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Journal of Microencapsulation Jun 2024This study aimed to encapsulate natural killer (NK) cells in a hydrogel to sustain their function within the hypoxic tumour microenvironments.
AIMS
This study aimed to encapsulate natural killer (NK) cells in a hydrogel to sustain their function within the hypoxic tumour microenvironments.
METHODS
An alginate-gelatine hydrogel was generated via electrospray technology. Hydrogel biocompatibility was assessed through cell counting kit-8 and Live/Dead assays to ascertain cell. Moreover, we analysed lactate dehydrogenase assays to evaluate the cytotoxicity against tumours and utilised RT-qPCR to analyse cytokine gene level.
RESULTS
Alginate and gelatine formed hydrogels with diameters ranging from 489.2 ± 23.0 μm, and the encapsulation efficiency was 34.07 ± 1.76%. Encapsulated NK cells exhibited robust proliferation and tumour-killing capabilities under normoxia and hypoxia. Furthermore, encapsulation provided a protective shield against cell viability under hypoxia. Importantly, tumour-killing cytotoxicity through cytokines upregulation such as granzyme B and interferon-gamma was preserved under hypoxia.
CONCLUSION
The encapsulation of NK cells not only safeguards their viability but also reinforces anticancer capacity, countering the inhibition of activation induced by hypoxia.
PubMed: 38945166
DOI: 10.1080/02652048.2024.2362170 -
Journal of Inorganic Biochemistry Jun 2024Anticancer activity has been extensively studies. In this article, three ligands 2-(6-bromobenzo[d][1,3]dioxol-5-yl)-1H-imidazo[4,5-f][1,10]phenanthroline (BDIP),...
Anticancer activity has been extensively studies. In this article, three ligands 2-(6-bromobenzo[d][1,3]dioxol-5-yl)-1H-imidazo[4,5-f][1,10]phenanthroline (BDIP), 2-(7-methoxybenzo[d][1,3]dioxol-5-yl)-1H-imidazo[4,5-f][1,10]phenanthroline (MDIP), 2-(6-nitrobenzo[d][1,3]dioxol-5-yl)-1H-imidazo[4,5-f][1,10]phenanthroline (NDIP) and their iridium(III) complexes: [Ir(ppy)(BDIP)](PF) (ppy = deprotonated 2-phenylpyridine, 3a), [Ir(ppy)(MDIP)](PF) (3b) and [Ir(ppy)(NDIP)](PF) (3c) were synthesized. The cytotoxicity of 3a, 3b, 3c against Huh7, A549, BEL-7402, HepG2, HeLa, and non-cancer NIH3T3 was tested using 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) method. The results obtained from the MTT test stated clearly that these complexes demonstrated moderate or non-cytotoxicity toward Huh7, BEL-7402, HepG2 and HeLa except A549 cells. To improve the anticancer efficacy, we used white light to irradiate the mixture of cells and complexes for 30 min, the anticancer activity of the complexes was greatly enhanced. Particularly, 3a and 3b exhibited heightened capability to inhibit A549 cells proliferation with IC (half maximal inhibitory concentration) values of 0.7 ± 0.3 μM and 1.8 ± 0.1 μM, respectively. Cellular uptake has shown that 3a and 3b can be accumulated in the cytoplasm. Wound healing and colony forming showed that 3a and 3b significantly hinder the cell migration and growth in the S phase. The complexes open mitochondrial permeability transition pore (MPTP) channel and cause the decrease of membrane potential, release of cytochrome C, activation of caspase 3, and finally lead to apoptosis. In addition, 3a and 3b cause autophagy, increase the lipid peroxidation and lead to ferroptosis. Also, 3a and 3b increase the expression of calreticulin (CRT), high mobility group box 1 (HMGB1), heat shock protein 70 (HSP70), thereby inducing immunogenic cell death.
PubMed: 38945112
DOI: 10.1016/j.jinorgbio.2024.112652 -
Thrombosis Research Jun 2024Primary liver cancer is the third leading cause of cancer related deaths worldwide, and the disease is associated with high incidence rate of thrombosis. Studies...
BACKGROUND
Primary liver cancer is the third leading cause of cancer related deaths worldwide, and the disease is associated with high incidence rate of thrombosis. Studies indicate that Tissue Factor Pathway Inhibitor (TFPI) plays a role in cancer development. We aimed to study its expression, clinical role and regulation by micro RNAs (miRNAs) in hepatocellular carcinoma (HCC).
METHODS
Publically available datasets were used for clinical analysis of TFPI and miRNAs expression by web analysis tools. miRNA mimics targeting TFPIα 3'untranslated region (UTR) were selected from target prediction programs and verified by luciferase reporter assay. In vitro effects of miRNAs overexpression in HCC cell lines on TFPI expression and cell proliferation and apoptosis were analysed.
RESULTS
TFPI expression was significantly increased in HCC tumours compared to normal tissue. Low TFPI tumour expression was associated with better survival probability. Four candidate miRNAs were selected from the target prediction programs. miR-7-5p and miR-1236-3p were validated in HepG2 and Huh7 cells to reduce TFPI mRNA and protein levels following overexpression. Furthermore, miR-7-5p and miR-1236-3p reduced TFPIα-3'UTR-controlled luciferase activity. The two validated miRNAs inhibited proliferation of HepG2 cells, and had clinical significance in HCC.
CONCLUSIONS
TFPI was increased in HCC tumours compared to normal tissue and high TFPI expression was associated with an unfavorable outcome in HCC patients. miR-7-5p and miR-1236-3p were identified as novel regulators of TFPI in vitro.
PubMed: 38945092
DOI: 10.1016/j.thromres.2024.109073 -
Biomedicine & Pharmacotherapy =... Jun 2024Inflammation and immune responses are intricately intertwined processes crucial for maintaining homeostasis and combating against pathogens. These processes involve...
Inflammation and immune responses are intricately intertwined processes crucial for maintaining homeostasis and combating against pathogens. These processes involve complex signaling pathways, notably the Nuclear Factor kappa-light-chain-enhancer of activated B-cells (NF-κB) and Mitogen-Activated Protein Kinase (MAPK) pathways, which play crucial roles. Sulforaphane (SFN), a nutraceutic, has emerged as a potential regulator of NF-κB and MAPK signaling pathways, exhibiting anti-inflammatory properties. However, limited knowledge exists regarding SFN's effects on immune cell modulation. This study aimed to assess the immunomodulatory capacity of SFN pretreatment in human dendritic cells (DCs), followed by exposure to a chronic inflammatory environment induced by lipopolysaccharide. SFN pretreatment was found to inhibit the NF-κB and MAPK signaling pathways, resulting in phenotypic changes in DCs characterized by a slight reduction in the expression of surface markers, as well as a decrease of TNF-α/IL-10 ratio. Additionally, SFN pretreatment enhanced the proliferation of Treg-cells and promoted the production of IL-10 by B-cells before exposure to the chronic inflammatory environment. Furthermore, these changes in DCs were found to be influenced by the inhibition of NF-κB and MAPK pathways (specifically p38 MAPK and JNK), suggesting that these pathways may play a role in the regulation of the differentiation of adaptive immune responses (proliferation of T- and IL-10-producing regulatory-cells), prior to SFN pretreatment. Our findings suggest that SFN pretreatment may induce a regulatory response by inhibiting NF-κB and MAPK signaling pathways in an inflammatory environment. SFN could be considered a promising strategy for utilizing functional foods to protect against inflammation and develop immunoregulatory interventions.
PubMed: 38945082
DOI: 10.1016/j.biopha.2024.117056 -
Biomedicine & Pharmacotherapy =... Jun 2024Ginseng, the dried root of Panax ginseng C.A. Mey., is widely used in Chinese herbal medicine. Ginsenosides, the primary active components of ginseng, exhibit diverse... (Review)
Review
Ginseng, the dried root of Panax ginseng C.A. Mey., is widely used in Chinese herbal medicine. Ginsenosides, the primary active components of ginseng, exhibit diverse anticancer functions through various mechanisms, such as inhibiting tumor cell proliferation, promoting apoptosis, and suppressing cell invasion and migration. In this article, the mechanism of action of 20 ginsenoside subtypes in tumor therapy and the research progress of multifunctional nanosystems are reviewed, in order to provide reference for clinical prevention and treatment of cancer.
PubMed: 38945081
DOI: 10.1016/j.biopha.2024.117049 -
Redox Biology Jun 2024Tumors develop in an oxidative environment characterized by peroxynitrite production and downstream protein tyrosine (Y) nitration. We showed that tyrosine nitration...
Tumors develop in an oxidative environment characterized by peroxynitrite production and downstream protein tyrosine (Y) nitration. We showed that tyrosine nitration supports schwannoma cell proliferation and regulates cell metabolism in the inheritable tumor disorder NF2-related Schwannomatosis (NF2-SWN). Here, we identified the chaperone Heat shock protein 90 (Hsp90) as the first nitrated protein that acts as a metabolic switch to promote schwannoma cell proliferation. Doubling the endogenous levels of nitrated Hsp90 in schwannoma cells or supplementing nitrated Hsp90 into normal Schwann cells increased their proliferation. Metabolically, nitration on either Y33 or Y56 conferred Hsp90 distinct functions; nitration at Y33 (Hsp90) down-regulated mitochondrial oxidative phosphorylation, while nitration at Y56 (Hsp90) increased glycolysis by activating the purinergic receptor P2X7 in both schwannoma and normal Schwann cells. Hsp90 and Hsp90 showed differential subcellular and spatial distribution corresponding with their metabolic and proliferative functions in schwannoma three-dimensional cell culture models. Collectively, these results underscore the role of tyrosine nitration as a post-translational modification regulating critical cellular processes. Nitrated proteins, particularly nitrated Hsp90, emerge as a novel category of tumor-directed therapeutic targets.
PubMed: 38945076
DOI: 10.1016/j.redox.2024.103249 -
Journal of Hazardous Materials Jun 2024Dialkyldimethyl ammonium compound (DADMAC) is widely used in daily life as a typical disinfectant and often co-exists with the heavy metal zinc in sewage environments....
Exposure to zinc and dialkyldimethyl ammonium compound alters bacterial community structure and resistance gene levels in partial sulfur autotrophic denitrification coupled with the Anammox process.
Dialkyldimethyl ammonium compound (DADMAC) is widely used in daily life as a typical disinfectant and often co-exists with the heavy metal zinc in sewage environments. This study investigated the effects of co-exposure to zinc (1 mg/L) and DADMAC (0.2-5 mg/L) on the performance, bacterial community, and resistance genes (RGs) in a partial sulfur autotrophic denitrification coupled with anaerobic ammonium oxidation (PSAD-Anammox) system in a sequencing batch moving bed biofilm reactor for 150 days. Co-exposure to zinc and low concentration (0.2 mg/L) DADMAC did not affect the nitrogen removal ability of the PASD-Anammox system, but increased the abundance and transmission risk of free RGs in water. Co-exposure to zinc and medium-to-high (2-5 mg/L) DADMAC led to fluctuations in and inhibition of nitrogen removal, which might be related to the enrichment of heterotrophic denitrifying bacteria dominated by Denitratisoma. Co-exposure to zinc and high concentration DADMAC (5 mg/L) stimulated the secretion of extracellular polymeric substances and increased the proliferation risk of intracellular RGs in sludge. This study provided insights into the application of PSAD-Anammox system and the ecological risks of wastewater containing zinc and DADMAC.
PubMed: 38944986
DOI: 10.1016/j.jhazmat.2024.135070 -
Biomaterials Jun 2024We present a bioprinted three-layered airway model with a physiologically relevant microstructure for the study of severe acute respiratory syndrome coronavirus 2...
We present a bioprinted three-layered airway model with a physiologically relevant microstructure for the study of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection dynamics. This model exhibited clear cell-cell junctions and mucus secretion with an efficient expression of angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2). Having infected air-exposed epithelial cells in the upper layer with a minimum multiplicity of infection of 0.01, the airway model showed a marked susceptibility to SARS-CoV-2 within one-day post-infection (dpi). Furthermore, the unique longevity allowed the observation of cytopathic effects and barrier degradation for 21 dpi. The in-depth transcriptomic analysis revealed dramatic changes in gene expression affecting the infection pathway, viral proliferation, and host immune response which are consistent with COVID-19 patient data. Finally, the treatment of antiviral agents, such as remdesivir and molnupiravir, through the culture medium underlying the endothelium resulted in a marked inhibition of viral replication within the epithelium. The bioprinted airway model can be used as a manufacturable physiological platform to study disease pathogeneses and drug efficacy.
PubMed: 38944967
DOI: 10.1016/j.biomaterials.2024.122689 -
International Immunopharmacology Jun 2024Acute lung injury (ALI) is manifested by increased blood vessel permeability within the lungs and subsequent impairment of alveolar gas exchange. Methylprednisolone (MP)...
BACKGROUND
Acute lung injury (ALI) is manifested by increased blood vessel permeability within the lungs and subsequent impairment of alveolar gas exchange. Methylprednisolone (MP) is commonly used as a treatment for ALI to reduce inflammation, yet its molecular mechanism remains unclear. This study aims to explore the underlying mechanisms of MP on ALI in a model induced by lipopolysaccharide (LPS).
MATERIAL AND METHODS
The proliferation, viability, apoptosis, and miR-151-5p expression of alveolar type II epithelial cells (AECII) were detected using the cell EdU assay, Annexin V/PI Apoptosis Kit, counting kit-8 (CCK-8) assay, and RT-qPCR. Western blot analysis was used to detect the Usp38 protein level. IL-6 and TNF-α were measured by ELISA. The combination of miR-151-5p and USP38 was determined by chromatin immunoprecipitation (ChIP)-PCR and dual-luciferase reporter assay.
RESULTS
MP greatly improved pulmonary function in vivo, reduced inflammation, and promoted the proliferation of the alveolar type II epithelial cells (AECII) in vitro. By comparing the alterations of microRNAs in lung tissues between MP treatment and control groups, we found that miR-151-5p exhibited a significant increase after LPS-treated AECII, but decreased after MP treatment. Confirmed by a luciferase reporter assay, USP38, identified as a downstream target of miR-151-5p, was found to increase after MP administration. Inhibition of miR-151-5p or overexpression of USP38 in AECII significantly improved the anti-inflammatory, anti-apoptotic, and proliferation-promotive effects of MP.
CONCLUSION
In summary, our data demonstrated that MP alleviates the inflammation and apoptosis of AECII induced by LPS, and promotes the proliferation of AECII partially via miR-151-5p suppression and subsequent USP38 activation.
PubMed: 38944949
DOI: 10.1016/j.intimp.2024.112548 -
Neoplasia (New York, N.Y.) Jun 2024Hepatocellular carcinoma (HCC) is the most common form of liver cancer, accounting for approximately 90 % of all cases. ONC201, a member of the imipridone drug family,...
Hepatocellular carcinoma (HCC) is the most common form of liver cancer, accounting for approximately 90 % of all cases. ONC201, a member of the imipridone drug family, has shown promising therapeutic potential and a good safety profile in both malignant pediatric central nervous system tumors (diffuse midline glioma [DMG]) and hematologic malignancies. ONC206 is a more potent analog of ONC201. However, the ONC206 potential and mechanism of action in HCC remain to be elucidated. We found that ONC206 hindered HCC growth by suppressing cell proliferation and inducing apoptosis. Moreover, ONC206 induced cytoprotective autophagy, and blocking autophagy enhanced the proapoptotic effect of ONC206. Additionally, ONC206 induced mitochondrial swelling, reduced the mitochondrial membrane potential (MMP), and led to the accumulation of mitochondrial ROS in HCC cells, ultimately resulting in mitochondrial dysfunction. The HCC patient samples exhibited notably elevated levels of caseinolytic protease proteolytic subunit (ClpP), which serves as a mediator of ONC206-induced mitochondrial dysfunction and the activation of protective autophagy. knockdown of ClpP reversed the cytotoxic effects of ONC206 on HCC cells. In summary, our results provide the first insight into the mechanism by which ONC206 exerts its anti-HCC effects and induces protective autophagy in HCC cells through ClpP.
PubMed: 38944913
DOI: 10.1016/j.neo.2024.101015