/pdf/aging-drives-tet2-clonal-hematopoiesis-via-il-1-signaling-297haer2.pdf

Aging drives Tet2+/- >clonal hematopoiesis via IL-1 signaling.

Cancer stem cells (CSCs) are subpopulations of tumor masses with unique abilities in self-renewal, stemness maintenance, drug resistance, and the promotion of cancer recurrence. Recent studies have suggested that breast CSCs play essential roles in chemoresistance. Therefore, new agents that selectively target such cells are urgently required. Reactive oxygen species (ROS)-producing enzymes are the reason for an elevated tumor oxidant status. The nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcriptional factor, which upon detecting cellular oxidative stress, binds to the promoter region of antioxidant genes. By triggering a cytoprotective response, Nrf2 maintains cellular redox status. Cripto-1 participates in the self-renewal of CSCs. Herein, luteolin, a flavonoid found in Taraxacum officinale extract, was determined to inhibit the expressions of stemness-related transcriptional factors, the ATP-binding cassette transporter G2 (ABCG2), CD44, aldehyde dehydrogenase 1 activity as well as the sphere formation properties of breast CSCs. Furthermore, luteolin suppressed the protein expressions of Nrf2, heme oxygenase 1 (HO-1), and Cripto-1 which have been determined to contribute critically to CSC features. The combination of luteolin and the chemotherapeutic drug, Taxol, resulted in enhanced cytotoxicity to breast cancer cells. These findings suggest that luteolin treatment significantly attenuated the hallmarks of breast cancer stemness by downregulating Nrf2-mediated expressions. Luteolin constitutes a potential agent for use in cancer stemness-targeted breast cancer treatments.

Luteolin Inhibits Breast Cancer Stemness and Enhances Chemosensitivity through the Nrf2-Mediated Pathway.

Mesenchymal stem cells (MSCs) are adult stem cells owing to their regenerative potential and multilineage potency. MSCs have wide-scale applications either in their native cellular form or in conjugation with specific biomaterials as nanocomposites. Majorly, these natural or synthetic biomaterials are being used in the form of metallic and non-metallic nanoparticles (NPs) to encapsulate MSCs within hydrogels like alginate or chitosan or drug cargo loading into MSCs. In contrast, nanofibers of polymer scaffolds such as polycaprolactone (PCL), poly-lactic-co-glycolic acid (PLGA), poly-L-lactic acid (PLLA), silk fibroin, collagen, chitosan, alginate, hyaluronic acid (HA), and cellulose are used to support or grow MSCs directly on it. These MSCs based nanotherapies have application in multiple domains of biomedicine including wound healing, bone and cartilage engineering, cardiac disorders, and neurological disorders. This review focused on current approaches of MSCs-based therapies and has been divided into two major sections. The first section elaborates on MSC-based nano-therapies and their plausible applications including exosome engineering and NPs encapsulation. The following section focuses on the various MSC-based scaffold approaches in tissue engineering. Conclusively, current review mainly discussed the MSC-based nanocomposite's current approaches their advantages and limitations for building effective regenerative medicines. 

Mesenchymal stem cell-based nanoparticles and scaffolds in regenerative medicine

Targeting PI3K/Akt signaling in prostate cancer therapy.

Abstract Cancer stem cells (CSCs), a small subset of cells in tumors that are characterized by self-renewal and continuous proliferation, lead to tumorigenesis, metastasis, and maintain tumor heterogeneity. Cancer continues to be a significant global disease burden. In the past, surgery, radiotherapy, and chemotherapy were the main cancer treatments. The technology of cancer treatments continues to develop and advance, and the emergence of targeted therapy, and immunotherapy provides more options for patients to a certain extent. However, the limitations of efficacy and treatment resistance are still inevitable. Our review begins with a brief introduction of the historical discoveries, original hypotheses, and pathways that regulate CSCs, such as WNT/β-Catenin, hedgehog, Notch, NF-κB, JAK/STAT, TGF-β, PI3K/AKT, PPAR pathway, and their crosstalk. We focus on the role of CSCs in various therapeutic outcomes and resistance, including how the treatments affect the content of CSCs and the alteration of related molecules, CSCs-mediated therapeutic resistance, and the clinical value of targeting CSCs in patients with refractory, progressed or advanced tumors. In summary, CSCs affect therapeutic efficacy, and the treatment method of targeting CSCs is still difficult to determine. Clarifying regulatory mechanisms and targeting biomarkers of CSCs is currently the mainstream idea. 

Cancer stem cells: advances in knowledge and implications for cancer therapy

Cancer stem cells targets and combined therapies to prevent cancer recurrence

Abstract The high magnitude zoonotic event has caused by Severe Acute Respitarory Syndrome CoronaVirus-2 (SARS-CoV-2) is Coronavirus Disease-2019 (COVID-19) epidemics. This disease has high rate of spreading than mortality in humans. The human receptor, Angiotensin-Converting Enzyme 2 (ACE2), is the leading target site for viral Spike-protein (S-protein) that function as binding ligands and are responsible for their entry in humans. The patients infected with COVID-19 with comorbidities, particularly cancer patients, have a severe effect or high mortality rate because of the suppressed immune system. Nevertheless, there might be a chance wherein cancer patients cannot be infected with SARS-CoV-2 because of mutations in the ACE2, which may be resistant to the spillover between species. This study aimed to determine the mutations in the sequence of the human ACE2 protein and its dissociation with SARS-CoV-2 that might be rejecting viral transmission. The in silico approaches were performed to identify the impact of SARS-CoV-2 S-protein with ACE2 mutations, validated experimentally, occurred in the patient, and reported in cell lines. The identified changes significantly affect SARS-CoV-2 S-protein interaction with ACE2, demonstrating the reduction in the binding affinity compared to SARS-CoV. The data presented in this study suggest ACE2 mutants have a higher and lower affinity with SARS-Cov-2 S-protein to the wild-type human ACE2 receptor. This study would likely be used to report SARS-CoV-2 resistant ACE2 mutations and can be used to design active peptide development to inactivate the viral spread of SARS-CoV-2 in humans. 

https://www.nature.com/articles/s41598-022-20773-9.pdf

Experimental and clinical data analysis for identification of COVID-19 resistant ACE2 mutations

Therapeutic Effect of Natural Compounds in Targeting ROS-Induced Cancer

Systems Biology Resources and Their Applications to Understand the Cancer

Since the inception of the COVID-19 pandemic, a large number of clinical trials on Complementary and Alternative Medicine (CAM) for SARS-CoV-2 infection (COVID-19 disease) have been registered. The information is scattered at different resources making it difficult for researchers, scientists, health care professionals, and the general public to remain up-to-date on the latest CAM clinical trials being registered for COVID-19. The Complementary and Alternative Medicine Clinical Trials Database CoVAM is developed to provide the scientific community easy access to the latest information on the CAM clinical trials registered globally for COVID-19 disease. To develop the CoVAM, MySQL was used. API management was done through NodeJs (with express), and Angular 11 was used as front end. The CoVAM is a single platform organized by ten CAM subtypes such as Acupuncture, Auricular point pressing, Ayurveda, Chiropractic, Homeopathy, Psychotherapy, Siddha, Traditional Chinese Medicine (TCM), Vitamins and dietary supplements, and Yoga/Exercise. Each subtype has information on CAM medicines/ therapy being registered, the full title of the clinical trial, sponsor name, sponsor protocol number/ID, age of the population, study type, actual number of participant enrolment for the trial, followed by the start date, phase, and status of the clinical trial. Each fact is linked to the clinical trial databases from where the information was procured. Additionally, CoVAM is hyperlinked with PubMed for providing recent updates on COVID-19 and CAM research. To the best of our knowledge, CoVAM is a first-of-its-kind database that provides comprehensive information on globally registered CAMs related clinical trials conducted on COVID-19 disease.

/pdf/covam-complementary-and-alternative-medicine-clinical-trials-ifidf4ou4e.pdf

CoVAM: Complementary and Alternative Medicine Clinical Trials Database for COVID-19 Disease

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