Crosstalk between hypoxia-induced pyroptosis and immune escape in cancer: From mechanisms to therapy.

Pyroptosis can be triggered through both canonical and non-canonical inflammasome pathways, involving the cleavage of gasdermin (GSDM) protein family members, like GSDMD and GSDME. The impact of pyroptosis on tumors is nuanced, because its role in regulating cancer progression and anti-tumor immunity may vary depending on the tumor type, stage, location, and immune status. However, pyroptosis cannot be simply categorized as promoting or inhibiting tumors based solely on whether it is acute or chronic in nature. The interplay between pyroptosis and cancer is intricate, with some evidence suggesting that chronic pyroptosis may facilitate tumor growth, while the acute induction of pyroptosis could stimulate anti-cancer immune responses. Tumor hypoxia activates hypoxia inducible factor (HIF) signaling to modulate pyroptosis and immune checkpoint expression. Targeting this hypoxia-pyroptosis-immune escape axis could be a promising therapeutic strategy. This review highlights the complex crosstalk between hypoxia, pyroptosis, and immune evasion in the TME.

Immune checkpoint inhibitors promising role in cancer therapy: clinical evidence and immune-related adverse events.

The advent of immune checkpoint inhibitors (ICIs) has led to noteworthy progressions in the management of diverse cancer types, as evidenced by the pioneering "ipilimumab" medication authorized by US FDA in 2011. Importantly, ICIs agents have demonstrated encouraging potential in bringing about transformation across diverse forms of cancer by selectively targeting the immune checkpoint pathways that are exploited by cancerous cells for dodging the immune system, culminating in progressive and favorable health outcomes for patients. The primary mechanism of action (MOA) of ICIs involves blocking inhibitory immune checkpoints. There are three approved categories including Programmed Death (PD-1) inhibitors (cemiplimab, nivolumab, and pembrolizumab), Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) (Ipilimumab), and Programmed Death-Ligand 1 (PDL-1) (Avelumab). Although ICIs promisingly increase therapeutic response and cancer survival rates, using ICIs has demonstrated some limitations including autoimmune reactions and toxicities, requiring close monitoring. The present review endeavors to explicate the underlying principles of the MOA and pharmacokinetics of the approved ICIs in the realm of cancer induction, including an appraisal of their level of practice-based evidence.

The function of LncRNA-ATB in cancer

Cancer as a progressive and complex disease is caused by early chromosomal changes and stimulated cellular transformation. Previous studies reported that long non-coding RNAs (lncRNAs) play pivotal roles in the initiation, maintenance, and progression of cancer cells. LncRNA activated by TGF-β (ATB) has been shown to be dysregulated in different types of cancer. Aberrant expression of lncRNA-ATB plays an important role in the progression of diverse malignancies. High expression of LncRNA-ATB is associated with cancer cell growth, proliferation, metastasis, and EMT. LncRNA-ATB by targeting various signaling pathways and microRNAs (miRNAs) can trigger cancer pathogenesis. Therefore, lncRNA-ATB can be a novel target for cancer prediction and diagnosis. In this review, we will focus on the function of lncRNA-ATB in various types of human cancers (AU)

Eplerenone reduces renal ischaemia/reperfusion injury by modulating Klotho, NF-κB and SIRT1/SIRT3/PGC-1α signalling pathways.

OBJECTIVES: Acute kidney injury (AKI) is a sudden impairment in kidney function that is associated with high morbidity and mortality. Inflammation, oxidative stress, mitochondrial impairment and energy depletion, along with organ dysfunction are hallmarks of AKI. This study aimed to evaluate the effects of Eplerenone, an aldosterone receptor antagonist, on the kidney injury caused by ischaemia/reperfusion (I/R). METHODS: Male Wistar rats (n = 24) were randomly allocated into four groups: sham, IR, Eplerenone and Eplerenone+IR. Rats in the two last groups 1 h before I/R induction, were treated with Eplerenone (100 mg/kg) via intraperitoneal injection. Protein levels of Klotho, heat shock protein 70 (HSP70), sirtuin1 (SIRT1), SIRT3 and peroxisome proliferator-activated receptor-gamma coactivator 1-α (PGC-1α) along with antioxidant, apoptotic (caspase 3, Bax and Bcl2) and inflammatory [nuclear factor kappa-B (NF-κB) p65, Interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α) and cyclooxygenase-2 (COX-2)] factors were evaluated in the kidney tissues of the experimental groups. KEY FINDINGS: Eplerenone pre-treatment significantly could improve IR-induced pathological changes and kidney function and increase the renal antioxidant factors compared to the IR group (P < 0.05). Furthermore, in the Eplerenone + IR group, significant elevation of the Klotho, SIRT1, SIRT3 and PGC-1α at the protein level was identified compared to the IR group. Eplerenone pretreatment could not only downregulate NF-κB signalling and its downstream inflammatory factors (IL-6, COX-2 and TNF-α) but also could decrease apoptotic factors (P ≤ 0.01). CONCLUSIONS: The results recommended that Eplerenone exerts a protective effect against kidney IR injury by up-regulating Klotho, HSP70, sirtuins and PGC-1α to preserve mitochondrial function and cell survival. Moreover, it hinders renal inflammation by suppressing NF-κB signalling. These results offer insight into the prevention or treatment of AKI in the future.

The function of LncRNA-ATB in cancer.

Cancer as a progressive and complex disease is caused by early chromosomal changes and stimulated cellular transformation. Previous studies reported that long non-coding RNAs (lncRNAs) play pivotal roles in the initiation, maintenance, and progression of cancer cells. LncRNA activated by TGF-ß (ATB) has been shown to be dysregulated in different types of cancer. Aberrant expression of lncRNA-ATB plays an important role in the progression of diverse malignancies. High expression of LncRNA-ATB is associated with cancer cell growth, proliferation, metastasis, and EMT. LncRNA-ATB by targeting various signaling pathways and microRNAs (miRNAs) can trigger cancer pathogenesis. Therefore, lncRNA-ATB can be a novel target for cancer prediction and diagnosis. In this review, we will focus on the function of lncRNA-ATB in various types of human cancers.

Emerging roles of JMJD3 in cancer.

Histone lysine methylation plays a key role in gene activation and repression. The trimethylation of histone H3 on lysine-27 (H3K27me3) is a critical epigenetic event that is controlled by Jumonji domain-containing protein-3 (JMJD3). JMJD3 is a histone demethylase that specifically removes methyl groups. Previous studies have suggested that JMJD3 has a dual role in cancer cells. JMJD3 stimulates the expression of proliferative-related genes and increases tumor cell growth, propagation, and migration in various cancers, including neural, prostate, ovary, skin, esophagus, leukemia, hepatic, head and neck, renal, lymphoma, and lung. In contrast, JMJD3 can suppress the propagation of tumor cells, and enhance their apoptosis in colorectal, breast, and pancreatic cancers. In this review, we summarized the recent advances of JMJD3 function in cancer cells.

Co-Delivery of Letrozole and Cyclophosphamide via Folic Acid-Decorated Nanoniosomes for Breast Cancer Therapy: Synergic Effect, Augmentation of Cytotoxicity, and Apoptosis Gene Expression.

Breast cancer is one of the most prevalent causes of cancer mortality in women. In order to increase patient prognosis and survival rates, new technologies are urgently required to deliver therapeutics in a more effective and efficient manner. Niosome nanoparticles have been recently employed as therapeutic platforms capable of loading and carrying drugs within their core for both mono and combination therapy. Here, niosome-based nanoscale carriers were investigated as a targeted delivery system for breast cancer therapy. The platform developed consists of niosomes loaded with letrozole and cyclophosphamide (NLC) and surface-functionalized with a folic-acid-targeting moiety (NLCPFA). Drug release from the formulated particles exhibited pH-sensitive properties in which the niosome showed low and high release in physiological and cancerous conditions, respectively. The results revealed a synergic effect in cytotoxicity by co-loading letrozole and cyclophosphamide with an efficacy increment in NLCPFA use in comparison with NLC. The NLCPFA resulted in the greatest drug internalization compared to the non-targeted formulation and the free drug. Additionally, downregulation of cyclin-D, cyclin-E, MMP-2, and MMP-9 and upregulating the expression of caspase-3 and caspase-9 genes were observed more prominently in the nanoformulation (particularly for NLCPFA) compared to the free drug. This exciting data indicated that niosome-based nanocarriers containing letrozole and cyclophosphamide with controlled release could be a promising platform for drug delivery with potential in breast cancer therapy.