Previously, we have shown that hepatic lipid accumulation induces the secretion of cathepsin D (CTSD), and that plasma CTSD levels are associated with increased inflammation and disease severity in nonalcoholic fatty liv...Previously, we have shown that hepatic lipid accumulation induces the secretion of cathepsin D (CTSD), and that plasma CTSD levels are associated with increased inflammation and disease severity in nonalcoholic fatty liver disease (NAFLD). Although it is clear that the liver is a major source of plasma CTSD, it is unknown whether other metabolically active organs such as the muscle, also associate with plasma CTSD levels in NAFLD patients. Therefore, the aim of this study was to explore the relation between lipid accumulation in the muscle (myosteatosis) and plasma CTSD levels in forty-five NAFLD patients. We observed that hepatic steatosis positively associated with plasma CTSD levels, confirming the previously established link between plasma CTSD and the liver. Furthermore, a positive association between myosteatosis and plasma CTSD levels was observed, which was independent of sex, age, BMI, waist circumference and hepatic steatosis. By establishing a positive association between myosteatosis and plasma CTSD levels, our findings suggest that, in addition to the liver, the muscle is also linked to plasma CTSD levels in NAFLD patients. The observed link between myosteatosis and plasma CTSD levels supports the concept of a significant role of the skeletal muscle in metabolic disturbances in metabolic syndrome-related disorders.
To K, Cao R, Yegiazaryan A
… +7 more, Owens J, Sasaninia K, Vaughn C, Singh M, Truong E, Sathananthan A, Venketaraman V
Biomol Concepts
· 2021 May · PMID 33966361
·
Full text
Tuberculosis (TB) caused by () still remains a devastating infectious disease in the world. There has been a daunting increase in the incidence of Type 2 Diabetes Mellitus (T2DM) worldwide. T2DM patients are three times...Tuberculosis (TB) caused by () still remains a devastating infectious disease in the world. There has been a daunting increase in the incidence of Type 2 Diabetes Mellitus (T2DM) worldwide. T2DM patients are three times more vulnerable to infection compared to healthy individuals. TB-T2DM coincidence is a challenge for global health control. Despite some progress in the research, still has unexplored characteristics in successfully evading host defenses. The lengthy duration of treatment, the emergence of multi-drug-resistant strains and extensive-drug-resistant strains of have made TB treatment very challenging. Previously, we have tested the antimycobacterial effects of everolimus within granulomas generated from immune cells derived from peripheral blood of healthy subjects. However, the effectiveness of everolimus treatment against mycobacterial infection in individuals with T2DM is unknown. Furthermore, the effectiveness of the combination of glutathione (GSH) supplementation in individuals with T2DM along with treatment of isolated immune cells with everolimus against mycobacterial infection has never been tested. Therefore, we postulated that liposomal glutathione (L-GSH) and everolimus would offer great hope for developing adjunctive therapy for mycobacterial infection. L-GSH or placebo was administered to T2DM individuals orally for three months. Study subjects' blood was drawn pre- and post-L-GSH/or placebo supplementation, where Peripheral Blood Mononuclear Cells (PBMCs) were isolated from whole blood to conduct studies with everolimus. We found that treatment with everolimus, an mTOR (membrane target of rapamycin) inhibitor, significantly reduced intracellular BCG infection alone and in conjunction with L-GSH supplementation. Furthermore, we found L-GSH supplementation coupled with everolimus treatment produced a greater effect in inhibiting the growth of intracellular BCG, than with the everolimus treatment alone. We also demonstrated the functions of L-GSH along with everolimus treatment in modulating the levels of cytokines such as IFN-γ, TNF-α, and IL-2 and IL-6, in favor of improving control of the mycobacterial infection. In summary, everolimus-treatment alone and in combination with oral L-GSH supplementation for three months in individuals with T2DM, was able to increase the levels of T-helper type 1 (Th1) cytokines IFN-γ, TNF-α, and IL-2 as well as enhance the abilities of granulomas from individuals with T2DM to improve control of a mycobacterial infection.
Doxorubicin (DOX) is an effective chemotherapeutic agent used for the treatment of various types of cancer. However, its poor solubility, undesirable side effects, and short half-life have remained a challenge. We used a...Doxorubicin (DOX) is an effective chemotherapeutic agent used for the treatment of various types of cancer. However, its poor solubility, undesirable side effects, and short half-life have remained a challenge. We used a formulation based on graphene oxide as an anticancer drug delivery system for DOX in MCF-7 breast cancer cells, to address these issues. release studies confirmed that the synthesized formulation has an improved release profile in acidic conditions (similar to the tumor microenvironment). Further studies, including MTT, uptake, and apoptosis assays were performed. The toxic effects of the nanocarrier on the kidney, heart and liver of healthy rats were also evaluated. We observed that the DOX-loaded carrier improved the cytotoxic effect of DOX on the breast cell line compared to free DOX. In summary, our results introduce the DOX-loaded carrier as a potential platform for targeting of cancer cells and suggest further studies are necessary to investigate its anti-cancer potential.
Staphylococcus aureus (S. aureus) is a gram-positive bacteria, which causes various fatal respiratory infections including pneumonia. The emergence of Methicillin-Resistance Staphylococcus aureus (MRSA) demands a thoroug...Staphylococcus aureus (S. aureus) is a gram-positive bacteria, which causes various fatal respiratory infections including pneumonia. The emergence of Methicillin-Resistance Staphylococcus aureus (MRSA) demands a thorough understanding of host-pathogen interactions. Here we report the role of calcium in regulating defence responses of S. aureus in macrophages. Regulating calcium fluxes in cells by different routes differentially governs the expression of T cell costimulatory molecule CD80 and Th1 promoting IL-12 receptor. Inhibiting calcium influx from extracellular medium increased expression of IFN-γ and IL-10 while blocking calcium release from the intracellular stores inhibited TGF-β levels. Blocking voltage-gated calcium channels (VGCC) inhibited the expression of multiple cytokines. While VGCC regulated the expression of apoptosis protein Bax, extracellular calcium-regulated the expression of Cytochrome-C. Similarly, VGCC regulated the expression of autophagy initiator Beclin-1. Blocking VGCC or calcium release from intracellular stores promoted phagosome-lysosome fusion, while activating VGCC inhibited phagosomelysosome fusion. Finally, calcium homeostasis regulated intracellular growth of Staphylococcus, although using different mechanisms. While blocking extracellular calcium influx seems to rely on IFN-γ and IL-12Rβ receptor mediated reduction in bacterial survival, blocking either intracellular calcium release or via VGCC route seem to rely on enhanced autophagy mediated reduction of intracellular bacterial survival. These results point to fine-tuning of defence responses by routes of calcium homeostasis.
The advent of genome editing technology promises to transform human health, livestock and agriculture, and to eradicate pest species. This transformative power demands urgent scrutiny and resolution of the ethical confli...The advent of genome editing technology promises to transform human health, livestock and agriculture, and to eradicate pest species. This transformative power demands urgent scrutiny and resolution of the ethical conflicts attached to the creation and release of engineered genomes. Here, I discuss the ethics surrounding the transformative CRISPR/Cas9-mediated genome editing technology in the contexts of human genome editing to eradicate genetic disease and of gene drive technology to eradicate animal vectors of human disease.
Couples with infertility issues have been assisted by in vitro fertilization reproduction technologies with high success rates of 50-80%. However, complications associated with ovarian stimulation remain, such as ovarian...Couples with infertility issues have been assisted by in vitro fertilization reproduction technologies with high success rates of 50-80%. However, complications associated with ovarian stimulation remain, such as ovarian hyperstimulation. Oocyte quality is a significant factor impacting the outcome of in vitro fertilization procedures, but other processes are also critical for fertilization success. Increasing evidence points to aberrant inflammation as one of these critical processes reflected in molecular changes, including glycosylation of proteins. Here we report results from a MALDI-TOF-MS-based glycomic profiling of the total IgG and total proteome N-glycomes isolated from the follicular fluid obtained from patients undergoing fertilization through either (1) assisted reproduction by modified natural cycle or (2) controlled ovarian stimulation (GnRH antagonist, GnRH Ant) protocols. Significant inflammatory-related differences between analyzed N-glycomes were observed from samples and correlated with the ovarian stimulation protocol used in patients.
The mitochondrial permeability transition (MPT) has been one of the longstanding enigmas in biology. Its cause is currently at the center of an extensive scientific debate, and several hypotheses on its molecular nature...The mitochondrial permeability transition (MPT) has been one of the longstanding enigmas in biology. Its cause is currently at the center of an extensive scientific debate, and several hypotheses on its molecular nature have been put forward. The present view holds that the transition arises from the opening of a high-conductance channel in the energy-transducing membrane, the permeability transition pore (PTP), also called the mitochondrial megachannel or the multiconductance channel (MMC). Here, the novel hypothesis is proposed that the aqueous access channels at the interface of the c-ring and the a-subunit of FO in the FOF1-ATP synthase are repurposed during induction of apoptosis and constitute the elusive PTP/ MMC. A unifying principle based on regulation by local potentials is advanced to rationalize the action of the myriad structurally and chemically diverse inducers and inhibitors of PTP/MMC. Experimental evidence in favor of the hypothesis and its differences from current models of PTP/MMC are summarized. The hypothesis explains in considerable detail how the binding of Ca2+ to a β-catalytic site (site 3) in the F1 portion of ATP synthase triggers the opening of the PTP/MMC. It is also shown to connect to longstanding proposals within Nath's torsional mechanism of energy transduction and ATP synthesis as to how the binding of MgADP to site 3 does not induce PTP/MMC, but instead catalyzes physiological ATP synthesis in cell life. In the author's knowledge, this is the first model that explains how Ca2+ transforms the FOF1-ATP synthase from an exquisite energy-conserving enzyme in cell life into an energy-dissipating structure that promotes cell death. This has major implications for basic as well as for clinical research, such as for the development of drugs that target the MPT, given the established role of PTP/MMC dysregulation in cancer, ischemia, cardiac hypertrophy, and various neurodegenerative diseases.
Endothelins are powerful vasoconstrictor peptides that play numerous other roles. Endothelin-1 (ET1) is the principal isoform produced by the endothelium in the human cardiovascular system. Endothelin-3 (ET3) and its rPp...Endothelins are powerful vasoconstrictor peptides that play numerous other roles. Endothelin-1 (ET1) is the principal isoform produced by the endothelium in the human cardiovascular system. Endothelin-3 (ET3) and its rPptor affinity have been demonstrated to support neuronal repair mechanisms throughout life. In multiple sclerosis (MS), the role of vasoactive peptides are not well defined. Here we focus on ET3, specifically the plasma levels between MS patients and healthy subjects. Furthermore, we evaluated the changes in ET1 and ET3 plasma levels during different disease phases, the correlation between ET3 and cerebral circulation time, and the relationship between ET1 and ET3. In MS patients, the ET3 plasma levels were altered in a time-dependent manner. These results could support a putative role of ET3 in neuroprotection and/or neuroimmune modulation over time.
Objective this study was conducted to determine the distribution of high-risk human papillomavirus (HR-HPV) genotypes in women in the general population of three regions of Burkina Faso. Method This multicenter, descript...Objective this study was conducted to determine the distribution of high-risk human papillomavirus (HR-HPV) genotypes in women in the general population of three regions of Burkina Faso. Method This multicenter, descriptive cross-sectional study involved 1321 sexually active women in five cities in three regions of Burkina Faso: Central, Central-Eastern and Hauts-Bassins regions. After collection of endocervical specimens, pre-cervical lesions were screened by visual inspection with acetic acid and lugol (VIA / VILI). HR-HPV genotypes were characterized by multiplex real-time PCR after extraction of viral DNA. Results The mean age of women was 31.98 ± 10.09 years. The HR-HPV infection in the three regions ranged from 26.16% to 43.26% with 35.42% as overall prevalence in women. The most common HR-HPV genotypes in descending order were: HPV 56, 52, 66, 59, 39, 51, 18, 35. The prevalence of bivalent vaccine genotypes (HPV16 / 18) was 7.83% against 63.78% of genotypes not covered by HPV vaccine; 36.32% (170/468) of women had multiple concomitant HR-HPV infections. Conclusion this study showed significant regional variation and high prevalence of HR-HPV infection in women. The predominant genotypes differ from those covered by available vaccines in Burkina Faso. These results will help guide our health policies towards better prevention of cervical cancer. The diversity of oncogenic genotypes is sparking a large-scale study in the West African sub-region, particularly in cases of cancer and the introduction of the nonavalent vaccine which includes HPV 52 found among the predominant genotypes in this study.
Bado P, Djigma Wendkuuni F, Zohoncon Théodora M
… +12 more, Obiri-Yeboah D, Traoré Esther Mah A, Ouattara Abdoul K, Ouedraogo Teega-Wendé C, Bello Shoukrat Ohuwa T, Setor Marius A, Traore Ina Marie A, Horo A, Kouakou Kouame P, Yonli Albert T, Ouedraogo C, Simpore J
The single nucleotide polymorphism (SNP) of the promoter region of MMP-1 (at 1607 bp) and MMP-3 (at 1171 bp) create Ets binding sites. Correlations between these SNPs and sensitivity to several biological processes such...The single nucleotide polymorphism (SNP) of the promoter region of MMP-1 (at 1607 bp) and MMP-3 (at 1171 bp) create Ets binding sites. Correlations between these SNPs and sensitivity to several biological processes such as metastasis and recurrence of cancer have been reported in several studies. In this case-control study, we looked for these SNPs in women infected with or not with high-risk human papillomaviruses (HR-HPV). The frequency, distribution and correlation of these SNPs with the presence or absence of HR-HPV infection were evaluated. Genotypes 1G1G, 1G2G and 2G2G for MMP1 and genotypes 5A5A, 5A6A, 6A6A for MMP3 were found in our study population. In general, we noted that the 1G (40.8%) and 2G (64.8%) alleles were more frequent in non-infected women and infected women, respectively, and more specifically this difference was significant in women from Côte d'Ivoire. These results, although yet to be reaffirmed with assays for quantifying the mRNA of these genes, suggest that the SNP of the MMP-1 promoter could promote infection with HR-HPV.
Atomic force microscopy, AFM, is a powerful tool that can produce detailed topographical images of individual nano-structures with a high signal-to-noise ratio without the need for ensemble averaging. However, the applic...Atomic force microscopy, AFM, is a powerful tool that can produce detailed topographical images of individual nano-structures with a high signal-to-noise ratio without the need for ensemble averaging. However, the application of AFM in structural biology has been hampered by the tip-sample convolution effect, which distorts images of nano-structures, particularly those that are of similar dimensions to the cantilever probe tips used in AFM. Here we show that the tip-sample convolution results in a feature-dependent and non-uniform distribution of image resolution on AFM topographs. We show how this effect can be utilised in structural studies of nano-sized upward convex objects such as spherical or filamentous molecular assemblies deposited on a flat surface, because it causes 'magnification' of such objects in AFM topographs. Subsequently, this enhancement effect is harnessed through contact-point based deconvolution of AFM topographs. Here, the application of this approach is demonstrated through the 3D reconstruction of the surface envelope of individual helical amyloid filaments without the need of cross-particle averaging using the contact-deconvoluted AFM topographs. Resolving the structural variations of individual macromolecular assemblies within inherently heterogeneous populations is paramount for mechanistic understanding of many biological phenomena such as amyloid toxicity and prion strains. The approach presented here will also facilitate the use of AFM for high-resolution structural studies and integrative structural biology analysis of single molecular assemblies.
Objectives Natural products commonly used in traditional medicine, such as essential oils (EOs), are attractive sources for the development of molecules with anti-proliferative activities for future treatment of human ca...Objectives Natural products commonly used in traditional medicine, such as essential oils (EOs), are attractive sources for the development of molecules with anti-proliferative activities for future treatment of human cancers, e.g., prostate and cervical cancer. In this study, the chemical composition of the EO from Cymbopogon nardus was characterized, as well as its antioxidativeproperties and anti-inflammatory and antiproliferative activities on LNCaP cells derived from prostate cancer. Methods The chemical composition of the EO was determined by GC/FID and GC/MS analyses. The antioxidative properties were assessed using DPPH radical scavenging assay and ABTS+• radical cation decolorization assay, and the anti-inflammatory capacity was determined by the inhibition of the lipoxygenase activity. Antiproliferative activity was evaluated by MTT assay. Results Collectively, our data show that the major constituents of C. nardus EO are citronellal (33.06 %), geraniol (28.40 %), nerol (10.94 %), elemol (5.25 %) and delta-elemene (4.09 %). C. nardus EO shows modest antioxidant and anti-inflammatory activity compared to the standard galic acid. C. nardus EO exhibits the best antiproliferative activity on the prostate cancer cell line LNCaP with an IC50 of 58.0 ± 7.9 μg/mL, acting through the induction of the cell cycle arrest. Conclusions This study has determined that C. nardus EO efficiently triggers cytotoxicity and pens a new field of investigation regarding the putative use of this EO in vivo.
Human papillomavirus (HPV) infection is the most common sexually transmitted infection worldwide. Persistence infection can lead to the development of cervical cancer potentially due to some genetic factors such as polym...Human papillomavirus (HPV) infection is the most common sexually transmitted infection worldwide. Persistence infection can lead to the development of cervical cancer potentially due to some genetic factors such as polymorphisms in regulatory and coding regions of cytokine genes. The purpose of this study was to determine whether there is a relationship between TNF-308 G/A or IL18 polymorphisms and high-risk HPV infection among sexually active women from Burkina Faso. Ninety-one HPV infected and two hundred and nine HPV negative women (the latter used as healthy controls) were screened. TNFA-308 G/A and IL18-607 C/A polymorphisms were detected using the TaqMan allelic discrimination. HPV 52 (21.19%), HPV 39 (11.86%) and HPV 33 (11.02%) were the most common HPV genotypes. The TNFA-308A and IL18-607 C alleles were predominant in all women in the study. None of the TNFA and IL18 alleles were associated with HPV infection. The results suggest that there is no relationship between TNF-308 G/A or IL18-607C/A polymorphisms and HPV infection among women in the study.
Interferon-gamma (IFN-γ) is a key cytokine that mediates immunity to tuberculosis (TB). Mycobacterium tuberculosis (M. tb) is known to downregulate the surface expression of IFN-γ receptor (IFN-γR) on macrophages and per...Interferon-gamma (IFN-γ) is a key cytokine that mediates immunity to tuberculosis (TB). Mycobacterium tuberculosis (M. tb) is known to downregulate the surface expression of IFN-γ receptor (IFN-γR) on macrophages and peripheral blood mononuclear cells (PBMCs) of patients with active TB disease. Many M. tb antigens also downmodulate IFN-γR levels in macrophages when compared with healthy controls. In the current study, we aimed at deciphering key factors involved in M. tb mediated downregulation of IFN-γR levels on macrophage surface. Our data showed that both M. tb H37Rv and M. bovis BCG infections mediate downmodulation of IFN-γR on human macrophages. This downmodulation is regulated at the level of TLR signaling pathway, second messengers such as calcium and cellular kinases i.e. PKC and ERK-MAPK, indicating that fine tuning of calcium response is critical to maintaining IFN-γR levels on macrophage surface. In addition, genes in the calcium and cysteine protease pathways which were previously identified by us to play a negative role during M. tb infection, also regulated IFN-γR expression. Thus, modulations in IFN-γR levels by utilizing host machinery may be a key immune suppressive strategy adopted by the TB pathogen to ensure its persistence and thwart host defense.
Background Polycystic Ovary Syndrome (PCOS) is one of the most common endocrine abnormalities in women. Due to the side effects of drugs, the tendency to use natural antioxidants and anti-inflammatory agents to regulate...Background Polycystic Ovary Syndrome (PCOS) is one of the most common endocrine abnormalities in women. Due to the side effects of drugs, the tendency to use natural antioxidants and anti-inflammatory agents to regulate metabolism, hyperinsulinemia, and hyperlipidemia in PCOS patients has been increased. This review aimed to investigate the role of herbal substances on the treatment of PCOS. Methods The present review was carried out using keywords such as polycystic ovary syndrome and/or PCOS and/or herb. Databases including Web of Science, PubMed, and Science Direct were used to collect all related articles published from 1990 to 2019. We excluded studies unrelated to the PCOS and medical herbs. Results Overall, 361 records were identified through database searching. After primary screening and the full-texts assessment, 323 records were excluded, and 38 articles were finally included. The results indicate that some medicinal herbs may have a key role in treating PCOS. The compounds in these medical herbs can affect lipid profiles (Aloe vera, chamomile, and cinnamon), insulin resistance (cinnamon, chamomile, Aloe vera, and Camellia sinensis), blood glucose (Aloe vera, cinnamon, and Camellia sinensis), hormones (Aloe vera, silymarin, chamomile, fenugreek, Camellia sinensis, Heracleum persicum, Potentilla, Mentha spicata, Foeniculum vulgar, licorice, and Marrubium), and ovarian tissue (Aloe vera, chamomile, Camellia sinensis, Mentha spicata, and silymarin). Conclusion Natural substances such as Aloe vera, cinnamon, green tea, fenugreek, and silymarin can be used as a new supportive care for PCOS. Further clinical trials are warranted to confirm their benefits and safety.
The inefficiency of cyanide/HCN (CN) binding with heme proteins (under physiological regimes) is demonstrated with an assessment of thermodynamics, kinetics, and inhibition constants. The acute onset of toxicity and CN's...The inefficiency of cyanide/HCN (CN) binding with heme proteins (under physiological regimes) is demonstrated with an assessment of thermodynamics, kinetics, and inhibition constants. The acute onset of toxicity and CN's mg/Kg LD50 (μM lethal concentration) suggests that the classical hemeFe binding-based inhibition rationale is untenable to account for the toxicity of CN. In vitro mechanistic probing of CN-mediated inhibition of hemeFe reductionist systems was explored as a murburn model for mitochondrial oxidative phosphorylation (mOxPhos). The effect of CN in haloperoxidase catalyzed chlorine moiety transfer to small organics was considered as an analogous probe for phosphate group transfer in mOxPhos. Similarly, inclusion of CN in peroxidase-catalase mediated one-electron oxidation of small organics was used to explore electron transfer outcomes in mOxPhos, leading to water formation. The free energy correlations from a Hammett study and IC50/Hill slopes analyses and comparison with ligands ( CO/ H 2 S/ N 3 - ) $\left( {\text{CO}}/{{{{\text{H}}_{2}}\text{S}}/{\text{N}_{3}^{\text{-}}}\;}\; \right)$ provide insights into the involvement of diffusible radicals and proton-equilibriums, explaining analogous outcomes in mOxPhos chemistry. Further, we demonstrate that superoxide (diffusible reactive oxygen species, DROS) enables in vitro ATP synthesis from ADP+phosphate, and show that this reaction is inhibited by CN. Therefore, practically instantaneous CN ion-radical interactions with DROS in matrix catalytically disrupt mOxPhos, explaining the acute lethal effect of CN.
The ability to construct a functional system from its individual components is foundational to understanding how it works. Synthetic biology is a broad field that draws from principles of engineering and computer science...The ability to construct a functional system from its individual components is foundational to understanding how it works. Synthetic biology is a broad field that draws from principles of engineering and computer science to create new biological systems or parts with novel function. While this has drawn well-deserved acclaim within the biotechnology community, application of synthetic biology methodologies to study biological systems has potential to fundamentally change how biomedical research is conducted by providing researchers with improved experimental control. While the concepts behind synthetic biology are not new, we present evidence supporting why the current research environment is conducive for integration of synthetic biology approaches within biomedical research. In this perspective we explore the idea of synthetic biology as a discovery science research tool and provide examples of both top-down and bottom-up approaches that have already been used to answer important physiology questions at both the organismal and molecular level.
Two decades of evidence-based exploratory pursuits in heme-flavin enzymology led to the formulation of a new biological electron/moiety transfer paradigm, called murburn concept. Murburn is a novel literary abstraction f...Two decades of evidence-based exploratory pursuits in heme-flavin enzymology led to the formulation of a new biological electron/moiety transfer paradigm, called murburn concept. Murburn is a novel literary abstraction from "mured burning" or "mild unrestricted burning". This concept was invoked to explain the longstanding conundrum of maverick physiological dose responses and also applied to remodel the prevailing understanding of drug metabolism and cellular respiration. A conglomeration of simple ideas grounded in the known principles of thermodynamics and reaction chemistry, murburn concept invokes catalytic/functional roles for diffusible reactive species or radicals. Hitherto, diffusible reactive species were primarily seen as toxic agents of chaos, non-conducible to the maintenance of life-order. Since the murburn paradigm offers a distinctly different perspective for several biological phenomena, researchers holding conventional views of cellular metabolism pose a direct conflict of interests to the advancement of murburn concept. Murburn schemes are poised to integrate numerous metabolic motifs with holistic physiological outcomes; redefining pursuits in biology and medicine. To advance this agenda, I present a brief account of murburn concept and point out how redundant ideas are still advocated in some prestigious journals.
Here we have proposed a new biological definition of life based on the function and reproduction of existing genes and creation of new ones, which is applicable to both unicellular and multicellular organisms. First, we...Here we have proposed a new biological definition of life based on the function and reproduction of existing genes and creation of new ones, which is applicable to both unicellular and multicellular organisms. First, we coined a new term "genetic information metabolism" comprising functioning, reproduction, and creation of genes and their distribution among living and non-living carriers of genetic information. Encompassing this concept, life is defined as organized matter that provides genetic information metabolism. Additionally, we have articulated the general biological function of life as Tetz biological law: "General biological function of life is to provide genetic information metabolism" and formulated novel definition of life: "Life is an organized matter that provides genetic information metabolism". New definition of life and Tetz biological law allow to distinguish in a new way living and non-living objects on Earth and other planets based on providing genetic information metabolism.