Cell Survival Research Articles

New Application of Ombuoside in Protecting Auditory Cells from Cisplatin-induced Ototoxicity via the Apoptosis Pathway

Hearing loss is caused by many factors including ototoxic drug-induced hair cell damage. Ombuoside, an antioxidant isolated from Gynostemma pentaphyllum, has been suggested to serve as a new neuroprotective drug. However, the role of ombuoside in protecting inner ear hair cells from ototoxic drug-induced damage has not been investigated. Here, we demonstrated the protective potential of ombuoside in mitigating drug-induced ototoxicity in vivo and in vitro. We used cisplatin, a highly ototoxic anti-tumor drug, to induce hair cell damage. Our results showed that ombuoside significantly increased the survival of cisplatin-treated HEI-OC1 cells. Further mechanism research suggested that ombuoside protects HEI-OCI cells from cisplatin-induced apoptosis by reducing the cisplatin-induced upregulation of apoptosis-promoting proteins Bax, Bak, as well as apoptosis indicator proteins cytochrome C and cleaved-caspase-3, and the downregulation of apoptosis-inhibiting proteins Bcl-2. Ombuoside also protects the cells from the excessive ROS production and mitochondrial membrane depolarization triggered by cisplatin. These results demonstrated the potential for ombuoside in protecting hair cells from cisplatin by suppressing ROS generation and the mitochondrial apoptotic cascade. Ombuoside showed promise in protecting hair cells from cisplatin-induced apoptosis by suppressing ROS generation and the mitochondrial apoptotic cascade. Furthermore, ombuoside co-treatment in mouse cochlear explants and zebrafish lateral neuromasts rescued the decreased number and deformed morphology of hair cells resulting from cisplatin exposure. These findings further validated our conclusions and indicated that ombuoside is a potential protector against hearing loss caused by ototoxicity as a clinical side effect of cisplatin.

Microscopic mechanistic study of the penetration distributions for plasma reactive oxygen and nitrogen species based on sialic acid targeting on the cell membrane surface

The ability of cold atmospheric plasmas (CAPs) to produce a wide range of active constituents while maintaining a low or even room temperature of the gas has made it a novel research area of great interest. During plasma action, cancer cell membrane surface components are susceptible to oxidative modification by reactive oxygen and nitrogen species (RONS). In this study, the process of oxidative modification of membrane surface components sialic acid by RONS was investigated based on molecular dynamics simulations, and the penetration mechanism of long-lived particles ONOOH and its homolytic products at the membrane-water interface and the effect of appropriate electric field action were studied. The results showed that cancer cells with high sialic acid expression were less stable than healthy cells. Plasma treatment may promote the ONOOH homolysis process, and its homolysis product OH free radical is more likely to adsorb near sialic acid molecules by hydrogen bonding, resulting in oxidative modification. The interaction force between OH free radical and sialic acid molecules is stronger than ONOOH, which helps to further understand the oxidative modification reaction in membrane environment. At the same time, appropriate electric field stimulation can enhance the depth of penetration of RONS to more effectively treat the pathological state of biological tissues. The study proposes the use of membrane surface sialic acid as a cancer therapeutic target and provides guidance for improving the depth of RONS penetration and maximizing the survival of healthy cells, which contributes to the further clinical translation of plasma biomedicine.

Biomimetic composite gelatin methacryloyl hydrogels for improving survival and osteogenesis of human adipose-derived stem cells in 3D microenvironment

Gelatin methacryloyl (GelMA) hydrogels are used for stem cell encapsulation in bone tissue engineering due to their fast and stable photo-crosslinking. However, cell viability and ability to induce osteogenesis are reduced by reactive oxygen species (ROS) produced during the crosslinking reaction. In this study, we developed biomimetic nanoparticles (TMNs) by combining tannic acid (TA) and simulated body fluid (SBF) minerals, and used them to synthesize GelMA-based composite hydrogels for addressing those limitations. The optimal concentrations of TA and SBF were investigated to create nanoparticles that can effectively scavenge ROS and induce osteogenesis. The incorporation of TMNs into composite hydrogels (G-TMN) significantly enhanced the survival and proliferation of encapsulated human adipose-derived stem cells (hADSCs) by providing resistance to oxidative conditions. In addition, the ions that were released, such as Ca2+ and PO43-, stimulated stem cell differentiation into bone cells. The hADSCs encapsulated in G-TMN had 2.0 ± 0.8-fold greater viability and 1.3 ± 1.8 times greater calcium deposition than those encapsulated in the hydrogel without nanoparticles. Furthermore, the in vivo transplantation of G-TMN into a subcutaneous mouse model demonstrated the rapid degradation of the gel-network while retaining the osteoinductive particles and cells in the transplanted area. The increased cellular activity observed in our multifunctional composite hydrogel can serve as a foundation for novel and effective therapies for bone deformities.

Radiofrequency ablation: mechanisms and clinical applications.

Radiofrequency ablation (RFA), a form of thermal ablation, employs localized heat to induce protein denaturation in tissue cells, resulting in cell death. It has emerged as a viable treatment option for patients who are ineligible for surgery in various diseases, particularly liver cancer and other tumor-related conditions. In addition to directly eliminating tumor cells, RFA also induces alterations in the infiltrating cells within the tumor microenvironment (TME), which can significantly impact treatment outcomes. Moreover, incomplete RFA (iRFA) may lead to tumor recurrence and metastasis. The current challenge is to enhance the efficacy of RFA by elucidating its underlying mechanisms. This review discusses the clinical applications of RFA in treating various diseases and the mechanisms that contribute to the survival and invasion of tumor cells following iRFA, including the roles of heat shock proteins, hypoxia, and autophagy. Additionally, we analyze‌ the changes occurring in infiltrating cells within the TME after iRFA. Finally, we provide a comprehensive summary of clinical trials involving RFA in conjunction with other treatment modalities in the field of cancer therapy, aiming to offer novel insights and references for improving the effectiveness of RFA.

Antihyperglycemic activity of a novel polyherbal formula (HF344), a mixture of fifteen herb extracts, for the management of type 2 diabetes: Evidence from in vitro, ex vivo, and in vivo studies

Antihyperglycemic effects of a novel polyherbal formula (HF344), comprising fifteen Thai herbal extracts, were elucidated for pharmacological mechanisms and potential for managing type 2 diabetes mellitus, by employing in vitro, ex vivo, and in vivo approaches. LC/MS analysis of HF344 extract revealed several phytoconstituents, with piperine identified as the major active compound. HF344 extract significantly enhanced insulin secretion in RINm5F cells in vitro and inhibited glucose uptake into the everted sacs of the mouse small intestine ex vivo in a concentration-dependent manner compared to the control (p < 0.05). It exhibited potent α-glucosidase inhibition in vitro, with an IC50 of 96.74 μg/mL. Moreover, HF344 extract upregulated mRNA levels of GLUT1 in L6 skeletal myoblasts, suggesting increased glucose uptake into skeletal muscle. In addition, in vivo antihyperglycemic effects were assessed in streptozotocin (STZ)-nicotinamide (NA)-induced diabetic mice. Acute oral toxicity testing confirmed the HF344 extract's safety, with an LD50 exceeding 2000 mg/kg. Oral administration of HF344 extract (500 and 1000 mg/kg) in STZ-NA-induced diabetic mice significantly reduced the area under the fasting blood glucose (FBG)-time curve (AUC) in the oral glucose tolerance test (OGTT) model and treatment for 28-day reduced the FBG levels as compared with control (p < 0.05). This was accompanied by increased serum insulin levels and improved insulin resistance. HF344 extract also demonstrated a concentration-dependent inhibitory effect on malondialdehyde (MDA) production in vitro, with an IC50 of 7.24 μg/mL. Oral treatment with HF344 extract decreased MDA production in the homogenized muscle ex vivo collected from STZ-NA-induced mice. Furthermore, pretreatment with HF344 extract effectively restored the survival of RINm5F cells from STZ-induced damage. These findings suggest that HF344 is a promising polyherbal formula for managing blood glucose levels, enhancing insulin production, and providing antioxidant benefits in T2DM. Further research is required to evaluate the clinical efficacy and safety profiles of HF344.

Major regulatory factors for reproductive performances of female chickens

The reproductive performance of female chickens is critical for determining the efficiency of production and productivity and thus profitability. Studies have shown that the reproductive performance of female chickens is mainly regulated by the feed, hormones, genes, and light conditions. Herein, we review the major factors regulating female chicken reproductive performance and assess the reproductive organs and their functions. In the current review, we highlight how the interconnections of hormones, candidate genes, and photo-stimulation regulate female chicken reproductive hormones and thus regulate the reproductive organ performance. In this regard, the roles of main hormones [gonadotropinreleasing hormone (GnRH) and genes (GnRH-I)] in regulating sexual maturation and ovarian development and maintenance by influencing the survival and function of follicular granulosa cells were also reviewed. In addition, the current review also highlights how feeding female chickens with diets and artificial light-emitting diodes (LEDs) support the effective functioning of their reproductive capacity through the stimulation of sexual maturity at an appropriate age and regeneration of aged reproductive organs.

Defining precancer: a grand challenge for the cancer community.

The term 'precancer' typically refers to an early stage of neoplastic development that is distinguishable from normal tissue owing to molecular and phenotypic alterations, resulting in abnormal cells that are at least partially self-sustaining and function outside of normal cellular cues that constrain cell proliferation and survival. Although such cells are often histologically distinct from both the corresponding normal and invasive cancer cells of the same tissue origin, defining precancer remains a challenge for boththe research and clinical communities. Once sufficient molecular and phenotypic changes have occurred in the precancer, the tissue is identified as a 'cancer' by a histopathologist. While even diagnosing cancer can at times be challenging, the determination of invasive cancer is generally less ambiguous and suggests a high likelihood of and potential for metastatic disease. The 'hallmarks of cancer' set out the fundamental organizing principles of malignant transformation but exactly how many of these hallmarks and in what configuration they define precancer has not been clearly and consistently determined. In this Expert Recommendation, we provide a starting point for a conceptual framework for defining precancer, which is based on molecular, pathological, clinical and epidemiological criteria, with the goal of advancing our understanding of the initial changes that occur and opportunities to intervene at the earliest possible time point.

Elucidating the effective age for dietary restriction and the key metabolites involved

Dietary restriction (DR) extends lifespan in various species, but its effect at different ages, especially when started later, is unclear. This study used Caenorhabditis elegans to explore the impact of DR at different ages. Worms were divided into control and DR groups, with daily survival monitored. To confirm the occurrence of DR, the expression of DR-sensitive genes namely acdh-1, pyk-1, pck-2 and cts-1 were determined using RT-qPCR. Liquid chromatography mass spectrometry (LC-MS) was employed to observe the changes in metabolites affected by DR. The results indicated that young worms subjected to mild DR displayed the longest lifespan, highlighting the effectiveness of initiating DR at a young age. Increased expression of acdh-1 and pck-2 suggests activation of beta-oxidation and gluconeogenesis, while decreased cts-1 expression indicates a reduced citric acid cycle, further supporting the observed effects of DR in these worms. Metabolomic results indicated that DR decreased the activity of mechanistic Target of Rapamycin (mTOR) and the synthesis of amino acids namely leucine, tyrosine and tryptophan to conserve energy for cell repair and survival. DR also decreased levels of N-acetyl-L-methionine and S-adenosyl-methionine (SAM) in methionine metabolism, thereby promoting autophagy, reducing inflammation, and facilitating the removal of damaged cells and proteins. In conclusion, initiating dietary restriction early in life extends the lifespan by modulating amino acid metabolism and enhancing the autophagy pathway, thereby maintaining cellular wellbeing.

Enhancing CAR-T cell therapy against solid tumor by drug-free triboelectric immunotherapy

Chimeric antigen receptor (CAR) T cell therapy is a highly effective immunotherapy for hematological tumors, but its efficacy against most solid tumors remains challenging. Herein, a novel synergistic combination therapy of drug-free triboelectric immunotherapy and CAR-T cell therapy against solid tumor was proposed. A triboelectric nanogenerator (TENG) that can generate pulsed direct-current by coupling triboelectrification effect and electrostatic breakdown effect was fabricated. The TENG can generate up to 30 pulse direct-current peaks with peak current output ≈35 μA in a single sliding to power the triboelectric immunotherapy. The pulsed direct-current stimulation induced immunogenic cell death of tumor cells (survival rate of 35.9 %), which promoted dendritic cells maturation, accelerated the process of antigen presentation to CAR-T cells and enhanced the systemic adaptive immune response. Furthermore, triboelectric immunotherapy promoted M1-like macrophage polarization, reduced regulatory T cells differentiation and reprogrammed the tumor immunosuppressive microenvironment, which ultimately enhanced the efficacy of CAR-T cells to eradicate nearly 60 % of NALM6 solid tumor mass. Notably, considering that triboelectric immunotherapy is a safe and effective drug-free antitumor strategy, the combined therapy did not increase the burden of double-medication on patients.

Transcriptome profiling of DPP stimulated DPSCs identifies the role of autophagy in odontogenic differentiation

Dentin phosphophoryn (DPP), synthesized and processed predominantly by the odontoblasts, serves both a structural and signaling role in dentin. In the ECM, DPP functions as an avid calcium and collagen binding protein and it also plays a crucial role as a scaffold for cell attachment and survival. The signaling function of DPP was demonstrated when undifferentiated mesenchymal cells stimulated with DPP, mediated calcium signaling through release of intracellular Ca2+. The objective of this study was to identify potentially novel signaling mechanisms that mediate odontoblast differentiation. Therefore, transcriptomes of DPSCs (dental pulp stem cells) with or without DPP stimulation were compared by bulk RNA-seq. Analysis of the unbiased RNA-seq data were subjected to functional enrichment analysis using Gene Ontology (GO) and KEGG pathways. Results identified several upregulated genes which were associated with autophagy, that were subsequently validated by RT-PCR. Western blotting analysis confirmed the up regulation of several autophagy markers such as ATG5, BECN1 and LC3A/B at specific time points. Autophagosome formation was also observed with DPP treatment. Additionally, autophagy supported a role for odontoblast differentiation of DPSCs. These findings suggest that DPP mediated autophagy might be a potential mechanism for the survival and terminal differentiation of DPSCs.

KRAS-Driven Tumorigenesis and KRAS-Driven Therapy in Pancreatic Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is associated with significant morbidity and mortality and is projected to be the second leading cause of cancer-related deaths by 2030. Mutations in KRAS are found in the vast majority of PDAC cases and plays an important role in the development of the disease. KRAS drives tumor cell proliferation and survival through activating the MAPK pathway to drive cell cycle progression and to lead to MYC-driven cellular programs. Moreover, activated KRAS promotes a protumorigenic microenvironment through forming a desmoplastic stroma and by impairing antitumor immunity. Secretion of granulocyte-macrophage colony-stimulating factor and recruitment of myeloid-derived suppressor cells and protumorigenic macrophages results in an immunosuppressive environment while secretion of secrete sonic hedgehog and TGFβ drive fibroblastic features characteristic of PDAC. Recent development of several small molecules to directly target KRAS marks an important milestone in precision medicine. Many molecules show promise in preclinical models of PDAC and in early phase clinical trials. In this review, we discuss the underlying cell intrinsic and extrinsic roles of KRAS in PDAC tumorigenesis, the pharmacologic development of KRAS inhibition, and therapeutic strategies to target KRAS in PDAC.

PHD-BAH Domain in ASH1L Could Recognize H3K4 Methylation and Regulate the Malignant Behavior of Cholangio Carcinoma.

Histone methyltransferase absent, small, or homeotic discs1-like (ASH1L) is composed of su(var)3-9, enhancer of zeste, trithorax (SET) domain, pleckstrin homology domain (PHD) domain, middle (MID) domain, and bromo adjacent homology (BAH) domain. The SET domain of ASH1L is known to mediate mediate H3K36 dimethylation (H3K36me2) modification. However, the specific functions of the PHD-BAH domain remain largely unexplored. This study aimed to explore the biological function of the PHD-BAH domain in ASH1L. We employed a range of techniques, including a prokaryotic fusion protein expression purification system, pull-down assay, Isothermal Titration Calorimetry (ITC), polymerase chain reaction (PCR), and sitedirected mutagenesis, Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR-Cas9) gene editing, cell culture experiment, western blot, cell proliferation assay, and cell apoptosis test. The PHD-BAH domain in ASH1L preferentially binds to the H3K4me2 peptide over H3K4 monomethylation (H3K4me1) and H3K4 trimethylation (H3K4me3) peptide. Notably, the W2603A mutation within the PHD-BAH domain could disrupt the interaction with H3K4me2 in vitro. Compared with wild-type Cholangiocarcinoma (CHOL) cells, deletion of the PHD-BAH domain in ASH1L led to increased CHOL cell apoptosis and reduced cell proliferation (P < 0.001). Additionally, the W2603A mutation affected the regulation of the proteasome 20S subunit beta (PSMB) family gene set. W2603A mutation was crucial for the interaction between the PHD-BAH domain and the H3K4me2 peptide. ASH1L regulated CHOL cell survival and proliferation through its PHD-BAH domain by modulating the expression of the PSMB family gene set.

Preparation and characterization of carvacrol/soybean protein isolate composite film with efficient antimicrobial and antioxidant activities and its application in grape preservation

There is an urgent need for a simple and effective method to enhance the freshness of fruits during transportation. In this study, we developed a composite antibacterial film (CAR film) using carvacrol and soy protein isolate (SPI). The mechanical properties, hydrophobicity, antibacterial activity, and antioxidant capacity of the film were characterized. The results demonstrated that, compared to the soy protein isolate film, the film with 2.5 % carvacrol content exhibited superior mechanical properties (tear strength decreased by approximately 37 %, elongation at break increased by about 108 %), hydrophobicity (water vapor permeability decreased by 38 %), antibacterial activity (inhibition zone diameters against E. coli and S. aureus were 14.21 mm and 11.83 mm, respectively), antioxidant capacity (increased by 5 to 6 times), and biocompatibility (cell survival rate exceeded 90 %). Grape preservation experiments further confirmed that the CAR film effectively prolongs shelf life. Therefore, CAR film is a promising packaging material for fruit preservation.

Dose-rate effects and tumor control probability in 177Lu-based targeted radionuclide therapy: a theoretical analysis

Objective.177Lu-based targeted radionuclide therapy (TRT) has become an important cancer treatment option in recent years, in particular in the treatment of advanced prostate cancer and metastasized neuroendocrine tumors. Although it is known from conventional radiotherapy that the temporal dynamics of the dose-rate can be of relevance for tumor cell survival, the analysis of TRT efficacy usually considers only the absorbed dose. Thus, the aim of this theoretical analysis is to shed light on the possible effects of the pattern of dose-rate in TRT on tumor control probability (TCP).Approach.For this purpose, TCP is studied numerically in a typical four-cycle treatment regime based on the mechanistic lethal-potentially lethal model and the Zaider-Minerbo model for TCP including repopulation of tumor cells.Main results.It is shown that the dose-rate pattern in TRT can have a substantial effect on TCP even though the absorbed dose in the tumor lesion is unchanged. These dose-rate effects are particularly evident when repair of potentially lethal lesions is slow.Significance.The results indicate that in some situations in the analysis of the efficacy of TRT it is necessary to consider the full dose-rate pattern instead of the absorbed dose alone. This can be highly relevant for optimization and further development of TRTs. In particular, it could be of relevancy in studying the efficacy of newly emerging treatment concepts that combine the use of TRT and drugs that inhibit DNA damage repair.

New horizon of the combined BCG vaccine with probiotic and liraglutide in augmenting beta cell survival via suppression of TXNIP/NLRP3 pyroptosis signaling in Streptozocin–Induced diabetes mellitestype-1 in rats

BackgroundAn ideal anti-diabetic type-1 pharmacotherapy should combine abrogation of beta cell pyroptosis with enhancement of beta cell mass. ObjectivesThe study investigated the potential synergism from combining the Bacillus Calmette-Guerin (BCG) vaccine with liraglutide (LIR) and probiotics in mitigating Streptozocin (STZ)-induced Type1diabetes mellitus in albino rats via suppression of TXNIP/NLRP3 signaling. Methods: Induction of diabetes was performed by two I.V. injections of 50 mg/kg of STZ in male Wistar rats. Forty-eight rats were randomly allocated into six groups: Normal control group; STZ -diabetic group; BCG group; BCG + LIR group; BCG + probiotic group; BCG + LIR + probiotic group. The rats were sacrificed after 8 weeks of treatment. ResultsThe STZ-diabetic group exhibited significant elevation of fasting blood sugar and HbA1c with remarkably decreased serum insulin along with a considerable increase in pancreatic proinflammatory cytokines (TNF-α, NLRP3, IL-1β, and NFκB) and apoptotic markers (ASK-1, IAPP, TXNIP, and Caspase-3) with prominently compromised oxidative scavenging capacity in addition to structural alteration in the pancreatic histoarchitecture with decreased insulin immunostaining. Conversely, diabetic-treated groups, especially the BCG + LIR + probiotic group, were superior in amelioration of STZ-induced pyroptosis of pancreatic islets evidenced by a significant decline in inflammatory cytokines and apoptotic markers with a remarkable upgrade in redox balance, Furthermore, the mitigation in the altered histopathological picture of the pancreas with enhanced insulin immunostaining has been was mirrored on the significant improvement of glucose homeostasis parameters. ConclusionsNoteworthy, BCG combination with liraglutide and probiotic might be a promising repurposed therapeutic modality in the management of type-1 diabetes mellites via targeting pancreatic TXNIP/NLRP3 signaling pathway.

In situ growth of ZIF-8 on Cellulose microspheres with high doxorubicin loading capacity and pH-sensitive for oral drug delivery

Metal-organic framework (MOF) nanoparticles are a class of porous nanomaterials with wide application prospects. Zeolitic imidazolate framework (ZIF) materials have high loading performance and pH-sensitive characteristics, which means they have great development prospects in the development of drug carrier systems. Herein, cellulose microspheres (CM) were used as a carrier for the nucleation and growth of ZIF-8 nanocrystals. CM@ZIF-8 was prepared in situ, which was more convenient, flexible, cost-effective, and highly safe. CM@ZIF-8, as a novel carrier, was used to monitor the release of the anticancer drug Doxorubicin (DOX) and prevent it from dissipating before reaching its goal. The designed DOX-loaded CM@ZIF-8 (CM@ZIF-8-DOX) system was characterized by FTIR, SEM, N2 sorption isotherm, XRD, and Cytotoxicity assay (cells survival rate 95.08 %). CM@ZIF-8-DOX exhibited controlled drug release behavior in simulated in-vitro tumor microenvironments (81.2 % drug release throughout 72h). CM@ZIF-8 simultaneously had a high loading capacity of DOX (Qe = 159.71 mg∙g-1), and the amount released under acidic conditions (pH 5.0) was greater (63.4 % after 15 hours) than under neutral conditions (pH 7.4) due to the detachment of the coordination between metal ions and ligands (37.6 % after 15 hours).

O-GlcNAcylation promotes malignancy and cisplatin resistance of lung cancer by stabilising NRF2.

The transcription factor NRF2 plays a significant role in regulating genes that protect cells from oxidative damage. O-GlcNAc modification, a type of posttranslational modification, is crucial for cellular response to stress. Although the involvement of both NRF2 and O-GlcNAc in maintaining cellular redox balance and promoting cancer malignancy has been demonstrated, the potential mechanisms remain elusive. The immunoblotting, luciferase reporter, ROS assay, co-immunoprecipitation, and immunofluorescence was used to detect the effects of global cellular O-GlcNAcylation on NRF2. Mass spectrometry was utilised to map the O-GlcNAcylation sites on NRF2, which was validated by site-specific mutagenesis and O-GlcNAc enzymatic labelling. Human lung cancer samples were employed to verify the association between O-GlcNAc and NRF2. Subsequently, the impact of NRF2 O-GlcNAcylation in lung cancer malignancy and cisplatin resistance were evaluated in vitro and in vivo. NRF2 is O-GlcNAcylated at Ser103 residue, which hinders its binding to KEAP1 and thus enhances its stability, nuclear localisation, and transcription activity. Oxidative stress and cisplatin can elevate the phosphorylation of OGT at Thr444 through the activation of AMPK kinase, leading to enhanced binding of OGT to NRF2 and subsequent elevation of NRF2 O-GlcNAcylation. Both in cellular and xenograft mouse models, O-GlcNAcylation of NRF2 at Ser103 promotes the malignancy of lung cancer. In human lung cancer tissue samples, there was a significant increase in global O-GlcNAcylation, and elevated levels of NRF2 and its O-GlcNAcylation compared to paired adjacent normal tissues. Chemotherapy promotes NRF2 O-GlcNAcylation, which in turn decreases cellular ROS levels and drives lung cancer cell survival. Our findings indicate that OGT O-GlcNAcylates NRF2 at Ser103, and this modification plays a role in cellular antioxidant, lung cancer malignancy, and cisplatin resistance.

Differences in cellular and molecular processes in exposure to PM2.5 and O3

Epidemiological and toxicological studies have shown that PM2.5 and O3 could pose significant risks to human health, such as an increased incidence of respiratory and cardiovascular diseases. Usually, the adverse health outcomes induced by PM2.5 and O3 exposure are similar. However, PM2.5 and O3 have distinct physical and chemical properties, with PM2.5 being a solid–liquid mixture and O3 being a strongly oxidizing gaseous pollutant. Therefore, we speculated that there are some differences in biological processes induced by PM2.5 and O3 exposure. In the present study, we investigated the differences induced by PM2.5 and O3 exposure from the perspective of cellular and molecular processes. Firstly, the pulmonary epithelial cells (BEAS-2B) were exposed to different concentrations of PM2.5 or O3 at different durations. Then, we chose experimental models with the concentrations and duration at which the cell survival rate was 50 % after exposure to PM2.5 and O3, which were 100 μg/mL for 24 h for PM2.5, and 200 ppb for 4 h for O3. Our findings indicate that PM2.5 infiltrates cells via endocytosis without causing significant damage to cell membranes, while O3 induces lipid peroxidation at the cell surface. Moreover, the detection of mitochondrial function showed that the content of ATP was significantly reduced after exposure to both PM2.5 and O3. However, we found a significant difference in mtDNA copy number. PM2.5 exposure increased the mtDNA copy number by up-regulating the expression of fission genes (Fis1, Mff, Dnm1). O3 exposure decreased it by up-regulating the expression of fusion gene (Mfn1, Mfn2) and down-regulating the expression of fission gene (Fis1, Dnm1). These results indicate that although both PM2.5 and O3 exposure induced almost exactly similar adverse health outcomes, significant differences do exist in cellular and molecular processes.

Melatonin enhances therapeutic outcomes of adipose tissue-derived mesenchymal stem cell therapy in rat osteoarthritis by reducing TNF-α and IL-1β-induced injuries.

Although adipose tissue-derived mesenchymal stem cell (ADSC) transplantation has been effectively used to treat osteoarthritis (OA), the low cell survival rate induced by the inflammatory and oxidative stress, severely affects the therapeutic efficiency of ADSC transplantation in OA. This study was designed to evaluate whether melatonin pretreatment could improve ADSC survival and its therapeutic efficacy in OA. The papain-induced OA rats were pretreated with melatonin via intra-articular injection and then intra-articular injected with indocyanine green (ICG)-labeled ADSCs (3 × 106/rat). Afterward, ADSC retention was evaluated by NIR-II fluorescence imaging. The tibia and synovial fluid were collected for histopathological examination and ELISA assay, respectively. To confirm the anti-inflammatory effect of melatonin, a TNF-α and IL-1β-induced cell model was used to evaluate the protective effects of melatonin on ADSC viability, cell apoptosis, and migration. Our results showed that melatonin pretreatment enhanced ADSC survival and improved the therapeutic effects of ADSC transplantation on cartilage repair, and anti-inflammation by reducing TNF-α, IL-6, IL-1β, and IL-12 in vivo. In particular, we also found that melatonin promoted ADSC viability and migration, and reduced cell apoptosis in vitro. In conclusion, this study supports that melatonin pretreatment can effectively improve ADSC survival and therapeutic efficiency in OA by reducing inflammatory injuries, which provides a novel strategy for enhancing ADSC therapy.

Two bis-maltol-polyamines: Synthesis, characterization and studies of their palladium(II) complexes exploring their potential anticancer activity

The interest in the antineoplastic and binding properties shown by the bis-maltol polyamine family, particularly Malten and Maltonis, prompted us to study the Pd2+ complexes of these latter from both a biological and metallo-receptor point of view. The Malten-Pd2+ complex can lodge hard species such as Sr2+ in its coordination-driven preorganized pocket, as confirmed by X-ray diffraction. UV–Vis and NMR data showed that Malten-Pd2+ forms even at acidic pH and exists in aqueous solution in a wide range of pH. The mononuclear complex is stable enough not to release Pd2+ in solution for a long period of time (at least one week), thus Malten-Pd2+, similarly to Maltonis-Pd2+, is suitable to be tested in biological analyses. Studies on the U937 cell line revealed that the effect on cell survival reduction induced by Malten is partially lost in Malten-Pd2+, while no differences where monitored between the effects of Maltonis-Pd2+ and Maltonis, suggesting that the availability of free maltol moieties, that is retained in Maltonis-Pd2+, but not in Malten-Pd2+, is crucial to guarantee the biological activity of these compounds.