Heat shock protein 90 (HSP90) is a pivotal molecular chaperone with multifaceted roles in cellular health and disease. Herein, we explore how HSP90 orchestrates cellular stress responses, particularly through its partnership with heat shock factor 1 (HSF-1). PU-H71, a selective inhibitor of HSP90, demonstrates significant potential in cancer therapy by targeting a wide array of oncogenic pathways. By inducing the degradation of multiple client proteins, PU-H71 disrupts critical signaling pathways such as MAPK, PI3K/Akt, JAK/STAT, EGFR, and mTOR, which are essential for cancer cell survival, proliferation, and metastasis. We examined its impact on combating triple-negative breast cancer and enhancing the effectiveness of carbon-ion beam therapy, offering new avenues for cancer treatment. Furthermore, the dual inhibition of HSP90A and HSP90B1 by PU-H71 proves highly effective in the context of myeloma, providing fresh hope for patients with this challenging malignancy. We delve into its potential to induce apoptosis in B-cell lymphomas that rely on Bcl6 for survival, highlighting its relevance in the realm of hematologic cancers. Shifting our focus to hepatocellular carcinoma, we explore innovative approaches to chemotherapy. Moreover, the current review elucidates the potential capacity of PU-H71 to suppress glial cell activation paving the way for developing novel therapeutic strategies for neuroinflammatory disorders. Additionally, the present report also suggests the promising role of PU-H71 in JAK2-dependent myeloproliferative neoplasms. Eventually, our report sheds more light on the multiple functions of HSP90 protein as well as the potential therapeutic benefit of its selective inhibitor PU-H71 in the context of an array of diseases, laying the foundations for the development of novel therapeutic approaches that could achieve better treatment outcomes.

Multidrug resistance (MDR) pathogens are usually associated with higher morbidity and mortality rates. Flavonoids are good candidates for the development of new potential antimicrobials. This research investigated whether luteolin 4′-neohesperidoside (L4N) has antibacterial and synergistic activities against four antibiotic-resistant pathogens: methicillin-resistant Staphylococcus aureus (MRSA), Klebsiella pneumoniae, fosA-positive shiga toxin producing the Escherichia coli serogroup O111 (STEC O111), and Bacillus cereus. In vitro antimicrobial susceptibility testing revealed highly potent anti-MRSA (MIC of 106.66 ± 6.95 µg/mL), anti-K. pneumoniae (MIC of 53.33 ± 8.47 µg/mL) and anti-STEC O111 (MIC of 26.66 ± 5.23 µg/mL) activities. Significant synergistic combination was clearly noted in the case of gentamycin (GEN) against Gram-negative bacteria. In the case of B. cereus, the combination of vancomycin (VAN) with L4N could efficiently inhibit bacterial growth, despite the pathogen being VAN-resistant (MIC of 213.33 ± 7.9 µg/mL). In vivo evaluation of L4N showed significant decreases in K. pneumoniae and STEC shedding and colonization. Treatment could significantly diminish the levels of pro-inflammatory markers, tumor necrosis factor-alpha (TNF-α), and immunoglobulin (IgM). Additionally, the renal and pulmonary lesions were remarkably enhanced, with a significant decrease in the bacterial loads in the tissues. Finally, this study presents L4N as a potent substitute for traditional antibiotics with anti-STEC O111 and anti-K. pneumoniae potential, a finding which is reported here for the first time.

Breast cancer is one of the most prevalent and biologically diverse malignancies in women worldwide, encompassing subtypes such as ductal carcinoma in situ (DCIS), lobular carcinoma, and triple-negative breast cancer (TNBC). These variants present complex therapeutic challenges. Chemotherapy remains a core treatment modality, particularly in aggressive or advanced stages, yet its systemic toxicity and lack of specificity limit its efficacy. In recent years, laser-based therapies have emerged as adjunctive strategies to enhance therapeutic precision. This review explores breast cancer classification, progression, and treatment, with an emphasis on chemotherapy, and critically examines the emerging role of laser technologies, including low-level laser therapy (LLLT), Photochemotherapy, and Photodynamic Therapy (PDT), as adjunctive or alternative therapeutic options. We highlight the potential of laser to modulate the tumor microenvironment, improve drug delivery, regulate mitochondrial function, and enhance apoptosis. PDT showed promise in activating localized cytotoxic effects while sparing surrounding tissues. However, heterogeneity in laser parameters and treatment protocols remains a significant barrier to clinical translation. This review underscores the translational potential of laser-assisted chemotherapy, identifies current gaps, and suggests future research directions for optimized treatment strategies in breast oncology.

Idiopathic pulmonary fibrosis is considered the most common type of interstitial lung disease. The principal aim of our research was to investigate the potential role of pazopanib treatment in alleviating bleomycin‐elicited pulmonary fibrosis and elucidate the underlying molecular mechanisms. Twenty‐four male mice were allocated into four groups ( n = 6): control animals (received saline intraperitoneally (i.p.)), bleomycin group received bleomycin (40 U/kg, i.p.) on 5 days, 0, 3, 7, 10, and 14, and bleomycin and pazopanib‐treated group received bleomycin on the specified days and then received pazopanib (10 mg/kg, i.p.) once daily starting on Day 15 to Day 28, plus pazopanib‐treated group, which received pazopanib only in the previously specified dose and duration. Our results demonstrated the promising role of pazopanib in mitigating pulmonary fibrosis, as reflected by the remarkable improvement in body weight loss and pulmonary histopathological features. This finding was primarily ascribed to the documented suppression of mitogen‐activated protein kinase kinase kinase 2 (MEKK2) and MEKK3 mRNA expressions, which subsequently repressed p‐c‐Jun N‐terminal kinase (p‐JNK1/2) and p‐P38 group of protein kinases (p‐P38) protein expressions. Moreover, pazopanib administration to bleomycin‐treated mice remarkably adjusted the bleomycin‐mediated dysregulation of the levels of examined cytokines, including interleukin (IL)‐1β, IL‐13, IL‐33, tumor necrosis factor‐alpha (TNF‐α), and nuclear factor kappa‐B (NF‐κB) P65. Remarkably, pazopanib treatment reversed the bleomycin‐induced elevation in transforming growth factor‐beta‐1 (TGF‐β1) and α‐smooth muscle actin (α‐SMA) levels. Our research highlighted the beneficial role of pazopanib in attenuating bleomycin‐elicited lung fibrosis through the suppression of MEKK2 and MEKK3 and the modulation of JNK and P38 cascades.