Unveiling the mechanisms and challenges of cancer drug resistance

Cell Communication and Signaling, Год журнала: 2024, Номер 22(1)

Опубликована: Фев. 12, 2024

Abstract Cancer treatment faces many hurdles and resistance is one among them. Anti-cancer strategies are evolving due to innate acquired capacity, governed by genetic, epigenetic, proteomic, metabolic, or microenvironmental cues that ultimately enable selected cancer cells survive progress under unfavorable conditions. Although the mechanism of drug being widely studied generate new target-based drugs with better potency than existing ones. However, broader flexibility in resistance, advanced therapeutic options efficacy need be explored. Combination therapy an alternative a success rate though risk amplified side effects commonplace. Moreover, recent groundbreaking precision immune ways overcome has revolutionized anticancer greater extent only limitation individual-specific needs further attention. This review will focus on challenges opted withstand current therapies at molecular level also highlights emerging -like immunological, stem cell-based may prove have potential challenge problem resistance.

Язык: Английский

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The neuroprotective effects of targeting key factors of neuronal cell death in neurodegenerative diseases: The role of ER stress, oxidative stress, and neuroinflammation

Frontiers in Cellular Neuroscience, Год журнала: 2023, Номер 17

Опубликована: Март 6, 2023

Neuronal loss is one of the striking causes various central nervous system (CNS) disorders, including major neurodegenerative diseases, such as Alzheimer’s disease (AD), Parkinson’s (PD), Huntington’s (HD), and Amyotrophic lateral sclerosis (ALS). Although these diseases have different features clinical manifestations, they share some common mechanisms pathology. Progressive regional neurons in patients responsible for motor, memory, cognitive dysfunctions, leading to disabilities death. cell death linked pathways conditions. Protein misfolding aggregation, mitochondrial dysfunction, generation reactive oxygen species (ROS), activation innate immune response are most critical hallmarks diseases. Thus, endoplasmic reticulum (ER) stress, oxidative neuroinflammation pathological factors neuronal Even though exact not fully discovered, notable role mentioned well known. On this basis, researchers been prompted investigate neuroprotective effects targeting underlying determine a promising therapeutic approach treatment. This review provides an overview ER death, mainly discussing or molecules involved factors.

Язык: Английский

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Neuroinflammation: The central enabler of postoperative cognitive dysfunction

Biomedicine & Pharmacotherapy, Год журнала: 2023, Номер 167, С. 115582 - 115582

Опубликована: Сен. 23, 2023

The proportion of advanced age patients undergoing surgical procedures is on the rise owing to advancements in and anesthesia technologies as well an overall aging population. As a complication surgery, older frequently suffer from postoperative cognitive dysfunction (POCD), which may persist for weeks, months or even longer. POCD complex pathological process involving multiple pathogenic factors, its mechanism yet unclear. Potential theories include inflammation, deposition proteins, imbalance neurotransmitters, chronic stress. identification, prevention, treatment are still exploratory stages absence standardized diagnostic criteria. Undoubtedly, comprehending development remains crucial overcoming illness. Neuroinflammation leading hypothesis component network have interactions with other mechanisms. In this review, we discuss possible ways surgery cause neuroinflammation investigate connection between POCD. Understanding these mechanisms likely ensure that future options more effective.

Язык: Английский

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Endoplasmic reticulum stress-mediated cell death in cardiovascular disease

Cell Stress and Chaperones, Год журнала: 2024, Номер 29(1), С. 158 - 174

Опубликована: Янв. 29, 2024

The endoplasmic reticulum (ER) plays a vital function in maintaining cellular homeostasis. Endoplasmic stress (ERS) can trigger various modes of cell death by activating the unfolded protein response (UPR) signaling pathway. Cell crucial role occurrence and development diseases such as cancer, liver diseases, neurological cardiovascular diseases. Several including hypertension, atherosclerosis, heart failure are associated with ER stress. stress-mediated is interest disease. Moreover, an increasing body evidence supports potential modulating ERS for treating This paper provides comprehensive review UPR pathway, mechanisms that induce death, Additionally, we discuss common along therapeutic strategies.

Язык: Английский

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Molecular mechanism of autophagy and apoptosis in endometriosis: Current understanding and future research directions

Reproductive Medicine and Biology, Год журнала: 2024, Номер 23(1)

Опубликована: Янв. 1, 2024

Abstract Background Endometriosis is a common gynecological condition, with symptoms including pain and infertility. Regurgitated endometrial cells into the peritoneal cavity encounter hypoxia nutrient starvation. Endometriotic have evolved various adaptive mechanisms to survive in this inevitable condition. These adaptations include escape from apoptosis. Autophagy, self‐degradation system, controls apoptosis during stress conditions. However, date, regulating interplay between autophagy are still poorly understood. In review, we summarize current understanding of molecular characteristics endometriosis discuss future therapeutic challenges. Methods A search PubMed Google Scholar databases were used identify relevant studies for narrative literature review. Results Autophagy may be dynamically regulated through intrinsic (e.g., PI3K/AKT/mTOR signal transduction network) extrinsic iron‐mediated oxidative stress) pathways, contributing development progression endometriosis. Upregulation mTOR expression suppresses via inhibiting pathway, whereas or excess iron often inhibits promoting autophagy. Conclusion acquired antiapoptotic unique pathways changing environments.

Язык: Английский

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Quercetin attenuates cisplatin-induced mitochondrial apoptosis via PI3K/Akt mediated inhibition of oxidative stress in pericytes and improves the blood labyrinth barrier permeability

Chemico-Biological Interactions, Год журнала: 2024, Номер 393, С. 110939 - 110939

Опубликована: Март 13, 2024

Язык: Английский

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Deciphering The Emerging Role of Programmed Cell Death in Diabetic Wound Healing

International Journal of Biological Sciences, Год журнала: 2023, Номер 19(15), С. 4989 - 5003

Опубликована: Янв. 1, 2023

Diabetic wounds are characterized by delayed and incomplete healing.As one of the most common complications diabetes, diabetic can be fatal in some cases.Programmed cell death (PCD) is an active ordered mode determined genes, including apoptosis, autophagy, pyroptosis, necroptosis, ferroptosis, cuproptosis.It currently believed that PCD plays a crucial role wound healing.Diabetic hyperglycemic environments lead to abnormal various cells during healing processes, thereby affecting activity function interfering with healing.Therefore, this review focuses on new roles mechanisms healing.Moreover, challenges perspectives related presented, which will bring insights improve healing.

Язык: Английский

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The neuroprotective potential of phytochemicals in traumatic brain injury: mechanistic insights and pharmacological implications

Frontiers in Pharmacology, Год журнала: 2024, Номер 14

Опубликована: Янв. 4, 2024

Traumatic brain injury (TBI) leads to damage, comprising both immediate primary damage and a subsequent cascade of secondary mechanisms. The results in localized while the initiates inflammatory responses, followed by disruption blood-brain barrier, infiltration peripheral blood cells, edema, release various immune mediators, including chemotactic factors interleukins. TBI disrupts molecular signaling, cell structures, functions. In addition physical tissue such as axonal injuries, contusions, haemorrhages, interferes with functioning, impacting cognition, decision-making, memory, attention, speech capabilities. Despite deep understanding pathophysiology TBI, an intensive effort evaluate underlying mechanisms effective therapeutic interventions is imperative manage repercussions TBI. Studies have commenced explore potential employing natural compounds for These are characterized their low toxicity limited interactions conventional drugs. Moreover, many demonstrate capacity target aspects process. While our there urgent need mitigate its consequences. Here, we aimed summarize mechanism action role phytochemicals against progression. This review discusses implications phytonutrients addresses consequences addition, highlighted roles emerging promising candidates intervention highlights neuroprotective mechanistic approach. Furthermore, efforts focused on mechanisms, providing better therapeutics.

Язык: Английский

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Activating autophagy to eliminate toxic protein aggregates with small molecules in neurodegenerative diseases

Pharmacological Reviews, Год журнала: 2025, Номер unknown, С. 100053 - 100053

Опубликована: Март 1, 2025

Neurodegenerative diseases (NDs), such as Alzheimer disease, Parkinson Huntington amyotrophic lateral sclerosis, and frontotemporal dementia, are well known to pose formidable challenges for their treatment due intricate pathogenesis substantial variability among patients, including differences in environmental exposures genetic predispositions. One of the defining characteristics NDs is widely reported be buildup misfolded proteins. For example, disease marked by amyloid beta hyperphosphorylated Tau aggregates, whereas exhibits α-synuclein aggregates. Amyotrophic sclerosis dementia exhibit TAR DNA-binding protein 43, superoxide dismutase 1, fused-in sarcoma involves mutant huntingtin polyglutamine These proteins key biomarkers also serve potential therapeutic targets, they can addressed through autophagy, a process that removes excess cellular inclusions maintain homeostasis. Various forms macroautophagy, chaperone-mediated microautophagy, hold promise eliminating toxic implicated NDs. In this review, we focus on elucidating regulatory connections between autophagy NDs, summarizing cause exploring impact mechanisms, discussing how regulate aggregation. Moreover, underscore activation strategy across different small molecules capable activating pathways, rapamycin targeting mTOR pathway clear Sertraline AMPK/mTOR/RPS6KB1 Tau, further illustrate NDs' intervention. Together, these findings would provide new insights into current research trends propose small-molecule drugs promising strategies future ND therapies. SIGNIFICANCE STATEMENT: This review provides an in-depth overview eliminate aggregates neurodegenerative diseases. It elucidates fascinating interrelationships "chasing escaping" phenomenon. discusses progress utilizing activate improve efficacy therapies removing

Язык: Английский

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Acute nitrite exposure-induced oxidative damage, endoplasmic reticulum stress, autophagy and apoptosis caused gill tissue damage of grass carp (Ctenopharyngodon idella): Relieved by dietary protein

Ecotoxicology and Environmental Safety, Год журнала: 2022, Номер 243, С. 113994 - 113994

Опубликована: Авг. 19, 2022

Nitrite poses a serious threat to intensive aquaculture. Protein, as major nutrient in animals, is vital for protecting animal tissues from damage. In this study, we investigated the protective effect of dietary protein on gill tissue structure and underlying mechanisms sub-adult grass carp (Ctenopharyngodon idella) exposed nitrite stress. Six iso-energetic semi-purified diets containing different levels (16-31 %) were formulated, fed fish 60 d. The then solution 4 Histopathological observation determination related indices (serum glucose, serum cortisol, nitric oxide, peroxynitrite, reactive oxygen species, malondialdehyde, carbonyl) showed that 22-25 % significantly alleviated nitrite-induced stress response, damage oxidative Further research found suitable suppressed endoplasmic reticulum (ERS) 78 kDa glucose-regulated (GRP78) signaling pathway which possibly activated autophagy apoptosis. Interestingly, discovered proper reduced autophagy, probably through unc-51-like kinase 1 (Ulk1), BCL-2-interacting myosin-like coiled-coil (Beclin1), autophagy-related gene 5 (Atg5), Atg12, microtubule-associated protein1 light chain 3 (LC3), BCL-2 interacting (BNIP3) receptor P62 (p62). We also an appropriate inhibited apoptosis via mitochondrial death pathways. summary, our findings are first demonstrate can play role against injury.

Язык: Английский

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