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Chinese hamster ovary (CHO) cells are by far the most important mammalian cell lines used for producing antibodies and other therapeutic proteins. It is critical to fully understand their physiological conditions during a bioprocess in order to achieve the highest productivity and the desired product quality. Flow cytometry technology possesses unique advantages for measuring multiple cellular attributes for a given cell and examining changes in cell culture heterogeneity over time that can be used as metrics for enhanced process understanding and control strategy. Flow cytometry-based assays were utilized to examine the progression of cell cycle and apoptosis in three case studies using different antibody-producing CHO cell lines in both fed-batch and perfusion bioprocesses. In our case studies, we found that G0/G1 phase distribution and early apoptosis accumulation responded to subtle changes in culture conditions, such as pH shifting or momentary glucose depletion. In a perfusion process, flow cytometry provided an insightful understanding of the cell physiological status under a hypothermic condition. More importantly, these changes in cell cycle and apoptosis were not detected by a routine trypan blue exclusion-based cell counting and viability measurement. In summary, integration of flow cytometry into bioprocesses as a process analytical technology tool can be beneficial for establishing optimum process conditions and process control., (© 2021 American Institute of Chemical Engineers.)

In this article, the authors comment on the research paper "Dynamics of serum-induced endothelial cell apoptosis in patients with myocardial infarction" by researcher named Forteza and colleagues. They state that endothelial cell (EC) apoptosis occur late after the onset of reperfusion and EC necrosis appears as a rare event. They also state that EC can be used in the treatment of acute myocardial infarction (AMI).

Many anticarcinogenic drugs kill tumour cells by inducing apoptosis. We examined the effects of hydrogen peroxide (H2O2) on arsenic trioxide (As2O3)-induced cell killing. Low concentrations of H2O2 (200 μmol/l) inhibited the ability of As2O3 to induce apoptosis in the Burkitt's lymphoma cell line Raji. H2O2 altered the form of cell death from apoptosis to pyknosis/ necrosis and also lowered the degree of cell killing by As2O3. H2O2 was capable of preventing caspase-3 activation induced by As2O3 in Raji cells. Incubation of cells with a phosphoinositide-3 kinase (PI-3K) inhibitor, wortmannin (100 nmol/l), blocked the effects of H2O2 on As2O2-induced caspase-3 activation. In addition, the PI-3K inhibitor partially blocked the effects of H2O2 on up-regulation of Bcl-2 and Bcl-X1. protein expression, down-regulation of Bax protein expression, and phosphorylation of Bcl-2 and IκBα. This investigation demonstrated for the first time that low concentrations of H2O2 provide protection against the in vivo of As2O3- induced apoptosis. PI-3K plays a crucial role in enhancing cell survival during H2O2, inhibiting As2O3-induced apoptosis in the Burkitt's lymphoma cells. As2O3-induced cancer cell apoptosis may be enhanced by certain antioxidants in the treatment protocol. [ABSTRACT FROM AUTHOR]

Terminal B-cell differentiation is a multi-step process, from short-lived plasmablasts to mature long-lived plasma cells (PC). The anti-apoptotic Bcl-2 family member Bfl-1/A1 plays a critical role in the survival of mature B cells. However, its potential involvement at the later stages of B-cell development remains highly controversial. Our aim was thus to clarify the place of Bfl-1/A1 in the biology of normal PC and in the pathogenesis of multiple myeloma (MM), the major PC dyscrasia. Using gene expression profiling and quantifiable reverse transcription polymerase chain reaction experiments, we found a similar down-regulation of Bfl-1/A1 in both normal immature plasmablasts and mature PC when compared with B cells. In myeloma cells, the level of Bfl-1/A1 was low and Bfl-1/A1 was not a nuclear factor κB-inducible gene. Collectively, these data demonstrate that Bfl-1/A1 is not involved in the prolonged survival of normal mature PC, and that Bfl-1/A1 deregulation is not a common oncogenic event in MM. However, overexpression of Bfl-1/A1 by retroviral transduction promoted autonomous survival of an interleukin-6-dependent myeloma cell line and rendered it less sensitive to dexamethasone. Thus, Bfl-1/A1 transduction could be an interesting tool to obtain myeloma cell lines from primary samples and to favour the in vitro generation of antibody-secreting, long-lived normal PC. [ABSTRACT FROM AUTHOR]

Multiple myeloma (MM) is a neoplastic proliferation of plasma cells and remains an incurable disease because of the development of drug resistance. Histone deacytylase (HDAC) inhibitors are a new class of chemotherapeutic reagents that cause growth arrest and apoptosis of neoplastic cells. Depsipeptide, a new member of the HDAC inhibitors, was found to be safe in humans and has been shown to induce apoptosis in various cancers. In order to evaluate the effects of depsipeptide, a MM cell line, U266 [interleukin (IL)-6 dependent], was analysed for viability and apoptosis. The combined effect of depsipeptide with melphalan and changes in BCL-2 family proteins (BCL-2, BCL-XL, BAX and MCL-1) were also investigated. In addition, the RPMI 8226 cell line (IL-6 independent), and primary patient myeloma cells were also analysed for apoptosis after depsipeptide treatment. Depsipeptide induced apoptosis in both U266 and RPMI 8226 cell lines in a time- and dose-dependent fashion, and in primary patient myeloma cells. We also demonstrated that depsipeptide had an additive effect with melphalan (10 μmol/l). BCL-2, BCL-XL and MCL-1 showed decreased expression in depsipeptide-treated samples. Based on recent clinical trials demonstrating minimal clinical toxicity, our study supports the future clinical utilization of depsipeptide in the management of MM. [ABSTRACT FROM AUTHOR]

Multiple mechanisms exist by which tumour cells can escape CD95-mediated apoptosis. Previous studies by our laboratory have shown that primary B cells from non-Hodgkin's Lymphoma (B-NHL) were resistant to CD95-induced cell death. In the current study, we have analysed the mechanisms underlying CD95 resistance in primary human lymphoma B cells. We report that FADD (FAS-associated death domain protein) and caspase-8 were constitutively expressed in lymphoma B cells and that the CD95 pathway was blocked upstream to caspase-8 activation. However, caspase-8 was processed and functional after treatment with staurosporine (STS). We found that the expression levels of FLICE (FADD-like interleukin-1 beta-converting enzyme)-Inhibitory Protein (c-FLIP) and Bcl-2-related proteins were heterogeneous in B-NHL cells and were not related to CD95 resistance. Finally, we report the absence of a CD95-induced signalling complex [death-inducing signalling complex (DISC)] in lymphoma B cells, with no FADD and caspase-8 recruitment to CD95 receptor. In contrast, DISC formation was observed in CD95-resistant non-tumoural (NT) B cells. Therefore, we propose that the absence of DISC formation in primary lymphoma B cells may contribute to protect these cells from CD95-induced apoptosis. [ABSTRACT FROM AUTHOR]

Myeloma cells and human umbilical vein endothelial cells (HUVECs) were co-cultured to model in vitro the interactions between myeloma and endothelium, and treated with thalidomide and two selective cytokine inhibitory drugs (SelCIDs, phosphodiesterase-4 inhibitors). Flow cytometry and enzyme-linked immunosorbent assay were used to assess production of two key cytokines – vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6) – and apoptosis in co-cultured HUVECs and myeloma cells. VEGF was produced by both myeloma cells and HUVECs, while IL-6 was almost exclusively produced by endothelial cells. In co-culture, there was significant up-regulation of VEGF and IL-6 production compared with the sum of separate myeloma and endothelial cell cultures. SelCIDs markedly inhibited production of both cytokines in co-cultures, with CC-10004 being more potent than CC-1088. In addition, SelCIDs induced myeloma cell apoptosis. Apoptosis in co-cultured myeloma cells was significantly lower than in those cultured separately, suggesting that co-culture partially protected myeloma cells from drug-induced apoptosis. This protective effect was probably due to IL-6 produced by endothelial cells in co-culture as addition of anti-IL-6 neutralizing antibody, but not anti-VEGF antibody, abrogated it. In conclusion, SelCIDs can exert their anti-myeloma activity through two mechanisms, i.e. inhibition of VEGF and IL-6 production by interacting myeloma and endothelium and induction of myeloma cell apoptosis. [ABSTRACT FROM AUTHOR]

The thienopyridine platelet antagonist ticlopidine is associated with development of thrombotic thrombocytopenic purpura (TTP) but the pathophysiology of this link is unclear. Severe deficiency of disintegrin and metalloproteinase with thrombospondin motif-13 (ADAMTS13), described in familial cases and a significant fraction of idiopathic TTP, has been reported in only a few ticlopidine-linked cases. As ticlopidine can disrupt production of extracellular matrix (ECM) components critical to microvascular endothelial cell (MVEC) integrity in vitro, we explored the hypotheses that ticlopidine and ticlopidine-linked TTP plasmas induce MVEC apoptosis in a manner similar to that of idiopathic TTP plasmas, and that ECM components and related mitogen-activated protein kinase (MAPK) signalling cascades may be involved in this process. Replicating the activity of plasmas from patients with idiopathic TTP, plasma from five ticlopidine-linked TTP patients induced apoptosis of primary human dermal, glomerular and hepatic MVEC, but had no effect on pulmonary MVEC or large vessel endothelial cells (EC). Pharmacological levels of ticlopidine initiated apoptosis with similar EC lineage restriction. In parallel, ticlopidine and plasmas from idiopathic and ticlopidine-TTP patients decreased transcripts for the ECM component thrombospondin-1 in MVEC, but not in large vessel EC. These changes were accompanied by prolonged induction of MAPKs extracellular signal-related kinase (ERK)-1/2 and p38 only in TTP susceptible MVEC. Induction of apoptosis by ticlopidine and TTP plasma was abrogated by inhibitors of ERK-1/2 and p38 phosphorylation. In conclusion, MVEC apoptosis related to altered ECM–MVEC interactions may be a key part of the pathology of ticlopidine-linked and idiopathic TTP. [ABSTRACT FROM AUTHOR]

Apicidin, a histone deacetylase inhibitor, is a novel cyclic tetrapeptide with potent antiproliferative activity against various cancer cells. We examined whether apicidin potentiates the imatinib-induced apoptosis of Bcr–Abl-positive human leukaemia cells. In K562 cells, the co-administration of minimally toxic concentrations of imatinib and apicidin (imatinib/apicidin) for 48 h produced a marked increase in mitochondrial damage, processing of caspase cascades and apoptosis. Similar results were observed in leukaemic blasts obtained from patients with chronic myeloid leukaemia in blast crisis. Imatinib/apicidin co-treatment for 48 h resulted in a near complete loss of the full-length XIAP (X-linked inhibitor of apoptosis) protein, with a corresponding increase in the 29-kDa XIAP cleavage product. Both the degradation of XIAP and increased release of second mitochondria-derived activator of caspase/direct IAP-binding protein with low pI (Smac/DIABLO) into the cytosol were abrogated by pretreatment with the caspase-3 inhibitor DEVD-CHO. Imatinib/apicidin co-treatment for 48 h produced a prominent decrease in Bcr–Abl protein levels in a caspase-dependent manner. In summary, these data indicate that apicidin potentiates the imatinib-induced apoptosis of Bcr–Abl-positive leukaemia cells through the enhanced activation of the mitochondria-dependent caspase cascades, accompanied by caspase-dependent downregulation of Bcr–Abl and XIAP. These findings generate a rationale for further investigation of apicidin and imatinib as a potential therapeutic strategy in Bcr–Abl-positive leukaemias. [ABSTRACT FROM AUTHOR]

Osteoporosis (OP) is a systemic metabolic bone disease that is characterized by decreased bone mineral density and microstructural damage to bone tissue. Recent studies have demonstrated significant advances in the research of programmed cell death (PCD) in OP. However, there is no bibliometric analysis in this research field. This study searched the Web of Science Core Collection (WoSCC) database for literature related to OP and PCD from 2000 to 2023. This study used VOSviewers 1.6.20, the "bibliometrix" R package, and CiteSpace (6.2.R3) for bibliometric and visualization analysis. A total of 2905 articles from 80 countries were included, with China and the United States leading the way. The number of publications related to PCD in OP is increasing year by year. The main research institutions are Shanghai Jiao Tong University, Chinese Medical University, Southern Medical University, Zhejiang University, and Soochow University. Bone is the most popular journal in the field of PCD in OP, and the Journal of Bone and Mineral Research is the most co‐cited journal. These publications come from 14,801 authors, with Liu Zong‐Ping, Yang Lei, Manolagas Stavros C, Zhang Wei, and Zhao Hong‐Yan having published the most papers. Ronald S. Weinstein was co‐cited most often. Oxidative stress and autophagy are the current research hot spots for PCD in OP. This bibliometric study provides the first comprehensive summary of trends and developments in PCD research in OP. This information identifies the most recent research frontiers and hot directions, which will provide a definitive reference for scholars studying PCD in OP. [ABSTRACT FROM AUTHOR]

Presents a list of research papers scheduled to be published in future issues of the journal 'Immunology,' as of September 1, 2003. Article on induction of apoptosis by interleukin-2-activated cytotoxic lymphocytes in squamous cell carcinoma cell line; Research paper on paradoxical effects of interleukin-10 on the maturation of murine myeloid dendritic cells; Paper on selective regulation of CD40 expression in murine dendritic cells by thiol antioxidants.

Mangiferin (MGF) is a phenolic compound, which is a major source of MGF is the mango tree. MGF possesses some antioxidant, anti‐inflammatory, and cytoprotective properties, enabling it to play its role against various diseases such as diabetes, obesity, lung injuries, and cancer. The word "Cancer" depicts an uncontrolled and abnormal growth of cells. This review paper reveals MGF's therapeutic, curative and protective potential impact against lung, liver, ovarian, prostate, breast, stomach, and oral cancers. MGF is used in various types of research in the form of powder, liquid extract, intramuscular, intravenous, nanoparticles coated with gold, in the form of a solution, or in combination with other drugs to evaluate synergistic effects. Many studies showed that MGF is safe to use but has less bioavailability in the body and 0.111 mg/mL solubility in water. However, certain studies indicated that its bioavailability and retention time increased when taken in the form of nanoparticles and in combination with other drugs. MGF also increases the sensitivity of other drugs (i.e., cisplatin) resistant to tumors. MGF has different mechanisms of action for different cancers. It mainly targets enzymes, interleukins, tumor growth factors, signaling pathways, apoptotic proteins, and genes to inhibit the growth of tumors, volume, angiogenesis, cellular functionality, further progression, and movement to other areas of the body. Moreover, MGF increases apoptosis and body weight with no or fewer side effects on normal cells. MGF unveiled a novel gate toward the treatment of cancer. Further research and human trials are needed in this regard. [ABSTRACT FROM AUTHOR]

This paper is dedicated to solving the model reconstruction problem of Boolean networks (BNs) based on incomplete information. By resorting to semi‐tensor product, the issue of finding logical functions is converted into designing corresponding structure matrices. In line with desired attractors, two circumstances, standard BNs and delayed BNs, are taken into consideration, and several new results are presented. For the model reconstruction of standard BNs, an algebraic condition is put forward and an algorithm is developed for reconstructing unknown logical functions. For the model reconstruction of delayed BNs, an augmented system is deduced, based on which, several criteria and the corresponding algorithm are proposed. Finally, as an application to gene regulatory networks, the results obtained in this paper are used to analyze the WNT5A network and the apoptosis network. [ABSTRACT FROM AUTHOR]

The vestibular lamina (VL) forms as an epithelial outgrowth parallel to the dental lamina (DL) in the oral cavity. During late development, it opens to create a furrow that divides the dental tissue from the cheeks and lips and is known as the vestibule. Defects in this process lead to failure in the separation of the teeth from the lips and cheeks, including the presence of multiple frenula. In this paper, the development of the VL is followed in the mouse, from epithelial placode in the embryo to postnatal opening and vestibule formation. During early outgrowth, differential proliferation controls the curvature of the VL as it extends under the forming incisors. Apoptosis plays a role in thinning the deepest part of the lamina, while terminal differentiation of the epithelium, highlighted by the expression of loricrin and flattening of the nuclei, predates the division of the VL into two to create the vestibule. Development in the mouse is compared to the human VL, with respect to the relationship of the VL to the DL, VL morphology and mechanisms of opening. Overall, this paper provides insight into an understudied part of the oral anatomy, shedding light on how defects could form in this region. [ABSTRACT FROM AUTHOR]

Wound healing is an extremely complex process involving multiple levels of cells and tissues. It is mainly completed through four stages: haemostasis, inflammation, proliferation, and remodelling. When any one of these stages is impaired, it may lead to delayed healing or even transformation into chronic refractory wounds. Diabetes is a kind of common metabolic disease that affects approximately 500 million people worldwide, 25% of whom develop skin ulcers that break down repeatedly and are difficult to heal, making it a growing public health problem. Neutrophils extracellular traps and ferroptosis are new types of programmed cell death identified in recent years and have been found to interact with diabetic wounds. In this paper, the normal wound healing and interfering factors of the diabetic refractory wound were outlined. The mechanism of two kinds of programmed cell death was also described, and the interaction mechanism between different types of programmed cell death and diabetic refractory wounds was discussed. [ABSTRACT FROM AUTHOR]

RETRACTION: R. Sun, R. Zhai, C. Ma, and W. Miao, "Combination of Aloin and Metformin Enhances the Antitumor Effect by Inhibiting the Growth and Invasion and Inducing Apoptosis and Autophagy in Hepatocellular Carcinoma Through PI3K/AKT/mTOR Pathway," Cancer Medicine 9, no. 3 (2020): 1141–1151, https://doi.org/10.1002/cam4.2723. The above article, published online on 12 December 2019 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the authors; the journal Editor‐in‐Chief, Stephen Tait; and John Wiley and Sons Ltd. The authors asked to retract the article as they found significant errors in the data collection and analysis, therefore the conclusions of the paper are not supported. Subsequently, an investigation into concerns raised by a third party revealed inappropriate duplication of images (Figure 1C, 2B and 4C, D) between this and other articles that were previously published or published shortly after in a different scientific context. Thus, the editors consider the conclusions of this manuscript substantially compromised. Although the authors initially asked for the retraction, when asked to approve the retraction wording, they remained unresponsive. [ABSTRACT FROM AUTHOR]

BACKGROUND RESULT CONCLUSION Sulforaphene is a derivative of glucosinolate and a potential bioactive substance used for treating colon cancer. This study aimed to evaluate the potential inhibitory effect and mechanisms of sulforaphene in human colon cancer Caco‐2 cells. Network pharmacology, molecular docking, and experimental verification were performed to elucidate potential sulforaphene mechanisms in the treatment of this condition.Network pharmacology predicted 27 intersection target genes between sulforaphene and colon cancer cell inhibition. Key sulforaphene targets associated with colon cancer cell inhibition were identified as EGFR, MAPK14, MCL1, GSK3B, PARP1, PTPRC, NOS2, CTSS, TLR9, and CTSK. Gene ontology functional enrichment analysis revealed that the above genes were primarily related to the positive regulation of peptidase activity, cytokine production in the inflammatory response, and the cell receptor signaling pathway. Kyoto Encyclopedia of Genes and Genomes enrichment analysis indicated that sulforaphene mainly inhibited the proliferation of cancer cells by affecting apoptosis as well as the signaling pathways of PD‐1, Toll‐like receptor, T cell receptor, and P13k–Akt. Molecular docking results further confirmed that CTSS, GSK3B, and NOS2 were significantly up‐regulated and had good binding affinity with sulforaphene. In vitro experiments also indicated that sulforaphene had a significant inhibitory effect on human colon cancer Caco‐2 cells.This paper revealed the pharmacodynamic mechanism of sulforaphene in the treatment of colon cancer for the first time. It provides scientific insight into the development of sulforaphene as a medicinal resource. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

One of the hottest topics in biomedical research is to decipher the functional implications of the Gasdermin (GSDM) protein family in human pathologies. These proteins are the key effectors of a lytic and pro‐inflammatory cell death type termed pyroptosis (also known as "Gasdermin‐mediated programmed cell death"). However, ever‐growing evidence showed that GSDMs can play multiple and complex roles in a context‐dependent manner. In this sense, Gasdermin‐B (GSDMB; the only GSDM gene absent in mice and rats) has been implicated in antibacterial defense, numerous inflammatory pathologies (e.g., asthma, ulcerative colitis), and cancer, but both cell death‐dependent and ‐independent functions have been reported in these diseases, fueling the debate on whether GSDMB has genuine pyroptotic capacity. Recently, a series of seminal papers cast light on the GSDMB multitasking capacity by showing that different GSDMB transcriptional isoforms have distinct biological activities. Nonetheless, there are still obscure areas to be clarified on the precise functional involvement of GSDMB translated variants in physiological and pathological conditions. In this viewpoint, we critically discuss the most recent and exciting data on this topic and propose a series of relevant challenges that need to be overcome before GSDMB‐driven biomedical applications (as a biomarker of disease risk/progression/outcome or as specific therapeutic target) become a reality in clinical settings. [ABSTRACT FROM AUTHOR]

Melanoma is an aggressive malignancy and remains a major cause of skin cancer mortality, highlighting the need for new treatment strategies. Recent findings revealed that L‐kynurenine and quinolinic acid induce cytotoxicity and morphological changes in B16 F10 melanoma cells in vitro. This paper highlights the effects of L‐kynurenine and quinolinic acid at previously determined half‐maximal inhibitory concentrations on cell cycle progression, cell death and extracellular signal‐regulated protein kinase inhibition. Melanoma, B16 F10 and murine macrophages, RAW 264.7 cells were used in this study, as both cell lines express all the enzymes associated with the kynurenine pathway. Post exposure to the compounds at half‐maximal inhibitory concentrations, transmission electron microscopy was used to assess intracellular morphological changes. Flow cytometry was used to analyse cell cycle progression and quantify apoptosis via the dual staining of Annexin V and propidium iodide and cell survival via extracellular signal‐regulated protein kinase. L‐kynurenine and quinolinic acid at half‐maximal inhibitory concentrations induced intracellular morphological changes representative of cell death. Flow cytometry revealed alterations in cell cycle distribution, increased apoptosis and significantly inhibition of cell survival. L‐kynurenine and quinolinic acid are exogenous kynurenine compounds which inhibited cell survival through extracellular signal‐regulated protein kinase inhibition, induced cell cycle alterations and induced apoptosis in B16 F10 melanoma cells. Significance statement: Data obtained in the current study revealed information regarding the in vitro effects of L‐kynurenine and quinolinic acid on B16 F10 melanoma cell cycle progression, intracellular morphology, extracellular signal‐regulated kinase 1/2 inhibition and cell death. Evaluating the therapeutic effects of kynurenine metabolites against melanoma may potentially result in improved future cancer treatment options to manage the global melanoma burden. [ABSTRACT FROM AUTHOR]

Drug resistance is a hot topic issue in cancer research and therapy. Although cancer therapy including radiotherapy and anti‐cancer drugs can kill malignant cells within the tumor, cancer cells can develop a wide range of mechanisms to resist the toxic effects of anti‐cancer agents. Cancer cells may provide some mechanisms to resist oxidative stress and escape from apoptosis and attack by the immune system. Furthermore, cancer cells may resist senescence, pyroptosis, ferroptosis, necroptosis, and autophagic cell death by modulating several critical genes. The development of these mechanisms leads to resistance to anti‐cancer drugs and also radiotherapy. Resistance to therapy can increase mortality and reduce survival following cancer therapy. Thus, overcoming mechanisms of resistance to cell death in malignant cells can facilitate tumor elimination and increase the efficiency of anti‐cancer therapy. Natural‐derived molecules are intriguing agents that may be suggested to be used as an adjuvant in combination with other anticancer drugs or radiotherapy to sensitize cancer cells to therapy with at least side effects. This paper aims to review the potential of triptolide for inducing various types of cell death in cancer cells. We review the induction or resistance to different cell death mechanisms such as apoptosis, autophagic cell death, senescence, pyroptosis, ferroptosis, and necrosis following the administration of triptolide. We also review the safety and future perspectives for triptolide and its derivatives in experimental and human studies. The anticancer potential of triptolide and its derivatives may make them effective adjuvants for enhancing tumor suppression in combination with anticancer therapy. [ABSTRACT FROM AUTHOR]

Currently, challenges such as chemotherapy resistance, resulting from preoperative and postoperative chemotherapy, postoperative recurrence, and poor bone regeneration quality, are becoming increasingly prominent in osteosarcoma (OS) treatment. There is an urgent need to find more effective ways to address these issues. Ferroptosis is a novel form of iron‐dependent programmed cell death, distinct from other forms of cell death. In this paper, we summarize how, through the three major defense systems of ferroptosis, not only can substances from traditional Chinese medicine, antitumor drugs, and nano‐drug carriers induce ferroptosis in OS cells, but they can also be combined with immunotherapy, differentiation therapy, and other treatment modalities to significantly enhance chemotherapy sensitivity and inhibit tumor growth. Thus, ferroptosis holds great potential in treating OS, offering more choices and possibilities for future clinical interventions. Significance Statement: This article highlights some key challenges in osteosarcoma (OS) treatment, such as chemotherapy resistance, postoperative recurrence, and poor bone regeneration quality, and points out the urgent need to find more effective treatment options. It discusses ferroptosis, a form of iron‐dependent programmed cell death, which differs from other cell death mechanisms, demonstrating its unique value and potential in OS treatment. The importance of the article lies in its explanation of how the three major defense systems of ferroptosis not only can utilize traditional Chinese medicine, antitumor drugs, and nano‐drug carriers to induce ferroptosis in OS cells, but can also be combined with immunotherapy, differentiation therapy, and other treatment methods to significantly enhance chemotherapy sensitivity and inhibit tumor growth. This approach offers more choices and possibilities for the clinical treatment of OS, with significant prospects for clinical application and scientific research. Furthermore, the significance of the article is also evident in its promotion of the integration of traditional and modern medical methods, advocating for a multi‐angle, multi‐strategy comprehensive treatment approach to address complex medical issues. This interdisciplinary treatment strategy not only aids in developing new therapeutic drugs and methods but also provides new directions and insights for future OS research and treatment. [ABSTRACT FROM AUTHOR]

Ferroptosis is a novel type of cell death that is dependent on lipid peroxidation and iron accumulation, which distinguishes it from other types of programmed cell death. Current research indicates a significant association between ferroptosis and various pathological conditions, including cancer, neurological disorders, and cardiovascular diseases, albeit with a relatively unexplored role in dermatological afflictions. This paper elaborates on the mechanisms and signalling pathways of ferroptosis, summarizing the recent studies on ferroptosis and its related factors in dermatosis. Our objective is to shed light on novel perspectives and therapeutic strategies for dermatosis, enhancing the understanding of this under‐researched area through this comprehensive review. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is the most common type of liver cancer with a high death rate in the world. The molecular mechanisms related to the pathogenesis of HCC have not been precisely defined so far. Hence, this review aimed to address the potential cross‐talk between noncoding RNAs (ncRNAs) and programmed cell death in HCC. All related papers in the English language up to June 2023 were collected and screened. The searched keywords in scientific databases, including Scopus, PubMed, and Google Scholar, were HCC, ncRNAs, Epigenetic, Programmed cell death, Autophagy, Apoptosis, Ferroptosis, Chemoresistance, Tumor recurrence, Prognosis, and Prediction. According to the reports, ncRNAs, comprising long ncRNAs, microRNAs, circular RNAs, and small nucleolar RNAs can affect cell proliferation, migration, invasion, and metastasis, as well as cell death‐related processes, such as autophagy, ferroptosis, necroptosis, and apoptosis in HCC by regulating cancer‐associated genes and signaling pathways, for example, phosphoinositide 3‐kinase/Akt, extracellular signal‐regulated kinase/MAPK, and Wnt/β‐catenin signaling pathways. It seems that ncRNAs, as epigenetic regulators, can be utilized as biomarkers in diagnosis, prognosis, survival and recurrence rates prediction, chemoresistance, and evaluation of therapeutic response in HCC patients. However, more scientific evidence is suggested to be accomplished to confirm these results. Highlights: Noncoding RNA (NcRNAs) can affect cell proliferation, migration, invasion, and metastasis, as well as cell death‐related processes in hepatocellular carcinoma (HCC).Autophagy, ferroptosis, necroptosis, and apoptosis are influenced by ncRNAs in HCC by regulating associated signaling pathways.NcRNAs, as epigenetic regulators, can be utilized as biomarkers in diagnosis, prognosis, survival and recurrence rates prediction, chemoresistance, and evaluation of therapeutic response in HCC patients. [ABSTRACT FROM AUTHOR]

Acute pancreatitis (AP) is one of the life‐threatening diseases of the digestive system. MicroRNA has been asserted to be a regulator of AP. This paper explored the miR‐374a‐5p expression in AP patients and investigated the efficacy of AR42J cells. In this study, 60 healthy people, 58 MAP patients and 58 SAP patients were included, and the serum miR‐374a‐5p levels of the subjects were detected by RT‐qPCR technology. The pancreatitis cell model was structured by stimulating AR42J cells with cerulein. Next, cell viability and apoptosis were detected by CCK‐8 assay and flow cytometry. ELISA was used to measure the concentration of cytokines, such as TNF‐α, IL‐6, and IL‐1β. The data showed that miR‐374a‐5p was downregulated in samples from AP patients, while showing discriminative power for AP populations. Attenuated miR‐374a‐5p were negatively bound up with patients' Ranson score and APACHE II score. Besides, miR‐374a‐5p was declined in cerulein‐treated AR42J cells and forced elevation of miR‐374a‐5p was beneficial to increase cell viability, and inhibit cell apoptosis and inflammation. The present study found that miR‐374a‐5p was reduced in AP serum samples, and up‐regulated expression level of miR‐374a‐5p in cell models had a protective effect on cerulein‐induced inhibition of cell function and inflammatory response. [ABSTRACT FROM AUTHOR]

Cancer stem cells (CSCs) are a small proportion of tumor cells with great tumorigenicity, self‐renewal ability, and intrinsic resistance to conventional and targeted cancer therapy; thus, targeting CSC is becoming an emerging cancer treatment. In this paper, five novel copper (II) complexes [Cu(OH‐PIP)(Tyr)(H2O)]PF6 (1), [Cu(m‐OH‐PIP)(Gly)]NO3·2.25H2O (2), [Cu(Cl‐PIP)(Gly)Br] (3), [Cu(F‐PIP)(Tyr)Cl] (4), and [Cu(F‐PIP)(Phe)Br] (5) have been synthesized and characterized by infrared spectroscopy and single crystal X‐ray diffraction analysis. All the complexes were screened for their in vitro cytotoxicity activity against a panel of human breast cancer cells (CAL‐51, MDA‐MB‐231, and MCF‐7), human liver cancer cells (HepG 2, SMMC‐7721) and human pancreatic cancer cells (PANC‐1) using MTT assay. They have potential proliferative inhibition for all the tested cancer cell lines, especially the triple‐negative breast cancer (TNBC) CAL‐51 cells are inhibited significantly with IC50 values ranging from 0.11 to 2.35 μM. Cellular functional assays showed that representative complexes 1 and 5 could trigger apoptosis, evidenced by Hoechst 33258 staining, flow cytometry assays, and the alteration of Bax, Bcl‐2, Caspase‐3, and PARP levels. In addition, they dramatically suppressed colony and mammosphere formation, inhibited cancer cell stemness and migration, and reversed epithelial–mesenchymal transition (EMT) progression in CAL‐51 cells, indicating their great potential as anti‐CSC agents for therapy of TNBC. [ABSTRACT FROM AUTHOR]

Acrylamide (ACR) is used in many fields such as cosmetics, paper, and textile industries. It also occurs at very high temperatures in some foods. Gonadotoxic effects of ACR have been found in experimental animals. Many studies use flavonoids to prevent the reproductive side effects of ACR. Naringin (NA) is a flavonoid and it has been determined by studies that it has no toxic effect on tissues. In our study, we aimed to determine the protective effect of NA against the damage of ACR on testicular tissue and the reproductive system in rats. In our study, 50 Spraque Dawley male rats weighing 220‐250 grams were used. Control: Only intragastric saline was administered for 10 days. ACR: Animals received ACR (40 mg/kg, intraperitoneally) for 10 days. NA50+ACR: Animals were given NA for 10 days and each NA was one hour after the administration of ACR. NA100+ACR: Animals received NA for 10 days and one hour after each NA was given ACR. NA100: Animals were given NA for 10 days. At the end of the applications, the rats were euthanized by cervical dislocation under anesthesia. Serum FSH, LH, and Dihydrotestosterone levels were compared between the groups. In addition, oxidative stress, inflammation, expression of some reproductive enzymes, and apoptosis markers were determined in testicular tissues. When these parameters were compared between groups, ACR induced testicular dysfunction and tissue damage in rats. We determined that only the NA application did not cause tissue damage. and the administration of NA along with ACR significantly reduced ACR‐induced testis toxicity. [ABSTRACT FROM AUTHOR]

In this paper, a new diastereomerically pure isoxazolines were efficiently prepared from (S)‐verbenone, the procedure involves a regioselective and a diastereoselective 1,3‐dipolar cycloaddition of nitrile oxides on the monoterpene's enone. The structures of the newly obtained cycloadducts were confirmed by analytical and spectral studies (HRMS, 1H NMR, and 13C NMR). The relative stereochemistry of isoxazoline compounds 3a, 3c, and 3d were confirmed by x‐ray single crystal analysis. Hirshfeld surface analysis and two‐dimensional fingerprint plots were performed to analyze the different intermolecular contacts in crystal packing. Further, density functional theory calculations have been used to analyze the electronic and geometric frontier molecular orbital and molecular electrostatic map analyses of the compounds to predict the reactive site. All compounds were evaluated in vitro for their cytotoxic activity against four human cancer cell lines including fibrosarcoma HT‐1080, lung carcinoma A‐549 and breast adenocarcinoma (MCF‐7 and MDA‐MB‐231). Compound 3d was the most potent compound especially against HT‐1080 and A‐549 cancer cells with IC50 values of 21.35 ± 1.51 and 14.92 ± 1.74 μM, respectively. Mechanistically, the compound 3d induced apoptosis by significant caspase activation in HT‐1080 and A‐549 cancer cell lines utilizing flow cytometric analysis and caspase 3/7 activation assay. The examined compound 3d caused S cell cycle arrest in both HT‐1080 and A‐549 cells. [ABSTRACT FROM AUTHOR]

Background: Kava is a beverage made from the ground roots of the plant Piper Methysticum and has long-held a significant place within Pacific island communities. Active compounds were extracted from kava, and secondary metabolites include kavalactones, chalcones, cinnamic acid derivatives and flavanones. It is thought that components of kava may exert an antiproliferative effect through cell cycle arrest and promotion of apoptosis.Methods: We conducted a systematic review to summarize available evidence of the anticancer effects of kava components and investigate their potential use for oral squamous cell carcinoma (OSCC) treatment. Eligible studies were identified through a comprehensive search of OVID EMBASE, OVID MEDLINE and Web of Science, as at April 2018.Results: Of 39 papers that met the inclusion criteria, 32 included in vitro models and 13 included animal studies. A total of 26 different cancers were assessed with 32 studies solely assessing epithelial cancers, 6 mesenchymal cancers and 1 study including both. There was only one report assessing an OSCC cell line. Antiproliferative properties were demonstrated in 32 out of 39 papers. The most researched constituent of kava was flavokavain B followed by flavokavain A. Both were associated with increased expression of pro-apoptotic proteins and decreased expression of anti-apoptotic proteins. Further, they were associated with a dose-dependent reduction of angiogenesis.Conclusion: There was heterogeneity of study models and methods of investigation across the studies identified. Components of kava appear to present an area of interest with chemotherapeutic potential in cancer prevention and treatment, particularly for epithelial neoplasms. To date, there is a paucity of literature of the utility of kava components in the prevention and treatment of oral squamous cell carcinoma. [ABSTRACT FROM AUTHOR]

In this paper, we report the Yb(OTf)3‐mediated etherification reaction that allowed obtaining R,R and S,R isomers of ferrocenyl glycol nucleic acid (Fc‐GNA) nucleosides from their corresponding stereo‐defined (S,R) precursor. The R,R absolute configuration of the chiral carbon atoms in one of the Fc‐nucleoside isomers was assigned by single‐crystal X‐ray diffraction. Density functional theory calculations showed that the stereochemical outcome of the reaction can be explained by an exo attack of ethylene glycol on the pro‐R‐ or pro‐S‐configured α‐ferrocenyl carbenium ion intermediate. The R,R isomer was transformed into the corresponding nucleotide diethyl ester which is, to the best of our knowledge, the first Fc‐GNA nucleotide ever reported. The obtained compounds feature reversible one‐electron oxidation of the ferrocenyl portion of their molecular structures. Anticancer activity studies showed that the (S,R) nucleoside was the most active against HeLa and Ishikawa cancer cells, while it did not show any activity against nontumorigenic L929 cells. The compound induced apoptosis in HeLa cells at IC50=66.0 μM concentration upon 72 h of treatment. [ABSTRACT FROM AUTHOR]

Aim: Platinum‐based chemotherapy is the standard treatment for ovarian cancer. However, tumor cells' resistance to platinum drugs often occurs. This paper provides a review of Forkhead box O (FOXO) protein's role in platinum resistance of ovarian cancer which hopefully may provide some further guidance for the treatment of platinum‐resistant ovarian cancer. Methods: We reviewed a 128 published papers from authoritative and professional journals on FOXO and platinum‐resistant ovarian cancer, and adopts qualitative analyses and interpretation based on the literature. Results: Ovarian cancer often has abnormal activation of cellular pathways, the most important of which is the PI3K/AKT pathway. FOXOs act as crucial downstream factor of the PI3K/Akt pathway and are negatively regulated by it. DNA damage response and apoptosis including the relationship between FOXOs and ATM‐Chk2‐p53 are essential for platinum resistance of ovarian cancer. Through gene expression analysis in platinum‐resistant ovarian cancer cell model, it was found that FoxO‐1 is decreased in platinum‐resistant ovarian cancer, so studying the role of FOXO in the pathway on platinum‐induced apoptosis may further guide the treatment of platinum‐resistant ovarian cancer. Conclusions: There are many drug resistance mechanisms in ovarian cancer, wherein the decrease in cancer cells apoptosis is one of the important causes. Constituted by a series of transcription factors evolving conservatively and mainly working in inhibiting cancer, FOXO proteins play various roles in cells' antitumor response. More and more evidence suggests that we need to re‐understand the role that FOXOs have played in cancer development and treatment. [ABSTRACT FROM AUTHOR]

Over the past decade, the prevalence of diabetes has increased significantly worldwide, leading to an increase in vascular complications of diabetes (VCD), such as diabetic cardiomyopathy (DCM), diabetic nephropathy (DN), and diabetic retinopathy (DR). Noncoding RNAs (ncRNAs), such as microRNAs (miRNAs), long Noncoding RNAs (lncRNAs), and circular RNAs (circRNAs), play a key role in cellular processes, including the pathophysiology of diabetes and VCD via pyroptosis. ncRNAs (e.g., miR‐17, lnc‐MEG3, and lnc‐KCNQ1OT1) can regulate pyroptosis in pancreatic β cells. Some ncRNAs are involved in VCD progression. For example, miR‐21, lnc‐KCNQ1OT1, lnc‐GAS5, and lnc‐MALAT1 were reported in DN and DCM, and lnc‐MIAT was identified in DCM and DR. Herein, this review aimed to summarize recent research findings related to ncRNAs‐mediated pyroptosis at the onset and progression of diabetes and VCD. Significance statement: Metabolic disease, such as diabetes, have seriously caused economic and social burden. The role of noncoding RNAs (ncRNAs) in diabetes and its vascular complications has been widely concerned. ncRNAs is a new discovery in the field of pyroptosis, which may provide a new idea for the regulation of VCD. There are many tandem parts in the regulation process of ncRNAs and pyroptosis. This paper summarized the involvement of ncRNAs including microRNAs, long Noncoding RNAs, and circular RNAs in mediating pyroptosis, an inflammatory form of programmed cell death, in diabetes and diabetic vascular complications. [ABSTRACT FROM AUTHOR]

Summary: Glioma, the predominant form of central nervous system (CNS) malignancies, presents a significant challenge due to its high prevalence and low 5‐year survival rate. The efficacy of current treatment methods is limited by the presence of the blood–brain barrier, the immunosuppressive microenvironment, and other factors. Immunotherapy has emerged as a promising approach, as it can overcome the blood–brain barrier. A tumor's immune privilege, which is induced by an immunosuppressive environment, constricts immunotherapy's clinical impact in glioma. Pyroptosis, a programmed cell death mechanism facilitated by gasdermins, plays a significant role in the management of glioma. Its ability to initiate and regulate tumor occurrence, progression, and metastasis is well‐established. However, it is crucial to note that uncontrolled or excessive cell death can result in tissue damage, acute inflammation, and cytokine release syndrome, thereby potentially promoting tumor advancement or recurrence. This paper aims to elucidate the molecular pathways involved in pyroptosis and subsequently discuss its induction in cancer therapy. In addition, the current treatment methods of glioma and the use of pyroptosis in these treatments are introduced. It is hoped to provide more ideas for the treatment of glioma. [ABSTRACT FROM AUTHOR]

In this paper, we generated a short hairpin RNA growth differentiation factor‐11 (sh‐GDF11) and evaluated the effects of sh‐GDF11 on the pathogenesis of acute liver failure (ALF) in vitro and in vivo. Through bioinformatics study, the key gene related to ALF was assayed. Lipopolysaccharide (LPS) and D‐galactoamine (D‐GalN) were applied to establish the mouse model of LPS/D‐GalN‐induced liver injury, and TNF‐α and D‐Gal were used to construct an in vitro cell model, followed by treatment of sh‐GDF11 for analysis of liver cell proliferation. Bioinformatics analysis showed that the protective effect of sh‐GDF11 on ALF may be mediated by phosphatidylinositol‐3‐kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway. The results of in vitro study found that sh‐GDF11 could promote cell proliferation and inhibit death by blocking the PI3K/Akt/mTOR signaling pathway. In vivo animal experiments further confirmed that sh‐GDF11 could suppress hepatocyte apoptosis by inhibiting the PI3K/Akt/mTOR signaling pathway. sh‐GDF11 relieved LPS/D‐GalN‐induced ALF by blocking the PI3K/Akt/mTOR signaling pathway, emphasizing its critical role in LPS/D‐GalN‐induced ALF treatment. [ABSTRACT FROM AUTHOR]

Targeting nuclear factor kappa B (NF‐κB) signaling pathway has become a promising strategy for the development of new antitumor drugs. In this paper, we found that anti‐infection drug furazolidone (FZD) could significantly inhibit NF‐κB‐driven luciferase activity, and FZD could markedly inhibit both of the constitutive and tumor necrosis factor‐α (TNFα)‐triggered phosphorylation of NF‐κB p65 in small cell lung cancer (SCLC). Further studies revealed that FZD inhibited the expression of inhibitor of kappa B kinase β (IKKβ) in SCLC cells. In addition, we found that FZD had significant antitumor activities in SCLC cells. FZD could markedly suppress the cell viability of SCLC cells dose‐dependently, and FZD could significantly induce the cleavages of poly ADP‐ribose polymerase (PARP) and Caspase3, the biomarkers of cell apoptosis, in SCLC cells. The flow cytometry also revealed that FZD induced cell apoptosis in SCLC cells. Finally, we also found that overexpression of constitutively activated IKKβ could significantly abolish FZD‐induced cell growth inhibition in SCLC cells, which further confirmed that FZD displayed its anti‐SCLC activity through regulating NF‐κB signaling pathway. [ABSTRACT FROM AUTHOR]

This paper reviews provenance, processing and properties of rooibos (Aspalathus linearis, Brum.f) and its numerous biologically active constituents, as well as the currently available knowledge concerning their physiological and medicinal effects and their possible extra‐ and intracellular mechanisms of action. Search for literature was performed in agreement with the preferred reporting items for systematic review criteria in Cochrane Library, PubMed, Web of Science and SCOPUS databases between the years 2000 and 2021. The limited number of in vitro studies suggests an influence of rooibos on basic ovarian cell functions, as well as its potential applicability to control female reproduction and prevent the effect of environmental contaminants on ovarian functions. Nevertheless, further studies are required for better understanding of the character and mechanisms of action, as well as of rooibos' application in reproductive biology and medicine. [ABSTRACT FROM AUTHOR]

Andrew Wyllie was a key figure in the discovery of the programmed cell death process termed apoptosis. He pioneered the study of apoptosis when this was a little‐known phenomenon and discovered the first biochemical marker of the process, internucleosomal DNA degradation. Andrew recently passed away, aged 78, but leaves a legacy of scientific achievement that opened up a new field of research. [ABSTRACT FROM AUTHOR]

Background: Absence of Golgi microtubule‐associated protein 210 (GMAP210), encoded by the TRIP11 gene, results in achondrogenesis. Although TRIP11 is thought to be specifically required for chondrogenesis, human fetuses with the mutation of TRIP11 also display bony skull defects where chondrocytes are usually not present. This raises an important question of how TRIP11 functions in bony skull development. Results: We disrupted Trip11 in neural crest‐derived cell populations, which are critical for developing skull in mice. In Trip11 mutant skulls, expression levels of ER stress markers were increased compared to controls. Morphological analysis of electron microscopy data revealed swollen ER in Trip11 mutant skulls. Unexpectedly, we also found that Golgi stress increased in Trip11 mutant skulls, suggesting that both ER and Golgi stress‐induced cell death may lead to osteopenia‐like phenotypes in Trip11 mutant skulls. These data suggest that Trip11 plays pivotal roles in the regulation of ER and Golgi stress, which are critical for osteogenic cell survival. Conclusion: We have recently reported that the molecular complex of ciliary protein and GMAP210 is required for collagen trafficking. In this paper, we further characterized the important role of Trip11 being possibly involved in the regulation of ER and Golgi stress during skull development. Key Findings: Trip11 is expressed in cranial neural crest cells.Trip11 in neural crest cells is critical for developing skull in mice.Trip11 plays pivotal roles in the regulation of ER and Golgi stress, which are critical for osteogenic cell survival. [ABSTRACT FROM AUTHOR]

The article lists the forthcoming papers in immunology which includes "Apoptosis-induced inhibition of CD1d-mediated antigen presentation: different roles for caspases and signal transduction pathways," by Randy Brutkiewicz, Masood Khan, Venkataraman Sriram, Gourapura Renukaradhya, Wenjun Du, and Jacquelyn Gervay-Hague, "Dexamethasone transforms LPS-stimulated human blood myeloid dendritic cells (MDC) into MDC that prime IL-10 production in T-cells," by Jaap Kwekkeboom, Brenda Bosma, Herold Metselaar, Nicole Nagtzaam, Roel de Haan, Shanta Mancham, Luc van der Laan, and Ernst Kuipers, and "The immunomodulatory glycan LNFPIII initiates alternative activation of murine macrophages in vivo," by Olga Atochina, Akram Da'dara, Mirjam Walker, and Donald Harn.

Background: As a new technology for treating dry eye diseases, phototherapy has attracted great attention, but the research on its safety and effectiveness is limited. In this study, the therapeutic effects of low‐color‐temperature light‐emitting diodes on dry eye in humans, rabbits, and rats were investigated. Methods: In clinical experiments, subjects in both groups read the same paper for 3 h under light sources of two color temperatures: 1900 K (low‐color‐temperature light‐emitting diodes) or 4000 K (artificial fluorescent white light‐emitting diodes). The differences in the non‐invasive tear film breakup time, tear meniscus height, and conjunctival congestion scores before and after the experiment were compared between the two groups. In animal experiments, corneal epithelial barrier function and tear production of Sprague–Dawley rats and New Zealand white rabbits with dry eye were compared before and after low‐color‐temperature light‐emitting diodes treatment. TUNEL staining and Western blotting were used to detect the apoptosis of corneal and conjunctival cells and the expression of inflammatory factor IL‐1β. Results: Low‐color‐temperature light‐emitting diodes prolonged tear film breakup time in patients with dry eye. Moreover, it increased tear secretion, decreased fluorescein sodium staining scores, corneal and conjunctival cell apoptosis, and inflammatory factor expression in rabbits and rats with dry eye. Conclusions: Low‐color‐temperature light‐emitting diodes phototherapy can be used as an effective treatment for dry eye, reducing its symptoms and related ocular surface damage in humans, rabbits, and rats. [ABSTRACT FROM AUTHOR]

Background: Formaldehyde (FA) is associated with the occurrence of leukemia, and oxidative stress is considered to be a major reason. As an endogenous biomarker of oxidative stress, few studies focus on the relationship between peroxiredoxin III (PrxIII) and FA toxicity. Our previous research observed high expression of PrxIII occurred in the process of apoptosis of bone marrow cells (BMCs) induced by FA, however the exact mechanism is unclear. Therefore, this paper aimed to explore the possible association between FA toxicity and PrxIII gene. Methods: We first, used a Cell Counting Kit‐8 (CCK‐8) to detect the viability of BMCs after they were exposed to different doses of FA (50, 100, 200 μmol/L) for different exposure time (12, 24, 48 h), then chose 24 h as an exposure time to detect the expression of PrxIII for exposing different doses of FA by Quantitative reverse transcription‐PCR (qRT‐PCR) and Western blot analysis. Based on our preliminary experimental results, we chose 100 μmol/L FA as an exposure dose to expose for 24 h, and used a small interfering RNA (siRNA) to silenced PrxIII to examine the cell viability by CCK‐8, reactive oxygen species (ROS) level by DCFH‐DA, apoptosis by Annexin V/PI double staining and cell cycle by flow cytometry (FCM) so as to explore the possible regulatory effect of PrxIII silencing on FA‐induced bone marrow toxicity. Results: High expression of PrxIII occurred in the process of FA‐induced oxidative stress. Silencing of PrxIII prevented FA from inducing oxidative stress, thus increasing cell viability, decreasing ROS level, rescuing G0–G1 and G2–M arrest, and reducing cell apoptosis. Conclusion: PrxIII silencing might be a potential target for alleviating FA‐induced oxidative damage. [ABSTRACT FROM AUTHOR]

Bevacizumab (BV) has an inhibitory effect on tumor growth including lung adenocarcinoma. However, its efficacy is greatly affected by drug resistance. Astragaloside IV (AST‐IV) is effective in combination with other drugs is effective to treat cancer. This study aimed to investigate the effect of AST‐IV on enhancing the sensibility of lung adenocarcinoma cells to BV. A549 cells were treated by different concentrations of BV and AST‐IV. Cell viability, cell cycle, and apoptosis were detected by thiazolyl blue tetrazolium bromide (MTT) and flow cytometry, respectively. Quantitative reverse transcription‐polymerase chain reaction (qRT‐PCR) and western blotting were performed to detect the expression levels of autophagy‐ and apoptosis‐related proteins, protein kinase B (AKT), and mammalian target of rapamycin (mTOR). The results showed that BV or AST‐IV could inhibit the viability and promote the apoptosis of A549 cells in a concentration‐dependent manner. Moreover, BV or AST‐IV inhibited Bcl‐2 expression and increased the expressions of Bax and Cleaved caspase‐3, and promoted apoptosis. BV and AST‐IV in combination acted synergistically on viability and apoptosis of A549 cells. However, BV alone down‐regulated P62 expression, LC3I/LC3II level, the number of cells arrested at S phase and the phosphorylation levels of AKT and mTOR, but upregulated the number of cells arrested at G0/G1 phase and Beclin1 expression, whereas AST‐IV alone could reverse the effect of BV on autophagy‐related proteins, the phosphorylation levels of AKT and mTOR. This paper demonstrates that AST‐IV enhances the effect of BV on inhibiting proliferation and promoting apoptosis of lung adenocarcinoma cells through inhibiting autophagy pathway. [ABSTRACT FROM AUTHOR]

Breast cancer (BC), which is widely considered as the most common cancer in women around the world, evokes ~1.7 million new BC cases and 522,000 BC‐related deaths each year. Triple negative breast cancer (TNBC) is clinically confirmed as one of the most aggressive subtypes of BC. ORY‐1001, a clinically used lysine specific demethylase 1 (LSD1/KDM1A) inhibitor, was investigated herein to confirm its role in the progression of TNBC and reveal the potential mechanism. After treatment with ORY‐1001 in MDA‐MB‐231 and BT549 cells, the cell proliferation and apoptosis were respectively measured by CCK‐8 and TUNEL assays. The expression of proliferation‐ and apoptosis‐associated proteins was tested by means of western blot analysis. Then, R1881, an androgen receptor (AR) agonist, was used to evaluate whether the effects of ORY‐1001 on proliferation and apoptosis of TNBC cells was mediated by regulating AR. Results indicated that ORY‐1001 treatment restrained the proliferation while enhanced the apoptosis of BC cells, accompanied by the change of proliferation‐ and apoptosis‐related proteins expression. Furthermore, ORY‐1001 reduced the level of AR in BC cells. After the activation of AR by R1881, the decreased proliferation and enhanced apoptosis of BC cells triggered by ORY‐1001 intervention were partially abolished. In conclusion, this paper has presented the first evidence to suggest that ORY‐1001 inhibits proliferation and promotes apoptosis of TNBC cells by suppressing AR expression, which may constitute the theoretical basis for the clinical use of ORY‐1001 in the treatment of this disease. [ABSTRACT FROM AUTHOR]

This corrigendum addresses errors in a previously published paper titled "Plasma‐activated medium induces apoptosis in chemotherapy‐resistant ovarian cancer cells: High selectivity and synergy with carboplatin." The corrections involve clarifying a confusing sentence and replacing three images in Figure 3 due to naming discrepancies. The authors assure readers that these corrections do not affect the overall results or conclusions of the study. They apologize for any confusion or inconvenience caused by the errors. [Extracted from the article]

Objective: Nonexpression or expression inhibition of protective factors has been determined in the occurrence of heart failure (HF). Heat shock transcription factor 1 (HSF1) is among such factors, which reduces the incidence of HF by controlling cardiac hypertrophy and fibrosis. In this study, molecular mechanisms for nonexpression of HSF1 in HF patients have been investigated. Materials and methods: This review paper is based on the material obtained via PubMed search of 1996–2018. The key search terms were "heart failure," "heat shock transcription factor 1," "hypertrophy", "fibrosis," and "apoptosis." Results: Although factors such as janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) and heat shock proteins (HSPs) may respectively increase and decrease susceptibility to HF, in some circumstances, these factors may unexpectedly prevent HF progression. Conclusion: Finally, identification of molecular pathways expressed by various factors could be used to design appropriate treatments or to employ strategies inducing the expression of HSF1 to prevent HF. This paper is about the protective role of heat shock transcription factor 1 (HSF1) in heart failure. It also discusses about the therapeutic approach of HSF1 in heart failure. [ABSTRACT FROM AUTHOR]

Abstract: In this paper, we offer a minimal characterization of the concept of mechanism in biomedicine, according to which a mechanism is a theoretically described causal pathway. We argue that this conception can be drawn from scientific practice, as illustrated by how a central biological and biomedical mechanism, the mechanism of apoptosis, was first identified and characterized. We will use the example of cytological and biochemical theoretical descriptions of the mechanism of apoptosis to draw lessons about the meaning of the concept of mechanism in biomedical contexts and to contrast our preferred account of mechanism with some prominent accounts within the philosophical literature. The main outcome of our discussion will be that commitment to mechanism is first and foremost a methodological stance. [ABSTRACT FROM AUTHOR]

In this paper, a series of betulonic acid N‐methylpiperazinyl amide derivatives, especially holding C2‐nicotinoylidene/furfurylidene/fluorobenzylidene fragments, have been synthesized and evaluated for their cytotoxic activity against the NCI‐60 cancer cell line panel. N‐Methylpiperazinyl amide of betulinic acid 11 (GI50=0.49 μM for leukemia CCRF‐CEM cell line), 2‐(4‐pyridinoylidene)‐betulinic 9 and betulonic 14 acids (GI50=1.60 and 1.36 μM for colon cancer HCT‐116 cell line, respectively), as well as 2‐(furfurylidene)‐betulonic acid 16 (GI50=1.66 μM for melanoma LOX IMVI cell line) were found to be the lead compounds. The activity displayed for these compounds was higher than for the standard drug doxorubicin against colon cancer HCT‐15 and ovarian cancer NCI/ADR‐RES cell lines. Cell cycle analysis indicates that compound 11 promotes cytotoxic activity through the apoptosis induction both in conditionally normal (HEK293) and in cancer (A549, MCF‐7) cells, whereas compound 14 exhibits both cytostatic and cytotoxic activity, dependently on cell line evaluated. In particular, in HEK293 cells the compound 14 induces mainly apoptotic cell death, while in A549 and MCF‐7 cells cytostatic effect is dependent on cell cycle arrest in the G2/M phase. Compounds 11 and 14 are promising molecules for future antitumor drug development. [ABSTRACT FROM AUTHOR]

Entamoeba histolytica is the conductive agent of amoebiasis. Upon the parasite's infection, macrophages and neutrophils are activated by interferon γ, IL‐13 and tumour necrosis factor. These immune cells then carry out the amoebicidal activity by releasing nitric oxide synthase and reactive oxygen species (ROS). This review talks about the protective and destructive role of ROS in Eh. E. histolytica has defence strategies against oxidative stress which is a result of excess ROS production. They possess antioxidants for their defence such as L‐Cysteine, flavodiiron proteins, peroxiredoxin and trichostatin A, which contribute to the parasite's virulence. The ROS are harmful to the host cells as excess ROS production stimulates cell death by mechanisms like apoptosis and necroptosis. NADPH oxidase (NOX) is a key source of ROS in mammalian cells and causes apoptosis of host cells via the protein kinase transduction pathway. This review provides insights into why NOX inhibitors that could be a potent antiparasitic drug, is not effective for in vivo purposes. This paper also gives an insight into a solution that could be a potent source in generating new treatment and vaccines for amoebiasis by targeting parasite development. [ABSTRACT FROM AUTHOR]

The present review summarizes the current knowledge concerning physiological effects of resveratrol (RSV) with emphasis on the RSV action on female reproductive processes. The review outlines provenance, properties, mechanisms of action, physiological and therapeutic actions of RSV on female reproduction and other physiological processes, as well as areas of possible application of R. This review is based on the search for the related full papers indexed in Medline/Pubmed, Web of Science and SCOPUS databases between the year 2000 and 2021 according to the criteria of preferred reporting items for systematic reviews and meta‐analyses extension for scoping reviews and other related guidelines. The analysis of the available information suggests that RSV has a number of properties which enable its influence on various physiological processes including female reproduction at various regulatory levels via various extra‐ and intracellular signalling pathways. Despite some contradictions and limitations in the available data, they indicate applicability of both stimulatory and inhibitory effects of RSV for control and influence of various reproductive and non‐reproductive processes and treatment of their disorders in phytotherapy, animal production, medicine, biotechnology and assisted reproduction. To establish the clinical efficacy of RSV, further high quality studies are needed. [ABSTRACT FROM AUTHOR]

Background: Periodontitis is a chronic inflammatory disease that occurs in periodontal tissues and can cause tooth loosening and loss in severe cases. As the main effector of downstream of Hippo signaling pathway, yes-related protein 1 (YAP1) plays an important role in cell proliferation and differentiation. However, the role of YAP1 in periodontitis has not been reported.Methods: Cell activity was detected by Cell Counting Kit-8 (CCK-8). YAP1 was overexpressed by cell transfection, and then RT-qPCR and western blot were used to detect the expression of YAP1. The cell proliferation was determined by clone formation assay, and the expression of proliferation-related proteins was determined by western blot. The cell differentiation was detected by ELISA kit of alkaline phosphatase activity (ALP) and alizarin red staining. Finally, western blot was used to detect the expression of differentiation-related protein and Hippo signaling pathway-related proteins. Apoptosis was detected by flow cytometry.Results: With the increase of concentration induced by TNF-α, the cell survival rate of human periodontal ligament stem cells (HPDLSCs) decreased significantly. After the overexpression of YAP1, cell proliferation and proliferation-related protein expression increased. Overexpression of YAP1 can improve the differentiation and the formation of osteoblasts of HPDLSCs induced by TNF-α. The expression of Hippo signaling pathway-related proteins transcriptional coactivators with PDZ binding domains (TAZ), TEA domain family member (TRED) increased and proliferation-related protein P27 decreased, whereas there was no significant change in the expression of MST1.Conclusion: TNF-α can inhibit proliferation and osteogenic differentiation of HPDLSCs, which can be ameliorated by the YAP1 gene through the Hippo signaling pathway. Our paper suggested that YAP1 may be a potential therapeutic target for periodontitis. [ABSTRACT FROM AUTHOR]

LINKED CONTENT: This article is linked to Chen et al papers. To view these articles, visit https://doi.org/10.1111/apt.18131 and https://doi.org/10.1111/apt.18142 [ABSTRACT FROM AUTHOR]