Tiesuo Zhao

As a major gastrointestinal malignancy, colon cancer (CC) demands more effective therapies. Gene therapy is an emerging promising strategy, and pyroptosis, a novel lytic cell death form, serves as a vital antitumor target, with Gasdermin D (GSDMD)—a key pore-forming protein in pyroptosis—showing anti-CC potential. We constructed an engineered attenuated Salmonella strain to deliver a GSDMD-expressing plasmid, and verified its therapeutic efficacy via in vitro and in vivo studies. In CC cell lines, the Salmonella vector upregulated GSDMD and cleaved caspase-1 (its upstream activator), inhibiting cell proliferation and inducing pyroptosis. In CC-bearing mice, the strain significantly suppressed tumor progression, reduced Ki67 expression, elevated intratumoral GSDMD and cleaved caspase-1 levels, and enhanced CD4⁺ and CD8⁺ T cell infiltration to boost antitumor immunity. This study suggests that attenuated Salmonella-mediated GSDMD delivery combats CC by triggering pyroptosis and stimulating antitumor immunity, laying a foundation for GSDMD-targeted gene therapeutics.

Background: Lenvatinib is a first-line multi-target tyrosine kinase inhibitor for hepatocellular carcinoma (HCC) that exerts anti-angiogenic effects by blocking VEGF signaling. However, its clinical efficacy is often compromised by adaptive resistance. Nifuroxazide, an anti-diarrheal agent, has been identified by our group as a potent inhibitor of PD-L1 expression in HCC. Objective: This study aimed to evaluate the therapeutic potential and underlying molecular mechanisms of nifuroxazide combined with lenvatinib against HCC. Methods: In vitro , HCC cell proliferation, colony formation, and migration were assessed, and Western blot was used to detect p-STAT3, STAT3, PD-L1, and VEGF levels. In vivo , antitumor efficacy was evaluated in mouse xenograft models. Tumor tissues were analyzed by immunohistochemistry, TUNEL, and H&E staining, while flow cytometry was used to measure CD4 ⁺ and CD8 ⁺ T-cell proportions in the tumor microenvironment, peripheral blood, and spleen. Results: The combination synergistically inhibited HCC cell proliferation and migration, and downregulated PD-L1, p-STAT3, and VEGF expression. It also markedly suppressed tumor growth, induced apoptosis, and enhanced CD4 ⁺ and CD8 ⁺ T-cell infiltration and distribution. Conclusions: Nifuroxazide potentiates lenvatinib-induced antitumor activity by regulating the STAT3/PD-L1 axis and enhancing antitumor immune responses. This combination provides a promising therapeutic strategy for HCC.

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer. Epidemiological data indicate that HCC ranks as the sixth most prevalent cancer and the third leading cause of cancer...

Influenza viruses are adept at hijacking host cellular machinery to facilitate their replication and propagation. A critical aspect of this hijacking involves the reprogramming of host cell metabolism. This review summarizes current findings on how influenza virus infection alters major metabolic pathways, including enhanced glycolysis, suppression of oxidative phosphorylation, diversion of TCA cycle intermediates for biosynthesis, and upregulation of lipid and amino acid metabolism. Key nutrients like glucose, glutamine, and serine are redirected to support viral RNA synthesis, protein production, and membrane formation. Moreover, these metabolic changes also modulate host immune responses, potentially aiding in immune evasion. We highlight the role of transcription factors such as SREBPs in lipid synthesis and the impact of one-carbon metabolism on epigenetic regulation. Finally, we discuss how targeting virus-induced metabolic shifts, using agents like 2-deoxyglucose or fatty acid synthesis inhibitors, offers promising avenues for antiviral intervention, while emphasizing the need for selective approaches to minimize harm to normal cells.

Psoriasis is a persistent immune-mediated inflammatory dermatosis. The treatment of psoriasis now features natural medicine as an effective new alternative because of its notable effectiveness and few side effects. Nervonic acid (NA), a long-chain fatty acid mostly sourced from the seed oils of some wild plants, exhibits significant antidepressant and anti-inflammatory properties. Nonetheless, the pathogenic effects and mechanism of NA in the pathogenesis of psoriasis are unreported. This work demonstrated that NA markedly mitigated IMQ-triggered psoriasis-like skin inflammation and reduced the mRNA expression levels of chemokines (Cxcl1 and Ccl20) and inflammatory factors (S100a8, S100a9, IL-17, and IL-6) both in vitro and in vivo. Mechanistically, NA blocked the IL-17/IMQ-induced NF-κB and p38MAPK signaling pathways in keratinocytes or tissue lesions, downregulated Ccl20 production, and therefore disrupted positive inflammatory feedback by diminishing Th17 or γδT17 cell infiltration. Furthermore, 16s rRNA sequencing demonstrated that NA therapy significantly elevated the relative abundance of Bacteroidota, but the outcome for Mucispirillum was contrary within the gut microbiota. These bacteria are linked to the onset of psoriasis and inflammation, perhaps contributing to the alleviation of IMQ-induced lesions in mice. In conclusion, NA may alleviate dermatitis in psoriatic mice by inhibiting Th17/γδT17 cell invasion and modulating the gut microbiota. Consequently, NA stands as a highly promising choice for psoriasis treatment.

The cross-species transmission of influenza viruses represents a critical link in the pandemic of zoonotic diseases. This mechanism involves multi-level interactions, including viral genetic adaptability, host–receptor compatibility, and ecological drivers. Recent studies have highlighted the essential role of mutations in hemagglutinin and neuraminidase in overcoming host barriers, while elucidating the differences in the distribution of host sialic acid receptors. Furthermore, the “mixer” function of intermediate hosts, such as pigs, plays a significant role in viral redistribution. Advances in high-throughput sequencing and structural biology technologies have gradually resolved key molecular markers and host restriction factors associated with these viruses. However, challenges remain in understanding the dynamic evolutionary patterns of virus–host interaction networks, developing real-time early warning capabilities for cross-species transmission, and formulating broad-spectrum prevention and control strategies. Moving forward, it is essential to integrate multidisciplinary approaches to establish a multi-level defense system, leveraging the ‘One Health’ monitoring network, artificial intelligence prediction models, and new vaccine research and development to address the ongoing threat of cross-species transmission of influenza viruses. This paper systematically reviews the research progress and discusses bottlenecks in this field, providing a theoretical foundation for optimizing future prevention and control strategies.

Hepatocellular carcinoma (HCC), the most prevalent type of aggressive liver cancer, accounts for the majority of liver cancer diagnoses and fatalities. Despite recent advancements in HCC treatment, it remains one of the deadliest cancers. Radiation therapy (RT) is among the locoregional therapy modalities employed to treat unresectable or medically inoperable HCC. However, radioresistance poses a significant challenge. It has been demonstrated that RT induced the upregulation of programmed death ligand 1 (PD-L1) on tumor cells, which may affect response to PD-1-based immunotherapy, providing a rationale for combining PD-1/PD-L1 inhibitors with radiation. Here, we utilized attenuated Salmonella as a carrier to explore whether attenuated Salmonella carrying siRNA-PD-L1 could effectively enhance the antitumor effect of radiotherapy on HCC-bearing mice. Our results showed that a combination of siRNA-PD-L1 and radiotherapy had a synergistic antitumor effect by inhibiting the expression of PD-L1 induced by radiation therapy. Mechanistic insights indicated that the combination treatment significantly suppressed tumor cell proliferation, promoted cell apoptosis, and stimulated immune cell infiltration and activation in tumor tissues. Additionally, the combination treatment increased the ratios of CD4⁺ T, CD8⁺ T, and NK cells from the spleen in tumor-bearing mice. This study presents a novel therapeutic strategy for HCC treatment, especially for patients with RT resistance.

Hepatocellular carcinoma (HCC), the most prevalent type of aggressive liver cancer, accounts for the majority of liver cancer diagnoses and fatalities. Despite recent advancements in HCC treatment, it remains one of the deadliest cancers. Radiation therapy (RT) is among the locoregional therapy modalities employed to treat unresectable or medically inoperable HCC. However, radio-resistance poses a significant challenge. It has been demonstrated that RT induced the upregulation of programmed death ligand 1 (PD-L1) on tumor cells, which may affect response to PD-1-based immunotherapy, providing a rationale for combining PD-1/PD-L1 inhibitors with radiation. Here, we utilized attenuated Salmonella as a carrier to explore whether attenuated Salmonella carrying siRNA-PD-L1 could effectively enhance the anti-tumor effect of radiotherapy on HCC-bearing mice. Our results showed that a combination of siRNA-PD-L1 and radiotherapy had a synergistic anti-tumor effect by inhibiting the expression of PD-L1 induced by radiation therapy. Mechanistic insights indicated that the combination treatment significantly suppressed tumor cell proliferation, promoted cell apoptosis, and stimulated immune cell infiltration and activation in tumor tissues. Additionally, the combination treatment increased the ratios of CD4⁺ T, CD8⁺ T, and NK cells from the spleen in tumor-bearing mice. This study presents a novel therapeutic strategy for HCC treatment, especially for patients with RT resistance.