Anti-cancer properties of statins are controversial and possibly context dependent. Recent pathology/epidemiology studies of human lung adenocarcinoma showed reduced pro-tumourigenic macrophages associated with a shift to lower-grade tumours amongst statin users but, paradoxically, worse survival compared with that of non-users. To investigate the mechanisms involved, we have characterised mouse lung adenoma/adenocarcinoma models treated with atorvastatin. Here, we show that atorvastatin suppresses premalignant disease by inhibiting the recruitment of pro-tumourigenic macrophages to the tumour microenvironment, manifested in part by suppression of Rac-mediated CCR1 ligand secretion. However, prolonged atorvastatin treatment leads to drug resistance and progression of lung adenomas into invasive disease. Pathological progression is not driven by acquisition of additional driver mutations or immunoediting/evasion but is associated with stromal changes including the development of desmoplastic stroma containing Gr1+ myeloid cells and tertiary lymphoid structures. These findings show that any chemopreventive functions of atorvastatin in lung adenocarcinoma are overridden by stromal remodelling in the long term, thus providing mechanistic insight into the poor survival of lung adenocarcinoma patients with statin use.

The search for novel natural resources, such as extracts from algae and plant for use as reductants and capping agents for the synthesis of nanoparticles, may be appealing to medicine and nanotechnology. This study aimed to use Malva parviflora fruit extract as a novel source for the green synthesis of silver nanoparticles (AgNPs) and to evaluate their characterization. The results of biosynthesized AgNP characterization using multiple techniques, such as UV–Vis spectroscopy, scanning electron microscopy (SEM), FTIR analysis, and zeta potential (ZP), demonstrated that M. parviflora AgNPs exhibit a peak at 477 nm; possess needle-like and nanorod morphology with diameters ranging from 156.08 to 258.41 nm; contain –OH, C=O, C-C stretching from phenyl groups, and carbohydrates, pyranoid ring, and amide functional groups; and have a zeta potential of −21.2 mV. Moreover, the antibacterial activity of the M. parviflora AgNPs was assessed against two multidrug-resistant strains, including Staphylococcus aureus MRSA and Escherichia coli ESBL, with inhibition zones of 20.33 ± 0.88 mm and 13.33 ± 0.33 mm, respectively. The minimum bactericidal concentration (MBC) was 1.56 µg/mL for both. SEM revealed structural damage to the treated bacterial cells, and RAPD-PCR confirmed these genetic alterations. Additionally, M. parviflora AgNPs showed antioxidant activity (IC₅₀ = 0.68 mg/mL), 69% protein denaturation inhibition, and cytotoxic effects on MCF-7 breast cancer cells at concentrations above 100 µg/mL. These findings suggest that M. parviflora-based AgNPs are safe and effective for antimicrobial and biomedical applications, such as coatings for implanted medical devices, to prevent biofilm formation and facilitate drug delivery.

Laccase production was evaluated in 108 fungal isolates recovered from the eastern coast of Saudi Arabia, a critical element in environmental biodegradation and biotransformation. The most active isolate was identified as Curvularia lunata MLK46 (GenBank accession no. PQ100161). It exhibited maximal productivity at pH 6.5, 30 °C, and incubation for 5 d, with 1% sodium nitrate and 1% galactose as the preferred nitrogen and carbon sources, respectively. Productivity was enhanced by NaCl, CuSO₄, and FeCl₃ supplementation, with a maximum at 0.3 mM, 0.2 mM, and 61.7 mM concentrations, respectively. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) for the purified enzyme through diethylaminoethyl (DEAE)-Sepharose chromatography revealed a prominent band at 71.1 kDa with maximum activity at pH 6 and stability at pH 6–9. Furthermore, it was optimally active at 50 °C and thermally stable at 50–80 °C with a half-life time (T_1/2) of 333.7 min to 80.6 min, respectively. Its activity was also enhanced by many metallic ions, especially Fe³⁺ ions; however, it was inhibited by Hg²⁺ and Ag⁺ ions. The enzyme demonstrated significant degradation of specific substrates such as 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), guaiacol, o-dianisidine, and 2,6-dichlorophenol, with a kinetic efficiency constant which ranged from 40.95 mM⁻¹ s⁻¹ to 238.20 mM⁻¹ s⁻¹. UV spectrophotometry confirmed efficient oxidation peaks by electron transition against guaiacol (at 300 nm), o-dianisidine (at 480 nm), ABTS (at 420 nm), and 2,6-dichlorophenol (at 600 nm). The results collectively demonstrate the potential of laccase from C. lunata MLK46 as a promising agent for the effective biodegradation of several industrial pollutants under extreme conditions.

Lung cancer is one of the most common cancers worldwide, and despite improvements in treatment regimens, patient prognosis remains poor. Lung adenocarcinomas develop from the lung epithelia and understanding how specific genetic and environmental factors lead to oncogenic transformation in these cells is of great importance to define the pathways that contribute to tumorigenesis. The recent rise in the use of immunotherapy to treat different cancers has prompted the exploration of immune modulators in tumour cells that may provide new targets to manipulate this process. Of these, the B7 family of cell surface receptors, which includes PD-1, is of particular interest due to its role in modulating immune cell responses within the tumour microenvironment. B7-H3 (CD276) is one family member that is upregulated in many cancer types and suggested to contribute to tumour–immune interactions. However, the function and ligand(s) for this receptor in normal lung epithelia and the mechanisms through which the overexpression of B7-H3 regulate cancer progression in the absence of immune cell interactions remain unclear. Here, we present evidence that B7-H3 is associated with one of the key rate-limiting metabolic enzymes IMPDH2, and the localisation of this complex is altered in human lung cancer cells that express high levels of B7-H3. Mechanistically, the IMPDH2:B7-H3 complex provides a protective role in cancer cells to escape oxidative stress triggered by chemotherapy, thus leading to cell survival. We further demonstrate that the loss of B7-H3 in cancer cells has no effect on growth or migration in 2D but promotes the expansion of 3D spheroids in an IMPDH2-dependent manner. These findings provide new insights into the B7-H3 function in the metabolic homeostasis of normal and transformed lung cancer cells, and whilst this molecule remains an interesting target for immunotherapy, these findings caution against the use of anti-B7-H3 therapies in certain clinical settings.

L-asparaginase (L-ASNase) functions as a chemotherapeutic enzyme with antitumor properties. It facilitates the degradation of L-asparagine (L-ASN), a vital amino acid required for the proliferation of tumor cells. In this study, we have isolated 177 L-ASNase-producing strains from the aquatic environment of the Arabian–Persian Gulf. The most potent isolate, ASP-J1-4, was an endophyte recovered from the seablite Suaeda maritima and was molecularly identified as B. xiamenensis (accession number PQ593941). The enzyme purified through DEAE-Sepharose displayed a molecular weight of 37 kDa based on the SDS-PAGE profile and lacked detectable L-glutaminase (L-GTNase) activity. Optimal enzyme activity was at 40 °C and pH 9.0, with stability at pH 7–9. The maximum stimulation effect was found in the presence of Fe³⁺, Mn²⁺, and Na⁺ ions, respectively. The enzyme demonstrated a V_max of 35.71 U/mL and a K_m of 0.15 mM. Interestingly, ASP-J1-4 L-ASNase showed a dose-dependent inhibition against human colon carcinoma (HCT-116) and cervical Henrietta Lacks (HeLa) cell lines, with IC₅₀ values of 15.42 µg/mL and 12.13 µg/mL, respectively. These findings collectively suggest a biocompatible, efficient, and robust enzyme for potential applications in tumor therapy after validation of in vivo studies and clinical trials. This study introduces the first deep screening program for L-ASNase-producing bacteria harboring in the Arabian–Persian Gulf region. In addition, it launches B. xiamenensis and other species as new sources of L-ASNase.