Cells

Heat shock proteins (HSPs) are produced in response to stressful conditions, such as temperature, inflammation, infection, or exposure to environmental factors. HSPs are overexpressed in some malignancies, where they modulate the tumor microenvironment and influence cancer cell behavior and survival. Clinical trials for breast, prostate, colon, and lung cancers exist, but not for head and neck squamous cell carcinomas (HNSCCs). Nonetheless, clinical studies on HSPs in HNSCC are still lacking. We review the role of HSPs with regard to physiology and as potential targets for molecular therapy in HNSCC.

It is necessary to find novel therapeutic strategies for obesity-related diabetic nephropathy (DN) that target both metabolic dysfunction and renal inflammation. ST32da derived from Salvia miltiorrhiza (a well-recognized Traditional Chinese Medicine) induces activating transcription factor 3 (ATF3), a negative regulator of inflammation and metabolic stress. However, the effects of ST32da on obesity-related DN remain underexplored. We investigated the therapeutic potential of ST32da, a synthetic ATF3 inducer derived from Salvia miltiorrhiza, in mitigating obesity-related DN in both in vivo and in vitro models. The Nephroseq database analysis was performed to explore the relationship between Atf3 expression and DN progression. ST32da was administered to db/db knockout and DBA mice to establish obesity-related DN models, and a high-fat diet (HFD)-induced mouse model of obesity-related DN was used to investigate the effects of Atf3 knockout. Molecular and biochemical analyses were conducted in cultured mesangial cells to elucidate the underlying mechanisms. ATF3 deficiency worsened obesity-related DN, increasing glomerular fibrosis, mortality, and inflammation. ST32da restored ATF3 levels and reduced renal injury, glomerular expansion, and pro-inflammatory cytokine expression (e.g., IL-6, TGFβ, TNFα). ST32da-treated mice exhibited reduced hepatic lipid accumulation and improved serum lipid profiles. In mesangial cells, ST32da localized to the cytoplasm and increased ATF3 activity, which suppressed RARRES1 expression and cytokine signaling. Mechanistically, ATF3 interacted with HDAC2 to repress NF-κB—dependent inflammatory gene expression. The findings suggest ST32da is a promising therapeutic candidate for obesity-related DN and associated metabolic disturbances, acting through ATF3 induction to suppress renal inflammation, lipotoxicity, and fibrosis.

Esophageal cancer (EC) is a highly aggressive gastrointestinal malignancy, with a notable increase in incidence over recent decades, representing a significant global health burden. The main histological subtypes are esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC), with the former being closely associated with gastroesophageal reflux disease, Barrett’s esophagus, and obesity, and its incidence continues to increase in Western populations. The rising incidence of EC, combined with poor survival rates, underscores the need for new therapeutic approaches. A deeper understanding of the molecular basis of this prevalent malignancy may open new avenues for optimal therapeutic strategies, with immunotherapy now central in several clinical trials. Understanding the interplay between the tumor microenvironment (TME) and disease progression is pivotal for managing this malignancy, which remains highly challenging. This review highlights the role of the TME in EAC progression and drug resistance, and recent therapeutic advances.