An update on the secretory functions of brown, white, and beige adipose tissue: Towards therapeutic applications.

Adipose tissue, including white adipose tissue (WAT), brown adipose tissue (BAT), and beige adipose tissue, is vital in modulating whole-body energy metabolism. While WAT primarily stores energy, BAT dissipates energy as heat for thermoregulation. Beige adipose tissue is a hybrid form of adipose tissue that shares characteristics with WAT and BAT. Dysregulation of adipose tissue metabolism is linked to various disorders, including obesity, type 2 diabetes, cardiovascular diseases, cancer, and infertility. Both brown and beige adipocytes secrete multiple molecules, such as batokines, packaged in extracellular vesicles or as soluble signaling molecules that play autocrine, paracrine, and endocrine roles. A greater understanding of the adipocyte secretome is essential for identifying novel molecular targets in treating metabolic disorders. Additionally, microRNAs show crucial roles in regulating adipose tissue differentiation and function, highlighting their potential as biomarkers for metabolic disorders. The browning of WAT has emerged as a promising therapeutic approach in treating obesity and associated metabolic disorders. Many browning agents have been identified, and nanotechnology-based drug delivery systems have been developed to enhance their efficacy. This review scrutinizes the characteristics of and differences between white, brown, and beige adipose tissues, the molecular mechanisms involved in the development of the adipocytes, the significant roles of batokines, and regulatory microRNAs active in different adipose tissues. Finally, the potential of WAT browning in treating obesity and atherosclerosis, the relationship of BAT with cancer and fertility disorders, and the crosstalk between adipose tissue with circadian system and circadian disorders are also investigated.

Recent advances in cancer immunotherapy: Modulation of tumor microenvironment by Toll-like receptor ligands.

Immunotherapy is considered a promising approach for cancer treatment. An important strategy for cancer immunotherapy is the use of cancer vaccines, which have been widely used for cancer treatment. Despite the great potential of cancer vaccines for cancer treatment, their therapeutic effects in clinical settings have been limited. The main reason behind the lack of significant therapeutic outcomes for cancer vaccines is believed to be the immunosuppressive tumor microenvironment (TME). The TME counteracts the therapeutic effects of immunotherapy and provides a favorable environment for tumor growth and progression. Therefore, overcoming the immunosuppressive TME can potentially augment the therapeutic effects of cancer immunotherapy in general and therapeutic cancer vaccines in particular. Among the strategies developed for overcoming immunosuppression in TME, the use of toll-like receptor (TLR) agonists has been suggested as a promising approach to reverse immunosuppression. In this paper, we will review the application of the four most widely studied TLR agonists including agonists of TLR3, 4, 7, and 9 in cancer immunotherapy.

Up-down regulation of HIF-1α in cancer progression.

Hypoxia induicible factor-1 alpha (HIF-1α) is a key transcription factor in cancer progression and target therapy in cancer. HIF-1α acts differently depending on presence or absence of Oxygen. In an oxygen-immersed environment, HIF-1α completely deactivated and destroyed by the ubiquitin proteasome pathway (UPP). In contrast, in the oxygen-free environment, it escapes destruction and enters to the nucleus of cells then upregulates many genes involved in cancer progression. Overexpressed HIF-1α and downstream genes support cancer progression through various mechanisms including angiogenesis, proliferation and survival of cells, metabolism reprogramming, invasion and metastasis, cancer stem cell maintenance, induction of genetic instability, and treatment resistance. HIF-1α can be provoked by signaling pathways unrelated to hypoxia during cancer progression. Therefore, cancer development and progression can be modulated by targeting HIF-1α and its downstream signaling molecules. In this regard, HIF-1α inhibitors which are categorized into the agents that regulate HIF-1α in gene, mRNA and protein levels used as an efficient way in cancer treatment. Also, HIF-1α expression can be negatively affected by the agents suppressing the activation of mTOR, PI3k/Akt and MAPK pathways.

Thymoquinone Effects on Cell Viability, Apoptosis and VEGF-A Gene Expression Level in AGS(CRL-1739) Cell Line.

BACKGROUND: Cancer is one of the most fatal diseases across the world and it was reported that 90% of cancer fatality depends on its angiogenesis potential. Black seed or Nigella sativa L. is a medicinal plant native to southwest Asia. N. sativa has been used for medicinal purposes for centuries and predominantly has bioactive components like Thymoquinone, which is used as a candidate for anti-cancer and anti-angiogenesis drugs. METHODS: Callus was induced from leaf tissue, after that alcoholic extracts were prepared from three-month-old calluses. Thymoquinone content was measured by HPLC methods. AGS cell line was cultured and treated with standard Thymoquinone and extracts from callus. Then, cell proliferation, expression of angiogenic factor (VEGF-A gene), and apoptosis test were done by MTT assay, real-time PCR and Annexin-v kit, respectively. RESULTS: HPLC found the maximum amount of Thymoquinone in the extract of leaf calluses, which were grown in the dark. MTT assay revealed that particular doses of extracts reduced cell proliferation. Real-time and Fluorescence- Activated Cell Sorting (FACS) results demonstrated that standard Thymoquinone and callus extracts down-regulated the VEGF-A gene expression, and all three induced apoptosis in the AGS cell line. CONCLUSION: It has been shown that TQ has pro-apoptotic and anti-metastatic effects on stomach cancer cell line, and these properties can introduce it as an anti-cancer drug in the near future.