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As a significant biomarker during the apoptosis process, cytochrome c (Cyt c) is considered as a critical component in the inherent apoptotic pathway, but the simple and portable detection still remains challengeable. In this work, a portable and visual sensing platform for Cyt c was developed based upon the fluorescence quenching of graphene quantum dots (GQDs), which could be finished within a few seconds. Herein, the absorption spectrum of Cyt c matched the emission spectrum of GQDs well, which could cause the fluorescence quenching of GQDs via the inner filter effect (IFE) in the range of 1–50 μg/mL with the limit of detection as low as 0.1 μg/mL. Furthermore, the intracellular Cyt c was imaged to observe the apoptosis process of cancer cells induced by staurosporine. To achieve the portable and visual detection of Cyt c, GQDs were deposited on the filter paper to form the solid platform, which displayed a gradual fluorescence quenching when different concentrations of Cyt c were present. Compared to the conventional methods, the proposed assay is low-cost, fast, portable, and visual, which will be useful for the investigation of mitochondrial dysfunction and apoptotic cell death.

Introduction: Apoptosis dysregulation plays a substantial role in the pathophysiology of chronic inflammation and its related symptoms such as edema. Regulation of NF-ĸB activation is involved in apoptosis pattern change. The current study aimed at verifying the effects of local inflammation on edema and changes in apoptotic markers, and investigating the possible role of NF-ĸB in apoptosis pattern change during different stages of complete Freund’s adjuvant (CFA)-induced knee arthritis in rats. Methods: A total of 96 male Wistar rats were divided into different experimental groups. Arthritis was evoked into the right knee articular joint. Changes made in knee edema were assessed by caliper on the days 0, 7, 14, and 21 of the study. Synovial NF-ĸB and levels of apoptotic markers were evaluated during different stages of the study using Western blot technique. Results: CFA injection caused intense edema during the whole study period. Synovial NF-ĸB level increased during the whole study period. The level of apoptotic markers increased during the acute phase of study. But during chronic phase, the apoptosis level decreased. Inh-NF-ĸB administration increased synovial apoptosis during the whole study period. Conclusion: It seems that apoptosis pattern change plays an important role in the progression and modulation of CFA-induced inflammation and its related symptoms. Also, it can be concluded that synovial NF-ĸB had a crucial role in synovial apoptosis change during the study period.

Introduction. Alopecia areata (AA) is an autoimmune condition characterized by T-cell-mediated attack on hair follicles. Objective. Evaluation of efficacy of 308 nm excimer light in the treatment of alopecia areata. Material and methods. Patches of AA were treated twice weekly, but not on 2 consecutive days, with UVB excimer 308 nm light. In all patients, half of the AA patch was irradiated and the other half was spared, covered with a black rubber shield and taken as a control. Therapy was started with an initial dose of 300 mJ/cm 2 , with an incremental dose of 100 mJ/cm 2 at every sitting until fine erythema appeared. Results. At the end of the treatment, one patient (3.33%) at the test site showed > 50% hair regrowth vs. none at the control site. After a 2-month post-treatment period, successful hair regrowth (grades 3 and 4) was seen in 12 patients at test sites and in 2 patients at control sites. The differences were statistically significant (p < 0.05). After 4 months successful hair regrowth (grades 3 and 4) was seen in 16 patients at test sites and in 5 patients at control sites. The differences were statistically significant (p 0.05). Conclusions. Excimer light has the potential to stimulate hair regrowth in patches of alopecia areata.

Our previous study reported that galaxamide, which is a cyclo-pentapeptide containing five leucines that was extracted from Galaxaura filamentosa, displayed remarkable anticancer cytotoxicity. This novel cyclo-peptide provided a new skeleton for the structural modifications used in finding new drugs with better anticancer properties. In this study, five analogues were synthesized based on changing the number of d/l amino acids by adding a new amino acid, phenylalanine. Galaxamide and five of its analogues were evaluated through MTT assays to examine their cytotoxic activities. We found that modified analogue 5, which is referred to as A5, displayed broad spectrum cytotoxic activity toward every cell line tested; in addition, the IC50 of A5 was lower than that of galaxamide and the other analogues. Furthermore, we used flow cytometry and western blot assays to investigate whether galaxamide and A5 could induce cancer cell apoptosis. The flow cytometric studies showed that HepG2 cells treated with different concentrations of galaxamide or A5 over 72 h displayed significant and dose-dependent increases in the percentages of early-stage apoptotic cells. Western blotting revealed that both compounds induce caspase-dependent apoptosis in HepG2 cells through a mitochondria-mediated pathway. The results demonstrate that galaxamide and its analogues have potential applications as clinical anticancer drugs.

Introduction: Monosodium glutamate (MSG) is the sodium salt of glutamic acid widely spread in modern nutrition. Numerous recent studies have shown the existance of glutamic receptors on different non-neuronal cells, which among others also include lymphocytes and thymocytes. However, it has not yet been precisely established what modulatory effect is created by the activation of these receptors on the immune system cells. Material and methods: We have evaluated the effect of different MSG doses on the intensity of apoptosis of rat thymocytes, as well as the expression of their antiapoptotic protein, Bcl-2. Apoptosis was detected using the Annexin V-FITC apoptosis detection kit and cells were analysed using a flow cytometer. Expression of Bcl-2 was determined with flow cytometry using respective monoclonal antibodies. Results: The current study results demonstrate that different MSG doses significantly increase the intensity of thymocyte apoptosis in a culture. Also, the expression of Bcl-2 proteins in the thymocyte culture, after it has been cultivated with different MSG doses, is significantly reduced. Conclusions: The results presented in our study indicate that different MSG doses significantly modulate the intensity of the apoptotic thymocyte process in a culture, and that one of the possible ways through which MSG induces apoptosis is the reduction of Bcl-2 protein expression.

Abstract Colorectal cancer (CRC) is a leading cause of cancer-related deaths worldwide, affecting millions each year. It emerges from the colon or rectum, parts of the digestive system, and is closely linked to both genetic and environmental factors. In CRC, genetic mutations such as APC, KRAS, and TP53, along with epigenetic changes like DNA methylation and histone modifications, play crucial roles in tumor development and treatment responses. This paper delves into the complex biological underpinnings of CRC, highlighting the pivotal roles of genetic alterations, cell death pathways, and the intricate network of signaling interactions that contribute to the disease's progression. It explores the dysregulation of apoptosis, autophagy, and other cell death mechanisms, underscoring the aberrant activation of these pathways in CRC. Additionally, the paper examines how mutations in key molecular pathways, including Wnt, EGFR/MAPK, and PI3K, fuel CRC development, and how these alterations can serve as both diagnostic and prognostic markers. The dual function of autophagy in CRC, acting as a tumor suppressor or promoter depending on the context, is also scrutinized. Through a comprehensive analysis of cellular and molecular events, this research aims to deepen our understanding of CRC and pave the way for more effective diagnostics, prognostics, and therapeutic strategies.

Abstract Background Intervertebral disc degeneration (IVDD) is one of the etiologic factors of degenerative spinal diseases, which can lead to a variety of pathological spinal conditions such as disc herniation, spinal stenosis, and scoliosis. IVDD is a leading cause of lower back pain, the prevalence of which increases with age. Recently, Sirtuins/SIRTs and their related activators have received attention for their activity in the treatment of IVDD. In this paper, a comprehensive systematic review of the literature on the role of SIRTs and their activators on IVDD in recent years is presented. The molecular pathways involved in the regulation of IVDD by SIRTs are summarized, and the effects of SIRTs on senescence, inflammatory responses, oxidative stress, and mitochondrial dysfunction in myeloid cells are discussed with a view to suggesting possible solutions for the current treatment of IVDD. Purpose This paper focuses on the molecular mechanisms by which SIRTs and their activators act on IVDD. Methods A literature search was conducted in Pubmed and Web of Science databases over a 13-year period from 2011 to 2024 for the terms “SIRT”, “Sirtuin”, “IVDD”, “IDD”, “IVD”, “NP”, “Intervertebral disc degeneration”, “Intervertebral disc” and “Nucleus pulposus”. Results According to the results, SIRTs and a large number of activators showed positive effects against IVDD.SIRTs modulate autophagy, myeloid apoptosis, oxidative stress and extracellular matrix degradation. In addition, they attenuate inflammatory factor-induced disc damage and maintain homeostasis during disc degeneration. Several clinical studies have reported the protective effects of some SIRTs activators (e.g., resveratrol, melatonin, honokiol, and 1,4-dihydropyridine) against IVDD. Conclusion The fact that SIRTs and their activators play a hundred different roles in IVDD helps to better understand their potential to develop further treatments for IVDD. Novelty This review summarizes current information on the mechanisms of action of SIRTs in IVDD and the challenges and limitations of translating their basic research into therapy.

BackgroundQuercetin, a widespread polyphenolic flavonoid, is known for its extensive health benefits and is commonly found in the plant kingdom. The natural occurrence and extraction methods of quercetin are crucial due to its bioactive potential.PurposeThis review aims to comprehensively cover the natural sources of quercetin, its extraction methods, bioavailability, pharmacokinetics, and its role in various cell death pathways and liver fibrosis.MethodsA comprehensive literature search was performed across several electronic databases, including PubMed, Embase, CNKI, Wanfang database, and ClinicalTrials.gov, up to 10 February 2024. The search terms employed were “quercetin”, “natural sources of quercetin”, “quercetin extraction methods”, “bioavailability of quercetin”, “pharmacokinetics of quercetin”, “cell death pathways”, “apoptosis”, “autophagy”, “pyroptosis”, “necroptosis”, “ferroptosis”, “cuproptosis”, “liver fibrosis”, and “hepatic stellate cells”. These keywords were interconnected using AND/OR as necessary. The search focused on studies that detailed the bioavailability and pharmacokinetics of quercetin, its role in different cell death pathways, and its effects on liver fibrosis.ResultsThis review details quercetin’s involvement in various cell death pathways, including apoptosis, autophagy, pyroptosis, necroptosis, ferroptosis, and cuproptosis, with particular attention to its regulatory influence on apoptosis and autophagy. It dissects the mechanisms through which quercetin affects these pathways across different cell types and dosages. Moreover, the paper delves into quercetin’s effects on liver fibrosis, its interactions with hepatic stellate cells, and its modulation of pertinent signaling cascades. Additionally, it articulates from a physical organic chemistry standpoint the uniqueness of quercetin’s structure and its potential for specific actions in the liver.ConclusionThe paper provides a detailed analysis of quercetin, suggesting its significant role in modulating cell death mechanisms and mitigating liver fibrosis, underscoring its therapeutic potential.

Heat stress has been one of the key research areas for researchers due to the wide-ranging effects and complex mechanisms of action of its stress product reactive oxygen species (ROS). The aim of this paper is to comprehensively review and summarize the effects of heat stress on ovarian granulosa cells and their mechanism of action. We systematically reviewed the effects of heat stress on ovarian granulosa cells, including intracellular steroid hormone changes, oxidative stress, apoptosis, and mitochondrial function. Meanwhile, this paper discusses in detail several major mechanisms by which heat stress induces apoptosis in ovarian granulosa cells, such as through the activation of apoptosis-related genes, induction of endoplasmic reticulum stress, and the mitochondrial pathway. In addition, we analyzed the mechanism of ferroptosis in ovarian granulosa cells under heat stress conditions, summarized the potential association between heat stress and ferroptosis in light of the existing literature, and explored the key factors in the mechanism of action of heat stress, such as the signaling pathways of Nrf2/Keap1, HSPs, and JNK, and analyzed their possible roles in the process of ferroptosis. Finally, this paper provides an outlook on the future research direction, describing the possible interaction between heat stress and ferroptosis, with a view to providing a theoretical basis for further understanding and revealing the complex mechanism of ferroptosis occurrence in ovarian granulosa cells under heat stress.

Abstract Caspase-8, a renowned cysteine-aspartic protease within its enzyme family, initially garnered attention for its regulatory role in extrinsic apoptosis. With advancing research, a growing body of evidence has substantiated its involvement in other cell death processes, such as pyroptosis and necroptosis, as well as its modulatory effects on inflammasomes and proinflammatory cytokines. PANoptosis, an emerging concept of cell death, encompasses pyroptosis, apoptosis, and necroptosis, providing insight into the often overlapping cellular mortality observed during disease progression. The activation or deficiency of caspase-8 enzymatic activity is closely linked to PANoptosis, positioning caspase-8 as a key regulator of cell survival or death across various physiological and pathological processes. Aberrant expression of caspase-8 is closely associated with the development and progression of a range of inflammatory diseases, including immune system disorders, neurodegenerative diseases (NDDs), sepsis, and cancer. This paper delves into the regulatory role and impact of caspase-8 in these conditions, aiming to elucidate potential therapeutic strategies for the future intervention.

Abstract Objective Diminished ovarian reserve (DOR) encompasses both reproductive and endocrine disorders, resulting in a decline in female fertility. This paper explored the mechanism of Yangjing Zhongyu Decoction (YJZYD) regulating mitochondrial dynamics of ovarian granulosa cells (GCs) to improve DOR. Methods DOR patients were treated with YJZYD, with ovarian volume (OV), antral follicle count (AFC), and endometrial thickness (EMT) detected. C57BL/6 female mice were treated by cyclophosphamide (Cy) intraperitoneal injection and YJZYD solution daily gavage, with serum anti-Mullerian hormone (AMH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2) levels determined. Ovarian GCs (KGN) were interfered with 4-Hydroperoxy-Cyclophosphamide (4-HC) and treated with the MAPK/ERK pathway inhibitor or activator. Results DOR patients showed increased levels of serum AMH, E2, OV, AFC and EMT, while reduced FSH and LH levels after YJZYD treatment. After Cy induction, DOR mice exhibited irregular estrous cycles, diminished serum AMH and E2 levels, elevated FSH and LH levels, reduced follicle number and atresia follicle number, disorderly arranged GCs, and severe interstitial fibrosis. After 4-HC treatment, KGN proliferation and Bcl-2, MFN1, and MFN2 were suppressed, while apoptotic rate, Bax, Cleaved-caspase-3, and p-Drp1 (Ser616) levels, and mitochondrial fission and quantity increased. YJZYD promoted 4-HC-treated KGN proliferation, boosted mitochondrial fusion, and inhibited apoptosis and mitochondrial fission via the MAPK/ERK pathway. Conclusion YJZYD promoted ovarian GC proliferation and mitochondrial fusion, suppressed cell apoptosis and mitochondrial fission, and effectively improved DOR in mice by activating the MAPK/ERK pathway, providing a theoretical basis for the clinical application value of YJZYD in DOR treatment.

Programmed cell death is an important biological process, including apoptosis, autophagy and other modalities, which is essential for maintaining homeostasis of tissue and organ. In recent years, several studies have shown that aberrant regulation of programmed cell death plays an important role in the development of colorectal cancer. Therefore, it is important to reveal the fine-turned regulatory network of programmed cell death in colorectal carcinogenesis and progression to develop new clinical treatment strategies for colorectal cancer. This paper aims to review the research progress of programmed cell death in colorectal cancer, and provide new ideas and approaches for the clinical diagnosis and treatment of colorectal cancer.

Abstract Osteoarthritis (OA) is a chronic joint disease characterized by the degeneration, destruction, and excessive ossification of articular cartilage. The prevalence of OA is rising annually, concomitant with the aging global population and increasing rates of obesity. This condition imposes a substantial and escalating burden on individual health, healthcare systems, and broader social and economic frameworks. The etiology of OA is multifaceted and not fully understood. Current research suggests that the death of chondrocytes, encompassing mechanisms such as cellular apoptosis, pyroptosis, autophagy, ferroptosis and cuproptosis, contributes to both the initiation and progression of the disease. These cell death pathways not only diminish the population of chondrocytes but also exacerbate joint damage through the induction of inflammation and other deleterious processes. This paper delineates the morphological characteristics associated with various modes of cell death and summarizes current research results on the molecular mechanisms of different cell death patterns in OA. The objective is to review the advancements in understanding chondrocyte cell death in OA, thereby offering novel insights for potential clinical interventions.

Abstract Colorectal cancer is a common malignant tumor of the digestive system. Its morbidity and mortality rank among the highest in the world. Cancer development is associated with aberrant signaling pathways. Autophagy is a process of cell self-digestion that maintains the intracellular environment and has a bidirectional regulatory role in cancer. Apoptosis is one of the important death programs in cancer cells and is able to inhibit cancer development. Studies have shown that a variety of substances can regulate autophagy and apoptosis in colorectal cancer cells through signaling pathways, and participate in the regulation of autophagy on apoptosis. In this paper, we focus on the relevant research on autophagy in colorectal cancer cells based on the involvement of related signaling pathways in the regulation of apoptosis in order to provide new research ideas and therapeutic directions for the treatment of colorectal cancer.

Lung cancer is the leading cause of cancer-related mortality worldwide, with non-small cell lung cancer (NSCLC) being the predominant type. The roles of autophagy and apoptosis in NSCLC present a dual and intricate nature. Additionally, autophagy and apoptosis interconnect through diverse crosstalk molecules. Owing to their multitargeting nature, safety, and efficacy, natural products have emerged as principal sources for NSCLC therapeutic candidates. This review begins with an exploration of the mechanisms of autophagy and apoptosis, proceeds to examine the crosstalk molecules between these processes, and outlines their implications and interactions in NSCLC. Finally, the paper reviews natural products that have been intensively studied against NSCLC targeting autophagy and apoptosis, and summarizes in detail the four most retrieved representative drugs. This paper clarifies good therapeutic effects of natural products in NSCLC by targeting autophagy and apoptosis and aims to promote greater consideration by researchers of natural products as candidates for anti-NSCLC drug discovery.

BackgroundSpinal cord injury (SCI) is a severe central nervous trauma that can cause serious consequences. Cell death is emerging as a common pathogenesis after SCI. In the last two decades, numerous studies have been published in the field of cell death after SCI. However, it is still rare to find relevant bibliometric analyses. This bibliometric study aims to visually represent global research trends in the field of cell death after SCI.MethodsBibliometric data were sourced from the Web of Science Core Collection (WoSCC) database. VOSviewer, CiteSpace, and R software (“bibliometrix” package) were used to analyze and visualize bibliometric data. Annual scientific production, countries/regions, institutions, authors, journals, highly cited papers, keywords, and literature co-citation were evaluated to determine research performance.ResultsAn analysis of 5,078 publications extracted from the WoSCC database revealed a fluctuating yet persistent growth in the field of cell death after SCI over the past 23 years. China and the United States, contributing 69% of the total publications, were the main driving force in this field. The Wenzhou Medical University from China contributed to the most papers. In terms of authors, Salvatore Cuzzocrea from the University of Messina had the highest number of publications. The “Journal of Neurotrauma” was the top journal in terms of the number of publications, however, the “Journal of Neuroscience” was the top journal in terms of the number of citations. The theme of the highly cited articles mainly focused on the mechanism of cell death after SCI. The keyword and literature co-citation analysis mainly focused on the mode of cell death, mechanism research of cell death, and functional recovery after SCI.ConclusionThis study analyzes the research hotspots, frontiers, and development trends in the field of cell death after SCI, which is important for future studies.

Abstract This review provides a comprehensive analysis of apoptotic signaling pathways in the context of bone metastatic lung cancer, emphasizing the intricate molecular mechanisms and microenvironmental influences. Beginning with an overview of apoptosis in cancer, the paper explores the specific molecular characteristics of bone metastatic lung cancer, highlighting alterations in apoptotic pathways. Focused discussions delve into key apoptotic signaling pathways, including the intrinsic and extrinsic pathways, and the roles of critical molecular players such as Bcl-2 family proteins and caspases. Microenvironmental factors, such as the tumor microenvironment, extracellular matrix interactions, and immune cell involvement, are examined in depth. The review also addresses experimental approaches and techniques employed in studying apoptotic signaling, paving the way for a discussion on current therapeutic strategies, their limitations, and future prospects. This synthesis contributes a holistic understanding of apoptosis in bone metastatic lung cancer, offering insights for potential therapeutic advancements.

Cancer cells refer to a group of malignant cells with strong division and proliferation abilities. Cancer cells rely on the unstable plunder of human nutrition to sustain the large amount of energy that they need for their own division and proliferation. The division and proliferation of cancer cells are linked to the synthesis and replication of genetic material in the nucleus. Blockage or destruction of the synthesis of genetic material in cancer cells is one of the mechanisms underlying the action of most antitumor drugs. As the key material that dominates cell division, proliferation, and death, nuclear genetic material which mainly refers to the deoxyribonucleic acid located on the chromatin in the nucleus, plays a decisive role in the final fate of cells. The final fate of cancer cells after the damage of the genetic material is worthy of investigation and analysis. In this paper, we discuss and analyze the fate of cancer cells after genetic material damage from the aspect of cellular cycle arrest, apoptosis, autophagy, and senescence to provide ideas for the mechanism research on antitumor drugs.

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

Siyan Pang,1,2 Chenchen Geng,1,2 Zihan Fan,2 Min Hou,1,3 Huilan Mao,1,2 Shuang Tao,1,4 Jing Wang,1,4 Yulun Wu,1,2 Ke Wei,1,4 Yunhao Li,1,2 Liuyang Yan,1,2 Qingling Yang,1,4,5 Changjie Chen,1,4,5 Wenrui Wang1,2,6 1Anhui Province Key Laboratory of Translational Cancer Research, Bengbu Medical University, Anhui, People’s Republic of China; 2Department of Life Sciences, Bengbu Medical University, Anhui, People’s Republic of China; 3School of Basic Courses, Bengbu Medical University, Anhui, People’s Republic of China; 4Clinical Testing and Diagnose Experimental Center, Bengbu Medical University, Anhui, People’s Republic of China; 5Department of Biochemistry and Molecular Biology, Bengbu Medical University, Anhui, People’s Republic of China; 6Department of Biotechnology, Bengbu Medical University, Anhui, People’s Republic of ChinaCorrespondence: Wenrui Wang; Changjie Chen, Anhui Province Key Laboratory of Cancer Translational Medicine, Bengbu Medical University, 2600 Donghai Avenue, Bengbu, Anhui, 233030, People’s Republic of China, Email wenrui-wang1983@163.com; tochenchangjie@163.comBackground: Breast cancer is the most common cancer in women and one of the leading causes of cancer death worldwide. Ferroptosis, a promising mechanism of killing cancer cells, has become a research hotspot in cancer therapy. Simvastatin (SIM), as a potential new anti-breast cancer drug, has been shown to cause ferroptosis of cancer cells and inhibit breast cancer metastasis and recurrence. The purpose of this study is to develop a novel strategy boosting ferroptotic cascade for synergistic cancer therapy.Methods: In this paper, iron base form of layered double hydroxide supported simvastatin (LDHs-SIM) was synthesized by hydrothermal co-precipitation method. The characterization of LDHs-SIM were assessed by various analytical techniques, including ultraviolet-visible (UV-vis) spectroscopy, X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, and transmission electron microscopy (TEM). Biological activity, ferroptosis mechanism and biocompatibility were analyzed through in vivo and in vitro analysis, so as to evaluate its therapeutic effect on breast cancer.Results: The constructed LDHs-SIM nanosystem can not only release SIM through mevalonate (MVA) pathway, inhibit the expression of glutathione peroxidase 4 (GPX4), inhibit the expression of SLC7A11 and reduce the synthesis efficiency of GSH, but also promote the accumulation of Fe2+ in cells through the release of Fe3+, and increase the intracellular ROS content. In addition, LDHs-SIM nanosystem can induce apoptosis of breast cancer cells to a certain extent, and achieve the synergistic effect of apoptosis and ferroptosis.Conclusion: In the present study, we demonstrated that nanoparticles of layered double hydroxides (LDHs) loaded with simvastatin were more effective than a free drug at inhibiting breast cancer cell growth, In addition, superior anticancer therapeutic effects were achieved with little systemic toxicity, indicating that LDHs-SIM could serve as a safe and high-performance platform for ferroptosis−apoptosis combined anticancer therapy.Keywords: layered double hydroxides, apoptosis, ferroptosis, simvastatin, breast cancer

Apoptosis, as a normal physiological process is active in the ovary of all species of mammals, representing the essential factor in maintaining the homeostasis of this organ. Both steroid hormones and various other factors actively involve in this process and regulates it. This paper represents a citohistologic study of the ovary of puber mouse, comprising the morphological changes accompanying cells through apoptosis, in different types of ovarian follicles and which lead ultimately to the establishment of bodies apoptotic and follicle atresia. The results obtained by histological analysis of ovarian tissue sections, in puber hood (28 days) shows that the apoptotic process occurs in all types of ovarian follicles, but with different intensity from one follicular stage to another and from one type of cell to another, the most critical stage being the transition to the stage of preantral follicle. From primordial follicle stage until the secundar follicle stage, a frequent cause of follicle atresia is the entry into apoptosis of the ovocyte, a process morphologically marked by the appearance of specific nucleo-cytoplasmic changes. Since preantral follicle stage until the stage, cause of atresia is the appearance of morphological changes, specific to apoptotic process first at granuloasa cells level and its subsequent expansion in oocytes and then in internal sheath cells.

In the last decade, researchers have paid much attention to the role of noncoding RNA molecules in human diseases. Among the most important of these molecules are LncRNAs, which are RNA molecules with a length of more than 200 nucleotides. LncRNAs can regulate gene expression through various mechanisms, such as binding to DNA sequences and interacting with miRNAs. Studies have shown that LncRNAs may be valuable therapeutic targets in treating various cancers, including upper-gastrointestinal cancers. Upper gastrointestinal cancers, mainly referring to esophageal and gastric cancers, are among the deadliest gastrointestinal cancers. Despite notable advances, traditional chemotherapy remains a common strategy for treating these cancers. However, chemoresistance poses a significant obstacle to the effective treatment of upper gastrointestinal cancers, resulting in a low survival rate. Chemoresistance arises from various events, such as the enhancement of efflux and detoxification of chemotherapy agents, reduction of drug uptake, alteration of drug targeting, reduction of prodrug activation, strengthening of EMT and stemness, and the attenuation of apoptosis in cancerous cells. Tumor microenvironment also plays an important role in chemoresistance. Interestingly, a series of studies have revealed that LncRNAs can influence important mechanisms associated with some of the aforementioned events and may serve as promising targets for mitigating chemoresistance in upper gastrointestinal cancers. In this review paper, following a concise overview of chemoresistance mechanisms in upper gastrointestinal cancers, we will review the most intriguing findings of these investigations in detail.

Abstract In the past, hydrogen sulfide (H2S) was recognized as a toxic and dangerous gas; in recent years, with increased research, we have discovered that H2S can act as an endogenous regulatory transmitter. In mammals, H2S‐catalyzing enzymes, such as cystathionine‐β‐synthase, cystathionine‐γ‐lyase, and 3‐mercaptopyruvate sulfurtransferase, are differentially expressed in a variety of tissues and affect a variety of biological functions, such as transcriptional and posttranslational modification of genes, activation of signaling pathways in the cell, and metabolic processes in tissues, by producing H2S. Various preclinical studies have shown that H2S affects physiological and pathological processes in the body. However, a detailed systematic summary of these roles in health and disease is lacking. Therefore, this review provides a thorough overview of the physiological roles of H2S in different systems and the diseases associated with disorders of H2S metabolism, such as ischemia–reperfusion injury, hypertension, neurodegenerative diseases, inflammatory bowel disease, and cancer. Meanwhile, this paper also introduces H2S donors and novel release modes, as well as the latest preclinical experimental results, aiming to provide researchers with new ideas to discover new diagnostic targets and therapeutic options.

Apoptosis signal-regulated kinase 1 (ASK1) is a member of the mitogen-activated protein kinase kinase (MAP3K) family, whose activation and regulation are intricately associated with apoptosis. ASK1 is activated in response to oxidative stress, among other stimuli, subsequently triggering downstream JNK, p38 MAPK, and mitochondria-dependent apoptotic signaling, which participate in the initiation of tumor cell apoptosis induced by various stimuli. Research has shown that ASK1 plays a crucial role in the apoptosis of lung cancer, breast cancer, and liver cancer cells. Currently, the investigation of effective ASK1 activators is a hot topic in research on tumor cell apoptosis. Synthetic compounds such as human β-defensin, triazolothiazide derivatives and heat shock protein 27 inhibitors; natural compounds such as quercetin, Laminarina japonica polysaccharide-1 peptide and theabrownin; and nanomedicines such as cerium oxide nanoparticles, magnetite FeO nanoparticles and silver nanoparticles can activate ASK1 and induce apoptosis in various tumor cells. This review extensively investigates the roles and activation mechanisms of ASK1, explores its impact on a variety of apoptotic signaling pathways, and discusses the potential therapeutic applications of various ASK1 activators in cancer treatment. In addition, this paper provides an in-depth discussion of the future development of this field and proposes a promising method for further research and clinical progress.

BackgroundHepatocellular carcinoma accounts for 80% of primary liver cancers, is the most common primary liver malignancy. Hepatocellular carcinoma is the third leading cause of tumor-related deaths worldwide, with a 5-year survival rate of approximately 18%. Chemotherapy, although commonly used for hepatocellular carcinoma treatment, is limited by systemic toxicity and drug resistance. Improving targeted delivery of chemotherapy drugs to tumor cells without causing systemic side effects is a current research focus. Chitosan, a biopolymer derived from chitin, possesses good biocompatibility and biodegradability, making it suitable for drug delivery. Enhanced chitosan formulations retain the anti-tumor properties while improving stability. Chitosan-based biomaterials promote hepatocellular carcinoma apoptosis, exhibit antioxidant and anti-inflammatory effects, inhibit tumor angiogenesis, and improve extracellular matrix remodeling for enhanced anti-tumor therapy.MethodsWe summarized published experimental papers by querying them.Results and ConclusionsThis review discusses the physicochemical properties of chitosan, its application in hepatocellular carcinoma treatment, and the challenges faced by chitosan-based biomaterials.

Retinitis pigmentosa (RP) is the most common type of inherited retinal dystrophy. The course of RP is irreversible and leads to progressive loss of vision. It is characterized by hypotrophic degeneration of photoreceptor cells and retinal pigment epithelium. Multiple factors are involved in the development of the disease, including apoptosis, oxidative stress, and inflammatory/immune responses. In the past decades, gene therapy, stem cell therapy and other therapeutic approaches have been extensively investigated. However, due to the heritability and high heterogeneity of the disease and the difficulty in diagnosis and treatment, there is still a lack of standardized and effective therapies. Therefore, there is a need to develop new diagnostic and therapeutic approaches suitable for diseases with pathogenic mutations. With the understanding of the interaction between gene expression regulation and retinal pathology, the value of clinical applications of non-coding RNAs (ncRNAs) in retinal degeneration has gained attention. There is growing evidence that ncRNAs are widely distributed and involved in the regulation of multiple biological processes in the retina as well as processes associated with the development of RP, making them promising biomarkers for the diagnosis, treatment, and prognosis of RP. This paper reviews the crosstalk between ncRNA and RP, systematically discusses the role of ncRNAs in normal retinal cell physiology and RP pathogenesis and explores the potential of ncRNAs as therapeutic agents for clinical applications in RP.

Study subject. Effect of capsaicin on tumorigenesis. Plants of the Capsicum family including chili peppers are one of the oldest domesticated crops. The constituents of chili peppers, particularly capsaicin, have become the subject of intense research because of their diverse effects on physiology and metabolism. The widespread use of capsaicin in various types of diseases has naturally led to attempts to use it to combat diseases that cause more than 25% of Poland's deaths - cancer. Purpose of the study. The purpose of the study was to gather and systematize knowledge on the effects of capsaicin and chili bell pepper extracts on tumorigenesis taking into account both its anticancer and prooncogenic properties described in the medical literature. Other properties of capsaicin resulting from its mechanism of action were also taken into account. Materials and Methods. The literature was reviewed by searching scientific databases: PubMed, ClinicalKey and Google Scholar. A search for relevant articles on chili peppers, capsaicin and their effects on tumorigenesis was conducted using the keywords "capsaicin" (Capsaicin), "cancer" (Cancer), TRPV1, "apoptosis" (Apoptosis), "oxidative stress" (Oxidative stress), "proliferation" (Proliferation), and in the following order: "obesity" (ang Obesity), "pain" (ang Pain). The present methodology made it possible to find current, both original and review papers on the properties of capsaicin, and in particular its effect on tumorigenesis. Results: Capsaicin, acts as an agonist of TRPV-1 receptors, which are widespread both in the nervous system (particularly in nopcyclic receptors) and outside nervous tissues. Studies indicate that the substance can effectively help regulate carbohydrate metabolism, help lower blood pressure, positively influence the lipid profile and reduce appetite. Thanks to these mechanisms, capsaicin can be used as an aid in the treatment of metabolic syndrome, obesity or type II diabetes. In the anti-cancer context, capsaicin shows the potential to inhibit cancer cell proliferation, induce apoptosis, reactivate the p53 protein and act as a radio- or chemosensitizer. Thanks to the discovery of its effects on the above mechanisms, capsaicin has been the subject of research for years into its use as an anticancer drug or an adjuvant to cancer treatment. Despite the promising results, there are conflicting reports on the effects of capsaicin on tumorigenesis. It seems that despite its undoubted anti-cancer effects confirmed by numerous studies, inappropriate use of capsaicin or products containing it may pose a risk of exacerbating existing cancer or the appearance of metastases. Conclusions: Despite its promising therapeutic properties, particularly in the anticancer context, the safety and efficacy of capsaicin remain controversial. Further research into the dose, duration of exposure and use of capsaicin is needed to accurately determine the scope of its applications and minimize possible negative side effects.

Abstract Background Myocardial ischemia–reperfusion injury (MIRI) is widespread in the treatment of ischemic heart disease, and its treatment options are currently limited. Adiponectin (APN) is an adipocytokine with cardioprotective properties; however, the mechanisms of APN in MIRI are unclear. Therefore, based on preclinical (animal model) evidence, the cardioprotective effects of APN and the underlying mechanisms were explored. Methods The literature was searched for the protective effect of APN on MIRI in six databases until 16 November 2023, and data were extracted according to selection criteria. The outcomes were the size of the myocardial necrosis area and hemodynamics. Markers of oxidation, apoptosis, and inflammation were secondary outcome indicators. The quality evaluation was performed using the animal study evaluation scale recommended by the Systematic Review Center for Laboratory animal Experimentation statement. Stata/MP 14.0 software was used for the summary analysis. Results In total, 20 papers with 426 animals were included in this study. The pooled analysis revealed that APN significantly reduced myocardial infarct size [weighted mean difference (WMD) = 16.67 (95% confidence interval (CI) = 13.18 to 20.16, P

Nerve cell death is the central aspect of human neurodegenerative disorders. Neuronal death in results leads to the onset of various human neurological disorders such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis, and stroke. In developing neurons, apoptosis is assumed to provide a counterbalance to overexuberant cell replication. Numerous signals may induce apoptosis in neurons, such as the absence of neurotrophic factor support, increased levels of metabolic and oxidative stress, and overstimulation of glutamate receptors (leading to the calcium influx). Cell death and neurological disorders have been related to oxidative stress, which creates an imbalance between antioxidant defenses and free radical production. In this paper, a summary of the engrossment of oxidative stress, neuronal apoptosis, and mitochondrial dysfunction in neurodegenerative disorders has been discussed. Antioxidant therapy’s potential assistance for neurodegenerative illnesses in human beings is still up for dispute, despite encouraging pre-clinical research findings. One elucidation for this disparity could be the non-existence of an accurate way to assess oxidative stress in the brain. The explosion in research on apoptosis in neurodegeneration has stemmed from the conception that persuading neuronal apoptotic death may be crucial to the progression of a disease and that anti-apoptotic approaches may be useful in the prevention of neurodegenerative processes. A deeper understanding of the role that apoptosis plays in neurodegenerative processes will serve as the foundation for future research into the development of focused, effective treatment modalities.

Sulforaphane (SFN) is an isothiocyanate with multiple biomedical applications. Sulforaphane can be extracted from the plants of the genus Brassica. However, broccoli sprouts are the chief source of sulforaphane and are 20 to 50 times richer than mature broccoli as they contain 1,153 mg/100 g. SFN is a secondary metabolite that is produced as a result of the hydrolysis of glucoraphanin (a glucosinolate) by the enzyme myrosinase. This review paper aims to summarize and understand the mechanisms behind the anticancer potential of sulforaphane. The data was collected by searching PubMed/MedLine, Scopus, Web of Science, and Google Scholar. This paper concludes that sulforaphane provides cancer protection through the alteration of various epigenetic and non-epigenetic pathways. It is a potent anticancer phytochemical that is safe to consume with minimal side effects. However, there is still a need for further research regarding SFN and the development of a standard dose.

Among follicles present on the surface of the ovary only a small part reach ovulation, the majority entering atresia, which is an apoptotic process regulated hormonally in general. Apoptosis (from greek: apo = from, ptosis = falling) - is a normal physiological process, genetically programmed cell death, which carries energy consumption by activating a program of internal suicide. This occurs at each stage of follicular development and is accompanied by a significant reduction in the number of follicles present at birth. Development stage-dependent mechanisms coordinate the evolution of follicles, leading to ovulation of a very small number of them. At follicular level apoptosis involves many morphological and biochemical processes that are based on pro-and anti-apoptotic members of Bcl-2 family of proteins (located on mitochondrial outer membrane) and caspases. These changes aim internucleosomal DNA fragmentation, cell retraction followed by its wrinkling, cytoskeleton disruption, preservation of cytoplasmic organelles structure and function, loss of intercellular ties with the reduced expression of conexine 43 (key protein of communication junctions between granulose cells), progressive fragmentation of nucleus and cytoplasm, and finally the appearance of apoptotic bodies, and their inclusion by phagocytes, without the involvement of any inflammatory response.

Cancer refers to the proliferation and multiplication of aberrant cells inside the human body, characterized by their capacity to proliferate and infiltrate various anatomical regions. Numerous biochemical pathways and signaling molecules have an impact on the cancer auto biogenesis process. The regulation of crucial cellular processes necessary for cell survival and proliferation, which are triggered by phytochemicals, is significantly influenced by signaling pathways. These pathways or components are regulated by phytochemicals. Medicinal plants are a significant reservoir of diverse anticancer medications employed in chemotherapy. The anticancer effects of phytochemicals are mediated by several methods, including induction of apoptosis, cessation of the cell cycle, inhibition of kinases, and prevention of carcinogenic substances. This paper analyzes the phytochemistry of seven prominent plant constituents, namely, alkaloids, tannins, flavonoids, phenols, steroids, terpenoids, and saponins, focusing on the involvement of the MAPK/ERK pathway, TNF signaling, death receptors, p53, p38, and actin dynamics. Hence, this review has examined a range of phytochemicals, encompassing their structural characteristics and potential anticancer mechanisms. It has underscored the significance of plant-derived bioactive compounds in the prevention of cancer, utilizing diverse molecular pathways. In addition, this endeavor also seeks to incentivize scientists to carry out clinical trials on anticancer medications derived from plants.

Curcumin (CUR) is a compound extracted from turmeric that has a variety of functions including antioxidant and anti-inflammatory. As an estrogen-like mycotoxin, zearalenone (ZEN) not only attacks the reproductive system, but also has toxic effects on the liver. However, whether CUR can alleviate ZEN-induced liver injury remains unclear. This paper aims to investigate the protective effect of CUR against ZEN-induced liver injury in mice and explore the molecular mechanism involved. BALB/c mice were randomly divided into control (CON) group, CUR group (200 mg/kg b. w. CUR), ZEN group (40 mg/kg b. w. ZEN) and CUR+ZEN group (200 mg/kg b. w. CUR+40 mg/kg b. w. ZEN). 28 d after ZEN exposure and CUR treatment, blood and liver samples were collected for subsequent testing. The results showed that CUR reversed ZEN-induced hepatocyte swelling and necrosis in mice. It significantly reduced the serum alkaline phosphatase (ALP), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in mice (p < 0.05). In addition, CUR significantly reduced hepatic ROS, malondialdehyde, hydrogen peroxide and apoptosis levels in mice (p < 0.05). Quantitative RT-PCR and Western blot results showed that CUR significantly reduced the expression of Bax and Caspase3, and reversed the increase of Nrf2, HO-1 and NQO1 expression in the liver of mice induced by ZEN (p < 0.05). In conclusion, CUR alleviated ZEN-induced liver injury in mice by scavenging ROS and inhibiting the mitochondrial apoptotic pathway.

Oxidative stress can trigger apoptosis and associated reduction of osteoblast activity. Hinokiflavone (HNK) with a biflavonoid-based structure might show potent antioxidant activity. However, before the application of this compound as a promising therapeutic bioactive material, its interaction with blood proteins should be investigated to further reveal its pharmacokinetic and pharmacodynamic properties. Therefore, in this paper, the interaction of HNK with γ-globulin, one of the main blood proteins, was assessed. Then, the antioxidant properties of HNK against H2O2-induced osteoblast cytotoxicity in MC3T3-E1 cells were assessed. It was shown that HNK can potentially bind to γ-globulin mostly with the aid of hydrophilic forces, with a slight effect on the protein structure. It was then determined that HNK significantly recovered cell survival and alkaline phosphatase (ALP) activity and collagen-I content in MC3T3-E1 cells exposed to H2O2. In addition, HNK decreased the production of intracellular reactive oxygen species (ROS) and malondialdehyde (MDA) in MC3T3-E1 cells triggered by H2O2. Finally, HNK was shown to control the apoptosis induction in MC3T3-E1 cells triggered by H2O2 mediated by regulation of Bax, Bcl-2 and caspase-3. Taken together, these data demonstrated that HNK with promising blood protein binding properties can show significant protective effects in MC3T3-E1 cells mediated by inhibition of osteoblast dysfunction, oxidative stress, and apoptosis.

BackgroundPatrinia villosa (Thunb.) Juss is one of the plant resources of the famous traditional Chinese medicine “Bai jiang cao (herba patriniae),” and it is considered to function at the liver meridian, thereby treating diseases of the liver as demonstrated by the traditional theory of TCM. Unfortunately, the therapeutic mechanism of the whole plant of PV is so far unknown.MethodUPLC QTOF-MS/MS was used to analyze the profile of PV. Male Sprague–Dawley rats were categorized into five groups, and PV groups (125 and 375 mg/kg) were administered by oral gavage for seven consecutive days. The model of liver injury was induced by intraperitoneal injection of 40% CCl4 oil solution. H&E staining was performed for histological evaluation. The ELISA method was used to assess the serum level of ALT, AST, and T-BIL. Serum and liver bile acid (BA) profiling was analyzed by LC-MS/MS. TUNEL-stained liver sections were used to monitor apoptosis caused by CCl4. HepG2 cells were used to detect autophagy caused by CCl4.ResultsA total of 16 compounds were identified from the 70% methanol extract of PV. PV (125 and 375 mg/kg) could reverse the ectopic overexpression of AST, ALT, and T-BIL caused by CCl4 administration. H&E staining indicated that PV (125 and 375 mg/kg) could reduce the infiltration of inflammatory cells and restore liver tissue and hepatocyte structures. Six bile acids, including DCA, HDCA, GCA, TCA, TCDCA, and TUDCA, were significantly altered both in the serum and liver tissue after CCl4 administration, and the level of all these six bile acids was restored by PV treatment. Moreover, PV inhibited apoptosis caused by CCl4 stimulation in liver tissue and suppressed autophagy in HepG2 cells treated with CCl4.ConclusionThe results in this paper for the first time reveal the alteration of the bile acid profile in CCl4-induced liver injury and demonstrate that inhibiting apoptosis and autophagy was involved in P. villosa-elicited liver protection, providing a scientific basis for the clinical utilization of P. villosa as a natural hepatic protective agent.

Background and purpose: The previous work on koetjapic acid (KA) isolated from Sandoricum koetjape showed its efficacy towards colorectal cancer however KA has poor water solubility which poses the biggest hindrance to its efficacy. In the present paper, an attempt was made to study the anti-colon cancer efficacy of KA’s potassium salt i.e. potassium koetjapate (KKA) applying in vitro and in vivo methods. Experimental approach: KKA was produced by a semi-synthetic method. A human apoptosis proteome profiler array was applied to determine the protein targets responsible for the stimulation of apoptosis. Three doses of KKA were studied in athymic nude mice models to examine the in vivo anti-tumorigenic ability of KKA. Findings/Results: The results of this study demonstrated that KKA regulates the activities of various proteins. It downregulates the expression of several antiapoptotic proteins and negative regulators of apoptosis including HSP60, HSP90, Bcl-2, and IGF-1 in HCT 116 cells with consequent upregulation of TRAILR-1 and TRAILR-2, p27, CD40, caspase 3, and caspase 8 proteins. Additionally, KKA showed an in vitro antimetastatic effect against HCT 116 cells. These results are feasibly related to the down-regulation of Notch, Wnt, hypoxia, and MAPK/JNK and MAPK/ERK signalling pathways in HCT 116 cells besides the up-regulation of a transcription factor for cell cycle (pRb-E2F) pathways. In addition, KKA revealed potent inhibition of tumor growth. Conclusion and implications: In sum, the findings indicate that KKA can be a promising candidate as a chemotherapeutic agent against colorectal cancer.

Abstract Background Prostate cancer poses a considerable threat to human health. At present, the mechanism of tumor progression remains unclear. ZNF692 is overexpressed in many tumors, and the high expression of ZNF692 is correlated with tumor aggressiveness and tumor phenotype of prostate cancer, suggesting that ZNF692 may play an important role in tumor biology of prostate cancer. This paper aims to elucidate the relationship between them. Methods The expression level of ZNF692 was verified in normal prostate cells (RWPE-1) and prostate cancer cells (LNCaP, PC3, DU145). PC3 cells were selected to construct the ZNF692 knockout prostate cancer cell line. The changes of cell proliferation, apoptosis, invasion and metastasis were detected by CCK8, Edu staining, Transwell assay and scratch assay. The expression levels of related proteins were detected by Western blot. Results At the cellular level, ZNF692 was overexpressed to varying degrees in prostate cancer cell lines, with the highest expression in PC3 cell lines. CCK8 and Edu results showed that the proliferation of prostate cancer PC3 cells that knocked down ZNF692 was slowed. Transwell assay and scratch assay showed reduced invasion and migration of prostate cancer PC3 cells that knocked out ZNF692. Flow cytometry showed that the apoptosis rate of prostate cancer PC3 cells after ZNF692 knockout was increased. In addition, after ZNF692 silencing, the expression level of epithelial phenotype E-cadherin increased in PC3 cells, while the expression level of interstitial phenotype N-cadherin, Vimentin, c-Myc, and CyclinA1 decreased. The state of prostate cancer PC3 cells that overexpressed ZNF692 was reversed from the state after ZNF692 was knocked down. Conclusion ZNF692 can be used as a new prognostic marker and a potential biologic therapeutic target for PCa. By inhibiting the expression of c-myc and cyclinA1, the EMT signaling pathway is regulated to provide evidence for its potential molecular mechanism.

Nerve growth factor (NGF) plays a dual role both in inflammatory states and cancer, acting both as a pro-inflammatory and oncogenic factor and as an anti-inflammatory and pro-apoptotic mediator in a context-dependent way based on the signaling networks and its interaction with diverse cellular components within the microenvironment. This report aims to provide a summary and subsequent review of the literature on the role of NGF in regulating the inflammatory microenvironment and tumor cell growth, survival, and death. The role of NGF in inflammation and tumorigenesis as a component of the inflammatory system, its interaction with the various components of the respective microenvironments, its ability to cause epigenetic changes, and its role in the treatment of cancer have been highlighted in this paper.

In recent years, many studies have reported that microRNAs play an important role in the pathogenesis of a variety of diseases, and the aim of this paper is to explore the role and mechanism of miR-346 in acute respiratory distress syndrome (ARDS). A mouse model of ARDS was constructed by LPS induction, and RT-qPCR assay was used to verify that the expression level of miR-346 in lung tissue was significantly increased, and was negatively correlated with oxygenation index. Inhibiting the expression of miR-346 in mice and HPMECs by miR-346 inhibitor confirmed that decreased miR-346 expression could lead to increased oxygenation index, decreased lung index, lung water content and NO content to reduce lung injury in mice, while lung inflammation was alleviated and apoptosis was reduced in mice. The same results were obtained in cells. BCL6 was predicted to be a target of miR-346 by targetscan and miRDB; when miR-346 was inhibited, BCL6 expression was increased, and if miR-346 and BCL6 expression were inhibited at the same time, it could aggravate lung injury and reduce the proliferation of HPMECs and increase their apoptosis and inflammation in mice. This shows that miR-346 inhibits the migration of HPMECs by regulating BCL6 expression, which in turn promotes the apoptosis of HPMECs, leading to inflammation and inducing ARDS.

Abstract Background Osteonecrosis of the femoral head (ONFH) is a common, refractory and disabling disease of orthopedic department, which is one of the common causes of hip pain and dysfunction. Recent studies have shown that much progress has been made in the research of programmed cell death (PCD) in ONFH. However, there is no bibliometric analysis in this research field. This study aims to provide a comprehensive overview of the knowledge structure and research hot spots of PCD in ONFH through bibliometrics. Method The literature search related to ONFH and PCD was conducted on the Web of Science Core Collection (WoSCC) database from 2002 to 2021. The VOSviewers, “bibliometrix” R package and CiteSpace were used to conduct this bibliometric analysis. Results In total, 346 articles from 27 countries led by China and USA and Japan were included. The number of publications related to PCD in ONFH is increasing year by year. Shanghai Jiao Tong University, Xi An Jiao Tong University, Wuhan University and Huazhong University of Science and Technology are the main research institutions. Molecular Medicine Reports is the most popular journal in the field of PCD in ONFH, and Clinical Orthopaedics and Related Research is the most cocited journal. These publications come from 1882 authors among which Peng Hao, Sun Wei, Zhang Chang-Qing, Zhang Jian and Wang Kun-zheng had published the most papers and Ronald S Weinstein was cocited most often. Apoptosis, osteonecrosis, osteonecrosis of the femoral head, glucocorticoid and femoral head appeared are the main topics the field of PCD in ONFH. Autophagy was most likely to be the current research hot spot for PCD in ONFH. Conclusion This is the first bibliometric study that comprehensively summarizes the research trends and developments of PCD in ONFH. This information identified recent research frontiers and hot directions, which will provide a reference for scholars studying PCD in ONFH.

Mastitis is a common disease worldwide that affects the development of the dairy industry due to its high incidence and complex etiology. Precise regulation of cell death and survival plays a critical role in maintaining internal homeostasis, organ development, and immune function in organisms, and regulatory abnormalities are a common mechanism of various pathological changes. Recent research has shown that regulated cell death (RCD) plays a crucial role in mastitis. The development of drugs to treat cell death and survival abnormalities that can be widely used in mastitis treatment has important clinical significance. This paper will review the molecular mechanisms of apoptosis, autophagy, pyroptosis, ferroptosis, and necroptosis and their regulatory roles in mastitis to provide a new perspective for the targeted treatment of mastitis.

This paper presents a multifaceted assessment of inhibitors of anti-apoptotic proteins (IAPs) in the context of head and neck squamous cell carcinoma (HNSCC). The article discusses the results of in vitro, in vivo, and clinical studies, highlighting the significance of IAPs in the resistance of cancer cells to apoptosis, which is a key factor hindering effective treatment. The main apoptosis pathways, including the intrinsic and extrinsic pathways, and the role of IAPs in their regulation, are presented. The study’s findings suggest that targeting IAPs with novel therapies may offer clinical benefits in the treatment of advanced HNSCC, especially in cases resistant to conventional treatment methods. These conclusions underscore the need for further research to develop more effective and safer therapeutic strategies.

Scientific knowledge evolves in small steps, with occasional backsteps to correct inaccuracies, all occurring within a competitive environment. This perspective for the first time looks at the history of latency-related RNA (LR-RNA) that was later renamed latency-associated transcript (LAT). At the 1986 International Herpesvirus Workshop (IHW) meeting in Leeds, England, Daniel L Rock and Anthony B Nesburn first reported the discovery of human herpes virus 1 (HSV-1) latency-related (LR) RNA that is antisense to ICP0. Less than a month after the IHW meeting, a paper was submitted to Science magazine and 8 months later appeared in print thanking “D. Rock for suggesting RNA complementary to the ICP0 message may be present in latently infected cells”. This perspective is not a review of the LAT literature but intends to clarify the timeline of LAT discovery and subsequent breakthroughs such as reactivation, apoptosis, CD8+ T cell exhaustion, and LAT expression in different cell types detected during latency. While many review articles have been written about LAT since 1987, the most comprehensive and balanced review about LAT was written by Dr. David Bloom’s group. In this overview, I will discuss our original collaboration with Dr. Dan Rock and subsequent work that our group performed, which is still ongoing. Finally, I will discuss the controversies associated with LAT from its inception to current times.

Objectives: to study the apoptotic response of auditory hair cells in the organ of Corti after exposure to neomycin within the first 6 hours. Materials and methods: auditory hair cells harvested on the postnatal day 7 from the cochleae of C57BL6 wild type mice were cultured in vitro in the presence (neomycin group, n= 59 cochleas) or absence of neomycin (control group, n= 31 cochleas). Apoptotic cells were evaluated within 6 hours of incubation for the expression of active caspases (8, 9 or 3) in the cytoplasm and counterstained using propidium iodide to highlight apoptotic nuclei. Cells were statistically quantified using average and standard deviation. The differences between the averages were tested with the help of Student T test (threshold p< 0,05). Results: The statistic comparison between the different caspase types (caspase 3, 8 and 9), the average and dispersion inside the cell groups, permitted us to detect the first step of apoptosis taking place in the cytoplasm. The comparison of the cell group where propidium iodide was accumulated in the nucleus with the cell group where both the caspase and propidium iodide appeared, permitted us to detect the initiation and development of the second step of apoptosis, the one where the nucleus has already been affected. Conclusions: Neomycin is initiating, right after 6 hours of incubation, the process of apoptosis in auditory hair cells, determining the activation of cytoplasm caspases.

Of ovarian follicular reserve, only a small part of these follicles reach maturity, most of them suffering an involution process called follicular atresia. In addition, for the initiation of a new wave of follicular development, a prerequisite is the corpus luteum regression. Last year studies showed that the two processes taking place in the ovaries are based on a complex mechanism, of genetically programmed cell death, significantly called apoptosis, a process conserved in terms of evolution, by which cells inactivate, disassemble and degrade their own structural and functional components systematically for completion of their own death. Ability of cells to enter in apoptosis in response to a specific death signal, depends on both their proliferative status and position in cell cycle, and on controlled expression of genes that promote, inhibit or affect cell death program. Any dysfunction that occurs in any of the key points of the programmed death can lead to erroneous apoptotic process, resulting in expression of pathological conditions.

Chicken Primordial Germ cells (PGCs) are emerging pioneers in the field of applied embryology and stem cell technology. Now-a-days transgenic chickens are promising models to study human disease pathophysiology and drug designing. However, most of the molecular mechanism, which govern the stemness and pluripotency of chicken PGCs, not known in details. Recent studies have indicated the role of HSP70 in early embryonic development in many vertebrate species. Exposure of chicken to heat stress result in activation of heat shock factors which activate the transcription of HSP70. Exposure chicken eggs to acute heat stress effects HSP70 expression in PGCs and gonads. HSP70 helps in maintaining the integrity of chicken PGCs. A new emerging role of HSP70 in apoptosis has emerged. In our lab, we aim to characterize the expression of cHsp70 in chicken PGCs and gonads during embryonic development by subjecting the parents to acute levels of heat stress. Chickens whose parents subjected to heat stress showed varied expression of cHsp70 and also improved thermo tolerance. In the future we plan to study other factors and miRNAs, which is characterized as an emerging player in regulating heat shock protein response in chicken and also plays an important role in apoptosis.

Follicular atresia is a process commonly encountered at ovarian level that limits the number of ovulations and, respectively, the reproductive potential of a female. Ovarian cells’ death is essential for maintaining homeostasis of this organ and is based on an apoptotic mechanism that ensures selection of the dominant follicle and the disappearance of follicles in excess. The present study evaluates the incidence of morphological changes specific for this process in the prepubescent mouse ovary by applying optical microscopy techniques. Microscopic analysis was performed on sections of ovarian tissue from mice females’ line NMRI aged 14-17 days. The results show, at this age, significant morphological changes at cellular level, specific for apoptotic process, as condensation and fragmentation of the genetic material, vacuolization of cell cytoplasm, destabilization of cell adhesion junctions and appearance of wide intercellular spaces, invasion of created spaces with infiltrated leukocytes, formation of apoptotic bodies.

ABSTRACTThe growing emergence of resistance to current anti-theilerial agents necessitates the exploration of alternative approaches to drug discovery. This study evaluated the antiparasitic efficacy of 148 compounds derived from an epigenetic inhibitor library against the schizont stage of a Theileria annulata-infected cell line. Initial screening at a concentration of 10 µM identified 27 compounds exhibiting promising anti-theilerial activity. Further investigation, including determination of the 50% inhibitory concentration (IC50) and host cell cytotoxicity assay, highlighted seven highly effective compounds (SAHA, BVT-948, Trichostatin A, Methylstat, Plumbagin, Ryuvidine, and TCE-5003) against T. annulata-infected cells. Analysis of the active compounds revealed their inhibitory action against various human targets, such as HDAC (SAHA and Trichostatin A), SET domain (Ryuvidine), PRMT (BVT-948 and TCE-5003), histone demethylase (Methylstat), and ROS/apoptosis inducer (Plumbagin). We identified gene orthologs of these targets in Theileria and conducted molecular docking studies, demonstrating effective binding of the compounds with their respective targets in the parasite, supported by in vitro data. Additionally, we performed in silico ADME/T predictions, which indicated potential mutagenic and hepatotoxic effects of Plumbagin, Methylstat, and TCE-5003, rendering them unsuitable for drug development. Conversely, SAHA, Trichostatin A, and BVT-948 showed promising characteristics and may represent potential candidates for future development as chemotherapeutic agents against tropical theileriosis. These findings provide valuable insights into the search for novel anti-theilerial drugs and offer a basis for further research in this area.IMPORTANCETheileria annulata is a protozoan parasite responsible for tropical theileriosis, a devastating disease affecting cattle. Traditional chemotherapy has limitations, and the study explores the potential of epidrugs as an alternative treatment approach. Epidrugs are compounds that modify gene expression without altering the underlying DNA sequence, offering a novel way to combat parasitic infections. This research is pivotal as it addresses the urgent need for innovative therapies against T. annulata, contributing to the development of more effective and targeted treatments for infected livestock. Successful implementation of epidrugs could not only enhance the well-being of cattle but also have broader implications for the control of parasitic diseases, showcasing the paper’s significance in advancing veterinary science and improving livestock health globally.

Natural compounds hold promise in the search for cancer therapies due to their unique chemical structures and combinations that may effectively combat cancer while minimizing toxicity and side effects compared to conventional treatments. Silibinin, a natural lignan, has been found to possess strong anti-cancer activity against several types of human cancers based on emerging research. This study aims to provide an overview of the therapeutic potential of silibinin in the treatment and prevention of cancers. A comprehensive search was conducted using various internet databases such as PubMed, Google Scholar, and ScienceDirect to identify relevant research papers. Silibinin has been shown to exhibit anticancer activity against several types of cancers, including liver, lungs, breast, prostate, colorectal, skin, and bladder cancers. Its multifaceted mechanisms of action contribute to its therapeutic effects. Silibinin exerts antioxidant, anti-inflammatory, anti-proliferative, pro-apoptotic, anti-metastatic, and anti-angiogenic activities, making it a promising candidate for cancer therapy. One of the key mechanisms underlying the anticancer effects of silibinin is its ability to modulate multiple signaling pathways involved in cancer development and progression. It can inhibit the activation of various oncogenic pathways, including PI3K/Akt, NF-κB, Wnt/β-catenin, and MAPK pathways, thereby suppressing cancer cell proliferation, inducing cell cycle arrest, and promoting apoptosis. Silibinin possesses great potential as an effective treatment agent for cancer. The multifaceted mechanisms of action, favorable safety profile, and potential synergistic effects of silibinin with conventional therapies make it an attractive candidate for further investigation and development as a cancer treatment. However, more extensive clinical studies are necessary to fully establish the efficacy, optimal dosage, and long-term effects of silibinin in cancer treatment.

Introduction Curcumin, the active ingredient in turmeric, is gaining increasing attention due to its potential health benefits, especially in the context of its immunomodulatory and anticancer properties. Aim of the study The aim of this review was to discuss recent findings regarding the impact of curcumin on the immune system and its potential applications in anticancer therapy. Materials and methods The paper was created based on the Pubmed and Scholar database. The literature was reviewed using the keywords: „curcumin”, „immunomodulatory effects”, „cytokines”, „anticancer”, „apoptosis”, „cell proliferation”, „radiosensitizing”. Results Studies have confirmed that curcumin, especially in the form of nanocurcumin, exhibits significant immunomodulatory effects. It reduces the number of Th17 cells, increases Treg cells, and regulates the expression of pro-inflammatory cytokines, which is crucial in controlling autoimmune reactions. Furthermore, it demonstrates anticancer activity by inhibiting the growth of cancer cells, stimulating apoptosis, and enhancing the effectiveness of anticancer therapy. Conclusions Despite promising results, further research on the safety of curcumin therapy, particularly in the long term, is essential. Limitations associated with bioavailability and pharmacokinetics suggest the need for the development of formulations with increased bioavailability to maximize the potential benefits of curcumin in the treatment of various disorders.