Lipotoxicity, ER Stress, and Cardiovascular Disease: Current Understanding and Future Directions.

The endoplasmic reticulum (ER) is a sub-cellular organelle that is responsible for the correct folding of proteins, lipid biosynthesis, calcium storage, and various post-translational modifications. In the disturbance of ER functioning, unfolded or misfolded proteins accumulate inside the ER lumen and initiate downstream signaling called unfolded protein response (UPR). The UPR signaling pathway is involved in lipolysis, triacylglycerol synthesis, lipogenesis, the mevalonate pathway, and low-density lipoprotein receptor recycling. ER stress also affects lipid metabolism by changing the levels of enzymes that are involved in the synthesis or modifications of lipids and causing lipotoxicity. Lipid metabolism and cardiac diseases are in close association as the deregulation of lipid metabolism leads to the development of various cardiovascular diseases (CVDs). Several studies have suggested that lipotoxicity is one of the important factors for cardiovascular disorders. In this review, we will discuss how ER stress affects lipid metabolism and their interplay in the development of cardiovascular disorders. Further, the current therapeutics available to target ER stress and lipid metabolism in various CVDs will be summarized.

Haematological and biochemical analysis of blood samples from early and late stage breast cancer patients in India.

Breast cancer is the most prevalent cancer with the maximum number of cases worldwide. Early diagnosis of the cancer is necessary for an effective treatment plan. Due to a lack of awareness, diagnosis of breast cancer at an early stage is difficult. The present study aims to evaluate and compare the haematological and biochemical profiles of the early and late-stage breast cancer patient's data records. A retrospective cohort study was conducted on 56 breast cancer patients at the Institute of Medical Sciences, Banaras Hindu University India. Patient data records were obtained and haematological and biochemical parameters were arranged on an Excel sheet and analyzed. Random blood sugar (RBS), alkaline phosphates (ALP) levels, and urea levels were significantly high in patients with late-stage breast cancer (Tumor stage III and IV). At the advanced stage of breast cancer hemoglobin level falls and patients became anemic. Further large-scale studies with a greater number of patient data can help establish these parameters individually or in combination as prognostic and diagnostic markers in breast cancer staging.

Unfolded Protein Response Signaling in Liver Disorders: A 2023 Updated Review.

Endoplasmic reticulum (ER) is the site for synthesis and folding of secreted and transmembrane proteins. Disturbance in the functioning of ER leads to the accumulation of unfolded and misfolded proteins, which finally activate the unfolded protein response (UPR) signaling. The three branches of UPR-IRE1 (Inositol requiring enzyme 1), PERK (Protein kinase RNA-activated (PKR)-like ER kinase), and ATF6 (Activating transcription factor 6)-modulate the gene expression pattern through increased expression of chaperones and restore ER homeostasis by enhancing ER protein folding capacity. The liver is a central organ which performs a variety of functions which help in maintaining the overall well-being of our body. The liver plays many roles in cellular physiology, blood homeostasis, and detoxification, and is the main site at which protein synthesis occurs. Disturbance in ER homeostasis is triggered by calcium level imbalance, change in redox status, viral infection, and so on. ER dysfunction and subsequent UPR signaling participate in various hepatic disorders like metabolic (dysfunction) associated fatty liver disease, liver cancer, viral hepatitis, and cholestasis. The exact role of ER stress and UPR signaling in various liver diseases is not fully understood and needs further investigation. Targeting UPR signaling with drugs is the subject of intensive research for therapeutic use in liver diseases. The present review summarizes the role of UPR signaling in liver disorders and describes why UPR regulators are promising therapeutic targets.

Striatin family proteins: The neglected scaffolds.

The Striatin family of proteins constitutes Striatin, SG2NA, and Zinedin. Members of this family of proteins act as a signaling scaffold due to the presence of multiple protein-protein interaction domains. At least two members of this family, namely Zinedin and SG2NA, have a proven role in cancer cell proliferation. SG2NA, the second member of this family, undergoes alternative splicing and gives rise to several isoforms which are differentially regulated in a tissue-dependent manner. SG2NA evolved earlier than the other two members of the family, and SG2NA undergoes not only alternative splicing but also other posttranscriptional gene regulation. Striatin also undergoes alternative splicing, and as a result, it gives rise to multiple isoforms. It has been shown that this family of proteins plays a significant role in estrogen signaling, neuroprotection, cancer as well as in cell cycle regulation. Members of the striatin family form a complex network of signaling hubs with different kinases and phosphatases, and other signaling proteins named STRIPAK. Here, in the present manuscript, we thoroughly reviewed the findings on striatin family members to elaborate on the overall structural and functional idea of this family of proteins. We also commented on the involvement of these proteins in STRIPAK complexes and their functional relevance.