S100A8 is a prognostic signature and associated with immune response in diffuse large B-cell lymphoma.

Background: S100A8, a calcium-binding protein belonging to the S100 family, is involved in immune responses and multiple tumor pathogens. Diffuse large B-cell lymphoma (DLBCL) is one of the most common types of B-cell lymphoma and remains incurable in 40% of patients. However, the role of S100A8 and its regulation of the immune response in DLBCL remain unclear. Methods: The differential expression of S100A8 was identified via the GEO and TCGA databases. The prognostic role of S100A8 in DLBCL was calculated using the Kaplan-Meier curve. The function enrichment of differentially expressed genes (DEGs) was explored through GO, KEGG, GSEA, and PPI analysis. In our cohort, the expression of S100A8 was verified. Meanwhile, the biological function of S100A8 was applied after the inhibition of S100A8 in an in vitro experiment. The association between S100A8 and immune cell infiltration and treatment response in DLBCL was analyzed. Results: S100A8 was significantly overexpressed and related to a poor prognosis in DLBCL patients. Function enrichment analysis revealed that DEGs were mainly enriched in the IL-17 signaling pathway. Our cohort also verified this point. In vitro experiments suggested that inhibition of S100A8 should promote cell apoptosis and suppress tumor growth. Single-cell RNA sequence analysis indicated that S100A8 might be associated with features of the tumor microenvironment (TME), and immune infiltration analyses discovered that S100A8 expression was involved in TME. In terms of drug screening, we predicted that many drugs were associated with preferable sensitivity. Conclusion: Elevated S100A8 expression is associated with a poor prognosis and immune infiltration in DLBCL. Inhibition of S100A8 could promote cell apoptosis and suppress tumor growth. Meanwhile, S100A8 has the potential to be a promising immunotherapeutic target for patients with DLBCL.

Effects of proanthocyanidins and dialdehyde chitosan on the proliferation and differentiation of bovine myoblast for cultured meat production.

Cultured meat technology intends to manufacture meat by cultivating muscle stem cells in vitro, which is an emerging methodology in meat production. However, the insufficient stemness of bovine myoblasts cultivated in vitro declined the ability of cell expansion and myogenic differentiation, which limited the production of cultured meat. Therefore, in this study, we introduced proanthocyanidins (PC, natural polyphenolic compounds) and dialdehyde chitosan (DAC, natural polysaccharides) to explore the effects of proliferation and differentiation of bovine myoblasts in vitro. The experiment results revealed that PC and DAC promoted cell proliferation by improving the transition from G1 to the S phase as well as cell division in G2. Meanwhile, the myogenic differentiation of cells was further boosted by the combined PC and DAC up-regulation of MYH3 expression. Moreover, the study revealed the synergistic effect of PC and DAC on enhancing the structural stability of collagen, and bovine myoblasts demonstrated excellent growth and dispersion ability on collagen scaffolds. It is concluded that both PC and DAC promote the proliferation and differentiation of bovine myoblasts, contributing to the development of cultured meat production systems.

γ-Fe2 O3 Loading Mitoxantrone and Glucose Oxidase for pH-Responsive Chemo/Chemodynamic/Photothermal Synergistic Cancer Therapy.

Traditional cancer therapy is limited by poor prognosis and risk of recurrence. Emerging therapies offer alternatives to these problems. In addition, synergistic therapy can combine the advantages of multiple therapies to eliminate cancer cells while attenuating damage to normal tissues. Herein, a theranostic nanoplatform based on the chemotherapeutic drug mitoxantrone (MTO) and glucose oxidase (GOx) co-loaded γ-Fe2 O3 nanoparticles (MTO-GOx@γ-Fe2 O3 NPs) is designed and prepared to realize photoacoustic imaging-guided chemo/chemodynamic/photothermal (CT/CDT/PTT) synergistic cancer therapy. With a particle size of about 86.2 nm, the synthesized MTO-GOx@γ-Fe2 O3 NPs can selectively accumulate at tumor sites by enhanced permeability and retention (EPR) effects. After entering cancer cells by endocytosis, MTO-GOx@γ-Fe2 O3 NPs decompose into Fe3+ ions and release cargo because of their pH-responsive characteristic. As a Food and Drug Administration (FDA)-approved chemotherapy drug, MTO shows strong DNA disruption ability and satisfying photothermal conversion ability under laser irradiation for photothermal therapy. Simultaneously, GOx catalyzes the decomposition of glucose and generates hydrogen peroxide (H2 O2 ) to enhance the chemodynamic therapy efficiency. In vitro and in vivo experiments reveal that MTO-GOx@γ-Fe2 O3 NPs possess a significant synergistic therapeutic effect in cancer treatment.

Efficacy and safety of alectinib in ALK-positive non-small cell lung cancer and blood markers for prognosis and efficacy: a retrospective cohort study.

Background: Alectinib is a second generation of ALK-tyrosine kinase inhibitors (ALK-TKIs), which has attracted much attention in the treatment of ALK-positive non-small cell lung cancer (NSCLC). At present, there are few reports on the efficacy and safety of alectinib in Chinese population. Moreover, biomarkers reflecting prognosis and efficacy are exceedingly needed. This study assessed the efficacy of alectinib in patients with ALK-positive NSCLC and analyzed the prognostic factors. Methods: Patients with ALK-positive NSCLC who were confirmed by histopathology or cytology at the Affiliated Cancer Hospital of Nanjing Medical University between October 2018 and October 2021 were enrolled. All patients were treated with alectinib. The clinical characteristics and circulating tumor biomarkers before and after treatment were collected. Kaplan-Meier test was used to calculate the progression-free survival (PFS). Univariate and multivariate Cox regression analyses were used to explore the influencing factors on PFS. Incidence of adverse events was observed. Results: Twenty patients progressed after first-line treatment (n=59) with alectinib, and 21 patients progressed following second-line treatment (n=36) with alectinib. The median PFS of first-line treatment patients was not achieved, and the median PFS of patients undergoing second-line treatment was 15.0 months [95% confidence interval (CI): 0.00-32.23]. The most common adverse reactions were liver dysfunction (37.50%), anemia (37.50%), and constipation (20.83%). The incidence of grade III and above adverse reactions was 6.25%. Univariate analysis showed that neutrophil-to-lymphocyte ratio [NLR; hazard ratio (HR) =0.424, P=0.005] carcinoembryonic antigen (CEA; HR =0.482, P=0.029), lactate dehydrogenase (LDH; HR =0.327, P<0.001), carbohydrate antigen (CA)199 (HR =0.313, P=0.002), and circulating cell free DNA (cfDNA; HR =0.229, P=0.008) concentration levels were associated with PFS, and multivariate analysis showed that NLR (HR =3.058, P=0.034) was independent prognostic factor. After three months of treatment, CEA, CA199, NLR, and LDH, could further predict the prognosis of alectinib treatment. Conclusions: The efficacy and safety of alectinib as a first-line or second-line treatment for ALK-positive NSCLC in keeping with published prospective studies. CEA, CA199, NLR, and LDH within the normal range after three months of treatment were associated with good prognosis. Detection of serum tumor markers can indicate therapeutic success in patients treated with alectinib.

Degraded Sericin Significantly Regulates Blood Glucose Levels and Improves Impaired Liver Function in T2D Rats by Reducing Oxidative Stress.

Sericin could be degraded well into low-molecular-weight sericin (SS) through a novel and environmentally friendly recycling process using an ultrasonically degumming method in Ca(OH)2 aqueous solution. The oral administration of the SS has an evidently hypoglycemic effect on STZ-induced T2D rats. At oral doses of 2.5 and 5% SS for four weeks, the fasting blood glucose decreased by over 60% compared with that in the untreated model group. Oral glucose tolerance and insulin tolerance were ameliorated by the peptide treatment. The serum insulin level was reduced by approximately 35%, the insulin resistance index was reduced by more than 66%. The 8-hydroxy-2 deoxyguanosine level showed a large reduction of 20%, and the total antioxidant activities significantly increased. Hematoxylin-eosin staining and fluorescent immunostaining sections showed that liver and pancreas damage was partly recovered in T2D rats. In summary, oral SS demonstrated evidently hypoglycemic effects mainly related to reducing oxidative stress in the damaged liver and pancreas of T2D rats. Therefore, these results have suggested that the degraded sericin has a potential use in SS-based healthy functional food or hypoglycemic drugs as a waste recovered from sericulture resources.

Mitoxantrone as photothermal agents for ultrasound/fluorescence imaging-guided chemo-phototherapy enhanced by intratumoral H2O2-Induced CO.

Multimodal imaging integrated theranostic nanomaterials provides broad prospects for noninvasive and precise cancer treatment. However, the uncertain physiological metabolism of the existing phototherapy nanoagents greatly prevents its clinical application. Herein, a smart nanoplatform based on clinically chemotherapeutic drugs mitoxantrone (MTO) was prepared to realize ultrasound/fluorescence imaging-guided chemo-photothermal combined therapy. The nanoplatform encapsulating MTO and manganese carbonyl (MnCO), which denoted as MCMA NPs, could accumulate at tumor sites by enhanced permeability and retention (EPR) effect and effectively induce cell apoptosis. MTO with near-infrared absorption (~676 nm) not only acted as chemotherapy drug, but also served as photothermal reagent with high photothermal conversion efficiency (ƞ = 42.2%). Especially, H2O2 in tumor sites and the photothermal effect of MTO could trigger MnCO to generate CO, which made cancer cells more sensitive to MTO and significantly alleviated cell resistance. Simultaneously, CO released in tumor also could act as contrast agent for tumor ultrasound imaging to provide accurate guidance for anticancer treatment. Moreover, MCMA NPs could further promote oxidative stress damage in mitochondria and protect normal cells from side effects of chemotherapy. Both in vivo and in vitro studies indicated that MCMA NPs possessed excellent synergetic tumor inhibition ability with high efficiency and low chemotherapy resistance.

Aza-BODIPY-Based Nanomedicines in Cancer Phototheranostics.

Cancer phototheranostics, composed of optical diagnosis and phototherapy (including photodynamic therapy and photothermal therapy), is a promising strategy for precise tumor treatment. Due to the unique properties of near-infrared absorption/emission, high reactive oxygen species generation, and photothermal conversion efficiency, aza-boron-dipyrromethene (aza-BODIPY), as an emerging organic photosensitizer, has shown great potential for tumor phototheranostics. By encapsulating aza-BODIPY photosensitizers within functional amphiphilic polymers, we can afford hydrophilic nanomedicines that selectively target tumor sites via an enhanced permeability and retention effect, thereby efficiently improving diagnosis and therapeutic efficacy. Herein, in this spotlight article, we attempt to highlight our recent contributions in the development of aza-BODIPY-based nanomedicines, which comprises three main sections: (1) to elucidate the design strategy of aza-BODIPY photosensitizers and corresponding nanomedicines; (2) to overview their photophysical properties and biomedical applications in phototheranostics, including fluorescence imaging, photoacoustic imaging, photodynamic therapy, photothermal therapy, and synergistic therapy; and (3) to depict the challenges and future perspectives of aza-BODIPY nanomedicines. It is believed that this Spotlight on Applications article would illuminate the way of developing new aza-BODIPY nanomedicines as well as other organic photosensitizer-based nanomedicines for future clinical translation.

A H2O2 self-sufficient nanoplatform with domino effects for thermal-responsive enhanced chemodynamic therapy.

Chemodynamic therapy (CDT), employing Fenton or Fenton-like catalysts to convert hydrogen peroxide (H2O2) into toxic hydroxyl radicals (˙OH) to kill cancer cells, holds high promise in tumor therapy due to its high selectivity. However, the anticancer efficacy is unsatisfactory owing to the limited concentration of endogenous H2O2. Herein, thermal responsive nanoparticles with H2O2 self-sufficiency are fabricated by utilizing organic phase change materials (PCMs) to encapsulate iron-gallic acid nanoparticles (Fe-GA) and ultra-small CaO2. PCMs, acting as the gatekeeper, could be melted down by the hyperthermia effect of Fe-GA under laser irradiation with a burst release of Fe-GA and CaO2. The acidic tumor microenvironment would further trigger CaO2 to generate a large amount of H2O2 and Ca2+. The self-supplied H2O2 would be converted into ˙OH by participating in the Fenton reaction with Fe-GA. Meanwhile, in situ generation of Ca2+ could cause mitochondrial damage and lead to apoptosis of tumor cells. With efficient tumor accumulation illustrated in in vivo photoacoustic imaging, Fe-GA/CaO2@PCM demonstrated a superior in vivo tumor-suppressive effect without inducing systemic toxicity. The study presents a unique domino effect approach of PCM based nanoparticles with thermal responsiveness, H2O2 self-supply, and greatly enhanced CDT effects, showing bright prospects for highly efficient tumor treatment.