Pharmacol Res. 2026 Apr 9:108186. doi: 10.1016/j.phrs.2026.108186. Online ahead of print.

ABSTRACT

Community-acquired pneumonia (CAP) remains a major global public health challenge with substantial morbidity and mortality. Although preclinical studies suggest that Maxing Huoqiao (MXHQ) granule may have therapeutic potential for pneumonia, high-quality clinical evidence is still limited. We conducted a multicenter, double-blind, randomized, placebo-controlled trial at two tertiary hospitals in China to evaluate the clinical efficacy of MXHQ as adjunctive therapy and to explore its potential mechanisms in adults with nonsevere CAP receiving standard moxifloxacin treatment. A total of 96 patients were enrolled and randomized (1:1:1) to receive standard-dose MXHQ, low-dose MXHQ, or placebo in addition to moxifloxacin for 7 days, with a 14-day follow-up. The primary endpoint was clinical cure, defined as composite recovery of major respiratory symptoms, lung rales, and fever; secondary endpoints included symptom relief, radiographic improvement, and safety. Compared with placebo, standard-dose MXHQ was associated with a higher day-14 clinical cure rate (30.78% vs. 68.97%; RR = 0.45, 95% CI = 0.24-0.83; P < 0.01). Furthermore, the standard-dose intervention was correlated with a shorter time to relief and recovery of cough and sputum (P < 0.05), as well as improvements in symptom scores (P < 0.05) and promoting lesion absorption on chest CT (P < 0.05). Low-dose MXHQ showed no significant clinical benefit, whereas safety profiles were comparable across all groups. Transcriptomic analyses of peripheral blood mononuclear cells, complemented by a Streptococcus pneumonia animal model, indicated that the clinical benefits of MXHQ are linked to the modulation of inflammation and innate immunity. These omics and in vivo observations suggest a potential mechanism underlying the protective effects of MXHQ against inflammatory injury and promotion of tissue repair, involving the regulation of anti-inflammatory mediators and tissue repair-related factors. (Chictr.org.cn, ID Number: ChiCTR2400082095).

PMID:41966499 | DOI:10.1016/j.phrs.2026.108186

NPJ Syst Biol Appl. 2026 Apr 10. doi: 10.1038/s41540-026-00697-0. Online ahead of print.

ABSTRACT

The extracellular matrix (ECM) critically shapes tumor fate and treatment outcome, serving as a potent prognostic factor. Yet, its compositional heterogeneity across tumors makes it difficult to assess its impact on tumor dynamics. To address this, we introduce an ECM-guided patient stratification pipeline through integration of multi-omic data in lung cancer patients. We obtained four patient groups, representing ECM-grades that showed distinct clinical features, mutation profiles, and cellular heterogeneity. Investigation of patient-specific ECM-induced intracellular signaling via network modeling revealed strong enrichment of pathways and transcriptional regulators related to epithelial-mesenchymal transition (EMT) and cancer stemness in higher ECM-grades. Drug proximity analysis on ECM-grade specific networks predicted olaparib as an ECM-grade dependent therapeutic while erlotinib to be ECM-insensitive which were validated experimentally on lung tumor cells with distinct mutational profiles in response to differing ECM microenvironments. Overall, our ECM-mediated stratification approach is a robust system for capturing ECM heterogeneity and identifying patient groups that can be selectively targeted by distinct therapeutic strategies.

PMID:41963365 | DOI:10.1038/s41540-026-00697-0

NPJ Syst Biol Appl. 2026 Apr 10. doi: 10.1038/s41540-026-00697-0. Online ahead of print.

ABSTRACT

The extracellular matrix (ECM) critically shapes tumor fate and treatment outcome, serving as a potent prognostic factor. Yet, its compositional heterogeneity across tumors makes it difficult to assess its impact on tumor dynamics. To address this, we introduce an ECM-guided patient stratification pipeline through integration of multi-omic data in lung cancer patients. We obtained four patient groups, representing ECM-grades that showed distinct clinical features, mutation profiles, and cellular heterogeneity. Investigation of patient-specific ECM-induced intracellular signaling via network modeling revealed strong enrichment of pathways and transcriptional regulators related to epithelial-mesenchymal transition (EMT) and cancer stemness in higher ECM-grades. Drug proximity analysis on ECM-grade specific networks predicted olaparib as an ECM-grade dependent therapeutic while erlotinib to be ECM-insensitive which were validated experimentally on lung tumor cells with distinct mutational profiles in response to differing ECM microenvironments. Overall, our ECM-mediated stratification approach is a robust system for capturing ECM heterogeneity and identifying patient groups that can be selectively targeted by distinct therapeutic strategies.

PMID:41963365 | DOI:10.1038/s41540-026-00697-0

bioRxiv [Preprint]. 2026 Mar 12:2026.03.10.710185. doi: 10.64898/2026.03.10.710185.

ABSTRACT

KRAS is mutated in over 90% of pancreatic ductal adenocarcinomas (PDAC), where hotspot alterations in codons 12, 13, and 61 drive tumor initiation and progression. Although distinct biochemical properties have been described for individual KRAS mutants, whether they generate unique allele-specific signaling programs in PDAC cells remains unresolved. Here, we systematically interrogated the molecular consequences of seven common KRAS mutant variants in reconstituted isogenic, KRAS-deficient PDAC cell lines by integrated transcriptomic, proteomic, and phosphoproteomic profiling. We found that baseline cellular state, rather than allele identity, was the predominant driver of molecular variation. Comparisons with established KRAS reference signatures revealed significant but moderate overlap at the mRNA level and less so at the proteome level. Pathway analyses highlighted interferon response and mitochondrial translation as recurrently altered across alleles, while phosphoproteomic data confirmed robust ERK1/2 activity and suppression of DYRK kinase substrates by mutant KRAS expression. Importantly, no robust allele-specific molecular programs were identified. Together, our study establishes a comprehensive multi-omics resource for KRAS signaling in PDAC and demonstrates that cellular context exerts a stronger influence than allele identity in shaping molecular profiles, with implications for interpreting putative allele-specific signaling dependencies and therapeutic vulnerabilities.

PMID:41959224 | PMC:PMC13060958 | DOI:10.64898/2026.03.10.710185