Collaboration between cancer treatment and inflammation management has emerged as an integral facet of comprehensive cancer care. Nevertheless, the development of interventions concurrently targeting both inflammation and cancer has encountered significant challenges stemming from various external factors. Herein, a bioactive agent synthesized by genetically engineering melanin-producing Bacillus thuringiensis (B. thuringiensis) bacteria, simultaneously achieves eco-friendly photothermal agent and efficient reactive oxygen/nitrogen species (RONS) scavenger benefits, perfectly tackling present toughies from inflammation to cancer therapies. The biologically derived melanin exhibits exceptional photothermal-conversion performance, facilitating potent photonic hyperthermia that effectively eradicates tumor cells and tissues, thereby impeding tumor growth. Additionally, the RONS-scavenging properties of melanin produced by B. thuringiensis bacteria contribute to inflammation reduction, augmenting the efficacy of photothermal tumor repression. This study presents a representative paradigm of genetic engineering in B. thuringiensis bacteria to produce functional agents tailored for diverse biomedical applications, encompassing inflammation and cancer therapy.

Bacteria-initiated cancer therapy has been demonstrated high therapeutic efficacy against cancer. However, the undesired therapeutic efficacy and induced systematic inflammation storm compromise the therapeutic effect and outcome. Herein, a thermally-activated living nanomedicine composed of reactive biohybrid (designated as Sa@FeS) is rationally designed and engineered for enhancing hydrogen sulfide (H2S)-combined chemodynamic oncotherapy by biomineralizing ferrous sulfide nanoparticles (FeS NPs) onto the surface of a Salmonella typhimurium strain (Sa) without reducing bacterial activity. Ascribed to the deep penetration capability of Sa, FeS NPs facilitate photothermally-enhanced catalytic Fenton reaction of decomposing endogenous H2O2 into cytotoxic hydroxyl radicals deep in tumor tissues upon near infrared irradiation. Meanwhile, Sa bacteria maintain sustained H2S release within tumor for achieving H2S-induced intracellular acidosis that favors the generation of reactive oxygen species synergistically. Of note, the thermally-triggered all-in-one strategy effectively inhibits bacterial viability, thus reducing the risk of systematic inflammation storm and ensuring biosafety. Therefore, the engineered nano-bacteria living system exerts the thermally-enhanced nanocatalytic and gas therapies to effectively eradicate tumors, providing a distinct paradigm for the combination of synthetic biology and nanomedicine in tumor therapy.

With the remarkable advances of bacteriotherapy and diverse functional nanoplatforms in biomedical applica-tions, nano-bacteria hybrids have been extensively exploited as the emerging and distinct theranostic platforms and strategies for enhanced tumor therapy. The nano-bacteria hybrids are highly competent for efficient anti-cancer therapy when combined the hypoxia tropism and chemotaxis, penetration capabilities, extracellular anticancer metabolites, immunogenic effects and specific respiration of specialty bacteria with the tunable physicochemical properties, easily modified surface, multifunctionality of versatile nanoparticles together. Herein, efforts are made to provide a comprehensive review on the current progress of anticancer nano-bacteria hybrid systems, ranging from the promising types of live bacteria such as obligate anaerobe Cyanobacteria and facultative anaerobe Salmonella, rational fabrication methods including covalent bond, physical adsorption, biomineralization process, and other binding forms, to their versatile applications in several distinct therapeutic modalities including drug delivery, immunotherapy, phototherapy, chemodynamic therapy, sonodynamic therapy, gas therapy, pyroptosis and bio-imaging in efficient cancer treatment. The biosafety evaluation, un-settled challenges, and future perspectives on the rational construction of nano-bacteria hybrids and their further clinical translations have also been discussed and outlooked. It is highly anticipated that the unique theranostic platforms of nano-bacteria hybrids will witness a leap-forward development in clinical translation for precise and personalized cancer therapy.

Objective:To investigate the effects of the B7-H4 gene rs10754339 and miR-125a gene rs12976445 on cancer susceptibility through a case-control study and meta-analysis.Methods:A total of 1,490 cancer patients (lung/gastric/liver/: 550/460/480) and 800 controls were recruited in this case-control study. The meta-analysis was performed by pooling the data from previous related studies and the present study.Results:The results of this study showed that in the Hubei Han Chinese population, the rs10754339 gene was significantly associated with the risk of lung and gastric cancer but not liver cancer, and the rs12976445 gene was significantly associated with the risk of lung cancer but not liver or gastric cancer. The meta-analysis results indicated that rs10754339 and rs12976445 contributed to cancer susceptibility in the Chinese population and also revealed a significant association between rs10754339 and breast cancer risk, as well as between rs12976445 and lung cancer risk.Conclusion:The B7-H4 gene rs10754339 and miR-125a gene rs12976445 may be the potential genetic markers for cancer susceptibility in the Chinese population, which should be validated in future studies with larger sample sizes in other ethnic populations.

Easy recurrence and bacteria infected-wound healing after surgery excision pose severe challenges to clinical melanoma therapy. Herein, an injectable CuO2 nanodots-engineered thermosensitive chitosan hydrogel (CuO2-BSO@Gel) for enhanced melanoma chemo-sonodynamic therapy and improved infected wound healing was rationally constructed by facilely integrating the CuO2 nanodots and L-Buthionine-(S, R)-sulfoximine (BSO) with thermoresponsive hydrogel. Favored by the Fenton catalytic activity of Cu2+, the CuO2 nanodots can achieve enhanced chemodynamic therapy (CDT) by self-supplying H2O2 under acidic tumor microenvironment. Simultaneously, the CuO2 nanodots with a narrow bandgap (2.29 ​eV) were proven to be the efficient sonosensitizers, and the corresponding quantum yield of singlet oxygen (1O2) could be boosted by the O2 generation during Fenton-like reactions. Additionally, combining with the glutathione (GSH) depletion of loaded BSO, intracellular oxidative stress induced by SDT and CDT was further amplified, leading to the specific ferroptosis. Importantly, this multifunctional hydrogel significantly promoted the proliferation of normal skin cells and accelerated the bacteria-infected wound healing by the effective chemo-sonodynamic antibacterial activity and the enhanced angiogenesis. Thus, the engineered thermogel features the distinct chemo-sonodynamic performance, desirable biocompatibility and bioactivity, providing a competitive strategy for eradicating melanoma and infected wound healing.

Recently, the rs41291957 polymorphism in the promoter region of miR-143/145 has been repeatedly investigated for its contribution to cancer susceptibility. However, the results remain conflicting rather than conclusive, which calls for further investigations. Therefore, we here conducted a case-control study and meta-analysis to explore the association between rs41291957 and cancer risk. In the case-control study, a total of 2277 cancer patients (lung, liver, gastric and colorectal cancers) and 800 normal controls were recruited, the genotyping of rs41291957 was performed with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and Sanger sequencing. In the meta-analysis, 5 previously published studies and our present study were included, the STATA 14.0 software was applied to conduct all statistical analyses. The results of case-control study showed that rs41291957 was significantly associated with the risk of gastric cancer, colon cancer, rectal cancer, and colorectal cancer in Hubei Han Chinese population. The results of meta-analysis demonstrated that rs41291957 was significantly associated with overall cancer risk, especially colorectal cancer risk and lung cancer risk. Collectively, the rs41291957 polymorphism of miR-143/145 may be a plausible susceptible locus for cancer risk, which should be validated in future studies with larger samples in different ethnic populations.

Previous studies have repeatedly investigated the effects of MALAT1 gene rs3200401 and MEG3 gene rs7158663 on cancer risk. However, their results remain conflicting rather than conclusive. Therefore, we here performed a case-control study and a followed meta-analysis to examine their contribution to the risk of lung, colorectal, gastric and liver cancer. 550 lung cancer patients, 787 colorectal cancer patients, 460 gastric cancer patients, 480 liver cancer patients and 800 normal controls were included. The genotyping of rs3200401 and rs7158663 was applied with Sanger sequencing technology. Our case-control study revealed that in Hubei Chinese population, rs3200401 was significantly associated with the risk of gastric cancer but not lung, colorectal, or liver cancer, rs7158663 was significantly associated with the risk of gastric and colorectal cancer but not lung or liver cancer. The followed meta-analysis, combining the data of previous studies and present study, showed that rs3200401 was significantly associated with the risk of gastric and colorectal cancer in the pooled population but not liver cancer in Chinese population, rs7158663 was significantly associated with the risk of lung, colorectal and gastric but not liver cancer in Chinese population. Collectively, MALAT1 gene rs3200401 may be a susceptive factor for the development of colorectal and gastric cancer, and MEG3 gene rs7158663 may be a susceptive factor for the development of lung, colorectal and gastric cancer. However, the findings should be validated in future studies with larger sample sizes of different ethnic populations.