A comprehensive review of the PTEN/PI3K/Akt axis in multiple myeloma: From molecular interactions to potential therapeutic targets.

Phosphatase and tensin homolog (PTEN), phosphatidylinositol 3-kinase (PI3K), and protein kinase B (Akt) signaling pathways contribute to the development of several cancers, including multiple myeloma (MM). PTEN is a tumor suppressor that influences the PI3K/Akt/mTOR pathway, which in turn impacts vital cellular processes like growth, survival, and treatment resistance. The current study aims to present the role of PTEN and PI3K/Akt/mTOR signaling in the development of MM and its response to treatment. In addition, the molecular interactions in MM that underpin the PI3K/Akt/mTOR pathway and address potential implications for the development of successful treatment plans are also discussed in detail. We investigate their relationship to both upstream and downstream regulators, highlighting new developments in combined therapies that target the PTEN/PI3K/Akt axis to overcome drug resistance, including the use of PI3K and mitogen-activated protein kinase (MAPK) inhibitors. We also emphasize that PTEN/PI3K/Akt pathway elements may be used in MM diagnosis, prognosis, and therapeutic targets.

Evaluation of C4d expression and staining patterns by immunohistochemistry in renal biopsy samples with focal segmental glomerulosclerosis and minimal change disease.

INTRODUCTION: C4d is an activation product of lectin pathway of complement. Glomerular deposition of C4d is associated with poor prognosis in different types of immune-related glomerulonephritis. The present study was conducted to investigate expression level of C4d and its staining pattern in renal biopsy of patients with focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD) by immunohistochemistry method. MATERIALS AND METHODS: In this retrospective cross-sectional study, renal biopsy specimens from 46 samples of MCD, 47 samples of FSGS, and 15 samples without glomerular disease as the controls, were subjected to immunohistochemistry staining with C4d. Demographic characteristics and information obtained from light and electron microscopy (EM) of patients were also extracted from their files. RESULTS: C4d positive staining was observed in 97.9 % of FSGS and 43.5 % of MCD samples, which showed a statistically significant difference (P < 0.001). The sensitivity and specificity of C4d expression for diagnosing FSGS were 97.9 % and 56.5 %, respectively. There was no significant correlation between C4d expression and any of the light and electron microscopy findings, including presence of foam cells, mesangial matrix expansion, interstitial fibrosis and tubular atrophy, and basement membrane changes in MCD patients. Also, no significant correlation was observed between C4d expression and clinical symptoms of proteinuria or prolonged high level of creatinine in patients with MCD. DISCUSSION AND CONCLUSION: The expression of C4d marker had a good sensitivity and negative predictive value in the diagnosis of FSGS.

Role of non-coding RNAs in osteoporosis.

Osteoporosis, a prevalent bone disorder influenced by genetic and environmental elements, significantly increases the likelihood of fractures and bone weakness, greatly affecting the lives of those afflicted. Yet, the exact epigenetic processes behind the onset of osteoporosis are still unclear. Growing research indicates that epigenetic changes could act as vital mediators that connect genetic tendencies and environmental influences, thereby increasing the risk of osteoporosis and bone fractures. Within these epigenetic factors, certain types of RNA, such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), have been recognized as key regulatory elements. These RNA types wield significant influence on gene expression through epigenetic regulation, directing various biological functions essential to bone metabolism. This extensive review compiles current research uncovering the complex ways in which miRNAs, lncRNAs, and circRNAs are involved in the development of osteoporosis, especially in osteoblasts and osteoclasts. Gaining a more profound understanding of the roles these three RNA classes play in osteoporosis could reveal new diagnostic methods and treatment approaches for this incapacitating condition. In conclusion, this review delves into the complex domain of epigenetic regulation via non-coding RNA in osteoporosis. It sheds light on the complex interactions and mechanisms involving miRNAs, lncRNAs, and circRNAs within osteoblasts and osteoclasts, offering an in-depth understanding of the less explored aspects of osteoporosis pathogenesis. These insights not only reveal the complexity of the disease but also offer significant potential for developing new diagnostic methods and targeted treatments. Therefore, this review marks a crucial step in deciphering the elusive complexities of osteoporosis, leading towards improved patient care and enhanced quality of life.

New emerging targets in osteosarcoma therapy: PTEN and PI3K/Akt crosstalk in carcinogenesis.

Osteosarcoma (OS) is a malignant bone carcinoma that affects people in childhood and adulthood. The heterogeneous nature and chromosomal instability represent certain characteristics of OS cells. These cancer cells grow and migrate abnormally, making the prognosis undesirable for patients. Conventional and current treatments fail to completely eradicate tumor cells, so new therapeutics targeting genes may be considered. PI3K/Akt is a regulator of events such as growth, cell death, migration, and differentiation, and its expression changes during cancer progression. PTEN reduces PI3K/Akt expression, and its mutations and depletions have been reported in various tumors. Experimental evidence shows that there is upregulation of PI3K/Akt and downregulation of PTEN in OS. Increasing PTEN expression may suppress PI3K/Akt to minimize tumorigenesis. In addition, PI3K/Akt shows a positive association with growth, metastasis, EMT and metabolism of OS cells and inhibits apoptosis. Importantly, overexpression of PI3K/Akt causes drug resistance and radio-resistance and its level can be modulated by miRNAs, lncRNAs and circRNAs. Silencing PI3K/Akt by compounds and drugs can suppress OS. Here, we review in detail the function of the PTEN/PI3K/Akt in OS, revealing its biological function, function in tumor progression, resistance to therapy, and pharmacological significance.

Versatile function of AMPK signaling in osteosarcoma: An old player with new emerging carcinogenic functions.

AMP-activated protein kinase (AMPK) signaling has a versatile role in Osteosarcoma (OS), an aggressive bone malignancy with a poor prognosis, particularly in cases that have metastasized or recurred. This review explores the regulatory mechanisms, functional roles, and therapeutic applications of AMPK signaling in OS. It focuses on the molecular activation of AMPK and its interactions with cellular processes like proliferation, apoptosis, and metabolism. The uncertain role of AMPK in cancer is also discussed, highlighting its potential as both a tumor suppressor and a contributor to carcinogenesis. The therapeutic potential of targeting AMPK signaling in OS treatment is examined, including direct and indirect activators like metformin, A-769662, resveratrol, and salicylate. Further research is needed to determine dosing, toxicities, and molecular mechanisms responsible for the anti-osteosarcoma effects of these compounds. This review underscores the complex involvement of AMPK signaling in OS and emphasizes the need for a comprehensive understanding of its molecular mechanisms. By elucidating the role of AMPK in OS, the aim is to pave the way for innovative therapeutic approaches that target this pathway, ultimately improving the prognosis and quality of life for OS patients.