Nanomaterial-assisted oncolytic bacteria in solid tumor diagnosis and therapeutics.

Cancer presents a formidable challenge in modern medicine due to the intratumoral heterogeneity and the dynamic microenvironmental niche. Natural or genetically engineered oncolytic bacteria have always been hailed by scientists for their intrinsic tumor-targeting and oncolytic capacities. However, the immunogenicity and low toxicity inevitably constrain their application in clinical practice. When nanomaterials, characterized by distinctive physicochemical properties, are integrated with oncolytic bacteria, they achieve mutually complementary advantages and construct efficient and safe nanobiohybrids. In this review, we initially analyze the merits and drawbacks of conventional tumor therapeutic approaches, followed by a detailed examination of the precise oncolysis mechanisms employed by oncolytic bacteria. Subsequently, we focus on harnessing nanomaterial-assisted oncolytic bacteria (NAOB) to augment the effectiveness of tumor therapy and utilizing them as nanotheranostic agents for imaging-guided tumor treatment. Finally, by summarizing and analyzing the current deficiencies of NAOB, this review provides some innovative directions for developing nanobiohybrids, intending to infuse novel research concepts into the realm of solid tumor therapy.

High adsorption of ammonia in a titanium-based metal-organic framework.

We report the high adsorption of NH3 in a titanium-based metal-organic framework, MFM-300(Ti), comprising extended [TiO6]∞ chains linked by biphenyl-3,3',5,5'-tetracarboxylate ligands. At 273 K and 1 bar, MFM-300(Ti) shows an exceptional NH3 uptake of 23.4 mmol g-1 with a record-high packing density of 0.84 g cm-3. Dynamic breakthrough experiments confirm the excellent uptake and separation of NH3 at low concentration (1000 ppm). The combination of in situ neutron powder diffraction and spectroscopic studies reveal strong, yet reversible binding interactions of NH3 to the framework oxygen sites.

Psychobiotics Lactiplantibacillus plantarum JYLP-326: Antidepressant-like effects on CUMS-induced depressed mouse model and alleviation of gut microbiota dysbiosis.

BACKGROUND: Depression affects a significant portion of the global population and has emerged as one of the most debilitating conditions worldwide. Recent studies have explored the relationship between depression and the microbiota of the intestine, revealing potential avenues for effective treatment. METHODS: To evaluate the potential alleviation of depression symptoms, we employed a depression C57BL/6 mice model induced by chronic unpredictable mild stress (CUMS). We administered Lactiplantibacillus plantarum JYLP-326 and conducted various animal behavior tests, including the open-field test (OFT), sucrose preference test (SPT), and tail-suspension test (TST). Additionally, we conducted immunohistochemistry staining and analyzed the hippocampal and colon parts of the mice. RESULTS: The results of the behavior tests indicated that L. plantarum JYLP-326 alleviated spontaneous behavior associated with depression. Moreover, the treatment led to significant improvements in GFAP and Iba1, suggesting its potential neuroprotective effects. Analysis of the hippocampal region indicated that L. plantarum JYLP-326 administration upregulated p-TPH2, TPH2, and 5-HT1AR, while downregulating the expression of pro-inflammatory cytokines IL-1ß, IL-6, and TNF-α. In the colon, the treatment inhibited the TLR4-MyD88-NF-κB pathway and increased the levels of occludin and ZO-1, indicating improved intestinal barrier function. Additionally, the probiotic demonstrated a regulatory effect on the HMGB1-RAGE-TLR4 signaling pathway. CONCLUSIONS: Our findings demonstrate that L. plantarum JYLP-326 exhibits significant antidepressant-like effects in mice, suggesting its potential as a therapeutic approach for depression through the modulation of gut microbiota. However, further investigations and clinical trials are required to validate its safety and efficacy for human use.

Bifidobacterium longum SX-1326 ameliorates gastrointestinal toxicity after irinotecan chemotherapy via modulating the P53 signaling pathway and brain-gut axis.

BACKGROUND: Colorectal cancer (CRC) is a prevalent malignant malignancy affecting the gastrointestinal tract that is usually treated clinically with chemotherapeutic agents, whereas chemotherapeutic agents can cause severe gastrointestinal toxicity, which brings great pain to patients. Therefore, finding effective adjuvant agents for chemotherapy is crucial. METHODS: In this study, a CRC mouse model was successfully constructed using AOM/DSS, and the treatment was carried out by probiotic Bifidobacterium longum SX-1326 (B. longum SX-1326) in combination with irinotecan. Combining with various techniques of modern biomedical research, such as Hematoxylin and Eosin (H&E), Immunohistochemistry (IHC), Western blotting and 16S rDNA sequencing, we intend to elucidate the effect and mechanism of B. longum SX-1326 in improving the anticancer efficacy and reducing the side effects on the different levels of molecules, animals, and bacteria. RESULTS: Our results showed that B. longum SX-1326 enhanced the expression of Cleaved Caspase-3 (M vs. U = p < 0.01) and down-regulated the expression level of B-cell lymphoma-2 (Bcl-2) through up-regulation of the p53 signaling pathway in CRC mice, which resulted in an adjuvant effect on the treatment of CRC with irinotecan. Moreover, B. longum SX-1326 was also able to regulate the gut-brain-axis (GBA) by restoring damaged enterochromaffin cells, reducing the release of 5-hydroxytryptamine (5-HT) in brain tissue (I vs. U = 89.26 vs. 75.03, p < 0.05), and further alleviating the adverse effects of nausea and vomiting. In addition, B. longum SX-1326 reversed dysbiosis in CRC model mice by increasing the levels of Dehalobacterium, Ruminnococcus, and Mucispirillum. And further alleviated colorectal inflammation by downregulating the TLR4/MyD88/NF-κB signaling pathway. CONCLUSIONS: In conclusion, our work reveals that B. longum SX-1326 has a favorable effect in adjuvant irinotecan for CRC and amelioration of post-chemotherapy side effects, and also provides the theoretical basis and data for finding a safe and efficient chemotherapeutic adjuvant.

Gut microbiota dysbiosis promotes the development of epithelial ovarian cancer via regulating Hedgehog signaling pathway.

Epithelial ovarian cancer (EOC) is the most lethal gynecological cancer, which remains a threat to female health at all ages. Hypotheses for EOC development include the continuous presence of inflammation, in which microbiota and inflammatory cytokines participate in cancer-related signaling pathway activation. Hedgehog (Hh) signaling is prominent for EOC progression, and interacts with inflammation response related to gut microbiota (GM). However, the precise roles of GM during this process are unknown. Here, we showed that the GM from patients with EOC differed from that of healthy women and had GM dysbiosis. We found that EOC modeling may lead to GM changes in mice, and it restored after the administration of GM from healthy controls, while GM from patients with EOC further exacerbated GM dysbiosis. Furthermore, we found that GM from EOC markedly promoted tumor progression and activated Hh signaling; meanwhile, it increased the extent of inflammation and activated NF-κB signaling, but GM from healthy controls improved them. Our results demonstrate how GM dysbiosis promoted EOC progression by activating Hh signaling mediated by TLR4/NF-κB signaling. We anticipate our assay to be a new thought for exploring the role of GM in EOC development. Furthermore, improving GM dysbiosis is a novel therapeutic approach for delaying EOC development.

Efficient capture and storage of ammonia in robust aluminium-based metal-organic frameworks.

The development of stable sorbent materials to deliver reversible adsorption of ammonia (NH3) is a challenging task. Here, we report the efficient capture and storage of NH3 in a series of robust microporous aluminium-based metal-organic framework materials, namely MIL-160, CAU-10-H, Al-fum, and MIL-53(Al). In particular, MIL-160 shows high uptakes of NH3 of 4.8 and 12.8 mmol g-1 at both low and high pressure (0.001 and 1.0 bar, respectively) at 298 K. The combination of in situ neutron powder diffraction, synchrotron infrared micro-spectroscopy and solid-state nuclear magnetic resonance spectroscopy reveals the preferred adsorption domains of NH3 molecules in MIL-160, with H/D site-exchange between the host and guest and an unusual distortion of the local structure of [AlO6] moieties being observed. Dynamic breakthrough experiments confirm the excellent ability of MIL-160 to capture of NH3 with a dynamic uptake of 4.2 mmol g-1 at 1000 ppm. The combination of high porosity, pore aperture size and multiple binding sites promotes the significant binding affinity and capacity for NH3, which makes it a promising candidate for practical applications.

Direct photo-oxidation of methane to methanol over a mono-iron hydroxyl site.

Natural gas, consisting mainly of methane (CH4), has a relatively low energy density at ambient conditions (~36 kJ l-1). Partial oxidation of CH4 to methanol (CH3OH) lifts the energy density to ~17 MJ l-1 and drives the production of numerous chemicals. In nature, this is achieved by methane monooxygenase with di-iron sites, which is extremely challenging to mimic in artificial systems due to the high dissociation energy of the C-H bond in CH4 (439 kJ mol-1) and facile over-oxidation of CH3OH to CO and CO2. Here we report the direct photo-oxidation of CH4 over mono-iron hydroxyl sites immobilized within a metal-organic framework, PMOF-RuFe(OH). Under ambient and flow conditions in the presence of H2O and O2, CH4 is converted to CH3OH with 100% selectivity and a time yield of 8.81 ± 0.34 mmol gcat-1 h-1 (versus 5.05 mmol gcat-1 h-1 for methane monooxygenase). By using operando spectroscopic and modelling techniques, we find that confined mono-iron hydroxyl sites bind CH4 by forming an [Fe-OH···CH4] intermediate, thus lowering the barrier for C-H bond activation. The confinement of mono-iron hydroxyl sites in a porous matrix demonstrates a strategy for C-H bond activation in CH4 to drive the direct photosynthesis of CH3OH.

Modification of the Thioglycosyl-Naphthalimides as Potent and Selective Human O-GlcNAcase Inhibitors.

ß-N-Acetylhexosaminidases are widely distributed exoglycosidases and have attracted significant attention due to their important roles in the field of pesticide and drug discovery. Remarkably, human O-GlcNAcase (hOGA) and human ß-N-acetylhexosaminidase (HsHex) possess the same catalytic mechanism but play different physiological actions in vivo. In this Letter, we aim to improve the inhibitory potency and selectivity of previously reported thioglycosyl-naphthalimides against hOGA. The rational compound design led to the synthesis of 13r bearing a 4-piperidylnaphthalimide moiety as a highly potent hOGA inhibitor (K i = 0.6 µM against hOGA) with good selectivity (K i > 100 µM against HsHexB). Furthermore, to investigate the basis for the potency and selectivity of 13r against hOGA, the possible inhibitory mechanisms of selected inhibitors (15b, 13b, and 13r) against hOGA and HsHexB were studied using molecular docking and MD simulations. These 4-substituted naphthalimide thioglycosides may potentially serve as useful tools for the further study of the function of hOGA.