Human Death Research Articles

Retracted: Nanoemulsion and Encapsulation Strategy of Hydrophobic Oregano Essential Oil Increased Human Prostate Cancer Cell Death via Apoptosis by Attenuating Lipid Metabolism.

[This retracts the article DOI: 10.1155/2022/9569226.].

The use of statins and inhibitors of proprotein convertase subtilisin-kexin type 9 (PCSK 9) in patients with dyslipidemia

Scientific relevance. According to the WHO data, cardiovascular diseases rank first as the cause of human death. In 2022, 18,601,923 people died from cardiovascular diseases, which amounted to 33 % of the total mortality in the world. Malignant neoplasms rank second with 9,958,133 deaths, representing 17.6 % of total mortality. Among cardiovascular diseases, ischemic heart disease (IHD), the pathogenesis of which is associated with impaired cholesterol and lipoprotein metabolism, is leading. The use of statin drugs is recommended as a first-line lipid-lowering therapy. As an alternative to HMG-CoA reductase inhibitors (statins), proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9) were discovered in 2003, however, they are less popular due to insuf ficient data on these drugs and their costliness. Purpose of the work: to study the safety of using proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors in patients with dyslipidemia and compare the advantages and disadvantages in relation to the ef fects of HMG-CoA reductase (statins). Discussion: The analysis of literature data has shown that the most frequent manifestations of intolerance to statins are muscle symptoms. The main mechanisms of statin-associated complications are mediated by inhibition of HMG-CoA reductase, as well as by the effect of drugs on cellular and subcellular processes, skeletal muscles and genetic features of patients. PCSK9 inhibitors have a fundamentally different mechanism of action — they bind and inactivate PCSK9, which leads to a decrease of low-density lipoprotein cholesterol in the blood level. A small number of undesirable reactions have been identified for drugs of this group, the most important of which is immunogenicity. However, even if patients have antibodies to PCSK9 inhibitor, the efficacy of the drug in reducing the level of low-density lipoproteins remains high.Conclusion. In medical studies, PCSK9 inhibitors have been shown to perform better compared to HMG-CoA reductase inhibitors; meanwhile, patients continue to use statins as lipid-lowering medications.

Anticancer activities of natural antimicrobial peptides from animals.

Cancer is the most common cause of human death worldwide, posing a serious threat to human health and having a negative impact on the economy. In the past few decades, significant progress has been made in anticancer therapies, but traditional anticancer therapies, including radiation therapy, surgery, chemotherapy, molecular targeted therapy, immunotherapy and antibody-drug conjugates (ADCs), have serious side effects, low specificity, and the emergence of drug resistance. Therefore, there is an urgent need to develop new treatment methods to improve efficacy and reduce side effects. Antimicrobial peptides (AMPs) exist in the innate immune system of various organisms. As the most promising alternatives to traditional drugs for treating cancers, some AMPs also have been proven to possess anticancer activities, which are defined as anticancer peptides (ACPs). These peptides have the advantages of being able to specifically target cancer cells and have less toxicity to normal tissues. More and more studies have found that marine and terrestrial animals contain a large amount of ACPs. In this article, we introduced the animal derived AMPs with anti-cancer activity, and summarized the types of tumor cells inhibited by ACPs, the mechanisms by which they exert anti-tumor effects and clinical applications of ACPs.

Uncontrolled organ donation after out-of-hospital cardiac arrest. Literature review

Organ transplantation is the best therapy for terminal and irreversible organ failure. The global development of organ transplantation as a type of medical care is inextricably linked to the establishment of neurological criteria for declaring human death (brain death). In the early evolutionary period of transplantation, organs were used, mainly kidneys, obtained from donors whose death was ascertained in accordance with the generally accepted criteria of cessation of blood circulation and respiration. As this type of organ donation developed, numerous terms were used in the world literature to designate it, such as ‘asystolic donors’, ‘non-heart beating donors’, ‘donors after cardiac death’, etc. In Russia, there is an established practice of dealing with donors after cardiac death (DCD), but the active development of Russian transplantology in the last 20 years is primarily associated with brain-dead organ donation. However, countries with the most active and advanced organ donation practices have in recent years been successfully dealing with donors who have suffered sudden out-of-hospital cardiac arrest (OHCA). Previously, this type of donation was considered inaccessible due to the unacceptable warm ischemia time and consequently severe damage to donor organs. Due to the development of new technologies in emergency medical care, it became possible to transport a patient with clinical death that occurred in an outof-hospital setting, to the hospital, while providing cardiopulmonary resuscitation by means of automatic chest compression and artificial ventilation. The article presents historical aspects of donation after cardiac death, and the most actualized definitions and practices of dealing with such donors.

Survey of Main Group Metals and Metalloids in Cancer Treatment

Cancer is one of the leading causes of human death among all major diseases. Metal-based complexes are considered as the most promising vital part in the existing arsenal of cytotoxic candidates used in cancer therapy and diagnostics. The efforts of many scientific groups resulted in the development of numerous metal-based compounds featuring different biologically active organic ligands in order to modulate their bioactivity. Along with the main representatives as potential therapeutic agents, such as the complexes Pt(II)/Pt(IV), Pd(II), Ru(II)/Ru(III), Ag(I), Au(I)/Au(III), Ti(IV), V(IV) and Ga(III), many other transition metal and lanthanide complexes possessing antiproliferative activity are widely discussed in the literature. However, such drugs remain outside the scope of this review. The main purpose of the current study is to review the potential activity of main group metal- and metalloid-based complexes against the most common cancer cell types, such as carcinomas (lung, liver, breast, kidney, gastric, colorectal, bladder, ovarian, cervical, prostate, etc.); sarcomas; blastomas; lymphomas; multiple myeloma; and melanoma. Overcoming the long disregard of organometallic compounds of metals and metalloids from the main groups, a growing number of emerging anticancer agents remarkably prove this field offers an extensive variety of new options for the design of innovative unexplored chemopharmaceutics. Moreover, some of the metal complexes and organometallic compounds from these elements can exhibit entirely different, specific modes of action and biological targets. Obviously, exploitation of their distinct properties deserves more attention.

Complexity of human death: its physiological, transcriptomic, and microbiological implications.

Human death is a complex, time-governed phenomenon that leads to the irreversible cessation of all bodily functions. Recent molecular and genetic studies have revealed remarkable experimental evidence of genetically programmed cellular death characterized by several physiological processes; however, the basic physiological function that occurs during the immediate postmortem period remains inadequately described. There is a paucity of knowledge connecting necrotic pathologies occurring in human organ tissues to complete functional loss of the human organism. Cells, tissues, organs, and organ systems show a range of differential resilience and endurance responses that occur during organismal death. Intriguingly, a persistent ambiguity in the study of postmortem physiological systems is the determination of the trajectory of a complex multicellular human body, far from life-sustaining homeostasis, following the gradual or sudden expiry of its regulatory systems. Recent groundbreaking investigations have resulted in a paradigm shift in understanding the cell biology and physiology of death. Two significant findings are that (i) most cells in the human body are microbial, and (ii) microbial cell abundance significantly increases after death. By addressing the physiological as well as the microbiological aspects of death, future investigations are poised to reveal innovative insights into the enigmatic biological activities associated with death and human decomposition. Understanding the elaborate crosstalk of abiotic and biotic factors in the context of death has implications for scientific discoveries important to informing translational knowledge regarding the transition from living to the non-living. There are important and practical needs for a transformative reestablishment of accepted models of biological death (i.e., artificial intelligence, AI) for more precise determinations of when the regulatory mechanisms for homeostasis of a living individual have ceased. In this review, we summarize mechanisms of physiological, genetic, and microbiological processes that define the biological changes and pathways associated with human organismal death and decomposition.

Allah is the Creator: An Analysis of Hadiths on Human Creation and Destiny

This article human creation and the concept of destiny according to Islamic teachings, using qualitative research methods. The process of human creation is explained in the Qur'an and hadith, including the stages of embryonic development in the womb according to the 4th Hadith of arbain. In addition, there is an explanation of the four levels of destiny that must be believed, as well as the redaction of the hadith that explains the process of human creation and the granting of destiny by Allah. Hadith Arbain 4 explains the process of human embryo development in the womb, starting from the stage of nutfah (sperm) to the blowing of the spirit. At the stage of spirit inhalation, Allah determines human destiny, including sustenance, death, charity, and happiness. Although destiny has been written, humans still have free will to do good or bad. The text emphasizes the importance of understanding the messages in this hadith and applying them in daily life. The implementation of this hadith can be done by developing gratitude, understanding destiny, respecting human position, and optimizing potential and responsibility. Thus, an understanding of human creation and destiny in Islam can serve as a foundation for individuals to live life with full awareness of the destiny that has been set, but still be responsible for their actions and choices fertilization.

Predicting coronary heart disease in Chinese diabetics using machine learning

Diabetes, a common chronic disease worldwide, can induce vascular complications, such as coronary heart disease (CHD), which is also one of the main causes of human death. It is of great significance to study the factors of diabetic patients complicated with CHD for understanding the occurrence of diabetes/CHD comorbidity. In this study, by analyzing the risk of CHD in more than 300,000 diabetes patients in southwest China, an artificial intelligence (AI) model was proposed to predict the risk of diabetes/CHD comorbidity. Firstly, we statistically analyzed the distribution of four types of features (basic demographic information, laboratory indicators, medical examination, and questionnaire) in comorbidities, and evaluated the predictive performance of three traditional machine learning methods (eXtreme Gradient Boosting, Random Forest, and Logistic regression). In addition, we have identified nine important features, including age, WHtR, BMI, stroke, smoking, chronic lung disease, drinking and MSP. Finally, the model produced an area under the receiver operating characteristic curve (AUC) of 0.701 on the test samples. These findings can provide personalized guidance for early CHD warning for diabetic populations.

Photoactive rhodamine-based photosensitizer eliminates Staphylococcus aureus via superoxide radical photosensitization

Due to the antibiotics abuse, bacterial infection has become one of the leading causes of human death worldwide. Novel selective antimicrobial agents are urgently needed, with the hope of maintaining the balance of the microbial environment. Photo-activated chemotherapeutics have shown great potential to eliminate bacteria with appealing spatiotemporal selectivity. In this work, we reported the structural modification to enhance the triplet excited state property of Rhodamine B, synthesizing a rhodamine-based photosensitizer RBPy. Upon light activation, RBPy exhibited much stronger photosensitization ability than the parent compound Rhodamine B both in solution and in bacteria. Importantly, RBPy can selectively inactivate Staphylococcus aureus and inhibit biofilm formation with high biocompatibility. This work provides a new strategy to develop rhodamine-based photoactive chemotherapeutics for antimicrobial photodynamic therapy.

Museums as Deathscapes

The museum is very often equivalent to a place that is filled with objects and references to human death. Accordingly, this article aims at bringing greater clarity into some of the precautions taken by museums when they choose to expose what can be considered as a highly sensitive matter, namely human remains. Put differently, the scope of the text concerns how museums deal with the task of displaying the dead in public. How do they act in order to facilitate the actual display, and at the same time minimize the risk for public criticism? The overall discussion is informed by the idea of museums as deathscapes, and the intentional use of a kind of ‘morbid aura’ that is sometimes attached to museum objects with a close association to human death.

Protocol for a phase II study to evaluate the efficacy and safety of nivolumab as a postoperative adjuvant therapy for patients with esophageal cancer treated with preoperative docetaxel, cisplatin plus 5-fluorouracil treatment (PENTAGON trial).

In Japan, preoperative adjuvant chemotherapy followed by surgical resection is the standard treatment for patients with locally advanced esophageal squamous cell carcinoma. However, the risk of recurrence after surgical resection remains high. Although a randomized controlled trial evaluating the efficacy of nivolumab, a fully human monoclonal anti-programmed death 1 antibody, as postoperative adjuvant therapy after neoadjuvant chemoradiotherapy and surgery established its superior efficacy as adjuvant therapy, the efficacy for patients who received preoperative adjuvant chemotherapy has not been demonstrated. This study aims to elucidate the efficacy and safety of nivolumab as postoperative adjuvant therapy for patients with esophageal squamous cell carcinoma after preoperative adjuvant chemotherapy with docetaxel and cisplatin plus 5-fluorouracil followed by surgical resection. This study is a multi-institutional, single-arm, Phase II trial. We plan to recruit 130 esophageal squamous cell carcinoma patients, who have undergone preoperative adjuvant chemotherapy with docetaxel and cisplatin plus 5-fluorouracil followed by surgical resection. If the patient did not have a pathological complete response, nivolumab is started as a postoperative adjuvant therapy within 4-16 weeks after surgery. The nivolumab dose is 480 mg/day every four weeks. Nivolumab is administered for up to 12 months. The primary endpoint is disease-free survival; the secondary endpoints are overall survival, distant metastasis-free survival, and incidence of adverse events. To our knowledge this study is the first trial establishing the efficacy of nivolumab as postoperative adjuvant therapy for patients with esophageal squamous cell carcinoma after preoperative adjuvant chemotherapy with docetaxel and cisplatin plus 5-fluorouracil followed by surgical resection. In Japan, preoperative adjuvant chemotherapy followed by surgery is a well-established standard treatment for resectable, locally advanced esophageal squamous cell carcinoma. Therefore, developing an effective postoperative adjuvant therapy has been essential for improving oncological outcomes.

Development of human innate immune responses in a humanized mouse model expressing four human myelopoiesis transgenes.

Dysregulated innate immune responses underlie multiple inflammatory diseases, but clinical translation of preclinical innate immunity research in mice is hampered by the difficulty of studying human inflammatory reactions in an in vivo context. We therefore sought to establish in vivo human inflammatory responses in NSG-QUAD mice that express four human myelopoiesis transgenes to improve engraftment of a human innate immune system. We reconstituted NSG-QUAD mice with human hematopoietic stem and progenitor cells (HSPCs), after which we evaluated human myeloid cell development and subsequent human responses to systemic and local lipopolysaccharide (LPS) challenges. NSG-QUAD mice already displayed engraftment of human monocytes, dendritic cells and granulocytes in peripheral blood, spleen and liver at 6 weeks after HSPC reconstitution, in which both classical, intermediate and non-classical monocytes were present. These huNSG-QUAD mice responded to intraperitoneal and intranasal LPS challenges with production of NF-κB-dependent human cytokines, a human type I interferon response, as well as inflammasome-mediated production of human IL-1β and IL-18. The latter were specifically abrogated by the NLRP3 inhibitor MCC950, while LPS-induced human monocyte death was not altered. Besides providing proof-of-principle for small molecule testing of human inflammatory reactions in huNSG-QUAD mice, this observation suggests that LPS-induced in vivo release of human NLRP3 inflammasome-generated cytokines occurs in a cell death-independent manner. HuNSG-QUAD mice are competent for the NF-κB, interferon and inflammasome effectors of human innate immunity, and can thus be utilized to investigate signaling mechanisms and pharmacological targeting of human inflammatory responses in an in vivo setting.

Biblijsko podzemlje o čistilištu

»He punishes us; then he shows us mercy. He sends us down to the world of the dead, then he brings us up from the grave« (Tob 13:2). The Old and New Testament theology of Sheol (hereinafter šeᵓôl) follows the logical sequence of human life and death. Man enters šeᵓôl as he has built himself during his lifetime. In other words, in šeᵓôl the basic human determination and nature does not change. It cannot happen in šeᵓôl that a righteous person turns into a wicked and a wicked person becomes a righteous. However, the key characteristic of šeᵓôl is not the immutability of the basic position but the impossibility of expressing praise to God. This virtue characterizes the life of a righteous person who glorifies God with his righteousness. Therefore, the righteous man by his nature does not belong to that place because the one who praised and blessed God during his life cannot stop glorifying him even in šeᵓôl. The wicked man, however, who does not glorify God during his lifetime is suited to the postmortem environment of šeᵓôl in which God’s name is not invoked. Thus we come to the conclusion that šeᵓôl belongs exclusively to sinners, or to those who do not praise God. The theology of šeᵓôl reached its peak in the teaching that šeᵓôl is not the eternal abode of the righteous. The righteous indeed descends to šeᵓôl but his soul does neither rot there nor does he become a part of the impersonal contents of šeᵓôl. Since it cannot remain in šeᵓôl, the justified soul after freeing itself from its habits that led it to sin during its life and having risen in holiness, rises to the heights and it is God himself who delivers it and who rewards it with a happy eternity. Therefore, for the dominant biblical theology it is not questionable that the righteous will see the face of God but what privileges one over the other is the time of stay in the place of the dead, i.e. šeᵓôl. The elaborate Christian theology calls that time of souls’ stay in the place of the dead the purgatory.

Архетип мифологического героя в новостных сюжетах о пандемии Covid-19

The article explores the mythological model of reality construction that underlies television news programs on domestic and Western TV channels. Analyzing the main trends and contradictions in visual image functioning within the media over the past decade reveals the creation of symbolic reality as a means for people’s spiritual and practical orientation in everyday life. In today’s media culture, which is saturated with visual images, the interpretation of what is seen in the context of simulacra, recognizable visual codes, and strict construction models, becomes crucial. Deciphering the hidden meanings embedded in media materials forms the basis for understanding the cultural context of society. The Covid-19 pandemic, apart from being an informational event that affected numerous countries, also emerged as a factor influencing various economic and demographic processes. Within the media, this topic has developed into a self-contained narrative with its own plotline, characters, and actions, characteristic of a mythological cliché. It delves into matters of human life and death, thus tapping into the primordial fears and unexplored depths of the viewer’s consciousness. The analysis highlights that the media employ a mythological structure when constructing reality and providing information about the pandemic.

Nanomaterial combined engineered bacteria for intelligent tumor immunotherapy.

Cancer remains the leading cause of human death worldwide. Compared to traditional therapies, tumor immunotherapy has received a lot of attention and research focus due to its potential to activate both innate and adaptive immunity, low toxicity to normal tissue, and long-term immune activity. However, its clinical effectiveness and large-scale application are limited due to the immunosuppression microenvironment, lack of spatiotemporal control, expensive cost, and long manufacturing time. Recently, nanomaterial combined engineered bacteria have emerged as a promising solution to the challenges of tumor immunotherapy, which offers spatiotemporal control, reversal of immunosuppression, and scalable production. Therefore, we summarize the latest research on nanomaterial-assisted engineered bacteria for precise tumor immunotherapies, including the cross-talk of nanomaterials and bacteria as well as their application in different immunotherapies. In addition, we further discuss the advantages and challenges of nanomaterial-engineered bacteria and their future prospects, inspiring more novel and intelligent tumor immunotherapy.

Comparison of Classification Algorithm Performance for Diabetes Prediction Using Orange Data Mining

Diabetes is a disease that contributes to a relatively high mortality rate. The human death rate due to diabetes is a widespread issue globally. The primary goal of this research is to predict individuals suffering from diabetes using a publicly available dataset from the UCI Repository with the Diabetes Disease dataset. To obtain the best classification algorithm, a comparison is made among three algorithms: KNN, Naive Bayes, and Random Forest, commonly used for predicting diabetes. The comparison results indicate that the Random Forest algorithm is the appropriate and accurate algorithm for predicting individuals with diabetes, with an accuracy rate of 97%.

Potential Application of Modified mRNA in Cardiac Regeneration.

Heart failure remains the leading cause of human death worldwide. After a heart attack, the formation of scar tissue due to the massive death of cardiomyocytes leads to heart failure and sudden death in most cases. In addition, the regenerative ability of the adult heart is limited after injury, partly due to cell-cycle arrest in cardiomyocytes. In the current post-COVID-19 era, urgently authorized modified mRNA (modRNA) vaccines have been widely used to prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Therefore, modRNA-based protein replacement may act as an alternative strategy for improving heart disease. It is a safe, effective, transient, low-immunogenic, and integration-free strategy for in vivo protein expression, in addition to recombinant protein and stem-cell regenerative therapies. In this review, we provide a summary of various cardiac factors that have been utilized with the modRNA method to enhance cardiovascular regeneration, cardiomyocyte proliferation, fibrosis inhibition, and apoptosis inhibition. We further discuss other cardiac factors, modRNA delivery methods, and injection methods using the modRNA approach to explore their application potential in heart disease. Factors for promoting cardiomyocyte proliferation such as a cocktail of three genes comprising FoxM1, Id1, and Jnk3-shRNA (FIJs), gp130, and melatonin have potential to be applied in the modRNA approach. We also discuss the current challenges with respect to modRNA-based cardiac regenerative medicine that need to be overcome to apply this approach to heart disease. This review provides a short description for investigators interested in the development of alternative cardiac regenerative medicines using the modRNA platform.

Cell membrane-coated biomimetic nanomedicines: productive cancer theranostic tools.

As the second-leading cause of human death, cancer has drawn attention in the area of biomedical research and therapy from all around the world. Certainly, the development of nanotechnology has made it possible for nanoparticles (NPs) to be used as a carrier for delivery systems in the treatment of tumors. This is a biomimetic approach established to craft remedial strategies comprising NPs cloaked with membrane obtained from various natural cells like blood cells, bacterial cells, cancer cells, etc. Here we conduct an in-depth exploration of cell membrane-coated NPs (CMNPs) and their extensive array of applications including drug delivery, vaccination, phototherapy, immunotherapy, MRI imaging, PET imaging, multimodal imaging, gene therapy and a combination of photothermal and chemotherapy. This review article provides a thorough summary of the most recent developments in the use of CMNPs for the diagnosis and treatment of cancer. It critically assesses the state of research while recognizing significant accomplishments and innovations. Additionally, it indicates ongoing problems in clinical translation and associated queries that warrant deeper research. By doing so, this study encourages creative thinking for future projects in the field of tumor therapy using CMNPs while also educating academics on the present status of CMNP research.

Hairpin self-assembly powered by exonuclease III for highly sensitive and cross-validated miRNA-155 detection.

Cancer is one of the most important causes of human death and poses a serious threat to human health. As a cancer biomarker, microRNA-155 (miRNA-155) is highly expressed in various types of cancer tissues and is involved in the proliferation of tumor cells. Therefore, developing a miRNA-155 detection technology with high specificity and sensitivity is of great significance for the early detection, accurate treatment and prognostic evaluation of tumors. Here, we developed a fluorescence detection method using exonuclease III-assisted target cycling and catalytic hairpin assembly (CHA) as a signal amplification technique. This study developed a biosensor for the detection of miRNA-155, utilizing a DNA hairpin (Hp) for target recognition and generating double-stranded DNA (dual-Hp-T). The 3' flat end of the double-stranded DNA can be cleaved by exonuclease III to achieve the target cycle, and a large amount of single-stranded DNA (fuel) can trigger CHA to achieve signal amplification. Simultaneously, the fluorescence resonance energy transfer (FRET) of signal probes with different fluorescence labels on H1 and H2 ends occurs with the CHA reaction. The two fluorescence signals obtained can be used to cross-validate the experimental results. The biosensor exhibits excellent performance of high recovery, high sensitivity and high operability, which can achieve the specific detection of miRNA-155 with a detection limit as low as 8.3 pM. Additionally, the detection efficacy in a human serum environment is also highly satisfactory. This technology provides strong technical support for the development of nucleic acid probes and the diagnosis and treatment of cancer, demonstrating significant practical application value.

First human death due to monkeypox virus in Pakistan: a public health concern for resource-limited non-endemic countries

As the global threat of COVID-19 escalates, countries like Pakistan are still reeling from outbreaks of monkeypox virus (mpox). The first reported death due to mpox has raised concerns among locals. Mpox, which is related to smallpox, transmits through contact and respiratory droplets. Diagnosis relies on laboratory tests, and although no specific vaccine for mpox exists, the smallpox vaccine provides some protection. Pakistan’s response strategy emphasizes surveillance, increasing public awareness, and enhancing healthcare readiness, highlighting the need for a coordinated approach to control and prevent further outbreaks.