Search

Pueraria Lobata Radix (P. Lobata Radix) is an edible traditional Chinese medicine that contains various active compounds. Proteins from P. LobataRadix have become the subject of increased interest in recent years. In evaluating the whitening effect on the skin, the present study found that the P. Lobata Radix water‑soluble total protein extract (PLP) had the strongest inhibitory effect on tyrosinase activity. In the present study, the anti‑melanogenic effect of PLP and the inhibitory effect on B16 melanoma cells were investigated. PLP significantly reduced the tyrosinase activity and melanin content in B16 melanoma cells. Mechanistically, PLP inhibited melanogenesis by decreasing the expression of tyrosinase, tyrosinase‑related protein (TRP)‑1 and TRP‑2 through down‑ regulation of the microphthalmia‑associated transcription factor (MITF) gene, which was mediated by inhibition of p38 mitogen‑activated protein kinase signaling. In addition, PLP inhibited cell viability and triggered apoptosis of B16 cells in a dose‑dependent manner. Exposure to PLP reduced the mito‑ chondrial membrane potential (MMP) and decreased ATP generation, leading to mitochondria‑related apoptosis of B16 melanoma cells. The expression levels of succinate dehydro‑ genase (SDH) and its two related subunits (SDHA and SDHB) were downregulated significantly by PLP, which may be asso‑ ciated with the regulation of mitochondrial energy metabolism by PLP. These results may explain why MMP collapse and reduced ATP generation were observed in B16 melanoma cells treated with PLP. Finally, the present study demonstrated that the inhibition of melanin synthesis by PLP was correlated with the regulation of antioxidant enzymes to reduce reac‑ tive oxygen species levels. These results suggested that PLP inhibits melanogenesis by downregulating the expression of MITF‑related melanogenic enzymes and triggering apoptosis through mitochondria‑related pathways. [ABSTRACT FROM AUTHOR]

Mitochondrial autophagy serves a key role in clearing damaged mitochondria. P‑hydroxybenzyl alcohol (pHBA) can improve neuronal injury induced by cerebral ischemia‑reperfusion (I/R). However, the mechanism of pHBA improving I/R damage through the mitochondrial pathway remains unclear. A rat model of middle cerebral artery occlu‑ sion and reperfusion (MCAO/R) was used in the present study. The rats were treated with sirtuin 1 (SIRT1) inhibitor EX527 and pHBA for 7 days, followed by reperfusion. At 24 h after reperfusion, the infarct size was calculated and the severity of nerve damage was evaluated. Hematoxylin and eosin and Nissl staining revealed cellular changes in the ischemic penumbra. Changes in mitochondrial structure were observed using electron microscopy. Mitochondrial function was evalu‑ ated by detecting mitochondrial membrane potential (MMP), mitochondrial permeability transition pore (mPTP) and ATP levels using commercially available kits. In addition, the ischemic penumbra tissues were used for immunofluorescence staining for p62 and LC3 proteins. The expression of SIRT1 and mitochondrial autophagy‑related proteins, PTEN‑induced kinase 1 (PINK1) and Parkin, were detected by western blot‑ ting. Finally, apoptosis was analyzed by TUNEL staining and the expression of apoptosis‑related proteins (Bax, Bcl‑2 and Caspase‑3) by western blotting. The results suggested that postoperative pHBA treatment may reduce the size of cere‑ bral infarction and damage to the nervous system, and may improve cell damage in the ischemic penumbra of MCAO/R rats. Compared with rats in the untreated MCAO/R group, the mitochondrial structure of the pHBA‑treated group was improved, the levels of MMP and ATP were increased, and the degree of opening of mPTP was decreased. Simultaneously, immunofluorescence and western blotting results showed that compared with the MCAO/R group, the number of LC3‑ and TUNEL‑positive cells increased, the number of p62‑positive cells decreased, SIRT1 and autophagy protein (PINK1, Parkin and LC3 II/I) expression levels increased and p62 expression decreased in the pHBA group. However, these improvements were blocked by treatment with EX527. In summary, results from the present study suggested that pHBA may improve neuronal injury in the ischemic penumbra of MCAO/R rats through SIRT1‑activated mitochondrial autophagy and mitochondrial‑mediated neuronal apoptosis. [ABSTRACT FROM AUTHOR]

Fibrosis is the basis of structural remodeling in atrial fibrillation (AF), during which inflammation is crucial. Programmed cell death factor 4 (PDCD4) is a newly identified inflammatory gene, with unknown mechanisms of action in AF. The present study aimed to elucidate the effects of PDCD4 on the inflammation and structural remodeling of atrial myocytes. For this purpose, a PDCD4 overexpression plasmid (oePDCD4) and PDCD4 small interfering (si)RNA (siPDCD4) were used to modulate PDCD4 expression in mouse atrial myocytes (HL-1 cells). The expression of PDCD4 was detected using reverse transcription-quantitative PCR and western blot analysis. The optimal drug concentrations of peroxisome proliferator-activated receptor γ (PPARγ) agonist (pioglitazone hydrochloride), NF-κB inhibitor (CBL0137), PPARγ inhibitor (GW9962) and NF-κB agonist (betulinic acid) were screened using a Cell Counting Kit-8 assay. The levels of inflammatory factors were detected using enzyme-linked immunosorbent assays, the expression levels of fibrosis-related proteins and NF-κB subunits were detected using western blot analysis, and the expression of phosphorylated (p-)p65/p65 was detected using immunofluorescence staining. The results revealed that PDCD4 overexpression increased the levels of fibrotic factors (collagen I, collagen III, fibronectin, α-smooth muscle actin and matrix metalloproteinase 2), pro-inflammatory cytokines (IFN-γ, IL-6, IL-17A and TNF-α) and p-p65, whereas it reduced the levels of anti-inflammatory cytokines (IL-4) in HL-1 cells. Additionally, treatment with the PPARγ agonist and NF-κB inhibitor reversed the levels of fibrotic-, pro-inflammatory and anti-inflammatory factors in oePDCD4-HL-1 cells. By contrast, PDCD4 silencing exerted the opposite effects on fibrotic factors, pro-inflammatory cytokines, anti-inflammatory cytokines and p-p65. In addition, treatment with the PPARγ inhibitor and NF-κB agonist reversed the levels of fibrotic-, pro-inflammatory and anti-inflammatory factors in siPDCD4-HL-1 cells. In conclusion, the present study demonstrated that PDCD4 may induce inflammation and fibrosis by activating the PPARγ/NF-κB signaling pathway, thereby promoting the structural remodeling of atrial myocytes in AF. [ABSTRACT FROM AUTHOR]

Lung cancer has the highest incidence and mortality rates of all cancer types in China and therefore represents a serious threat to human health. In the present study, the mechanism of rabdoternin E against the proliferation of the lung cancer cell line A549 was explored. It was found that rabdoternin E caused the accumulation of large amounts of reactive oxygen species (ROS), promoted cell S phase arrest by reducing the expression of CDK2 and cyclin A2, induced apoptosis by increasing the Bax/Bcl-2 ratio and promoted the phosphorylation of proteins in the ROS/p38 MAPK/JNK signaling pathway, which is associated with apoptosis and ferroptosis. In addition, it was also found that Z-VAD-FMK (an apoptosis inhibitor), ferrostatin-1 (ferroptosis inhibitor) and N-acetylcysteine (a ROS inhibitor) could partially or greatly reverse the cytotoxicity of rabdoternin E to A549 cells. Similarly, NAC (N-acetylcysteine) treatment notably inhibited the rabdoternin E-stimulated p38 MAPK and JNK activation. Furthermore, in vivo experiments in mice revealed that Rabdoternin E markedly reduced tumor volume and weight and regulated the expression levels of apoptosis and ferroptosis-related proteins (including Ki67, Bcl-2, Bax, glutathione peroxidase 4, solute carrier family 7 member 11 and transferrin) in the tumor tissues of mice. Histopathological observation confirmed that the number of tumor cells decreased markedly after administration of rabdoternin E. Taken together, rabdoternin E induced apoptosis and ferroptosis of A549 cells by activating the ROS/p38 MAPK/JNK signaling pathway. Therefore, the results of the present study showed that rabdoternin E is not toxic to MCF-7 cells (normal lung cells), had no significant effect on body weight and was effective and therefore may be a novel therapeutic treatment for lung cancer. [ABSTRACT FROM AUTHOR]

The regulation of cardiac function by the nuclear transcription factor signal transducer and activator of transcription 4 (STAT4) has been recently recognized. Nevertheless, the role and mechanisms of action of STAT4 in myocardial ischemia-reperfusion (I/R) injury remain unknown. Consequently, the present study constructed a rat model of I/R by ligation of the left anterior descending coronary artery. Following sacrifice, the rat hearts were excised and analyzed to investigated the effects of STAT4 on I/R-induced myocardial injury. Western blotting demonstrated that expression of STAT4 decreased significantly in the rat model of cardiac I/R and in H9C2 cells that were subjected to hypoxia and reoxygenation (H/R). The overexpression of STAT4 in H9C2 cells reduced cell damage and apoptosis induced by H/R. Furthermore, both in vivo and in vitro, the level of PI3K decreased significantly. Although the AKT protein expression levels were not altered, the AKT phosphorylation levels decreased significantly. STAT4 overexpression enhanced the expression of PI3K and AKT in the H9C2 cells. On the whole, the present study demonstrated that STAT4 alleviated I/R-induced myocardial injury through the PI3K/AKT signaling pathway. [ABSTRACT FROM AUTHOR]

This article, titled "[Retracted] Salidroside mitigates hypoxia/reoxygenation injury by alleviating endoplasmic reticulum stress-induced apoptosis in H9c2 cardiomyocytes," was published in Molecular Medicine Reports in 2018. However, it has since been retracted by the editor due to concerns raised by a reader. The reader pointed out that certain data in the article were similar to data from another article written by different authors at different research institutes. The authors were asked for an explanation but did not respond. The editor apologizes for any inconvenience caused. [Extracted from the article]

Cordycepin is a nucleoside molecule found in Cordyceps sinensis and can be obtained through chemical synthesis and biotransformation. Cordycepin has been extensively studied and has been shown to have antitumour activity. This activity includes effects on the autophagy process and inhibition of the MAPK/ERK and Hedgehog pathways. Ultimately, the inhibitory effect of cordycepin on tumour cells is due to the interplay of these effects. Cordycepin was shown to enhance the therapeutic effects of radiotherapy. There is increasing evidence indicating that cordycepin plays an anticancer role in the treatment of various cancers. The present review aims to provide a clear understanding of the antitumour mechanisms of cordycepin and discuss its present application in the treatment of tumours. This information can be an important theoretical basis and provide clinical guidance for the further development of cordycepin as an antitumour drug. [ABSTRACT FROM AUTHOR]

Pancreatic β‑cells are the only cells that synthesize insulin to regulate blood glucose levels. Various conditions can affect the mass of pancreatic β‑cells and decrease insulin levels. Diabetes mellitus is a disease characterized by insulin resistance and chronic hyperglycemia, mainly due to the loss of pancreatic β‑cells caused by an increase in the rate of apoptosis. Additionally, hyperglycemia has a toxic effect on β‑cells. Although the precise mechanism of glucotoxicity is not fully understood, several mechanisms have been proposed. The most prominent changes are increases in reactive oxygen species, the loss of mitochondrial membrane potential and the activation of the intrinsic pathway of apoptosis due to p53. The present review analyzed the location of p53 in the cytoplasm, mitochondria and nucleus in terms of post‑translational modifications, including phosphorylation, O‑GlcNAcylation and poly‑ADP‑ribosylation, under hyperglycemic conditions. These modifications protect p53 from degradation by the proteasome and, in turn, enable it to regulate the intrinsic pathway of apoptosis through the regulation of anti‑apoptotic and pro‑apoptotic elements. Degradation of p53 occurs in the proteasome and depends on its ubiquitination by Mdm2. Understanding the mechanisms that activate the death of pancreatic β‑cells will allow the proposal of treatment alternatives to prevent the decrease in pancreatic β‑cells.

Previous studies have highlighted the antitumor effects of mesenchymal stem cell‑derived extracellular vesicles (MSC‑EVs), positioning them as a promising therapeutic avenue for cancer treatment. However, some researchers have proposed a bidirectional influence of MSC‑EVs on tumors, determined by the specific tissue origin of the MSCs and the types of tumors involved. The present study aimed to elucidate the effects of human placenta MSC‑derived extracellular vesicles (hPMSC‑EVs) on the malignant behavior of a mouse breast cancer model of 4T1 cells in vitro . The findings revealed that hPMSC‑EVs significantly inhibited the proliferation, migration and colony formation of cultured 4T1 mouse breast cancer cells without inducing apoptosis. Exposure to conditioned medium from 4T1 cells pretreated with hPMSC‑EVs resulted in decreased angiogenic activity, accompanied by the downregulation of angiogenesis‑promoting genes in human umbilical vein endothelial cells. In murine xenograft models derived from the 4T1 cell line, local administration of hPMSC‑EVs substantially hindered tumor growth. Further results revealed that hPMSC‑EVs inhibited angiogenesis in vivo . The findings revealed that hPMSC‑EVs significantly inhibited the proliferation, migration and colony formation of cultured 4T1 mouse breast cancer cells without inducing apoptosis. Exposure to conditioned medium from 4T1 cells pretreated with hPMSC‑EVs resulted in decreased angiogenic activity, accompanied by the downregulation of angiogenesis‑promoting genes in human umbilical vein endothelial cells. In murine xenograft models derived from the 4T1 cell line, local administration of hPMSC‑EVs substantially hindered tumor growth. Further results revealed that hPMSC‑EVs inhibited angiogenesis in vivo , as reflected by the use of a vascular growth factor receptor 2‑Fluc transgenic mouse model. In summary, the results confirmed that hPMSC‑EVs negatively modulated breast cancer growth by suppressing tumor cell proliferation and migration via an indirect antiangiogenic mechanism. These results underscored the therapeutic potential of EVs, suggesting a promising avenue for alternative anticancer treatments in the future.

A subset of basal cell carcinomas (BCCs) are directly derived from hair follicles (HFs). In some respects, HFs can be defined as 'ordered' skin appendage growths, while BCCs can be regarded as 'disordered' skin appendage growths. The aim of the present study was to examine HFs and BCCs to define the expression of common and unique signaling pathways in each skin appendage. Human nodular BCCs, along with HFs and non‑follicular skin epithelium from normal individuals, were examined using microarrays, qPCR, and immunohistochemistry. Subsequently, BCC cells and root sheath keratinocyte cells from HFs were cultured and treated with Notch signaling peptide Jagged1 (JAG1). Gene expression, protein levels, and cell apoptosis susceptibility were assessed using qPCR, immunoblotting, and flow cytometry, respectively. Specific molecular mechanisms were found to be involved in the process of cell self‑renewal in the HFs and BCCs, including Notch and Hedgehog signaling pathways. However, several key Notch signaling factors showed significant differential expression in BCCs compared with HFs. Stimulating Notch signaling with JAG1 induced apoptosis of BCC cells by increasing Fas ligand expression and downstream caspase-8 activation. The present study showed that Notch signaling pathway activity is suppressed in BCCs, and is highly expressed in HFs. Elements of the Notch pathway could, therefore, represent targets for the treatment of BCCs and potentially in hair follicle engineering.

This article, titled "[Retracted] Effect of metformin on cell proliferation, apoptosis, migration and invasion in A172 glioma cells and its mechanisms," was published in Molecular Medicine Reports in 2019. However, it has since been retracted by the journal due to concerns about the authenticity of the data presented. A concerned reader pointed out that the data in Figures 2 and 6 were similar to data from other articles by different authors. The authors were asked for an explanation but did not respond. The journal apologizes for any inconvenience caused. [Extracted from the article]

Septic acute kidney injury (AKI) is considered as a severe and frequent complication that occurs during sepsis. Mounting evidence has confirmed the pivotal pathogenetic roles of microRNA (miRNA or miR) in sepsis-induced AKI; however, the role of miRNAs and their underlying mechanisms in sepsis-induced AKI have not been entirely understood. The present study aimed to elucidate the functions of special miRNAs during sepsis-induced AKI and its underlying mechanism. First, a number of differently expressed miRNAs was identified based on the microarray dataset GSE172044. Subsequently, lipopolysaccharide (LPS) was used to induce AKI in mice, and the role of miR-17-5p on AKI was clarified. Finally, the related molecular mechanisms were further examined by western blotting and immunohistochemical analysis. MiR-17-5p was found to be continuously decreased and reached the bottom at h 24 after AKI in mice. Functionally, injection of agomiR-17-5p could observably improve renal injury and survival rate, as well as inhibit inflammatory cytokine production and renal cell apoptosis in mice after AKI. On the contrary, injection of antagomiR-17-5p aggravated LPS-induced renal injury, inflammation and apoptosis in mice after AKI. Moreover, transforming growth factor β receptor 2 (TGFβR2) was identified as a direct target of miR-17-5p, and its downstream phosphorylated Smad3 was also suppressed by miR-17-5p upregulation. Taken together, these results demonstrated that miR-17-5p overexpression may exhibit a beneficial effect by attenuating LPS-induced inflammation and apoptosis via regulating the TGFβR2/TGF-β/Smad3 signaling pathway, indicating that miR-17-5p could act as a potential target for sepsis treatment. [ABSTRACT FROM AUTHOR]

This article, titled "[Retracted] Silencing of RTKN2 by siRNA suppresses proliferation, and induces G1 arrest and apoptosis in human bladder cancer cells," was published in Molecular Medicine Reports in 2016. However, it has since been retracted by the editor due to concerns raised by a reader. The reader pointed out that certain data in the article's Transwell migration assay were similar to data published in another article by different authors at a different research institute. The editor contacted the authors for an explanation, but did not receive a reply. The editor apologizes for any inconvenience caused. [Extracted from the article]

Stroke is a severe neurological disease that is associated with high rates of morbidity and mortality, and the underlying pathological processes are complex. Ferroptosis fulfills a significant role in the progression and treatment of stroke. It is well established that ferroptosis is a type of programmed cell death that is distinct from other forms or types of cell death. The process of ferroptosis involves multiple signaling pathways and regulatory mechanisms that interact with mechanisms inherent to stroke development. Inducers and inhibitors of ferroptosis have been shown to exert a role in the onset of this cell death process. Furthermore, it has been shown that interfering with ferroptosis affects the occurrence of stroke, indicating that targeting ferroptosis may offer a promising therapeutic approach for treating patients of stroke. Hence, the present review aimed to summarize the latest progress that has been made in terms of using therapeutic interventions for ferroptosis as treatment targets in cases of stroke. It provides an overview of the relevant pathways and molecular mechanisms that have been investigated in recent years, highlighting the roles of inducers and inhibitors of ferroptosis in stroke. Additionally, the intervention potential of various types of Traditional Chinese Medicine is also summarized. In conclusion, the present review provides a comprehensive overview of the potential therapeutic targets afforded by ferroptosis-associated pathways in stroke, offering new insights into how ferroptosis may be exploited in the treatment of stroke. [ABSTRACT FROM AUTHOR]

Astragaloside IV (AS-IV) has various pharmacological effects, including antioxidant and immunoregulatory properties, which can improve myasthenia gravis (MG) symptoms. However, the potential mechanism underlying the effects of AS-IV on MG remains to be elucidated. The present study aimed to investigate whether AS-IV has a therapeutic effect on MG and its potential mechanism of action. By subcutaneously immunizing rats with R97-116 peptide, an experimental autoimmune (EA) MG rat model was established. AS-IV (40 or 80 mg/kg/day) treatment was then applied for 28 days after modeling. The results demonstrated that AS-IV significantly ameliorated the weight loss, Lennon score and pathological changes in the gastrocnemius muscle of EAMG rats compared with the model group. Additionally, the levels of acetylcholine receptor antibody (AChR-Ab) were significantly decreased, whereas mitochondrial function [ATPase and cytochrome c (Cyt-C) oxidase activities] and ultrastructure were improved in the AS-IV treated rats. Moreover, the mRNA and protein expression levels of phosphatase and tensin homolog-induced putative kinase 1, Parkin, LC3II and Bcl-2, key signaling molecules for mitophagy and apoptosis, were upregulated, whereas the mRNA and protein expression levels of p62, Cyt-C, Bax, caspase 3 and caspase 9 were downregulated following AS-IV intervention. In conclusion, AS-IV may protect against EAMG in a rat model by modulating mitophagy and apoptosis. These findings indicated the potential mechanism underlying the effects of AS-IV on MG and provided novel insights into treatment strategies for MG. [ABSTRACT FROM AUTHOR]

Physiological stress such as excessive reactive oxygen species (ROS) production may contribute normal fibroblasts activation into cancer-associated fibroblasts, which serve a crucial role in certain types of cancer such as pancreatic, breast, liver and lung cancer. The present study aimed to examine the cytoprotective effects of luteolin (3′,4′,5,7-tetrahydroxyflavone) against hydrogen peroxide (H2O2)-generated oxidative stress in lung fibroblasts. To examine the effects of luteolin against H2O2-induced damages, cell viability, sub-G1 cell population, nuclear staining with Hoechst 33342, lipid peroxidation and comet assays were performed. To evaluate the effects of luteolin on the protein expression level of apoptosis, western blot assay was performed. To assess the antioxidant effects of luteolin, detection of ROS using H2DCFDA staining, O2− and ·OH using electron spin resonance spectrometer and antioxidant enzyme activity was performed. In a cell-free chemical system, luteolin scavenges superoxide anion and hydroxyl radical generated by xanthine/xanthine oxidase and the Fenton reaction (FeSO4/H2O2). Furthermore, Chinese hamster lung fibroblasts (V79-4) treated with H2O2 showed a significant increase in cellular ROS. Intracellular ROS levels and damage to cellular components such as lipids and DNA in H2O2-treated cells were significantly decreased by luteolin pretreatment. Luteolin increased cell viability, which was impaired following H2O2 treatment and prevented H2O2-mediated apoptosis. Luteolin suppressed active caspase-9 and caspase-3 levels while increasing Bcl-2 expression and decreasing Bax protein levels. Additionally, luteolin restored levels of glutathione that was reduced in response to H2O2. Moreover, luteolin enhanced the activity and protein expressions of superoxide dismutase, catalase, glutathione peroxidase, and heme oxygenase-1. Overall, these results indicated that luteolin inhibits H2O2-mediated cellular damage by upregulating antioxidant enzymes. [ABSTRACT FROM AUTHOR]

Although exogenous calcitonin gene-related peptide (CGRP) protects against hyperoxia-induced lung injury (HILI), the underlying mechanisms remain unclear. The present study attempted to elucidate the molecular mechanism by which CGRP protects against hyperoxia-induced alveolar cell injury. Human alveolar A549 cells were treated with 95% hyperoxia to establish a hyperoxic cell injury model. ELISA was performed to detect the CGRP secretion. Immunofluorescence, quantitative (q)PCR, and western blotting were used to detect the expression and localization of CGRP receptor (CGRPR) and transient receptor potential vanilloid 1 (TRPV1). Cell counting kit-8 and flow cytometry were used to examine the proliferation and apoptosis of treated cells. Digital calcium imaging and patch clamp were used to analyze the changes in intracellular Ca2+ signaling and membrane currents induced by CGRP in A549 cells. The mRNA and protein expression levels of Cyclin D1, proliferating cell nuclear antigen (PCNA), Bcl-2 and Bax were detected by qPCR and western blotting. The expression levels of CGRPR and TRPV1 in A549 cells were significantly downregulated by hyperoxic treatment, but there was no significant difference in CGRP release between cells cultured under normal air and hyperoxic conditions. CGRP promoted cell proliferation and inhibited apoptosis in hyperoxia, but selective inhibitors of CGRPR and TRPV1 channels could effectively attenuate these effects; TRPV1 knockdown also attenuated this effect. CGRP induced Ca2+ entry via the TRPV1 channels and enhanced the membrane non-selective currents through TRPV1 channels. The CGRP-induced increase in intracellular Ca2+ was reduced by inhibiting the phospholipase C (PLC)/protein kinase C (PKC) pathway. Moreover, PLC and PKC inhibitors attenuated the effects of CGRP in promoting cell proliferation and inhibiting apoptosis. In conclusion, exogenous CGRP acted by inversely regulating the function of TRPV1 channels in alveolar cells. Importantly, CGRP protected alveolar cells from hyperoxia-induced injury via the CGRPR/TRPV1/Ca2+ axis, which may be a potential target for the prevention and treatment of the HILI. [ABSTRACT FROM AUTHOR]

Knee osteoarthritis (KOA) is a chronic degenerative disease that affects the quality of life of middle-aged and elderly individuals, and is one of the major factors leading to disability. Rongjin Niantong Fang (RJNTF) can alleviate the clinical symptoms of patients with KOA, but the molecular mechanism underlying its beneficial effects on KOA remains unknown. Using pharmacological analysis and in vitro experiments, the active components of RJNTF were analyzed to explore their potential therapeutic targets and mechanisms in KOA. The potential targets and core signaling pathways by which RJNTF exerts its effects on KOA were obtained from databases such as Gene Expression Omnibus, Traditional Chinese Medicine Systems Pharmacology and Analysis Platform. Subsequently, chondrocyte apoptosis was modeled using hydrogen peroxide (H2O2). Cell Counting Kit-8 assay involving a poly [ADP-ribose] polymerase-1 (PARP1) inhibitor, DAPI staining, reverse transcription-quantitative PCR, Annexin V-FITC/PI staining and flow cytometry, western blotting and co-immunoprecipitation analysis were used to determine the therapeutic efficacy of RJNTF on KOA and to uncover the molecular mechanism. It was found that PARP1-knockdown lentivirus, incubation with PARP1 inhibitor PJ34, medium and high doses of RJNTF significantly reduced H2O2-induced chondrocyte apoptosis. Medium and high doses of RJNTF downregulated the expression of cleaved caspase-3, cleaved PARP1 and PAR total proteins, as well as nucleus proteins of apoptosis-inducing factor (AIF) and migration inhibitory factor (MIF), and upregulated the expression of caspase-3, PARP1 total protein, as well as the cytoplasmic expression of AIF and MIF, suggesting that RJNTF may inhibit chondrocyte apoptosis through the PARP1/AIF signaling pathway. [ABSTRACT FROM AUTHOR]

Estrogen‑related receptor (ERR) is an orphan nuclear receptor structurally akin to the estrogen receptor. ERR is expressed in tissues with active energy metabolism and regulates intracellular metabolic functions. Additionally, ERRs are known to be strongly expressed in the epidermis of skin tissue, but their functions are unknown. The present study investigated the function of ERRα in human skin fibroblasts. ERRα expressed in human dermal fibroblast TIG113 was knocked down using small interfering (si)RNA and gene expression was comprehensively analyzed using microarrays 48 h later. Pathway analysis was performed using Wikipathways on genes exhibiting expression changes of ≥1.5‑fold. Expression of cell cycle‑related and apoptosis‑related genes was compared using reverse transcription‑quantitative PCR. After treating TIG113 cells with siERRα for 72 h, cell proliferation was assessed using the Cell Counting Kit‑8 or a scratch wound healing assay and apoptotic cells were measured using the Poly Caspase Assay Kit. Cell cycle analysis was performed using flow cytometry. The expression of the ERRα gene was suppressed by siRNA. The expression of genes associated with cell cycle‑related pathways were decreased while that of those associated with apoptosis‑related pathways increased. Furthermore, the expression of cell cycle‑related genes such as cell division cycle 25C, cyclin E and cyclin B1 was decreased and the expression of apoptosis‑related genes such as caspase3 and Fas cell surface death receptor was increased. Cell proliferation was suppressed and the number of apoptotic cells increased ~2‑fold in ERRα‑knockdown TIG113 cells. Cell cycle analysis revealed that the number of cells in the Sub‑G 1 phase increased and that in the S and G 2 /M phases decreased. The present study suggested that ERRα is an essential for the survival of human skin fibroblasts.

Paridis Rhizoma saponins (PRS) are significant components of Rhizoma Paridis and have inhibitory effects on various tumors, such as bladder, breast, liver and colon cancer. Polyphyllin II (PPII), one of the PRS, has an unclear effect on breast cancer. The present study aimed to explore the effect and mechanism of PPII in breast cancer. A network pharmacology approach was employed to predict the core components and breast cancer‑related targets of PRS. Moreover, a xenograft tumor model was established to determine the anti‑breast cancer effect of PPII in vivo . The viability of MDA‑MB‑231 cells was determined by a Cell Counting Kit‑8 assay. Apoptosis was analyzed using annexin V/PI double staining. Additionally, Transwell and scratch assays were performed to evaluate invasion and migration. The potential mechanism was predicted by Kyoto Encyclopedia of Genes and Genomes enrichment analysis and molecular docking analysis and verified by western blot analysis. The effect of PPII on aerobic glycolysis in breast cancer cells was detected by lactic acid and pyruvate kits and Western blotting of glycolytic rate‑limiting enzymes. Network pharmacology analysis revealed 26 core targets involved in breast cancer and that PPII was the core active component of PRS. The in vivo studies showed that PPII could inhibit the growth of breast cancer in mice. In vitro experiments confirmed that PPII induced cancer cell apoptosis and inhibited invasion and migration. Furthermore, PPII was capable of suppressing the expression of key proteins in the PI3K/Akt signaling pathway, reducing the generation of aerobic glycolytic products, and diminishing the protein expression levels of hexokinase 2 and pyruvate kinase M2. The results indicated that PPII inhibited aerobic glycolysis in breast cancer cells through the PI3K/Akt signaling pathway, thereby inhibiting breast cancer growth.

Osteoarthritis (OA) is a chronic disease that involves chondrocyte injury. ADAMTS5 has been confirmed to mediate chondrocyte injury and thus regulate OA progression, but its underlying molecular mechanisms remain unclear. In the present study, interleukin‑1β (IL‑1β)‑induced chondrocytes were used to mimic OA in vitro . Cell proliferation and apoptosis were assessed by MTT assay, EdU assay and flow cytometry, and protein levels of ADAMTS5, specificity protein 1 (SP1), matrix‑related markers and Wnt/β‑catenin pathway‑related markers were examined using western blotting. In addition, ELISA was performed to measure the concentrations of inflammation factors, and oxidative stress was evaluated by detecting SOD activity and MDA levels. The mRNA expression levels of ADAMTS5 and SP1 were determined by reverse transcription‑quantitative PCR, and the interaction between SP1 and ADAMTS5 was analyzed using a dual‑luciferase reporter assay and chromatin immunoprecipitation assay. IL‑1β suppressed proliferation, but promoted apoptosis, extracellular matrix degradation, inflammation and oxidative stress in chondrocytes. ADAMTS5 was upregulated in IL‑1β‑induced chondrocytes, and its knockdown alleviated IL‑1β‑induced chondrocyte injury. SP1 could bind to the ADAMTS5 promoter region to promote its transcription, and SP1 knockdown relieved IL‑1β‑induced chondrocyte injury by reducing ADAMTS5 expression. The SP1/ADAMTS5 axis activated the Wnt/β‑catenin pathway, and the Wnt/β‑catenin pathway agonist, SKL2001, reversed the protective effect of ADAMTS5 knockdown on chondrocyte injury induced by IL‑1β. To the best of our knowledge, the present study was the first to reveal the interaction between SP1 and ADAMTS5 in OA progression and indicated that the SP1/ADAMTS5 axis mediates OA progression by regulating the Wnt/β‑catenin pathway.

Although exogenous calcitonin gene‑related peptide (CGRP) protects against hyperoxia‑induced lung injury (HILI), the underlying mechanisms remain unclear. The present study attempted to elucidate the molecular mechanism by which CGRP protects against hyperoxia‑induced alveolar cell injury. Human alveolar A549 cells were treated with 95% hyperoxia to establish a hyperoxic cell injury model. ELISA was performed to detect the CGRP secretion. Immunofluorescence, quantitative (q)PCR, and western blotting were used to detect the expression and localization of CGRP receptor (CGRPR) and transient receptor potential vanilloid 1 (TRPV1). Cell counting kit‑8 and flow cytometry were used to examine the proliferation and apoptosis of treated cells. Digital calcium imaging and patch clamp were used to analyze the changes in intracellular Ca 2+ signaling and membrane currents induced by CGRP in A549 cells. The mRNA and protein expression levels of Cyclin D1, proliferating cell nuclear antigen (PCNA), Bcl‑2 and Bax were detected by qPCR and western blotting. The expression levels of CGRPR and TRPV1 in A549 cells were significantly downregulated by hyperoxic treatment, but there was no significant difference in CGRP release between cells cultured under normal air and hyperoxic conditions. CGRP promoted cell proliferation and inhibited apoptosis in hyperoxia, but selective inhibitors of CGRPR and TRPV1 channels could effectively attenuate these effects; TRPV1 knockdown also attenuated this effect. CGRP induced Ca 2+ entry via the TRPV1 channels and enhanced the membrane non‑selective currents through TRPV1 channels. The CGRP‑induced increase in intracellular Ca 2+ was reduced by inhibiting the phospholipase C (PLC)/protein kinase C (PKC) pathway. Moreover, PLC and PKC inhibitors attenuated the effects of CGRP in promoting cell proliferation and inhibiting apoptosis. In conclusion, exogenous CGRP acted by inversely regulating the function of TRPV1 channels in alveolar cells. Importantly, CGRP protected alveolar cells from hyperoxia‑induced injury via the CGRPR/TRPV1/Ca 2+ axis, which may be a potential target for the prevention and treatment of the HILI.

During osteoarthritis (OA), chondrocytes become highly active, with increased matrix synthesis and inflammatory cytokine‑induced catabolic pathways. Early intervention strategies targeting pathological changes may attenuate or halt disease progression. The present study aimed to reveal the role of glutathione peroxidase (GPX)7 in OA. For this purpose, a research model was established by inducing C28/I2 human chondrocytes with interleukin (IL)‑1β, and the expression level of GPX7 was determined. To explore its roles, C28/I2 cells were transfected to gain GPX7 overexpression. The effects of GPX7 overexpression on intracellular inflammation, extracellular matrix (ECM) degradation, apoptosis and ferroptosis were then evaluated. In addition, the cells were treated with the ferroptosis inducer, erastin, and its effects on the aforementioned phenotypes were assessed. The level of GPX7 was decreased in response to IL‑1β treatment, and GPX7 overexpression suppressed cellular inflammation, ECM degradation and apoptosis. Moreover, the reduction of lipid peroxidation, ferrous ions and transferrin indicated that GPX7 overexpression inhibited ferroptosis. Subsequently, inflammation, ECM degradation and apoptosis were found to be promoted in the cells upon treatment with erastin. These findings suggested that the regulatory role of GPX7 may be mediated by a pathway involving ferroptosis. On the whole, the present study revealed that GPX7 reduces IL‑1β‑induced chondrocyte inflammation, apoptosis and ECM degradation partially through a mechanism involving ferroptosis. The results of the present study lay a theoretical foundation for subsequent OA‑related research and may enable the development of translational strategies for the treatment of OA.

Traumatic Brain Injury (TBI) represents a significant public health challenge. Recovery from brain injury necessitates the collaborative efforts of various resident neural cells, predominantly microglia. The present study analyzed rat and mouse RNA expression micro‑arrays, high‑throughput RNA sequencing and single‑cell sequencing data sourced from public databases. To construct an inflammation regulation network around TYRO protein tyrosine kinase‑binding protein (TYROBP), to evaluate the role of TYROBP in cell death after TBI. These findings indicate that following TBI, neurons predominantly communicate with one another through the CXC chemokine ligand (CXCL) and CC chemokine ligand (CCL) signaling pathways, employing a paracrine mechanism to activate microglia. These activated microglia intensify the pathological progression of brain injury by releasing factors such as tumor necrosis factor α (TNF‑α), vascular endothelial growth factor and transforming growth factor β via the NF‑κB pathway. Cells co‑culture experiments demonstrated that neurons, impaired by mechanical injury, interact with microglia through non‑contact mechanisms. Activated microglia secrete cytokines, including TNF‑α, CXCL‑8 and CCL2, which trigger an inflammatory response and facilitate neuronal apoptosis. TYROBP gene knockout in microglia was demonstrated to reduce this interaction and reduce neuronal cell apoptosis rates.

Polycystic ovary syndrome (PCOS) is a globally prevalent gynecological disorder among women of childbearing age. The present study aimed to investigate the role of tenascin C (TNC) in PCOS and its potential mechanisms. Fasting blood glucose and serum insulin, the homeostasis model assessment of insulin resistance and the serum hormone levels were determined in PCOS rats. In addition, H&E staining was used for assessing pathology. In addition, the effects of TNC on oxidative stress and inflammation response in PCOS rat and cell models was assessed. Furthermore, the roles of TNC on KGN cell proliferation and apoptosis were determined employing EdU assay and flow cytometry. TLR4/NF‑κB pathway‑related proteins were measured using western blotting, immunofluorescence and immunohistochemistry. It was found that the mRNA and protein expression was upregulated in PCOS rats and in KGN cells induced by dihydrotestosterone (DHT). Knockdown of TNC relieved the pathological characteristics and the endocrine abnormalities of PCOS rats. Knockdown of TNC inhibited ovarian cell apoptosis, oxidative stress and inflammation in PCOS rats. Knockdown of TNC reversed the DHT‑induced reduction in cell proliferation and increase in apoptosis in KGN cells. Furthermore, knockdown of TNC alleviated oxidative stress and inflammatory responses induced by DHT in KGN cells. Additionally, knockdown of TNC inhibited the toll‑like receptor 4 (TLR4)/NF‑κB signaling pathway in PCOS rats and DHT‑treated KGN cells. In conclusion, knockdown of TNC could ameliorate PCOS in both rats and a cell model by inhibiting cell apoptosis, oxidative stress and inflammation via the suppression of the TLR4/NF‑κB signaling pathway.

The article titled "[Retracted] miR-660-5p is associated with cell migration, invasion, proliferation and apoptosis in renal cell carcinoma" was published in Molecular Medicine Reports in 2018. The authors of the article contacted the Editorial Office to report errors in the data handling and labeling of representative images in Figures 3B and 5A. An independent investigation by the Editorial Office revealed overlapping data panels in Figures 6A and 6B, indicating a lack of confidence in the presented data. As a result, the Editor decided to retract the paper. The authors accepted this decision, and the Editor apologizes for any inconvenience caused. [Extracted from the article]

Pirarubicin (THP) is one of the most commonly used antineoplastic drugs in clinical practice. However, its clinical application is limited due to its toxic and heart-related side effects. It has been reported that oxidative stress, inflammation and apoptosis are closely associated with cardiotoxicity caused by pirarubicin (CTP). Additionally, it has also been reported that scutellarein (Sc) exerts anti-inflammatory, antioxidant, cardio-cerebral vascular protective and anti-apoptotic properties. Therefore, the present study aimed to investigate the effect of food therapy with Sc on CTP and its underlying molecular mechanism using echocardiography, immunofluorescence, western blot, ROS staining, and TUNEL staining. The in vivo results demonstrated that THP was associated with cardiotoxicity. Additionally, abnormal changes in the expression of indicators associated with oxidative stress, ferroptosis and apoptosis were observed, which were restored by Sc. Therefore, it was hypothesized that CTP could be associated with oxidative stress, ferroptosis and apoptosis. Furthermore, the in vitro experiments showed that Sc and the NADPH oxidase 2 (NOX2) inhibitor, GSK2795039 (GSK), upregulated glutathione peroxidase 4 (GPX4) and inhibited THP-induced oxidative stress, apoptosis and ferroptosis. However, cell treatment with the ferroptosis inhibitor, ferrostatin-1, or inducer, erastin, could not significantly reduce or promote, respectively, the expression of NOX2. However, GSK significantly affected ferroptosis and GPX4 expression. Overall, the results of the present study indicated that food therapy with Sc ameliorated CTP via inhibition of apoptosis and ferroptosis through regulation of NOX2-induced oxidative stress, thus suggesting that Sc may be a potential therapeutic drug against CTP. [ABSTRACT FROM AUTHOR]

Glaucoma is a group of progressive optic nerve disorders characterized by the loss of retinal ganglion cells, a thinner retinal nerve fibre layer and cupping of the optic disk. Apoptosis is a physiological cell death process regulated by genes and plays a crucial role in maintaining tissue homeostasis, ensuring the natural development and immune defence of organisms. Apoptosis has been associated with glaucoma and inhibiting apoptosis by activating phosphatidylinositol 3-kinase-protein kinase B or other medicines can rescue pathological changes in glaucoma. Due to the complex crosstalk of apoptosis pathways, the pathophysiological mechanism of apoptosis in glaucoma needs to be fully elucidated. The present review aimed to discuss the mechanism of cell apoptosis in glaucoma, improve the understanding of the pathophysiology of glaucoma, summarize new directions for the treatment of glaucoma and lay the foundation for new treatment strategies for glaucoma. [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinoma (PDAC) is the most prevalent and aggressive form of pancreatic cancer. Gemcitabine (GEM), the first-line treatment for PDAC, which alleviates symptoms and enhances the quality of life of patients. However, it is prone to lead to the development of drug resistance during treatment. Interferon (IFN)-γ exhibits antitumor and immunomodulatory properties. The present study aimed to explore the impact of IFN-γ on the viability, migration and apoptosis of GEM-resistant pancreatic cancer cells. Firstly, a GEM-resistant pancreatic cancer cell line, named PANC-1/GEM, was constructed. Hematoxylin and eosin staining analyzed the cell morphology, whereas reverse transcription-quantitative PCR (RT-qPCR) assessed the expression levels of the drug-resistance genes multidrug resistance-associated protein (MRP) and breast cancer resistance protein (BCRP). The MTT assay and cell counting techniques were used to determine the appropriate concentration of IFN-y and its effects on cell viability. The IFN-γ-induced apoptosis of PANC-1/GEM cells was assessed using an Apoptosis Detection Kit, whereas the impact of IFN-γ on the migration of these cells was evaluated using a wound-healing assay. The MTT assay revealed a resistance index of 22.4 in the PANC-1/GEM cell line. RT-qPCR indicated that, compared with in wild-type cells, the PANC-1/GEM resistant strain exhibited lower MRP and higher BCRP mRNA expression levels. The optimal concentration of IFN-γ for affecting PANC-1/GEM cells was determined to be 0.3 µg/ml. At this concentration, IFN-γ induced PANC-1/GEM cell apoptosis, along with a notable reduction in migration. Following treatment of PANC-1/GEM cells with IFN-γ, MRP expression increased whereas BCRP mRNA expression decreased, indicating a reversal in their drug-resistance gene expression. In conclusion, IFN-γ exhibited antitumor immune properties by upregulating MRP and downregulating BCRP expression, reversing drug-resistance gene expression, and reducing cell viability and migration, while promoting apoptosis in PANC-1/GEM cells. IFN-γ could potentially serve as a treatment option for patients with GEM-resistant pancreatic cancer. [ABSTRACT FROM AUTHOR]

The antitumor effect of norcantharidin (NCTD) has been widely reported. However, whether NCTD can inhibit cervical cancer remains unknown. In the present study, it was shown that NCTD inhibited the viability of cervical cancer cells and caused cell cycle arrest in a concentration-dependent manner. Further analysis revealed that the NCTD-induced reduction in cell viability could be reversed by the inhibitor of apoptosis z-VAD-FMK and by the inhibitor of endoplasmic reticulum (ER) stress, 4-phenylbutyric acid (4-PBA). Additionally, NCTD led to the accumulation of reactive oxygen species as well as a decrease in the mitochondrial membrane potential in cervical cancer cells, whereas 4-PBA pre-treatment attenuated these alterations. In addition, NCTD increased the expression of the apoptosis-related proteins Bip, activating transcription factor (ATF) 4 and C/EBP homologous protein in a concentration-dependent manner. Moreover, NCTD significantly increased the expression of the ER stress-related signaling molecules protein kinase R-like ER kinase, inositol-requiring enzyme 1 and ATF6, but 4-PBA abolished these effects. In vivo experiments showed that NCTD significantly inhibited the growth of subcutaneous tumors in mice. Additionally, the expression of ER stress-related molecules and apoptosis-related proteins increased significantly after NCTD treatment. In conclusion, NCTD induces apoptosis by activating ER stress and ultimately curtails the progression of cervical cancer. [ABSTRACT FROM AUTHOR]

The article titled "[Retracted] Activation of the LKB1-SIK1 signaling pathway inhibits the TGF-β-mediated epithelial-mesenchymal transition and apoptosis resistance of ovarian carcinoma cells" was published in Molecular Medicine Reports in 2018. However, it has since been retracted due to concerns raised by a reader regarding the similarity of certain data in the article to data in other articles published or under consideration for publication at the same time. The authors were asked for an explanation but did not respond. The editor apologizes for any inconvenience caused. [Extracted from the article]

Heart failure is a primary cause of global mortality. In the present study, whether larixyl acetate, an inhibitor of transient receptor potential cation channel subfamily C member 6, attenuates pressure overload-induced heart failure in mice was investigated. To test this hypothesis, a transverse aortic constriction (TAC) animal model and an angiotensin II (Ang II)-treated H9c2 cell model were used. Cardiac and cellular structure, function and the expression levels of hypertrophy, endoplasmic reticulum (ER) stress, apoptosis, autophagy and pmTOR/mTOR related mRNAs or proteins were assessed to explore the underlying molecular mechanisms. The results indicated that treatment with TAC or Ang II leads to significant hypertrophy and dysfunction of the heart or H9c2 cells, accompanied by an increase in ER stress, apoptosis and activation of the mTOR signaling pathway, and a decrease in autophagy. The administration of larixyl acetate attenuated these impairments, which can be reversed by inhibiting autophagy through the activation of the mTOR signaling pathway. These findings suggested that larixyl acetate can effectively protect against pressure overload-induced heart failure by enhancing autophagy and limiting ER stress and apoptosis through inhibition of the mTOR pathway. [ABSTRACT FROM AUTHOR]

This document is a corrigendum for an article published in Molecular Medicine Reports. The authors discovered errors in Figure 4 of their paper, where gel slices were mistakenly placed. The authors have corrected the data and provided the accurate version of Figure 4. They assure readers that these errors did not significantly impact the results or conclusions of the paper. The authors apologize for any inconvenience caused. The article discusses the association of FKBP11 expression levels with ER stress in IFN-γ/TNF-α-treated HT-29 cells. [Extracted from the article]

The article titled "[Retracted] Shengxian decoction decreases doxorubicin-induced cardiac apoptosis by regulating the TREM1/NF-κB signaling pathway" has been retracted from the journal Molecular Medicine Reports. A concerned reader brought to the editor's attention that the western blotting data in Figures 2D and 4C were similar to data published in other articles by different authors at different research institutes. Since the contentious data had already been published elsewhere before submission to the journal, the editor decided to retract the paper. The authors were asked for an explanation but did not respond. The editor apologizes for any inconvenience caused. [Extracted from the article]

Doxorubicin (Dox) exhibits a high efficacy in the treatment of numerous types of cancer. However, the beneficial cytotoxic effects of Dox are often accompanied by an increase in the risk of cardiotoxicity. Oxidative stress (OS) plays a key role in Dox‑induced cardiomyopathy (DIC). OS in cardiomyocytes disrupts endoplasmic reticulum (ER) function, leading to the accumulation of misfolded/unfolded proteins known as ER stress. ER stress acts as an adaptive mechanism; however, prolonged ER stress together with OS may lead to the initiation of cardiomyocyte apoptosis. The present study aimed to explore the potential of an anti‑diabetic drug, empagliflozin (EMPA), in mitigating Dox‑induced ER stress and cardiomyocyte apoptosis. In the present study, the effects of 1 h pretreatment of EMPA on Dox‑treated cardiomyocytes isolated from Sprague‑Dawley rats were investigated. After 24 h, EMPA pre‑treatment promoted cell survival in the EMPA + Dox group compared with the Dox group. Results of the present study also demonstrated that EMPA mitigated overall ER stress, as the increased expression of ER stress markers was reduced in the EMPA + Dox group. Additionally, OS, inflammation and expression of ER stress apoptotic proteins were also significantly reduced following EMPA pre‑treatment in the EMPA + Dox group. Thus, EMPA may exert beneficial effects on Dox‑induced ER stress and may exhibit potential changes that can be utilised to further evaluate the role of EMPA in mitigating DIC.

Reperfusion is a critical therapeutic intervention used following acute ischemic stroke; however, it may cause cerebral ischemia/reperfusion injury (CIRI) and aggravate brain damage. Piceatannol (Pic), a hydroxylated analog of resveratrol, has been reported to exhibit anti‑inflammatory effects. However, the detailed molecular mechanisms and its effects on CIRI have not been sufficiently assessed, and, to the best of our knowledge, current methods of prevention of CIRI are limited. The aim of the present study was to investigate the effects of Pic on improving neurological function in a mouse model of CIRI. For the animal experiments, 8‑week‑old C57BL/6 mice were raised and randomly grouped, and an in vivo model of CIRI was established. Mice were administered a low (10 mg/kg/day) or high‑dose (20 mg/kg/d) of Pic 1 h after CIRI orally and once daily for the next 6 days. Neurological dysfunction was assessed using a modified neurological severity score and a rotarod test 1 week after CIRI establishment, and the cognitive status of the mice was assessed using a Morris water maze. Hematoxylin and eosin staining was used to evaluate the histopathological changes. The expression levels of sirtuin 1 (Sirt1), FoxO1, cleaved caspase‑3 (CC‑3), Bax and Bcl‑2 were measured using western blotting. Intracellular reactive oxygen species (ROS) generation, antioxidant enzymes [superoxide dismutase, glutathione (GSH) peroxidase and catalase] and non‑enzymatic antioxidants (GSH) were also detected using spectrophotometry. After inhibition of the Sirt1/FoxO1 pathway, a TUNEL assay was used for the detection of apoptotic cells in vitro and in vivo. The co‑localization of neuron‑specific nuclear protein and CC‑3 was assessing using immunofluorescent staining. Pic improved neurological functions and ameliorated hippocampal neuronal pathology following CIRI. In addition, the expression levels of CC‑3 and Bax and intracellular ROS levels were increased, while levels of antioxidant and non‑enzymatic enzymes were decreased in the mouse model of CIRI. Low and high doses of Pic significantly decreased ROS production and the expression levels of apoptosis‑related proteins, but increased antioxidant enzyme levels. However, a high‑dose of Pic did not result in increased levels of non‑enzymatic enzymes. Furthermore, low and high doses of Pic treatment significantly activated the Sirt1/FoxO1 pathway. Following inhibition of the Sirt1/FoxO1 pathway, the percentage of TUNEL‑positive cells and expression of CC‑3 were increased, and CC‑3 was enriched in neurons. The antioxidant effects of Pic were blocked by inhibition of Sirt1 in vitro and in vivo. In conclusion, these results suggested that Pic may exert a neuroprotective effect against in hippocampal neurons via the Sirt1/FoxO1 pathway. [ABSTRACT FROM AUTHOR]

Accumulating evidence suggests that inflammation is linked to multiple pathological processes and induces cellular and molecular damage through the activation of inflammatory signaling pathways, including the NF‑κB pathway. The aim of the present study was to identify natural anti‑inflammatory products that can target NF‑κB activity, in order to establish a novel therapeutic approach for inflammatory diseases. Using a 4T1 breast cancer cell line that expresses the firefly luciferase gene under the control of an NF‑κB response element, 112 natural products were tested for their anti‑inflammatory properties. Sohakuhi (Morus alba Linn. bark) extract was observed to strongly suppress NF‑κB activity without affecting cell viability. To further examine the anti‑inflammatory effect of Sohakuhi, tumor necrosis factor‑related apoptosis‑inducing ligand (TRAIL)‑induced cellular damage of human HaCaT keratinocytes was evaluated. While TRAIL triggered the phosphorylation of the p65 subunit of NF‑κB, leading to cellular damage in HaCaT cells, treatment with Sohakuhi extract protected HaCaT cells against TRAIL‑induced cellular damage. Moreover, Sohakuhi treatment also upregulated the anti‑apoptotic proteins Bcl‑xL and Bcl‑2. Importantly, through chemical fractionation of Sohakuhi extract, moracin O and P were confirmed to mediate its anti‑inflammatory effects. Collectively, the present results indicated that Sohakuhi and moracin may represent potential candidates for the development of novel anti‑inflammatory drugs. [ABSTRACT FROM AUTHOR]

Acute myocardial infarction can be caused by ischemia/reperfusion (I/R) injury; however, the mechanism underlying I/R is not completely understood. The present study investigated the functions and mechanisms underlying microRNA (miR)‑494 in I/R‑induced cardiomyocyte apoptosis and autophagy. Hypoxia/reoxygenation (H/R)‑treated H9c2 rat myocardial cells were used as an in vitro I/R injury model. Apoptosis and autophagy were analyzed by Cell Counting Kit‑8 assay, Lactic dehydrogenase and superoxide dismutase assay, flow cytometry, TUNEL staining and western blotting. Reverse transcription‑quantitative PCR demonstrated that, H9c2 cells treated with 12 h hypoxia and 3 h reoxygenation displayed significantly downregulated miR‑494 expression levels compared with control cells. Compared with the corresponding negative control (NC) groups, miR‑494 mimic reduced H/R‑induced cell apoptosis and autophagy, whereas miR‑494 inhibitor displayed the opposite effects. Silent information regulator 1 (SIRT1) was identified as a target gene of miR‑494. Furthermore, miR‑494 inhibitor‑mediated effects on H/R‑induced cardiomyocyte apoptosis and autophagy were partially reversed by SIRT1 knockdown. Moreover, compared with si‑NC, SIRT1 knockdown significantly increased the phosphorylation levels of PI3K, AKT and mTOR in H/R‑treated and miR‑494 inhibitor‑transfected H9c2 cells. Collectively, the results indicated that miR‑494 served a protective role against H/R‑induced cardiomyocyte apoptosis and autophagy by directly targeting SIRT1, suggesting that miR‑494 may serve as a novel therapeutic target for myocardial I/R injury. [ABSTRACT FROM AUTHOR]

Human cathelicidin antimicrobial peptide and its active product, LL‑37 (CAMP/LL‑37), exhibit a broad spectrum of antimicrobial effects. An increasing number of studies have shown that human CAMP/LL‑37 also serves significant roles in various types of cancer. The primary aims of the present study were to investigate the roles and mechanisms of human CAMP/LL‑37 in oral squamous cell carcinoma (OSCC) cells. The results indicated that either LL‑37 C‑terminal deletion mutants (CDEL) or CAMP stable expression in HSC‑3 cells reduced colony formation, proliferation, migration and invasion ability of the cells. Expression analysis demonstrated that either CDEL or CAMP stable expression in HSC‑3 cells induced caspase‑3 mediated apoptosis via the P53‑Bcl‑2/BAX signalling pathway, whereas the levels of cell cycle‑related proteins, cyclin B1 and PKR‑like ER kinase, were significantly upregulated in the CAMP, but not in the CDEL overexpressing cells. Transcriptional profile comparisons revealed that CDEL or CAMP stable expression in HSC‑3 cells upregulated expression of genes involved in the IL‑17‑dependent pathway compared with the control. Taken together, these results suggest that CAMP may act as a tumour suppressor in OSCC cells, and the underlying mechanism involves the induction of caspase‑3 mediated apoptosis via the P53‑Bcl‑2/BAX signalling pathway. [ABSTRACT FROM AUTHOR]

Intestinal surface epithelial cells (IECs) have long been considered as an effective barrier for maintaining water and electrolyte balance, and are involved in the mechanism of nutrient absorption. When intestinal inflammation occurs, it is often accompanied by IEC malfunction. Berberine (BBR) is an isoquinoline alkaloid found in numerous types of medicinal plants, which has been clinically used in China to treat symptoms of gastrointestinal pathogenic bacterial infection, especially bacteria‑induced diarrhea and inflammation. In the present study, IEC‑18 rat intestinal epithelial cells were treated with lipopolysaccharide (LPS) to establish an in vitro model of epithelial cell inflammation, and the cells were subsequently treated with BBR in order to elucidate the anti‑inflammatory mechanism. Transcriptome data were then searched to find the differentially expressed genes (DEGs) compared between two of the treatment groups (namely, the LPS and LPS+BBR groups), and DEGs were analyzed using Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, Weighted Gene Correlation Network Analysis and Interactive Pathways Explorer to identify the functions and pathways enriched with DEGs. Finally, reverse transcription-quantitative PCR was used to verify the transcriptome data. These experiments revealed that, comparing between the LPS and LPS+BBR groups, the functions and pathways enriched in DEGs were ‘DNA replication’, ‘cell cycle’, ‘apoptosis’, ‘leukocyte migration’ and the ‘NF-κB and AP-1 pathways’. The results revealed that BBR is able to restrict DNA replication, inhibit the cell cycle and promote apoptosis. It can also inhibit the classic inflammatory pathways, such as those mediated by NF‑κB and AP-1, and the expression of various chemokines to prevent the migration of leukocytes. According to transcriptomic data, BBR can exert its anti‑inflammatory effects by regulating a variety of cellular physiological activities, including cell cycle, apoptosis, inflammatory pathways and leukocyte migration. [ABSTRACT FROM AUTHOR]

Oxyresveratrol (ORES) is a natural phenolic compound with multiple biological functions including antioxidation, anti‑inflammation and neuroprotection; however, the inhibitory effect of ORES on osteosarcoma remains largely unknown. The present study aimed to determine the effects of ORES on osteosarcoma cell Saos‑2. Cell Counting Kit‑8 assay was performed to detect Soas‑2 cell viability. Annexin‑FITC/PI staining and JC‑1 staining were used to measure cell apoptosis and the change of mitochondrial membrane potential. In addition, western blotting was conducted to determine the expression levels of apoptotic proteins and the phosphorylation of STAT3. It was found that ORES inhibited cell viability and induced apoptosis of osteosarcoma Saos‑2 cells in a concentration‑dependent manner. In addition, ORES increased the expression levels of apoptotic proteases caspase‑9 and caspase‑3 and reduced mitochondrial membrane potential. In response to ORES treatment, the expression levels of pro‑apoptotic proteins, Bad and Bax, were enhanced, whereas those of anti‑apoptotic proteins, Bcl‑2 and Bcl‑xL, were reduced. In addition, the phosphorylation of STAT3 was attenuated in Saos‑2 cells after treatment with ORES. Inhibition of cell viability and apoptosis induction by ORES were rescued by enhancement of STAT3 activation upon treatment with IL‑6. Collectively, the present study indicated that ORES induced apoptosis and inhibited cell viability, which may be associated with the inhibition of STAT3 activation; thus, ORES represents a promising agent for treating osteosarcoma. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS) is one of the most common endocrine metabolic disorders characterized by hyperandrogenism, polycystic ovaries and ovulatory dysfunction. Several studies have suggested that the aberrant expression of microRNAs (miRNAs/miRs) plays an important role in the pathogenesis of PCOS; however, the role and underlying mechanisms of miR‑132 in the development of PCOS remain unclear. In the present study, the expression of miR‑132 in granulosa cells (GCs) derived from 26 patients with PCOS and 30 healthy controls was detected by reverse transcription-quantitative PCR (RT-qPCR). The apoptosis of GCs was examined using a TUNEL assay. The human ovarian granulosa-like tumor cell line, KGN, was cultured for Cell Counting Kit-8 assays following the overexpression or knockdown of miR‑132. TargetScan was applied to identify the potential targets of miR‑132, which was further verified by a luciferase assay, RT‑qPCR and western blotting. The expression of miR‑132 was decreased in GCs from patients with PCOS. Moreover, the GCs of patients with PCOS exhibited significantly increased apoptotic nuclei. Furthermore, the overexpression of miR‑132 inhibited the viability of KGN cells. In addition, the results verified that miR‑132 directly targeted forkhead box protein A1 (Foxa1), the knockdown of which suppressed KGN cell viability. On the whole, the findings of the present study demonstrated that miR‑132 inhibited cell viability and induced apoptosis by directly interacting with Foxa1. Thus, miR‑132 may be a potential target for the treatment of patients with PCOS. [ABSTRACT FROM AUTHOR]

Tripartite motif-containing (TRIM) 14 is a protein of the TRIM family. Studies have indicated that TRIM14 may be used as an oncogene in tumor cells, such as osteosarcoma, non-small cell lung cancer and breast cancer through different pathways. However, the functions of TRIM14 in cervical cancer cells remain unclear. Therefore, this study aimed to investigate the functions of TRIM14 in cervical cancer cells and its underlying mechanism. Caski cells stably expressing TRIM14 and SiHa, and HeLa cells stably expressing TRIM14 short hairpin RNA were constructed by lentivirus-mediated overexpression or knockdown systems. The effects of TRIM14 on proliferation and apoptosis of cervical cancer cells were detected by Cell Counting Kit‑8 (CCK‑8) assay and flow cytometry, respectively. In addition, reverse transcription-quantitative (RT-q) PCR and western blotting were used to investigate the expression levels of TRIM14 and of signaling pathway marker protein including P21, caspase-3, cleaved caspase-3, Akt and phosphorylated Akt. The results of RT-qPCR and western blotting revealed that TRIM14 was highly expressed in human cervical cancer tissues and cell lines compared with adjacent normal tissues and normal cervical epithelial cells. TRIM14 also regulated cell proliferation and apoptosis of human SiHa, HeLa and Caski cervical cancer cell lines through the Akt signaling pathway. Additionally, TRIM14 protein levels were related to the clinical and pathological features of cervical cancer. CCK‑8 assay and flow cytometry demonstrated that TRIM14 expression could promote cervical cancer cell proliferation and autophagy suppression. Taken together, TRIM14-induced cell proliferation and apoptosis inhibition may by evoked by the activation of the Akt pathway. This study demonstrated the role of TRIM14 in cervical cancer, and reveals its mechanism of action as a potential therapeutic target for cervical cancer. [ABSTRACT FROM AUTHOR]