Down-regulation Of Bcl-2 Expression Research Articles

In vitro and in vivo investigation of the inhibitory effects of Sinoporphyrin sodium-mediated Sonodynamic therapy on human oral squamous cell carcinoma

ObjectiveSonodynamic therapy (SDT) is an innovative, non-invasive approach to cancer treatment, by using low-intensity ultrasound to trigger the activation of sonosensitizers localized within cancerous cells. This current study aimed to explore the therapeutic efficacy of a new sonosensitizer, Sinoporphyrin Sodium (DVDMS), under ultrasound irradiation, against oral squamous cell carcinoma (OSCC)-derived SCC-154 cells, both in vitro and in vivo. MethodsFluorescence spectra, cytotoxicity assessments, uptake mechanisms, and subcellular distributions of DVDMS within the SCC-154 cell line were detected. Additionally, the study comprehensively assessed the antitumor effect, oxidative stress responses, apoptosis, apoptosis-related proteins, autophagic processes, and ultrastructural changes in SCC-154 cells, both in vitro and in vivo, subsequent to treatment with low-intensity ultrasound (at 1.0 MHz, 1 W/cm2 in vitro and 3 W/cm2 in vivo) in conjunction with DVDMS also being examined. ResultsThe findings indicate that SCC-154 cells exhibit heightened sensitivity to DVDMS compared to SAS and HSC-3 cell lines. Within SCC-154 cells, DVDMS primarily localizes within the mitochondria and lysosomes. DVDMS-based SDT significantly increased the intracellular levels of reactive oxygen species (ROS), induced morphological changes such as mitochondrial swelling and formation of autolysosomes, and exhibited a notable dose-dependent reduction in cell viability in vitro. Also, DVDMS-SDT demonstrated significant inhibition of xenograft growth without discernible adverse effects. Mechanistically, DVDMS-SDT upregulated Bax expression while downregulating Bcl-2 expression, which led to the Bax/Bcl-2 ratio and induced autophagy. ConclusionDVDMS-SDT triggers mitochondrial-dependent apoptosis in SCC-154 cells, unlike 5-ALA and protoporphyrin IX (PpIX). Also, the combination of DVDMS with ultrasound stimulation induces autophagy, with the onset of autophagic processes preceding apoptosis.

The effects of Fe3O4NPs@SiO2 and Fe3O4NPs@pectin nanoparticles on the MCF-7 breast cancer cell line and the expression of BAX, TPX1 and BCL2 genes

Breast cancer is a cause of death in women, making it a significant issue in women's health. The aim of this study was to evaluate the effects of nanoparticles (NPs) of Fe3O4NPs@pectin and Fe3O4NPs@SiO2 on MCF-7 cells. Fe3O4NPs@pectin and Fe3O4NPs@SiO2 NPs were prepared using the chemical coprecipitation technique. The characteristics of the NPs were determined using physical methods. The cytotoxic effects of the NPs were assessed by the MTT assay. The expression levels of BAX, BCL2, and TPX1 genes were determined using real-time PCR. The results indicated a density ratio of 0.11, a saturation magnetism value of 68.5 emu/g, and a spherical with sizes of 98 nm for the NPs. The MTT assay showed that 500 μg/mL of NPs had 75 % toxicity on MCF-7 cells after five days. The increased expression of BAX with 250 μg/mL of Fe3O4@pectin showed a significant relationship (p-value = 0.0030). Down-regulated expression of BCL2 showed a significant relationship between the three groups treated with 250 μg/mL and 500 μg/mL of Fe3O4@SiO2 and 250 μg/mL of Fe3O4@pectin (p-values of 0.0014, 0.0009 and 0.0030, respectively). Additionally, decreased TPX indicated a significant relationship between treatment at 125, 250 and 500 μg/mL of Fe3O4@SiO2 (p-values of 0.0388, 0.0063 and 0.0496, respectively).

Thiazolidinedione-Conjugated Lupeol Derivatives as Potent Anticancer Agents Through a Mitochondria-Mediated Apoptotic Pathway.

To improve the potential of lupeol against cancer cells, a privileged structure, thiazolidinedione, was introduced into its C-3 hydroxy group with ester, piperazine-carbamate, or ethylenediamine as a linker, and three series of thiazolidinedione-conjugated compounds (6a-i, 9a-i, and 12a-i) were prepared. The target compounds were evaluated for their cytotoxic activities against human lung cancer A549, human breast cancer MCF-7, human hepatocarcinoma HepG2, and human hepatic LO2 cell lines, and the results revealed that most of the compounds displayed improved potency over lupeol. Compound 12i exhibited significant activity against the HepG2 cell line, with an IC50 value of 4.40 μM, which is 9.9-fold more potent than lupeol (IC50 = 43.62 μM). Mechanistic studies suggested that 12i could induce HepG2 cell apoptosis, as evidenced by AO/EB staining and annexin V-FITC/propidium iodide dual staining assays. Western blot analysis suggested that compound 12i can upregulate Bax expression, downregulate Bcl-2 expression, and activate the mitochondria-mediated apoptotic pathway. Collectively, compound 12i is worthy of further investigation to support the discovery of effective agents against cancer.

Pdk3's role in RANKL-induced osteoclast differentiation: insights from a bone marrow macrophage model.

Osteoporosis (OP) is a chronic disease characterized by decreased bone mass, loss of skeletal structural integrity and increased susceptibility to fracture. Available studies have shown that the pyruvate dehydrogenase kinase (PDK) family is associated with osteoclastogenesis and bone loss, but the specific role of Pdk3 in bone pathology has not been systematically investigated. A cell OP model was established in receptor activator for nuclear factor-κB Ligand (RANKL)-induced bone marrow macrophages (BMMs). Hereafter, the expression levels of Pdk3 and osteoclastogenesis feature genes including nuclear factor of activated T cells 1 (Nfatc1), Cathepsin K (Ctsk), osteoclast associated Ig-like receptor (Oscar) in BMMs-derived osteoclasts were examined based on real-time quantitative PCR and western blotting methods. Further, the phosphorylation of ERK, P65 and JAK/STAT and their correlation was Pdk3 was gauged. In particular, changes in the activity of these signaling pathways were observed by silencing experiments of the Pdk3 gene (using small interfering RNA). Finally, the effects of Pdk3 gene silencing on signaling pathway activity, osteoclastogenesis, and related inflammatory and apoptotic indicators were observed by transfection with PDK3-specific siRNA. Following RANKL exposure, the levels of Pdk3 and osteoclastogenesis feature genes were all elevated, and a positive correlation between Pdk3 and osteoclastogenesis feature genes was seen. Meanwhile, ERK, P65 and JAK/STAT phosphorylation was increased by RANKL, and Pdk3 was confirmed to be positively correlated with the phosphorylation of ERK, P65 and JAK/STAT. Additionally, in RANKL-exposed osteoclasts, Pdk3 knockdown diminished the phosphorylation of ERK, P65 and JAK/STAT, reduced the expressions of osteoclastogenesis feature genes. Importantly, knockdown of Pdk3 also reduced the expression of inflammatory cytokines and resulted in elevated levels of Bax and Casp3 expression, as well as downregulation of Bcl2 expression. This study reveals for the first time the role of Pdk3 in RANKL-induced osteoclastogenesis and OP. These findings provide a foundation for future studies on the role of Pdk3 in other bone diseases and provide new ideas for the development of OP therapeutics targeting Pdk3.

Mechanistic insights into Retama raetam's anti-proliferative and pro-apoptotic effects in A549 lung cancer cells: targeting PI3K/Akt pathway and ROS production.

Lung cancer, particularly non-small cell lung cancer (NSCLC), is a leading cause of cancer-related deaths worldwide. This study investigates the molecular mechanisms behind the anti-cancer effects of the tropical desert plant Retama raetam (R. raetam) on the A549 NSCLC cell line. The research examined R. raetam's anti-proliferative effects, cytotoxicity, apoptosis, reactive oxygen species (ROS) generation, mitochondrial membrane potential, and cell morphology in NSCLC A549 and L-132 cells. In addition, the influence of R. raetam on DNA fragmentation, apoptotic signaling, and PI3K/Akt pathways for its anti-cancer mechanism was examined. Our results indicated that R. raetam's effects were dose- and time-dependent to exhibit anti-proliferative effects on A549 cells. R. raetam treatment promoted apoptotic cell death cycle arrest, increased apoptotic cells, depolarized the mitochondrial membrane, and induced morphological alterations in cells and nuclei. It also inhibited A549 cell migration (P < 0.05), colonization, and invasiveness. Moreover, the study demonstrated that R. raetam treatment resulted in the upregulation of Bax expression, downregulation of Bcl-2 expression, and apoptotic fragmented DNA in A549 cells. The top five bioactive compounds derived from R. raetam exhibited molecular interactions that inhibit PIK3CA and AKT1. This inhibition leads to an increased frequency of apoptosis and subsequent death of cancer cells. Additionally, R. raetam extract induced an increase in ROS formation and cytochrome c levels, indicating that its toxic effects on A549 cells involve both ROS-dependent cytotoxicity through the disruption of mitochondrial transmembrane potential ΔΨm and ROS-independent cell cycle arrest through downregulation BCL-2, PARP, E-Cadherin, PI3K, and Akt expressions pathways.

The use of matrine to inhibit osteosarcoma cell proliferation via the regulation of the MAPK/ERK signaling pathway.

Matrine is an alkaloid extracted from Sophorus beans of the legume family, and it has significant effects and a variety of pharmacological activities. Osteosarcoma(OS) is a common malignant bone tumor that is characterized by high incidence and rapid progression. There have been some preliminary studies on the therapeutic effect of matrine on OS, but the specific mechanism remains unclear. The aim of this study was to investigate the antitumor effect of matrine on HOS cells and the underlying molecular mechanism. The effects of matrine on the proliferation, apoptosis and cell cycle progression of HOS cells were determined by CCK-8 assay, TUNEL assay and flow cytometry in vitro. Wound healing and Transwell invasion assays were used to observe the effect of matrine on the migration and invasion of HOS cells. The mechanism underlying the antitumor effect of matrine on HOS cells was investigated by Western blotting. Matrine significantly inhibited HOS cell proliferation, promoted HOS cell apoptosis, and arrested HOS cells in the G1 phase of the cell cycle. Both wound healing and Transwell invasion assays showed that matrine inhibited HOS cell migration and invasion. Western blotting results showed that matrine inhibited the activation of the MAPK/ERK signaling pathway. We found that matrine also downregulated Bcl-2 expression, which may be related to protein synthesis inhibition. Matrine can inhibit the proliferation of HOS cells, arrest HOS cells in the G1 phase, and promote HOS cell apoptosis through the MAPK/ERK signaling pathway.

The Anticancer Effects and Therapeutic Potential of Kaempferol in Triple-Negative Breast Cancer.

Breast cancer is the second-leading cause of cancer death among women in the United States. Triple-negative breast cancer (TNBC), a subtype of breast cancer, is an aggressive phenotype that lacks estrogen (ER), progesterone (PR), and human epidermal growth (HER-2) receptors, which is challenging to treat with standardized hormonal therapy. Kaempferol is a natural flavonoid with antioxidant, anti-inflammatory, neuroprotective, and anticancer effects. Besides anti-tumorigenic, antiproliferative, and apoptotic effects, kaempferol protects non-cancerous cells. Kaempferol showed anti-breast cancer effects by inducing DNA damage and increasing caspase 3, caspase 9, and pAMT expression, modifying ROS production by Nrf2 modulation, inducing apoptosis by increasing cleaved PARP and Bax and downregulating Bcl-2 expression, inducing cell cycle arrest at the G2/M phase; inhibiting immune evasion by modulating the JAK-STAT3 pathway; and inhibiting the angiogenic and metastatic potential of tumors by downregulating MMP-3 and MMP-9 levels. Kaempferol holds promise for boosting the efficacy of anticancer agents, complementing their effects, or reversing developed chemoresistance. Exploring novel TNBC molecular targets with kaempferol could elucidate its mechanisms and identify strategies to overcome limitations for clinical application. This review summarizes the latest research on kaempferol's potential as an anti-TNBC agent, highlighting promising but underexplored molecular pathways and delivery challenges that warrant further investigation to achieve successful clinical translation.

Brucine Inhibits Proliferation of Pancreatic Ductal Adenocarcinoma through PI3K/AKT Pathway-induced Mitochondrial Apoptosis.

The purpose of this research was to settle the role of brucine in pancreatic ductal adenocarcinoma (PDAC) and the mechanisms involved. The findings of this study suggest that brucine exerts inhibitory effects on cell growth, clonogenicity, and invasive potential of Panc02 and Mia Paca-2 cells. These effects may be linked to an increase in apoptotic-prone cell population. Gene sequencing data suggests that these effects are mediated through the induction of apoptosis. Experimental evidence further supports the notion that brucine reduces mitochondrial membrane potential and upregulates Bax expression while downregulating Bcl-2 expression. These effects are believed to be a result of brucine-mediated suppression of PI3K/Akt activity, which serves as a regulatory factor of mTOR, Bax, and Bcl-2. Suppression of PI3K activity enhances the tumor-suppressing effects of brucine. Overall, these findings suggest that brucine has therapeutic potential as a remedy option for PDAC.

Evaluation of nootropic and neuroprotective properties of Siddha drug Poorana Chandrothaya Chenthuram (PCC) in scopolamine-induced amnesia in mice

BackgroundPoorana Chandrothaya Chenthuram (PCC) is a gold-based Siddha drug, for treating diverse diseases. Rooted in centuries-old traditional use, Siddha texts categorize PCC as a kayakarpa entity that emphasizes holistic well-being. AimThis study assesses the nootropic potential of Poorana Chandrothaya Chenthuram (PCC) in scopolamine-induced amnesic mice, and elucidate the underlying mechanisms, specifically focusing on the modulation of cholinergic system and anti-oxidant effects. MethodsPreliminary finger printing with FTIR was done. Scopolamine-induced memory impaired mice were administered PCC (15 or 30 mg/kg) for 28 days. Memory assessments were done using elevated plus-maze and passive avoidance tasks. RT-PCR gauged mRNA expression levels of AChE, MChR, BAX, and BCL2 in brain samples were also done. ResultsFTIR confirmed the presence of functional groups in PCC. In the EPM test, pre-treatment with PCC (15 and 30 mg/kg) significantly reduced the time taken (p < 0.05 and 0.01, respectively), comparable to the reference control, piracetam. The PAT revealed a significant increase (p < 0.01) in the time taken to step down from the escape platform which demonstrates that significant efficacy in reversing scopolamine-induced amnesia in mice. Gene expression studies reported a significant up-regulation (p < 0.01) in AChE, MChR, and BAX mRNA expressions, along with a down-regulation in BCL2 expression compared to normal mice. ConclusionThis study demonstrates the anti-amnesic activity of the Siddha drug PCC, elucidating its mechanism involving a reduction in AChE levels and an augmentation of antioxidant levels in which implicates modulation of cholinergic and apoptotic pathways. In-depth exploration of PCC's neuroprotective properties may unveil novel avenues for combating memory and cognitive decline.

MiR-6839-5p inhibits cell proliferation, migration and invasion; a possible correlation with the suppressing VEGFA expression in human chondrosarcoma cells

MicroRNAs play an important role in the proliferation, invasion, and metastasis of malignancy. In previous studies (detailed in our previous paper), the expression of miR-6839-5p was significantly increased in SW1353 cells after 125I seed 6 Gy irradiation, which indicated miR-6839-5p may play a tumor suppression function in chondrosarcoma cells. This study aimed to identify the effects of miR-6839-5p on the human chondrosarcoma cells, and investigate the potential target genes of miR-6839-5p. Firstly, chondrosarcoma cells (SW1353 and CAL78) were transfected with hsa-miR-6839-5p specific mimic. Secondly, Cell viability assay (MTT assay), Colony formation assay, Wound healing assay, Transwell assay, TUNEL staining and Western blotting experiments were performed, and the results proved miR-6839-5p can inhibit chondrosarcoma cells proliferation, migration and invasion. Meanwhile, miR-6839-5p significantly down-regulated apoptosis facilitator Bcl-2 expression, and promoted apoptosis of chondrosarcoma cells. It is reasonable to speculate miR-6839-5p might downregulate Bcl-2 expression to induce apoptosis in SW1353 human chondrosarcoma cells. Lastly, RNA extraction and bioinformatic analysis was performed on SW1353 cells transfected with hsa-miR-6839-5p specific mimic to investigate the potential target genes of miR-6839-5p. A total of 253 differentially expressed mRNA genes (105 up-regulated genes and 148 down-regulated genes) were found, and 23 differentially expressed downregulated genes were identified. Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to validate the results, which demonstrated the expression of BST2, VEGFA, FPR3 and PPARA was significantly downregulated by miR-6839-5p mimic. Furthermore, miR-6839-5p inhibitor can restore or partially restore the expression value of the above four genes. The analysis results of miRNA target gene prediction database indicated VEGFA was the most likely direct target gene of miR-6839-5p.

Ptehosides A-I: Nine undescribed iridoids with in vitro cytotoxicity from the whole plant of Pterocephalus hookeri (C.B. Clarke) Höeck

Nine previously undescribed iridoids, ptehosides A-I (1–9), together with 12 known ones (10–21), were isolated from Pterocephalus hookeri (C.B. Clarke) Höeck. Their structures were elucidated using various spectroscopic methods including HR-ESI-MS, NMR, UV, IR and CD, etc. The cytotoxic activities of all isolates were evaluated using MTT method in three human cancer cell lines (Caco2, Huh-7, and SW982). As result, compound 9 exhibited substantial inhibitory activity on Caco2, Huh-7, and SW982 cells with IC50 values of 1.17 ± 0.05, 1.15 ± 0.05 and 1.14 ± 0.04 μM, respectively. A preliminary mechanism study showed that 9 arrested the cell cycle of SW982 cells in the G0/G1 phase and induced apoptosis by upregulating Bax expression and downregulating Bcl-2 expression.

Assessment of the in Vitro Effects of Folate Core-Shell Conjugated Iron Oxide Nanoparticles as a Potential Agent for Acute Leukemia Treatment.

There is a growing need to comprehend the potential outcomes of nanoparticles (NPs) on human well-being, including their potential for detecting and treating leukemia. This study examined the role of iron folate core-shell and iron oxide nanoparticles in inducing apoptosis and altering the expression of the B-cell lymphoma 2 (Bcl-2), Bcl-2 associated X-protein (Bax), and Caspase-3 genes in leukemia cells. The obtained iron oxide and iron folate core-shell nanoparticles were analyzed using a variety of analytical techniques, including ultraviolet-visible (UV-Vis) absorption spectroscopy, Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), dynamic light scattering (DLS), zeta potential, and transmission electron microscopy (TEM). Additionally, FTIR and UV-Vis were used to characterize doxorubicin. The MTT test was utilized to investigate the cytotoxicity of iron oxide and iron folate core-shell nanoparticles. The expression of the apoptotic signaling proteins Bcl-2, Bax, and Caspase-3 was evaluated using the real-time reverse transcription polymerase chain reaction (RT-qPCR) method. Additionally, flow cytometry was performed to gauge the degrees of necrosis and apoptosis. UV-Visible spectroscopy analysis showed that the generated iron oxide and iron folate core-shell NPs had a distinctive absorption curve in the 250-300 nm wavelength range. The XRD peaks were also discovered to index the spherical form with a size of less than 50 nm, which validated the crystal structure. The FTIR analysis determined the bonds and functional groups at wavenumbers between 400 and 4000 cm-1. A viable leukemia treatment approach is a nanocomposite consisting of iron and an iron folate core-shell necessary for inhibiting and activating cancer cell death. The nearly resistant apoptosis in the CCRF-CEM cells may have resulted from upregulating Bax and Casepase-3 while downregulating Bcl-2 expression. Our study documents the successful synthetization and characterization of iron oxide, which has excellent anticancer activities. A metal oxide conjugation with the nanoparticles' core-shell enhanced the effect against acute leukemia.

The Effect of Quercetin in the Yishen Tongluo Jiedu Recipe on the Development of Prostate Cancer through the Akt1-related CXCL12/ CXCR4 Pathway.

It remains a challenge to effectively treat prostate cancer (PCa) that affects global men's health. It is essential to find a natural alternative drug and explore its antitumor mechanism due to the serious toxic side effects of chemotherapy. The targets and signaling pathways were analyzed by network pharmacology and verified by molecular docking and LC-MS. The proliferation, apoptosis, invasion, and migration of DU145 cells were detected by the CCK-8 method, flow cytometry, and Transwell, respectively. The Bcl-2, caspase-3, CXCL12, and CXCR4 expressions and Akt1 phosphorylation were determined by Western blot. Akt1 overexpression was applied to identify the involvement of the Akt1- related CXCL12/CXCR4 pathway in regulating PCa. Nude mouse tumorigenesis was performed to analyze the effect of quercetin on PCa in vivo. Network pharmacology analysis displayed that quercetin was the main active component of the Yishen Tongluo Jiedu recipe and Akt1 was the therapy target of PCa. LC-MS analysis showed that quercetin existed in the Yishen Tongluo Jiedu recipe, and molecular docking proved that quercetin bound to Akt1. Quercetin inhibited the proliferation of DU145 cells by upregulating caspase-3 and downregulating Bcl-2 expression, promoting apoptosis and reducing invasion and migration abilities. In vivo, quercetin downregulated CXCL12 and CXCR4 expressions and inhibited PCa development by the Akt1-related CXCL12/CXCR4 pathway. As the active component of the Yishen Tongluo Jiedu recipe, quercetin inhibited PCa development through the Akt1-related CXCL12/CXCR4 pathway. This study provided a new idea for PCa treatment and a theoretical basis for further research.

Modulating oxidative stress, apoptosis, and mitochondrial dysfunctions on cardiotoxicity induced by aluminum phosphide pesticide using resveratrol

The agricultural fumigant pesticide aluminum phosphide (AlP) is cardiotoxic. Water causes AlP to emit phosphine gas, a cardiac toxin that affects heart function and causes cardiogenic shock. AlP poisoning’s high fatality rate is due to cardiotoxicity. This study examines how resveratrol reduces oxidative stress, mitochondrial activity, and apoptosis in human cardiac myocyte (HCM) cells. After determining the optimal doses of resveratrol using the MTT test, HCM cells were subjected to a 24-h treatment of resveratrol following exposure to AlP (2.36 μM). The levels of reactive oxygen species (ROS), superoxide dismutase (SOD) activity, mitochondrial swelling, mitochondrial cytochrome c release, and mitochondrial membrane potential (MMP) in HCM cells were investigated. Also, the expression of Bax and Bcl-2, caspace-3 activity, and apoptosis were assessed. The present investigation revealed that AlP substantially increased the level of ROS and decreased SOD activation, which were significantly modulated by resveratrol in a dose-dependent manner. Moreover, AlP induced an elevation of mitochondrial swelling, cytochrome c release, and MMP collapse. Co-administration of resveratrol significantly reduced above mitochondrial markers. AlP also significantly upregulated BAX and downregulated Bcl-2 expression, elevated caspace-3 activity, and apoptosis. Resveratrol co-administration was able to meaningfully modulate the mentioned parameters and finally reduce apoptosis. In conclusion, resveratrol, via its pleotropic properties, significantly demonstrated cytoprotective effects on HCM cytotoxicity induced by AlP.

Anti-proliferative and apoptotic effect of cannabinoids on human pancreatic ductal adenocarcinoma xenograft in BALB/c nude mice model

Human pancreatic ductal adenocarcinoma (PDAC) is a highly malignant and lethal tumor of the exocrine pancreas. Cannabinoids extracted from the hemp plant Cannabis sativa have been suggested as a potential therapeutic agent in several human tumors. However, the anti–tumor effect of cannabinoids on human PDAC is not entirely clarified. In this study, the anti–proliferative and apoptotic effect of cannabinoid solution (THC:CBD at 1:6) at a dose of 1, 5, and 10 mg/kg body weight compared to the negative control (sesame oil) and positive control (5-fluorouracil) was investigated in human PDAC xenograft nude mice model. The findings showed that cannabinoids significantly decreased the mitotic cells and mitotic/apoptotic ratio, meanwhile dramatically increased the apoptotic cells. Parallelly, cannabinoids significantly downregulated Ki-67 and PCNA expression levels. Interestingly, cannabinoids upregulated BAX, BAX/BCL-2 ratio, and Caspase-3, meanwhile, downregulated BCL-2 expression level and could not change Caspase-8 expression level. These findings suggest that cannabinoid solution (THC:CBD at 1:6) could inhibit proliferation and induce apoptosis in human PDAC xenograft models. Cannabinoids, including THC:CBD, should be further studied for use as the potent PDCA therapeutic agent in humans.

Retraction Note: Two Mixed-Ligand Co(II)-Based Coordination Polymers: Treatment Activity on Pediatric Asthma Via Inducing Eosinophil Apoptosis through Down-Regulating Bcl-2 Expression

Retraction Note: Two Mixed-Ligand Co(II)-Based Coordination Polymers: Treatment Activity on Pediatric Asthma Via Inducing Eosinophil Apoptosis through Down-Regulating Bcl-2 Expression

A slow-releasing donor of hydrogen sulfide inhibits neuronal cell death via anti-PANoptosis in rats with spinal cord ischemia‒reperfusion injury

BackgroundSpinal cord ischemia‒reperfusion injury (SCIRI) can lead to paraplegia, which leads to permanent motor function loss. It is a disastrous complication of surgery and causes tremendous socioeconomic burden. However, effective treatments for SCIRI are still lacking. PANoptosis consists of three kinds of programmed cell death, pyroptosis, apoptosis, and necroptosis, and may contribute to ischemia‒reperfusion-induced neuron death. Previous studies have demonstrated that hydrogen sulfide (H2S) exerts a neuroprotective effect in many neurodegenerative diseases. However, whether H2S is anti-PANoptosis and neuroprotective in the progression of acute SCIRI remains unclear. Thus, in this study we aimed to explore the role of H2S in SCIRI and its underlying mechanisms.MethodsMeasurements of lower limb function, neuronal activity, microglia/macrophage function histopathological examinations, and biochemical levels were performed to examine the efficacy of H2S and to further demonstrate the mechanism and treatment of SCIRI.ResultsThe results showed that GYY4137 (a slow-releasing H2S donor) treatment attenuated the loss of Nissl bodies after SCIRI and improved the BBB score. Additionally, the number of TUNEL-positive and cleaved caspase-3-positive cells was decreased, and the upregulation of expression of cleaved caspase-8, cleaved caspase-3, Bax, and Bad and downregulation of Bcl-2 expression were reversed after GYY4137 administration. Meanwhile, both the expression and activation of p-MLKL, p-RIP1, and p-RIP3, along with the number of PI-positive and RIP3-positive neurons, were decreased in GYY4137-treated rats. Furthermore, GYY4137 administration reduced the expression of NLRP3, cleaved caspase-1 and cleaved GSDMD, decreased the colocalization NeuN/NLRP3 and Iba1/interleukin-1β-expressing cells, and inhibited proinflammatory factors and microglia/macrophage polarization.ConclusionsH2S ameliorated spinal cord neuron loss, prevented motor dysfunction after SCIRI, and exerted a neuroprotective effect via the inhibition of PANoptosis and overactivated microglia-mediated neuroinflammation in SCIRI.

Resveratrol alleviates imidacloprid-induced mitochondrial apoptosis, necroptosis, and immune dysfunction in chicken lymphocyte lines by inhibiting the ROS/MAPK signaling pathway.

Imidacloprid (IMI) is a neonicotinoid insecticide with the highest global market share, and IMI exposure in the environment can negatively affect many nontarget organisms (a general term for organisms affected by drugs other than target organisms). Resveratrol (RSV), a non-flavonoid polyphenolic organic compound derived from peanuts, grapes, and other plants, has anti-inflammatory and antioxidant effects. It is currently unclear how RSV protects against cell damage caused by IMI. Therefore, we established an experimental model of chicken lymphocyte lines exposed to 110 μg/mL IMI and/or 0.5 μM RSV for 24 h. According to the experimental results, IMI markedly raised intracellular reactive oxygen species levels and diminished the activity of the cellular antioxidant enzymes (CAT, SOD, and GPx), leading to MDA accumulation and decreased T-AOC. JNK, ERK, and P38, the essential components of the mitogen-activated protein kinase (MAPK) signaling pathway, were also expressed more when IMI was present. Additionally, IMI resulted in upregulation of mitochondrial apoptosis (Caspase 3, Caspase 9, Bax, and Cyt-c) and necroptosis (Caspase 8, RIPK1, RIPK3, and MLKL) related factors expression, downregulation of Bcl-2 expression, induction of upregulation of cytokine IL-6 and TNF-α expression, and downregulation of IFN-γ expression. The combined treatment of RSV and IMI significantly reduced cellular oxidative stress levels, inhibited the MAPK signaling pathway, and alleviated IMI-induced mitochondrial apoptosis, necroptosis, and immune dysfunction. To summarize, RSV antagonized IMI-induced mitochondrial apoptosis, necroptosis, and immune dysfunction in chicken lymphocyte lines by inhibiting the ROS/MAPK signaling pathway.

Apoptosis and DNA damage mediated by ROS involved in male reproductive toxicity in mice induced by Nickel

Nickel (Ni) is the most important environmental pollution in the world. Ni has been confirmed to have multi-organ toxicology and carcinogenicity. Recently, Ni also can impair the male reproductive system, however, its precious mechanism still has not been clarified. The current work found that nickel chloride (NiCl2) induced histopathological lesions in testis. And, the Johnsen's score, seminiferous tubule diameter, and spermatogenic epithelium thickness were decreased in NiCl2-treated mice. The number of spermatogonium, primary spermatocyte, and round spermatid also were significantly reduced after Ni treatment. Next the potential molecular mechanism was measured. NiCl2 treatment elevated ROS production in the testis. Additionally, NiCl2 was found to induce apoptosis with features including up-regulation of Bax, cleaved-caspase-3, cleaved-caspase-8, caspase-9, and caspase-12, while down-regulation of Bcl-2 expression. In the meantime, the marker protein of DNA damage γ-H2AX was significantly increased in NiCl2-primed mice testis. To clarify effects of reactive oxygen species (ROS) in apoptosis and DNA damage induced by NiCl2, NiCl2 was used to co-treat antioxidant NAC (N-Acetyl-L-cysteine). NAC weakened ROS production induced by NiCl2, and played an inhibition role in apoptosis and DNA damage. Moreover, co-treatment using NiCl2 and NAC group also eliminated spermatogenesis disorders. In summary, research results reveal the relations of spermatogenesis disorder induced by NiCl2 with apoptosis and DNA damage mediated by ROS and apoptosis in the testis.

In vitro and in vivo killing effects of methionine enkephalin on osteosarcoma

ObjectiveThis study aimed to investigate the underlying regulatory effects of methionine enkephalin (MENK) on osteosarcoma. MethodsThe Cell Counting Kit-8 assay, clone formation, wound healing, transwell assay, and flow cytometry were performed to measure the effects of MENK on the proliferation, migration, invasion, and apoptosis of MG-63 and Saos-2 cells. Opiate growth factor receptor expression (OGFr) in cells was stably knocked down using siRNA. A tumor model was established by inoculating MG-63 cells into mice. Flow cytometry was performed to identify alterations in mice bone marrow, spleen, and tumor tissue immune cells. The phenotype of tumor-associated macrophages was determined using immunohistochemistry. After OGFr knockdown or/and treatment with MENK, Bax, Bcl-2, caspase 3, caspase 9, and PARP expression levels were characterized using qRT-PCR, western blot, and WES, respectively. ResultsMENK could significantly inhibit the proliferation, invasion, and migration of MG-63 and Saos-2, arrest the cell cycle in the G0/G1 phase, upregulate Bax, caspase 3, caspase 9, and PARP expression, and downregulate Bcl-2 expression. Tumor size and weight were lower in the MENK group than those in the control group. MENK-treated mice exhibited a reduced ratio of CD11b + Gr-1 + myeloid-derived suppressor cells. MENK increased the ratio of M1-type macrophages and decreased the proportion of M2-type macrophages in tumor tissue. Furthermore, the level of TNF-α significantly increased while that of IL-10 decreased in MENK-treated mice. The effect of MENK could be partly reversed by OGFr knockdown. ConclusionMENK reduces the abundance of myeloid-derived suppressor cells, induces M1 polarization of macrophages, and exhibits an inhibitory effect on osteosarcoma.