The heat shock response is an evolutionarily conserved mechanism that protects cells or organisms from the harmful effects of various stressors such as heat, chemicals toxins, UV radiation, and oxidizing agents. The heat shock response triggers the expression of a specific set of genes and proteins known as heat shock genes/proteins or molecular chaperones, including HSP100, HSP90, HSP70, HSP60, and small HSPs. Heat shock proteins (HSPs) play a crucial role in thermotolerance and aiding in protecting cells from harmful insults of stressors. HSPs are involved in essential cellular functions such as protein folding, eliminating misfolded proteins, apoptosis, and modulating cell signaling. The stress response to various environmental insults has been extensively studied in organisms from prokaryotes to higher organisms. The responses of organisms to various environmental stressors rely on the intensity and threshold of the stress stimuli, which vary among organisms and cellular contexts. Studies on heat shock proteins have primarily focused on HSP70, HSP90, HSP60, small HSPs, and ubiquitin, along with their applications in human biology. The current review highlighted a comprehensive mechanism of heat shock response and explores the function of heat shock proteins in stress management, as well as their potential as therapeutic agents and diagnostic markers for various diseases.

Cancer is a multifaceted disease influenced by various mechanisms, including the generation of reactive oxygen species (ROS), which have a paradoxical role in both promoting cancer progression and serving as targets for therapeutic interventions. At low concentrations, ROS serve as signaling agents that enhance cancer cell proliferation, migration, and resistance to drugs. However, at elevated levels, ROS induce oxidative stress, causing damage to biomolecules and leading to cell death. Cancer cells have developed mechanisms to manage ROS levels, including activating pathways such as NRF2, NF-κB, and PI3K/Akt. This review explores the relationship between ROS and cancer, focusing on cell death mechanisms like apoptosis, ferroptosis, and autophagy, highlighting the potential therapeutic strategies that exploit ROS to target cancer cells.

The ketone bodies (KBs) β-hydroxybutyrate and acetoacetate are important alternative energy sources for glucose during nutrient deprivation. KBs synthesized by hepatic ketogenesis are catabolized to acetyl-CoA through ketolysis in extrahepatic tissues, followed by the tricarboxylic acid cycle and electron transport chain for ATP production. Ketogenesis and ketolysis are regulated by the key rate-limiting enzymes, 3-hydroxy-3-methylglutaryl-CoA synthase 2 and succinyl-CoA:3-oxoacid-CoA transferase, respectively. KBs participate in various cellular processes as signaling molecules. KBs bind to G protein-coupled receptors. The most abundant KB, β-hydroxybutyrate, regulates gene expression and other cellular functions by inducing post-translational modifications. KBs protect tissues by regulating inflammation and oxidative stress. Recently, interest in KBs has been increasing due to their potential for treatment of various diseases such as neurological and cardiovascular diseases and cancer. Cancer cells reprogram their metabolism to maintain rapid cell growth and proliferation. Dysregulation of KB metabolism also plays a role in tumorigenesis in various types of cancer. Targeting metabolic changes through dietary interventions, including fasting and ketogenic diets, has shown beneficial effects in cancer therapy. Here, we review current knowledge of the molecular mechanisms involved in the regulation of KB metabolism and cellular signaling functions, and the therapeutic potential of KBs and ketogenic diets in cancer.

Ketone bodies (KBs), such as acetoacetate and β-hydroxybutyrate, serve as crucial alternative energy sources during glucose deficiency. KBs, generated through ketogenesis in the liver, are metabolized into acetyl-CoA in extrahepatic tissues, entering the tricarboxylic acid cycle and electron transport chain for ATP production. Reduced glucose metabolism and mitochondrial dysfunction correlate with increased neuronal death and brain damage during cerebral ischemia and neurodegeneration. Both KBs and the ketogenic diet (KD) demonstrate neuroprotective effects by orchestrating various cellular processes through metabolic and signaling functions. They enhance mitochondrial function, mitigate oxidative stress and apoptosis, and regulate epigenetic and post-translational modifications of histones and non-histone proteins. Additionally, KBs and KD contribute to reducing neuroinflammation and modulating autophagy, neurotransmission systems, and gut microbiome. This review aims to explore the current understanding of the molecular mechanisms underpinning the neuroprotective effects of KBs and KD against brain damage in cerebral ischemia and neurodegenerative diseases, including Alzheimer’s disease and Parkinson’s disease.

Aggressive and recurrent gynecological cancers are associated with worse prognosis and a lack of effective therapeutic response. Ovarian cancer (OC) patients are often diagnosed in advanced stages, when drug resistance, angiogenesis, relapse, and metastasis impact survival outcomes. Currently, surgical debulking, radiotherapy, and/or chemotherapy remain the mainstream treatment modalities; however, patients suffer unwanted side effects and drug resistance in the absence of targeted therapies. Hence, it is urgent to decipher the complex disease biology and identify potential biomarkers, which could greatly contribute to making an early diagnosis or predicting the response to specific therapies. This review aims to critically discuss the current therapeutic strategies for OC, novel drug-delivery systems, and potential biomarkers in the context of genetics and molecular research. It emphasizes how the understanding of disease biology is related to the advancement of technology, enabling the exploration of novel biomarkers that may be able to provide more accurate diagnosis and prognosis, which would effectively translate into targeted therapies, ultimately improving patients’ overall survival and quality of life.

Prolonged accumulation of misfolded proteins in the endoplasmic reticulum (ER) results in ER stress-mediated apoptosis. Cyclophilins are protein chaperones that accelerate the rate of protein folding through their peptidyl-prolyl cis-trans isomerase (PPIase) activity. In this study, we demonstrated that ER stress activates the expression of the ER-localized cyclophilin B (CypB) gene through a novel ER stress response element. Overexpression of wild-type CypB attenuated ER stress-induced cell death, whereas overexpression of an isomerase activity-defective mutant, CypB/R62A, not only increased Ca²⁺ leakage from the ER and ROS generation, but also decreased mitochondrial membrane potential, resulting in cell death following exposure to ER stress-inducing agents. siRNA-mediated inhibition of CypB expression rendered cells more vulnerable to ER stress. Finally, CypB interacted with the ER stress-related chaperones, Bip and Grp94. Taken together, we concluded that CypB performs a crucial function in protecting cells against ER stress via its PPIase activity.