PURPOSE OF REVIEW: Men face distinctive health-related challenges as a result of biological, behavioral, and sociocultural factors. In addition, the modern healthcare system does not offer men equal opportunities and options to ensure sex-specific access and delivery to health services. Men's health concerns are, indeed, often not addressed or even forgotten. In this review, we wanted to assess the impact of biology and sociocultural effects on sex-specific life-expectancy. RECENT FINDINGS: Globally, men have a shorter life expectancy than women. With a 5.8 years gender gap in the USA and 5.4 in the EU-27 (both in 2022). Cardiovascular disease, cancer, and accidents continue to represent the primary causes of mortality for both genders with all having disproportional preponderance in men. In recent years, there has been a notable decline in age-adjusted mortality rates related to cancer, while there has been an increase in deaths from accidental and intentional self-harm. Moreover, in the United States, men are more likely than women to develop and die from nonsex-specific cancers. As a result, men's poor health affects productivity, absenteeism, and employment. SUMMARY: The status of men in healthcare is complex. It is rooted in history, culture, and institutions. To address disparities, we need a comprehensive approach that includes policy reforms, sociocultural changes, and a fair and equitable public discourse. Grassroots and top-down strategies are needed to ensure a value-based societal healthcare system acknowledging the unique health needs of men.
- MeSH
- Healthcare Disparities statistics & numerical data MeSH
- Health Status Disparities MeSH
- Health Services Accessibility statistics & numerical data MeSH
- Humans MeSH
- Life Expectancy * MeSH
- Delivery of Health Care statistics & numerical data MeSH
- Health Equity MeSH
- Sex Factors MeSH
- Men's Health * MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
- Geographicals
- United States MeSH
BACKGROUND: Daratumumab, an anti-CD38 monoclonal antibody, has been approved for the treatment of multiple myeloma. Data are needed regarding the use of daratumumab for high-risk smoldering multiple myeloma, a precursor disease of active multiple myeloma for which no treatments have been approved. METHODS: In this phase 3 trial, we randomly assigned patients with high-risk smoldering multiple myeloma to receive either subcutaneous daratumumab monotherapy or active monitoring. Treatment was continued for 39 cycles, for 36 months, or until confirmation of disease progression, whichever occurred first. The primary end point was progression-free survival; progression to active multiple myeloma was assessed by an independent review committee in accordance with International Myeloma Working Group diagnostic criteria. RESULTS: Among the 390 enrolled patients, 194 were assigned to the daratumumab group and 196 to the active-monitoring group. With a median follow-up of 65.2 months, the risk of disease progression or death was 51% lower with daratumumab than with active monitoring (hazard ratio, 0.49; 95% confidence interval [CI], 0.36 to 0.67; P<0.001). Progression-free survival at 5 years was 63.1% with daratumumab and 40.8% with active monitoring. A total of 15 patients (7.7%) in the daratumumab group and 26 patients (13.3%) in the active-monitoring group died (hazard ratio, 0.52; 95% CI, 0.27 to 0.98). Overall survival at 5 years was 93.0% with daratumumab and 86.9% with active monitoring. The most common grade 3 or 4 adverse event was hypertension, which occurred in 5.7% and 4.6% of the patients in the daratumumab group and the active-monitoring group, respectively. Adverse events led to treatment discontinuation in 5.7% of the patients in the daratumumab group, and no new safety concerns were identified. CONCLUSIONS: Among patients with high-risk smoldering multiple myeloma, subcutaneous daratumumab monotherapy was associated with a significantly lower risk of progression to active multiple myeloma or death and with higher overall survival than active monitoring. No unexpected safety concerns were identified. (Funded by Janssen Research and Development; AQUILA ClinicalTrials.gov number, NCT03301220.).
- MeSH
- Progression-Free Survival MeSH
- Adult MeSH
- Smoldering Multiple Myeloma * diagnosis mortality therapy MeSH
- Injections, Subcutaneous MeSH
- Kaplan-Meier Estimate MeSH
- Middle Aged MeSH
- Humans MeSH
- Multiple Myeloma * diagnosis epidemiology prevention & control MeSH
- Antibodies, Monoclonal * administration & dosage adverse effects MeSH
- Watchful Waiting * statistics & numerical data MeSH
- Disease Progression MeSH
- Antineoplastic Agents * administration & dosage adverse effects MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Clinical Trial, Phase III MeSH
- Multicenter Study MeSH
- Randomized Controlled Trial MeSH
- Comparative Study MeSH
Nitrogen, phosphorus, and potassium are the three most essential micronutrients which play major roles in plant survivability by being a structural or non-structural component of the cell. Plants acquire these nutrients from soil in the fixed (NO3 ̄, NH4+) and solubilized forms (K+, H2PO4- and HPO42-). In soil, the fixed and solubilized forms of nutrients are unavailable or available in bare minimum amounts; therefore, agrochemicals were introduced. Agrochemicals, mined from the deposits or chemically prepared, have been widely used in the agricultural farms over the decades for the sake of higher production of the crops. The excessive use of agrochemicals has been found to be deleterious for humans, as well as the environment. In the environment, agrochemical usage resulted in soil acidification, disturbance of microbial ecology, and eutrophication of aquatic and terrestrial ecosystems. A solution to such devastating agro-input was found to be substituted by macronutrients-availing microbiomes. Macronutrients-availing microbiomes solubilize and fix the insoluble form of nutrients and convert them into soluble forms without causing any significant harm to the environment. Microbes convert the insoluble form to the soluble form of macronutrients (nitrogen, phosphorus, and potassium) through different mechanisms such as fixation, solubilization, and chelation. The microbiomes having capability of fixing and solubilizing nutrients contain some specific genes which have been reported in diverse microbial species surviving in different niches. In the present review, the biodiversity, mechanism of action, and genomics of different macronutrients-availing microbiomes are presented.
- MeSH
- Bacteria * metabolism genetics classification MeSH
- Biodiversity * MeSH
- Biotechnology * MeSH
- Potassium metabolism MeSH
- Nitrogen metabolism MeSH
- Phosphorus metabolism MeSH
- Microbiota * MeSH
- Soil chemistry MeSH
- Soil Microbiology MeSH
- Crops, Agricultural MeSH
- Agriculture MeSH
- Nutrients * metabolism MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
BACKGROUND: Cell cycle progression and leukemia development are tightly regulated processes in which even a small imbalance in the expression of cell cycle regulatory molecules and microRNAs (miRNAs) can lead to an increased risk of cancer/leukemia development. Here, we focus on the study of a ubiquitous, multifunctional, and oncogenic miRNA-hsa-miR-155-5p (miR-155, MIR155HG), which is overexpressed in malignancies including chronic lymphocytic leukemia (CLL). Nonetheless, the precise mechanism of how miR-155 regulates the cell cycle in leukemic cells remains the subject of extensive research. METHODS: We edited the CLL cell line MEC-1 by CRISPR/Cas9 to introduce a short deletion within the MIR155HG gene. To describe changes at the transcriptome and miRNome level in miR-155-deficient cells, we performed mRNA-seq/miRNA-seq and validated changes by qRT-PCR. Flow cytometry was used to measure cell cycle kinetics. A WST-1 assay, hemocytometer, and Annexin V/PI staining assessed cell viability and proliferation. RESULTS: The limited but phenotypically robust miR-155 modification impaired cell proliferation, cell cycle, and cell ploidy. This was accompanied by overexpression of the negative cell cycle regulator p21/CDKN1A and Cyclin D1 (CCND1). We confirmed the overexpression of canonical miR-155 targets such as PU.1, FOS, SHIP-1, TP53INP1 and revealed new potential targets (FCRL5, ISG15, and MX1). CONCLUSIONS: We demonstrate that miR-155 deficiency impairs cell proliferation, cell cycle, transcriptome, and miRNome via deregulation of the MIR155HG/TP53INP1/CDKN1A/CCND1 axis. Our CLL model is valuable for further studies to manipulate miRNA levels to revert highly aggressive leukemic cells to nearly benign or non-leukemic types.
- MeSH
- Leukemia, Lymphocytic, Chronic, B-Cell * genetics pathology MeSH
- Cyclin D1 genetics metabolism MeSH
- Cyclin-Dependent Kinase Inhibitor p21 * genetics metabolism MeSH
- Cell Cycle Checkpoints * genetics MeSH
- Humans MeSH
- MicroRNAs * genetics metabolism MeSH
- Cell Line, Tumor MeSH
- Cell Proliferation genetics MeSH
- Heat-Shock Proteins MeSH
- Gene Expression Regulation, Leukemic MeSH
- Carrier Proteins genetics metabolism MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
Microbial transglutaminase (MTG) is an enzyme widely used in the food industry because it creates cross-links between proteins, enhancing the texture and stability of food products. Its unique properties make it a valuable tool for modifying the functional characteristics of proteins, significantly impacting the quality and innovation of food products. In this study, response surface methodology was employed to optimize the fermentation conditions for microbial transglutaminase production by the strain Streptoverticillium cinnamoneum KKP 1658. The effects of nitrogen dose, cultivation time, and initial pH on the activity of the produced transglutaminase were investigated. The significance of the examined factors was determined as follows: cultivation time > nitrogen dose > pH. The interaction between nitrogen dose and cultivation time was found to be crucial, having the second most significant impact on transglutaminase activity. Optimal conditions were identified as 48 h of cultivation with a 2% nitrogen source dose and an initial medium pH of approximately 6.0. Under these conditions, transglutaminase activity ranged from 4.5 to 5.5 U/mL. The results of this study demonstrated that response surface methodology is a promising approach for optimizing microbial transglutaminase production. Future applications of transglutaminase include the development of modern food products with improved texture and nutritional value, as well as its potential use in regenerative medicine for creating biomaterials and tissue scaffolds. This topic is particularly important and timely as it addresses the growing demand for innovative and sustainable solutions in the food and biomedical industries, contributing to an improved quality of life.
Heavy metals are naturally occurring components of the Earth's crust and persistent environmental pollutants. Human exposure to heavy metals occurs via various pathways, including inhalation of air/dust particles, ingesting contaminated water or soil, or through the food chain. Their bioaccumulation may lead to diverse toxic effects affecting different body tissues and organ systems. The toxicity of heavy metals depends on the properties of the given metal, dose, route, duration of exposure (acute or chronic), and extent of bioaccumulation. The detrimental impacts of heavy metals on human health are largely linked to their capacity to interfere with antioxidant defense mechanisms, primarily through their interaction with intracellular glutathione (GSH) or sulfhydryl groups (R-SH) of antioxidant enzymes such as superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), glutathione reductase (GR), and other enzyme systems. Although arsenic (As) is believed to bind directly to critical thiols, alternative hydrogen peroxide production processes have also been postulated. Heavy metals are known to interfere with signaling pathways and affect a variety of cellular processes, including cell growth, proliferation, survival, metabolism, and apoptosis. For example, cadmium can affect the BLC-2 family of proteins involved in mitochondrial death via the overexpression of antiapoptotic Bcl-2 and the suppression of proapoptotic (BAX, BAK) mechanisms, thus increasing the resistance of various cells to undergo malignant transformation. Nuclear factor erythroid 2-related factor 2 (Nrf2) is an important regulator of antioxidant enzymes, the level of oxidative stress, and cellular resistance to oxidants and has been shown to act as a double-edged sword in response to arsenic-induced oxidative stress. Another mechanism of significant health threats and heavy metal (e.g., Pb) toxicity involves the substitution of essential metals (e.g., calcium (Ca), copper (Cu), and iron (Fe)) with structurally similar heavy metals (e.g., cadmium (Cd) and lead (Pb)) in the metal-binding sites of proteins. Displaced essential redox metals (copper, iron, manganese) from their natural metal-binding sites can catalyze the decomposition of hydrogen peroxide via the Fenton reaction and generate damaging ROS such as hydroxyl radicals, causing damage to lipids, proteins, and DNA. Conversely, some heavy metals, such as cadmium, can suppress the synthesis of nitric oxide radical (NO·), manifested by altered vasorelaxation and, consequently, blood pressure regulation. Pb-induced oxidative stress has been shown to be indirectly responsible for the depletion of nitric oxide due to its interaction with superoxide radical (O2·-), resulting in the formation of a potent biological oxidant, peroxynitrite (ONOO-). This review comprehensively discusses the mechanisms of heavy metal toxicity and their health effects. Aluminum (Al), cadmium (Cd), arsenic (As), mercury (Hg), lead (Pb), and chromium (Cr) and their roles in the development of gastrointestinal, pulmonary, kidney, reproductive, neurodegenerative (Alzheimer's and Parkinson's diseases), cardiovascular, and cancer (e.g. renal, lung, skin, stomach) diseases are discussed. A short account is devoted to the detoxification of heavy metals by chelation via the use of ethylenediaminetetraacetic acid (EDTA), dimercaprol (BAL), 2,3-dimercaptosuccinic acid (DMSA), 2,3-dimercapto-1-propane sulfonic acid (DMPS), and penicillamine chelators.
- MeSH
- Antioxidants metabolism MeSH
- Bioaccumulation MeSH
- Environmental Pollutants toxicity MeSH
- Humans MeSH
- Oxidative Stress * drug effects MeSH
- Metals, Heavy * toxicity MeSH
- Environmental Exposure adverse effects MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
Cyanobacteria are prokaryotic organisms characterised by their complex structures and a wide range of pigments. With their ability to fix CO2, cyanobacteria are interesting for white biotechnology as cell factories to produce various high-value metabolites such as polyhydroxyalkanoates, pigments, or proteins. White biotechnology is the industrial production and processing of chemicals, materials, and energy using microorganisms. It is known that exposing cyanobacteria to low levels of stressors can induce the production of secondary metabolites. Understanding of this phenomenon, known as hormesis, can involve the strategic application of controlled stressors to enhance the production of specific metabolites. Consequently, precise measurement of cyanobacterial viability becomes crucial for process control. However, there is no established reliable and quick viability assay protocol for cyanobacteria since the task is challenging due to strong interferences of autofluorescence signals of intercellular pigments and fluorescent viability probes when flow cytometry is used. We performed the screening of selected fluorescent viability probes used frequently in bacteria viability assays. The results of our investigation demonstrated the efficacy and reliability of three widely utilised types of viability probes for the assessment of the viability of Synechocystis strains. The developed technique can be possibly utilised for the evaluation of the importance of polyhydroxyalkanoates for cyanobacterial cultures with respect to selected stressor-repeated freezing and thawing. The results indicated that the presence of polyhydroxyalkanoate granules in cyanobacterial cells could hypothetically contribute to the survival of repeated freezing and thawing.
Acinetobacter baumannii thrives within eukaryotic cells, influencing persistence, treatment approaches, and progression of disease. We probed epithelial cell invasion by A. baumannii and the influence of antibodies raised to outer membrane protein 34 (Omp34) on epithelial interactions. We expressed and purified recombinant Omp34 and induced anti-Omp34 antibodies in Bagg albino or BALB/c mice. Omp34 was evaluated for acute toxicity in mice through histological analysis of six organs. The host cell line, A549, was exposed to both A. baumannii 19606 and a clinical isolate. The study also investigated serum resistance, adherence, internalization, and proliferation of A. baumannii in A549 cells, with and without anti-Omp34 sera, utilizing cell culture techniques and light microscopy. A549 cell viability was evaluated by A. baumannii challenge and exposure to anti-Omp34 sera. Actin disruption experiments using cytochalasin D probed microfilament and microtubule roles in A. baumannii invasion. Omp34 prompted antibody production without toxicity in mice. The serum showed bactericidal effects on both strains. Additionally, both A. baumannii strains were found to form biofilms. Omp34 serum was observed to decrease biofilm formation, bacterial adherence, internalization, and proliferation in A549 cells. Furthermore, the use of anti-Omp34 serum enhanced the post-infection survival of the host cell. Pre-exposure of A549 cells to cytochalasin D reduced bacterial internalization, highlighting the role of actin polymerization in the invasion process. Microscopic analysis revealed various interactions, such as adherence, membrane alterations, vacuolization, apoptosis, and cellular damage. Anti-Omp34 serum-exposed A549 cells were protected and showed reduced damage. The findings reveal that A. baumannii can significantly multiply intracellularly within host cells. This suggests the bacterium's ability to establish an environment conducive to its replication by preventing fusion with degradative lysosomes and inhibiting acidification. This finding contributes to the understanding of A. baumannii's intracellular persistence and highlights the role of Omp34 in influencing apoptosis, autophagy, and bacterial adherence, which may impact the development of effective treatments against A. baumannii infections.
- MeSH
- Acinetobacter baumannii * physiology immunology pathogenicity MeSH
- Bacterial Adhesion * MeSH
- Biofilms growth & development MeSH
- A549 Cells MeSH
- Epithelial Cells microbiology MeSH
- Acinetobacter Infections * microbiology immunology MeSH
- Humans MeSH
- Mice, Inbred BALB C MeSH
- Mice MeSH
- Antibodies, Bacterial * immunology MeSH
- Cell Survival MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
The precise measurement of cell temperature and an in-depth understanding of thermogenic processes are critical in unraveling the complexities of cellular metabolism and its implications for health and disease. This review focuses on the mechanisms of local temperature generation within cells and the array of methods developed for accurate temperature assessment. The contact and noncontact techniques are introduced, including infrared thermography, fluorescence thermometry, and other innovative approaches to localized temperature measurement. The role of thermogenesis in cellular metabolism, highlighting the integral function of temperature regulation in cellular processes, environmental adaptation, and the implications of thermogenic dysregulation in diseases such as metabolic disorders and cancer are further discussed. The challenges and limitations in this field are critically analyzed while technological advancements and future directions are proposed to overcome these barriers. This review aims to provide a consolidated resource for current methodologies, stimulate discussion on the limitations and challenges, and inspire future innovations in the study of cellular thermodynamics.
- MeSH
- Humans MeSH
- Temperature MeSH
- Thermogenesis * physiology MeSH
- Thermography * methods MeSH
- Thermometry methods MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a heterogeneous condition characterized by liver steatosis, inflammation, consequent fibrosis, and cirrhosis. Chronic impairment of lipid metabolism is closely related to oxidative stress, leading to cellular lipotoxicity, mitochondrial dysfunction, and endoplasmic reticulum stress. The detrimental effect of oxidative stress is usually accompanied by changes in antioxidant defense mechanisms, with the alterations in antioxidant enzymes expression/activities during MASLD development and progression reported in many clinical and experimental studies. This review will provide a comprehensive overview of the present research on MASLD-induced changes in the catalytic activity and expression of the main antioxidant enzymes (superoxide dismutases, catalase, glutathione peroxidases, glutathione S-transferases, glutathione reductase, NAD(P)H:quinone oxidoreductase) and in the level of non-enzymatic antioxidant glutathione. Furthermore, an overview of the therapeutic effects of vitamin E on antioxidant enzymes during the progression of MASLD will be presented. Generally, at the beginning of MASLD development, the expression/activity of antioxidant enzymes usually increases to protect organisms against the increased production of reactive oxygen species. However, in advanced stage of MASLD, the expression/activity of several antioxidants generally decreases due to damage to hepatic and extrahepatic cells, which further exacerbates the damage. Although the results obtained in patients, in various experimental animal or cell models have been inconsistent, taken together the importance of antioxidant enzymes in MASLD development and progression has been clearly shown.
- MeSH
- Antioxidants * metabolism MeSH
- Glutathione metabolism MeSH
- Humans MeSH
- Metabolic Diseases metabolism MeSH
- Oxidative Stress * MeSH
- Reactive Oxygen Species metabolism MeSH
- Vitamin E metabolism MeSH
- Fatty Liver metabolism MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
