CDPs) are crucial building blocks for a range of functional nanomaterials due to their simple chemical structure and high molecular stability. In this investigation, we synthesized a set of S-benzyl-L-cysteine-based CDPs (designated as P1-P6) and thoroughly examined their self-assembly behavior in a methanol-water solvent to elucidate the relationship between their structure and gelation properties. The hydrophobicity of the amino acids within the CDPs was gradually increased.

Structural and functional insights of itaconyl-CoA hydratase from Pseudomonas aeruginosa highlight a novel N-terminal hotdog fold.

Itaconyl-CoA hydratase in Pseudomonas aeruginosa (PaIch) converts itaconyl-CoA to (S)-citramalyl-CoA upon addition of a water molecule, a part of an itaconate catabolic pathway in virulent organisms required for their survival in humans host cells. Crystal structure analysis of PaIch showed that a unique N-terminal hotdog fold containing a 4-residue short helical segment α3-, named as an "eaten sausage", followed by a flexible loop region slipped away from the conserved β-sheet scaffold, whereas the C-terminal hotdog fold is similar to all MaoC. A conserved hydratase motif with catalytic residues provides mechanistic insights into catalysis, and existence of a longer substrate binding tunnel may suggest the binding of longer CoA derivatives.

MGMT in TMZ-based glioma therapy: Multifaceted insights and clinical trial perspectives.

Temozolomide (TMZ) is the most preferred and approved chemotherapeutic drug for either first- or second-line chemotherapy for glioma patients across the globe. In glioma patients, resistance to treatment with alkylating drugs like TMZ is known to be conferred by exalted levels of MGMT gene expression. On the contrary, epigenetic silencing through MGMT gene promoter methylation leading to subsequent reduction in MGMT transcription and protein expression, is predicted to have a response favoring TMZ treatment.

E3 ubiquitin ligases in lung cancer: Emerging insights and therapeutic opportunities.

Aim In this review, we have attempted to provide the readers with an updated account of the role of a family of proteins known as E3 ligases in different aspects of lung cancer progression, along with insights into the deregulation of expression of these proteins during lung cancer. A detailed account of the therapeutic strategies involving E3 ligases that have been developed or currently under development has also been provided in this review. MATERIALS AND METHODS: The review article employs extensive literature search, along with differential gene expression analysis of lung cancer associated E3 ligases using the DESeq2 package in R, and the Gene Expression Profiling Interactive Analysis (GEPIA) database (http://gepia.

DDX5 (p68) orchestrates β-catenin, RelA and SP1 mediated MGMT gene expression in human colon cancer cells: Implication in TMZ chemoresistance.

DDX5 (p68) upregulation has been linked with various cancers of different origins, especially Colon Adenocarcinomas. Similarly, across cancers, MGMT has been identified as the major contributor of chemoresistance against DNA alkylating agents like Temozolomide (TMZ). TMZ is an emerging potent chemotherapeutic agent across cancers under the arena of drug repurposing.

TGS1/PIMT knockdown reduces lipid accumulation in adipocytes, limits body weight gain and promotes insulin sensitivity in mice.

PRIP Interacting protein with Methyl Transferase domain (PIMT/TGS1) is an integral upstream coactivator in the peroxisome proliferator-activated receptor gamma (PPARγ) transcriptional apparatus. PPARγ activation alleviates insulin resistance but promotes weight gain. Herein, we show how PIMT regulates body weight while promoting insulin sensitivity in diet induced obese mice.

The E3 ubiquitin ligase CHIP drives monoubiquitylation-mediated nuclear import of the tumor suppressor PTEN.

Monoubiquitylation is a principal mechanism driving nuclear translocation of the protein PTEN (phosphatase and tensin homolog deleted on chromosome ten). In this study, we describe a novel mechanism wherein the protein CHIP (C-terminus of Hsc70-interacting protein) mediates PTEN monoubiquitylation, leading to its nuclear import. Western blot analysis revealed a rise in both nuclear and total cellular PTEN levels under monoubiquitylation-promoting conditions, an effect that was abrogated by silencing CHIP expression.

Ets1 facilitates EMT/invasion through Drp1-mediated mitochondrial fragmentation in ovarian cancer.

Ovarian cancer has sustained as a major cause of cancer-related female mortality owing to its aggressive nature and a dearth of early detection markers. Ets1 oncoprotein, a transcription factor belonging to the Ets family, is a well-established promoter of epithelial to mesenchymal transition (EMT) and a prospective malignancy marker in ovarian cancer. Our study establishes Ets1 as a regulator of mitochondrial fission-fusion dynamics through Drp1 augmentation via direct binding at DNM1L (DRP1) promoter.

Swietenolide isolated from King in Hook seeds shows anti-colorectal cancer activity through inhibition of mouse double minute 2 (MDM2) homolog.

King in Hook (SM) is known to have several medicinal properties. Chloroform extracts of SM seeds (SMCE) as well as two isolated limonoids swietenine () and swietenolide () showed significant anti-CRC activity in human colon carcinoma (HCT116) cell line. (IC = 5.

Targeting PD-1/PD-L1 in cancer immunotherapy: An effective strategy for treatment of triple-negative breast cancer (TNBC) patients.

Maintaining the balance between eliciting immune responses against foreign proteins and tolerating self-proteins is crucial for maintenance of homeostasis. The functions of programmed death protein 1 (PD-1) and its ligand programmed death ligand 1 (PD-L1) are to inhibit immune responses so that over-reacting immune cells does not cause any damage to its own body cells. However, cancer cells hijack this mechanism to attenuate immune cells functions and create an immunosuppressive environment that fuel their continuous growth and proliferation.

COVID-19 therapeutics: Clinical application of repurposed drugs and futuristic strategies for target-based drug discovery.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes the complicated disease COVID-19. Clinicians are continuously facing huge problems in the treatment of patients, as COVID-19-specific drugs are not available, hence the principle of drug repurposing serves as a one-and-only hope. Globally, the repurposing of many drugs is underway; few of them are already approved by the regulatory bodies for their clinical use and most of them are in different phases of clinical trials.

USP7 - a crucial regulator of cancer hallmarks.

Over the course of three decades of study, the deubiquitinase Herpesvirus associated Ubiquitin-Specific Protease/Ubiquitin-Specific Protease 7 (HAUSP/USP7) has gradually come to be recognized as a crucially important molecule in cellular physiology. The fact that USP7 is overexpressed in a number of cancers, including breast, prostate, colorectal, and lung cancers, supports the idea that USP7 is also an important regulator of tumorigenesis. In this review, we discuss USP7's function in relation to the cancer hallmarks described by Hanahan and Weinberg.

A small HDM2 antagonist peptide and a USP7 inhibitor synergistically inhibit the p53-HDM2-USP7 circuit.

HDM2, an E3 ubiquitin ligase, is a crucial regulator of many proliferation-related pathways. It is also one of the primary regulators of p53. USP7, a deubiquitinase, also plays a key role in the regulation of both p53 and HDM2, thus forming a small regulatory network with them.

Neurological damages in COVID-19 patients: Mechanisms and preventive interventions.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus, causes coronavirus disease 2019 (COVID-19) which led to neurological damage and increased mortality worldwide in its second and third waves. It is associated with systemic inflammation, myocardial infarction, neurological illness including ischemic strokes (e.g.

The DEAD-box RNA helicase DDX5 (p68) and β-catenin: The crucial regulators of FOXM1 gene expression in arbitrating colorectal cancer.

Forkhead box M1 (FOXM1), a vital member of the Forkhead box family of transcription factors, helps in mediating oncogenesis. However, limited knowledge exists regarding the mechanistic insights into the FOXM1 gene regulation. DDX5 (p68), an archetypal member of the DEAD-box family of RNA helicases, shows multifaceted action in cancer progression by arbitrating RNA metabolism and transcriptionally coactivating transcription factors.

Exploring structural features and potential lipid interactions of Pseudomonas aeruginosa type three secretion effector PemB by spectroscopic and calorimetric experiments.

Type Three Secretion System (T3SS) is a sophisticated nano-scale weapon utilized by several gram negative bacteria under stringent spatio-temporal regulation to manipulate and evade host immune systems in order to cause infection. To the best of our knowledge, this present study is the first report where we embark upon characterizing inherent features of native type three secretion effector protein PemB through biophysical techniques. Herein, first, we demonstrate binding affinity of PemB for phosphoinositides through isothermal calorimetric titrations.

USP7 imparts partial EMT state in colorectal cancer by stabilizing the RNA helicase DDX3X and augmenting Wnt/β-catenin signaling.

Epithelial mesenchymal transition (EMT) is a fundamental and highly regulated process that is normally observed during embryonic development and tissue repair but is deregulated during advanced cancer. Classically, through the process of EMT, cancer cells gradually transition from a predominantly epithelial phenotype to a more invasive mesenchymal phenotype. Increasing studies have, however, brought into light the existence of unique intermediary states in EMT, often referred to as partial EMT states.

USP7 targets XIAP for cancer progression: Establishment of a p53-independent therapeutic avenue for glioma.

Ubiquitin specific peptidase 7 (USP7) is a deubiquitinating enzyme (DUB) that removes ubiquitin tags from specific target protein substrates in order to alter their degradation rate, sub-cellular localization, interaction, and activity. The induction of apoptosis upon USP7 inhibition is well established in cancer containing wild type p53, which operates through the 'USP7-Mdm2-p53' axis. However, in cancers without functional p53, USP7-dependent apoptosis is induced through many other alternative pathways.

Cell-imaging studies of highly substituted oxazole derivatives as organelle targeting fluorophores (OTFPs).

The field of biomedical science has progressed enormously in the past decade. With the advent of newer diagnostic tools for imaging and detection, identification of root cause of a disease is now remarkably accurate and specific. Small organic fluorophores in these connections are in great demand currently for cellular organelle sensing and detecting, due to their non-invasiveness, excellent accuracy and bio-sensitivity.

COVID-19: Clinical status of vaccine development to date.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-induced COVID-19 is a complicated disease. Clinicians are continuously facing difficulties to treat infected patients using the principle of repurposing of drugs as no specific drugs are available to treat COVID-19. To minimize the severity and mortality, global vaccination is the only hope as a potential preventive measure.