Biofilms: The Microbial “Protective Clothing” in Extreme Environments

International Journal of Molecular Sciences, Journal Year: 2019, Volume and Issue: 20(14), P. 3423 - 3423

Published: July 12, 2019

Microbial biofilms are communities of aggregated microbial cells embedded in a self-produced matrix extracellular polymeric substances (EPS). Biofilms recalcitrant to extreme environments, and can protect microorganisms from ultraviolet (UV) radiation, temperature, pH, high salinity, pressure, poor nutrients, antibiotics, etc., by acting as “protective clothing”. In recent years, research works on have been mainly focused biofilm-associated infections strategies for combating biofilms. this review, we focus instead the contemporary perspectives biofilm formation describe fundamental roles protecting exposure environmental stresses regulatory factors involved formation. Understanding mechanisms environments is essential employment beneficial prevention harmful microorganisms.

Language: Английский

---

DNA damage repair: historical perspectives, mechanistic pathways and clinical translation for targeted cancer therapy

Signal Transduction and Targeted Therapy, Journal Year: 2021, Volume and Issue: 6(1)

Published: July 9, 2021

Abstract Genomic instability is the hallmark of various cancers with increasing accumulation DNA damage. The application radiotherapy and chemotherapy in cancer treatment typically based on this property cancers. However, adverse effects including normal tissues injury are also accompanied by chemotherapy. Targeted therapy has potential to suppress cells’ damage response through tailoring patients lacking specific functions. Obviously, understanding broader role repair became a basic attractive strategy for targeted therapy, particular, raising novel hypothesis or theory field basis previous scientists’ findings would be important future promising druggable emerging targets. In review, we first illustrate timeline steps roles promotion developed, then summarize mechanisms regarding associated highlighting proteins behind targeting that initiate functioning abnormally duo extrinsic harm environmental factors, also, baseline drift leads harmful intrinsic therapy. addition, clinical therapeutic drugs effects, as well scheme relative trials were intensive discussed. Based background, suggest two hypotheses, namely “environmental gear selection” describe pathway evolution, “DNA drift”, which may play magnified mediating during treatment. This new shed light provide much better more comprehensive holistic view promote development research direction overcoming strategies patients.

Language: Английский

---

Ageing, age-related diseases and oxidative stress: What to do next?

Ageing Research Reviews, Journal Year: 2019, Volume and Issue: 57, P. 100982 - 100982

Published: Nov. 13, 2019

Language: Английский

---

PARP inhibitor resistance: the underlying mechanisms and clinical implications

Molecular Cancer, Journal Year: 2020, Volume and Issue: 19(1)

Published: June 20, 2020

Abstract Due to the DNA repair defect, BRCA1/2 deficient tumor cells are more sensitive PARP inhibitors (PARPi) through mechanism of synthetic lethality. At present, several PAPRi targeting poly (ADP-ribose) polymerase (PARP) have been approved for ovarian cancer and breast indications. However, PARPi resistance is ubiquitous in clinic. More than 40% BRCA1/2-deficient patients fail respond PARPi. In addition, lots acquire with prolonged oral administration Homologous recombination (HRD), as an essential prerequisite lethality, plays a vital role killing cells. Therefore, restoration (HRR) becomes predominant reason resistance. Recently, it was reported that replication fork protection also contributed patients. Moreover, various factors, such reversion mutations, epigenetic modification, ADP-ribosylation (PARylation) pharmacological alteration lead well. this review, we reviewed underlying mechanisms inhibitor detail summarized potential strategies overcome increase sensitivity.

Language: Английский

---

The Unfolded Protein Response: Detecting and Responding to Fluctuations in the Protein-Folding Capacity of the Endoplasmic Reticulum

Cold Spring Harbor Perspectives in Biology, Journal Year: 2019, Volume and Issue: 11(9), P. a033886 - a033886

Published: Jan. 22, 2019

Most of the secreted and plasma membrane proteins are synthesized on membrane-bound ribosomes endoplasmic reticulum (ER). They require engagement ER-resident chaperones foldases that assist in their folding maturation. Since protein homeostasis ER is crucial for cellular function, protein-folding status organelle's lumen continually surveyed by a network signaling pathways, collectively called unfolded response (UPR). Protein-folding imbalances, or "ER stress," detected highly conserved sensors adjust ER's capacity according to physiological needs cell. We review recent developments field have provided new insights into stress-sensing mechanisms used UPR which they integrate various inputs organelle accommodate fluctuations demands.

Language: Английский

---

Comprehensive Review of Uterine Fibroids: Developmental Origin, Pathogenesis, and Treatment

Endocrine Reviews, Journal Year: 2021, Volume and Issue: 43(4), P. 678 - 719

Published: Nov. 6, 2021

Abstract Uterine fibroids are benign monoclonal neoplasms of the myometrium, representing most common tumors in women worldwide. To date, no long-term or noninvasive treatment option exists for hormone-dependent uterine fibroids, due to limited knowledge about molecular mechanisms underlying initiation and development fibroids. This paper comprehensively summarizes recent research advances on focusing risk factors, origin, pathogenetic mechanisms, options. Additionally, we describe current interventions Finally, future perspectives studies summarized. Deeper mechanistic insights into tumor etiology complexity can contribute progress newer targeted therapies.

Language: Английский

---

The Role of Oxidative Stress in Physiopathology and Pharmacological Treatment with Pro- and Antioxidant Properties in Chronic Diseases

Oxidative Medicine and Cellular Longevity, Journal Year: 2020, Volume and Issue: 2020, P. 1 - 16

Published: July 24, 2020

Oxidative stress (OS) has the ability to damage different molecules and cellular structures, altering correct function of organs systems. OS accumulates in body by endogenous exogenous mechanisms. Increasing evidence points involvement physiopathology various chronic diseases that require prolonged periods pharmacological treatment. Long-term treatments may contribute changes systemic OS. In this review, we discuss pathological mechanisms some diseases, pro- or antioxidant effects their treatments, possible adjuvant alternatives. Diseases such as high blood pressure, arteriosclerosis, diabetes mellitus increased risk cardiovascular disease. Antihypertensive, lipid-lowering, hypoglycemic help reduce with an additional benefit. Treatment methotrexate autoimmune inflammatory rheumatoid arthritis, a dual role stimulating production producing mitochondrial dysfunction. However, it can also indirectly decrease induced inflammation. Medicaments used treat neurodegenerative tend related reactive oxygen species (ROS) balance On other hand, immunosuppressive cancer human immunodeficiency virus infection increase ROS, causing significant oxidative systems without widely documented administration

Language: Английский

---

PRIMPOL-Mediated Adaptive Response Suppresses Replication Fork Reversal in BRCA-Deficient Cells

Molecular Cell, Journal Year: 2019, Volume and Issue: 77(3), P. 461 - 474.e9

Published: Oct. 30, 2019

Acute treatment with replication-stalling chemotherapeutics causes reversal of replication forks. BRCA proteins protect reversed forks from nucleolytic degradation, and their loss leads to chemosensitivity. Here, we show that fork degradation is no longer detectable in BRCA1-deficient cancer cells exposed multiple cisplatin doses, mimicking a clinical regimen. This effect depends on increased expression chromatin loading PRIMPOL regulated by ATR activity. Electron microscopy single-molecule DNA fiber analyses reveal rescues reinitiating synthesis past lesions. repriming accumulation ssDNA gaps while suppressing reversal. We propose adapt repeated doses activating under conditions would otherwise promote pathological degradation. generalizable other impaired (e.g., SMARCAL1 or PARP inhibition) suggests new strategy modulate chemosensitivity targeting the pathway.

Language: Английский

---

Measuring DNA modifications with the comet assay: a compendium of protocols

Nature Protocols, Journal Year: 2023, Volume and Issue: 18(3), P. 929 - 989

Published: Jan. 27, 2023

Language: Английский

---

DNA Damage and Associated DNA Repair Defects in Disease and Premature Aging

The American Journal of Human Genetics, Journal Year: 2019, Volume and Issue: 105(2), P. 237 - 257

Published: Aug. 1, 2019

Language: Английский

---