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Selective Non-toxics Inhibitors Targeting DHFR for Tuberculosis and Cancer Therapy: Pharmacophore Generation and Molecular Dynamics Simulation
In this study, we aimed to identify selective and non-toxic inhibitors against h-DHFR and mt-DHFR using an in silico approach. From a data set of 8 412 inhibitors, 11 compounds passed the toxicity and drug-likeness tests, and their interaction with h-DHFR and mt-DHFR was studied by performing molecular docking. To evaluate the inhibitory activity of the compounds against mt-DHFR, five known reference ligands and the natural ligand (dihydrofolate) were used to generate a pharmacophoric map. Two potential selective inhibitors for mt-DHFR and h-DHFR were selected for further investigation using molecular dynamics for 100 ns. ...
Source: Bioinformatics and Biology Insights - May 14, 2023 Category: Bioinformatics Authors: Ghyzlane El Haddoumi Mariam Mansouri Houda Bendani Mohammed Walid Chemao-Elfihri Jouhaina Kourou Hanane Abbou Lahcen Belyamani Ilham Kandoussi Azeddine Ibrahimi Source Type: research

Highlights into historical and current immune interventions for cancer
Int Immunopharmacol. 2023 Feb 27;117:109882. doi: 10.1016/j.intimp.2023.109882. Online ahead of print.ABSTRACTImmunotherapy is an additional pillar when combined with traditional standards of care such as chemotherapy, radiotherapy, and surgery for cancer patients. It has revolutionized cancer treatment and rejuvenated the field of tumor immunology. Several types of immunotherapies, including adoptive cellular therapy (ACT) and checkpoint inhibitors (CPIs), can induce durable clinical responses. However, their efficacies vary, and only subsets of cancer patients benefit from their use. In this review, we address three goal...
Source: International Immunopharmacology - February 27, 2023 Category: Allergy & Immunology Authors: Kathryn Cole Zaid Al-Kadhimi James E Talmadge Source Type: research

Designing coordination polymers as multi-drug-self-delivery systems for tuberculosis and cancer therapy: < em > in vitro < /em > viability and < em > in vivo < /em > toxicity assessment
Biomater Sci. 2022 Sep 13. doi: 10.1039/d2bm00752e. Online ahead of print.ABSTRACTA proof of concept for designing multi-drug-delivery systems suitable for self-drug-delivery is disclosed. Simple coordination chemistry was employed to anchor two kinds of drugs namely isoniazid (IZ - anti-tuberculosis), various non-steroidal-anti-inflammatory-drugs (NSAIDs) namely ibuprofen-IBU, fenoprofen-FEN, naproxen-NAP, diclofenac-DIC and mefenamic acid-MEF and Zn(NO3)2 to synthesize a series of 1D coordination polymers namely IZIBU, IZFEN, IZNAP, IZDIC and IZMEF which were structurally characterized by single crystal X-ray diffraction...
Source: Cell Research - September 13, 2022 Category: Cytology Authors: Protap Biswas Hemanta Kumar Datta Parthasarathi Dastidar Source Type: research

A BCG success story: From prevention of tuberculosis to optimal bladder cancer treatment
Vaccine. 2021 Aug 17:S0264-410X(21)01046-X. doi: 10.1016/j.vaccine.2021.08.026. Online ahead of print.ABSTRACTBCG remains the most important vaccine for tuberculosis 100 years after its first use, and over the past 4 decades it has become the most widely accepted, effective drug used in the treatment of aggressive localized bladder cancer. This review chronicles the narrow path that led to approval and world-wide acceptance of BCG immunotherapy for bladder cancer while immunotherapy trials in other malignancies were abandoned. Six intravesical instillations of 5x10^8 CFU of BCG weekly after bladder tumor resection, first r...
Source: Vaccine - August 21, 2021 Category: Allergy & Immunology Authors: Donald L Lamm Alvaro Morales Source Type: research

Fight Aging! Newsletter, March 29th 2021
Discussion of Systemic Inflammation and its Contribution to Dementia Fisetin Reduces D-Galactose Induced Cognitive Loss in Mice Reprogramming Cancer Cells into Normal Somatic Cells Considering Longevity Medicine and the Education of Physicians Researchers Generate Thyroid Organoids Capable of Restoring Function in Mice In Search of Transcriptional Signatures of Aging A Pace of Aging Biomarker Correlates with Manifestations of Aging Targeting Tissues with Extracellular Vesicles Calorie Restriction Slows Aging of the Gut Microbiome in Mice Mitochondrial DNA Heteroplasmy in the Aging Heart Evidence for Hea...
Source: Fight Aging! - March 28, 2021 Category: Research Authors: Reason Tags: Newsletters Source Type: blogs

Fight Aging! Newsletter, January 20th 2020
This study provides strong evidence that following a healthy lifestyle can substantially extend the years a person lives disease-free." Commentary on Recent Evidence for Cognitive Decline to Precede Amyloid Aggregation in Alzheimer's Disease https://www.fightaging.org/archives/2020/01/commentary-on-recent-evidence-for-cognitive-decline-to-precede-amyloid-aggregation-in-alzheimers-disease/ I can't say that I think the data presented in the research noted here merits quite the degree of the attention that it has been given in the popular science press. It is interesting, but not compelling if its role is t...
Source: Fight Aging! - January 19, 2020 Category: Research Authors: Reason Tags: Newsletters Source Type: blogs

Actinobacteria Isolated From Laminaria ochroleuca: A Source of New Bioactive Compounds
Conclusion This work adds to the knowledge available on actinobacteria associated with marine macroalgae and their bioactive potential. Our data indicates that the kelp forest alga L. ochroleuca is a valuable source for the isolation of actinobacteria, both in terms of abundance and diversity, and a reservoir of NP with antimicrobial and anticancer bioactivities. Author Contributions MG, PL, and MC designed and oversaw the whole study. MG and IR carried out the isolation of actinobacteria and taxonomic identification. MG and TR carried out cell line cytotoxicity assays. IA performed the kelp sampling. FP oversaw the mol...
Source: Frontiers in Microbiology - April 8, 2019 Category: Microbiology Source Type: research

Fight Aging! Newsletter, October 22nd 2018
In this report, we propose that the molecular mechanisms of beneficial actions of CR should be classified and discussed according to whether they operate under rich or insufficient energy resource conditions. Future studies of the molecular mechanisms of the beneficial actions of CR should also consider the extent to which the signals/factors involved contribute to the anti-oxidative, anti-inflammatory, anti-tumor and other CR actions in each tissue or organ, and thereby lead to anti-aging and prolongevity. RNA Interference of ATP Synthase Subunits Slows Aging in Nematodes https://www.fightaging.org/archives/...
Source: Fight Aging! - October 21, 2018 Category: Research Authors: Reason Tags: Newsletters Source Type: blogs

Fight Aging! Newsletter, August 15th 2016
In conclusion, our results demonstrate that circulating GDF11 levels are reduced in our mouse model of premature aging, which shares most of the symptoms that occur in normal aging. However, GDF11 protein administration is not sufficient to extend longevity in these progeroid mice. Although accelerated-aging mouse models can serve as powerful tools to test and develop anti-aging therapies common to both physiological and pathological aging, the existence of certain differences between the two processes implies that further investigation is still required to determine whether long-term GDF11 administration has a pro-surviva...
Source: Fight Aging! - August 14, 2016 Category: Research Authors: Reason Tags: Newsletters Source Type: blogs