Powering prescription: Mitochondria as "Living Drugs" - Definition, clinical applications, and industry advancements.

Mitochondria's role as engines and beacons of metabolism and determinants of cellular health is being redefined through their therapeutic application as "Living Drugs" (LDs). Artificial mitochondrial transfer/transplant (AMT/T), encompassing various techniques to modify, enrich, or restore mitochondria in cells and tissues, is revolutionizing acellular therapies and the future of medicine. This article proposes a necessary definition for LDs within the Advanced Therapeutic Medicinal Products (ATMPs) framework. While recognizing different types of LDs as ATMPs, such as mesenchymal stem cells (MSCs) and chimeric antigen receptor T (CAR T) cells, we focus on mitochondria due to their unique attributes that distinguish them from traditional cell therapies. These attributes include their inherent living nature, diverse sources, industry applicability, validation, customizability for therapeutic needs, and their capability to adapt and respond within recipient cells. We trace the journey from initial breakthroughs in AMT/T to the current state-of-the-art applications by emerging innovative companies, highlighting the need for manufacturing standards to navigate the transition of mitochondrial therapies from concept to clinical practice. By providing a comprehensive overview of the scientific, clinical, and commercial landscape of mitochondria as LDs, this article contributes to the essential dialogue among regulatory agencies, academia, and industry to shape their future in medicine.

Exploring the role of mitochondria transfer/transplant and their long-non-coding RNAs in regenerative therapies for skin aging.

Advancing age and environmental stressors lead to mitochondrial dysfunction in the skin, inducing premature aging, impaired regeneration, and greater risk of cancer. Cells rely on the communication between the mitochondria and the nucleus by tight regulation of long non-coding RNAs (lncRNAs) to avoid premature aging and maintain healthy skin. LncRNAs act as key regulators of cell proliferation, differentiation, survival, and maintenance of skin structure. However, research on how the lncRNAs are dysregulated during aging and due to stressors is needed to develop therapies to regenerate skin's function and structure. In this article, we discuss how age and environmental stressors may alter lncRNA homeodynamics, compromising cell survival and skin health, and how these factors may become inducers of skin aging. We describe skin cell types and how they depend on mitochondrial function and lncRNAs. We also provide a list of mitochondria localized and nuclear lncRNAs that can serve to better understand skin aging. Using bioinformatic prediction tools, we predict possible functions of lncRNAs based on their subcellular localization. We also search for experimentally determined protein interactions and the biological processes involved. Finally, we provide therapeutic strategies based on gene editing and mitochondria transfer/transplant (AMT/T) to restore lncRNA regulation and skin health. This article offers a unique perspective in understanding and defining the therapeutic potential of mitochondria localized lncRNAs (mt-lncRNAs) and AMT/T to treat skin aging and related diseases.

Scientific venturing for early-stage professionals (ESPs), a key concept in the innovation ecosystem.

Early-stage professionals (ESPs) and senior scientists who want to transition from academia to the industry need support to develop new skills and know-how to endeavor this challenge. However, this topic is significantly underserved in the field of cell and gene therapy, slowing down ESPs' potential to make this step. The authors of this article, members of the ESPs in the South and Central America Subcommittee at the International Society for Cell and Gene Therapy, propose the concept of "scientific venturing," which stands for the process by which scientists become entrepreneurs or part of a company. In our article, we provide key aspects to understand this concept, considering key personality traits that need to be developed and a discussion about the "innovation ecosystem." Later, we consider how scientific venturing may result in an increase in difficulty in nascent innovation ecosystems such as Latin America, in comparison with those more advanced and mature in high-income countries. Finally, we provide key information for the ESPs and other professionals about the stages of private and public investment, including information about the resources needed for the sustainability of companies and startups. Understanding what scientific venturing involves for ESPs is key to taking advantage of the maturity of an innovation ecosystem, its network, and available opportunities.

A new hope: Mitochondria, a critical factor in the war against prions.

Prion diseases encompass a group of incurable neurodegenerative disorders that occur due to the misfolding and aggregation of infectious proteins. The most well-known prion diseases are Creutzfeldt-Jakob disease (CJD), bovine spongiform encephalopathy (also known as mad cow disease), and kuru. It is estimated that around 1-2 persons per million worldwide are affected annually by prion disorders. Infectious prion proteins propagate in the brain, clustering in the cells and rapidly inducing tissue degeneration and death. Prion disease alters cell metabolism and energy production damaging mitochondrial function and dynamics leading to a fast accumulation of damage. Dysfunction of mitochondria could be considered as an early precursor and central element in the pathogenesis of prion diseases such as in sporadic CJD. Preserving mitochondria function may help to resist the rapid spread and damage of prion proteins and even clearance. In the war against prions and other degenerative diseases, studying how to preserve the function of mitochondria by using antioxidants and even replacing them with artificial mitochondrial transfer/transplant (AMT/T) may bring a new hope and lead to an increase in patients' survival. In this perspective review, we provide key insights about the relationship between the progression of prion disease and mitochondria, in which understanding how protecting mitochondria function and viability by using antioxidants or AMT/T may help to develop novel therapeutic interventions.

The war against Alzheimer, the mitochondrion strikes back!

Alzheimer's disease (AD) is a leading neurodegenerative pathology associated with aging worldwide. It is estimated that AD prevalence will increase from 5.8 million people today to 13.8 million by 2050 in the United States alone. AD effects in the brain are well known; however, there is still a lack of knowledge about the cellular mechanisms behind the origin of AD. It is known that AD induces cellular stress affecting the energy metabolism in brain cells. During the pathophysiological advancement of AD, damaged mitochondria enter a vicious cycle, producing reactive oxygen species (ROS), harming mitochondrial DNA and proteins, leading to more ROS and cellular death. Additionally, mitochondria are interconnected with the plaques formed by amyloid-ß in AD and have underlying roles in the progression of the disease and severity. For years, the biomedical field struggled to develop new therapeutic options for AD without a significant advancement. However, mitochondria are striking back existing outside cells in a new mechanism of intercellular communication. Extracellular mitochondria are exchanged from healthy to damaged cells to rescue those with a perturbed metabolism in a process that could be applied as a new therapeutic option to repair those brain cells affected by AD. In this review we highlight key aspects of mitochondria's role in CNS' physiology and neurodegenerative disorders, focusing on AD. We also suggest how mitochondria strikes back as a therapeutic target and as a potential agent to be transplanted to repair neurons affected by AD.

Long-acting reversible contraceptives effects in abnormal uterine bleeding, a review of the physiology and management.

Around two-thirds of women who are of reproductive age use some type of contraception. Two of the most effective long-acting reversible contraceptives (LARC) are the intrauterine device (IUD) and the subdermal contraceptive implant (SCI). Despite their effectiveness, women often report abnormal uterine bleeding as the reason for discontinuation. In this review, we analyze key aspects regarding the mechanisms of action of IUDs (both copper-containing and levonorgestrel-releasing) and SCIs, as well as how they change the intrauterine environment in order to provide effective contraception at a physiological level. Additionally, we introduce the pathophysiology of different types of abnormal intrauterine bleeding provoked by the mentioned LARCs. These three contraceptive methods work in diverse ways, thus, the etiology of abnormal uterine bleeding is different and multifactorial according to each LARC. This review intends to provide information in order to better our understanding of bleeding induced by these contraceptive methods, as well as introduce current and potential new therapies. Furthermore, this review intends to provide updated and concise information that could be available firsthand not only to health care providers but scientists who are innovating and revolutionizing this field. In 2013, the American College of Obstetricians and Gynecologists published a management of abnormal uterine bleeding, however, there is limited updated data regarding the physiology and pathophysiology of abnormal uterine bleeding and its treatment based on different LARCs (hormonal and non-hormonal).

Fighting Parkinson's disease: The return of the mitochondria.

Parkinson's disease (PD) is the most common neurodegenerative movement disorder, worldwide. PD neuro-energetically affects the extrapyramidal system, by the progressive loss of striatal dopaminergic neurons in the substantia nigra pars compacta, leading to motor impairment. During the progression of PD, there will be an increase in mitochondrial dysfunction, reactive oxygen species (ROS), stress and accumulation of α-synuclein in neurons. This results in mitochondrial mutations altering their function and fission-fusion mechanisms and central nervous system (CNS) degeneration. Intracellular mitochondrial dysfunction has been studied for a long time in PD due to the decline of mitochondrial dynamics inside neurons. Mitochondrial damage-associated molecular patterns (DAMPs) have been known to contribute to several CNS pathologies especially PD pathogenesis. New and exciting evidence regarding the exchange of mitochondria between healthy to damaged cells in the central nervous system (CNS) and the therapeutic use of the artificial mitochondrial transfer/transplant (AMT) marked a return of this organelle to develop innovative therapeutic procedures for PD. The focus of this review aims to shed light on the role of mitochondria, both intra and extracellularly in PD, and how AMT could be used to generate new potential therapies in the fight against PD. Moreover, we suggest that mitochondrial therapy could work as a preventative measure, motivating the field to move towards this goal.

Influenza and Measles-MMR: two case study of the trend and impact of vaccine-related Twitter posts in Spanish during 2015-2018.

Social media, and in particularly Twitter, can be a resource of enormous value to retrieve information about the opinion of general populaton to vaccines. The increasing popularity of this social media has allowed to use its content to have a clear picture of their users on this topic. In this paper, we perform a study about vaccine-related messages published in Spanish during 2015-2018. More specifically, the paper has focused on two specific diseases: influenza and measles (and MMR as its vaccine). By also including an analysis about the sentiment expressed on the published tweets, we have been able to identify the type of messages that are published on Twitter with respect these two pathologies and their vaccines. Results showed that in contrary on popular opinions, most of the messages published are non-negative. On the other hand, the analysis showed that some messages attracted a huge attention and provoked peaks in the number of published tweets, explaining some changes in the observed trends.

Breast cancer, screening and diagnostic tools: All you need to know.

Breast cancer is one of the most frequent malignancies among women worldwide. Methods for screening and diagnosis allow health care professionals to provide personalized treatments that improve the outcome and survival. Scientists and physicians are working side-by-side to develop evidence-based guidelines and equipment to detect cancer earlier. However, the lack of comprehensive interdisciplinary information and understanding between biomedical, medical, and technology professionals makes innovation of new screening and diagnosis tools difficult. This critical review gathers, for the first time, information concerning normal breast and cancer biology, established and emerging methods for screening and diagnosis, staging and grading, molecular and genetic biomarkers. Our purpose is to address key interdisciplinary information about these methods for physicians and scientists. Only the multidisciplinary interaction and communication between scientists, health care professionals, technical experts and patients will lead to the development of better detection tools and methods for an improved screening and early diagnosis.

Hydrogen Production via Steam Reforming: A Critical Analysis of MR and RMM Technologies.

'Hydrogen as the energy carrier of the future' has been a topic discussed for decades and is today the subject of a new revival, especially driven by the investments in renewable electricity and the technological efforts done by high-developed industrial powers, such as Northern Europe and Japan. Although hydrogen production from renewable resources is still limited to small scale, local solutions, and R&D projects; steam reforming (SR) of natural gas at industrial scale is the cheapest and most used technology and generates around 8 kg CO2 per kg H2. This paper is focused on the process optimization and decarbonization of H2 production from fossil fuels to promote more efficient approaches based on membrane separation. In this work, two emerging configurations have been compared from the numerical point of view: the membrane reactor (MR) and the reformer and membrane module (RMM), proposed and tested by this research group. The rate of hydrogen production by SR has been calculated according to other literature works, a one-dimensional model has been developed for mass, heat, and momentum balances. For the membrane modules, the rate of hydrogen permeation has been estimated according to mass transfer correlation previously reported by this research group and based on previous experimental tests carried on in the first RMM Pilot Plant. The methane conversion, carbon dioxide yield, temperature, and pressure profile are compared for each configuration: SR, MR, and RMM. By decoupling the reaction and separation section, such as in the RMM, the overall methane conversion can be increased of about 30% improving the efficiency of the system.

Primary allogeneic mitochondrial mix (PAMM) transfer/transplant by MitoCeption to address damage in PBMCs caused by ultraviolet radiation.

BACKGROUND: Artificial Mitochondrial Transfer or Transplant (AMT/T) can be used to reduce the stress and loss of viability of damaged cells. In MitoCeption, a type of AMT/T, the isolated mitochondria and recipient cells are centrifuged together at 4 °C and then co-incubated at 37 °C in normal culture conditions, inducing the transfer. Ultraviolet radiation (UVR) can affect mitochondria and other cell structures, resulting in tissue stress, aging, and immunosuppression. AMT/T could be used to repair UVR cellular and mitochondrial damage. We studied if a mitochondrial mix from different donors (Primary Allogeneic Mitochondrial Mix, PAMM) can repair UVR damage and promote cell survival. RESULTS: Using a simplified adaption of the MitoCeption protocol, we used peripheral blood mononuclear cells (PBMCs) as the recipient cell model of the PAMM in order to determine if this protocol could repair UVR damage. Our results showed that when PBMCs are exposed to UVR, there is a decrease in metabolic activity, mitochondrial mass, and mtDNA sequence stability as well as an increase in p53 expression and the percentage of dead cells. When PAMM MitoCeption was used on UVR-damaged cells, it successfully transferred mitochondria from different donors to distinct PBMCs populations and repaired the observed UVR damage. CONCLUSION: Our results represent an advancement in the applications of MitoCeption and other AMT/T. We showed that PBMCs could be used as a PAMM source of mitochondria. We also showed that these mitochondria can be transferred in a mix from different donors (PAMM) to UVR-damaged, non-adherent primary cells. Additionally, we decreased the duration of the MitoCeption protocol.

Mass Transfer Coefficient in Multi-Stage Reformer/Membrane Modules for Hydrogen Production.

Hydrogen is a promising energy carrier, and is exploitable to extract energy from fossil fuels, biomasses, and intermittent renewable energy sources and its generation from fossil fuels, with CO2 separation at the source being one of the most promising pathways for fossil fuels' utilization. This work focuses on a particular configuration called the Reformer and Membrane Module (RMM), which alternates between stages of Steam Reforming (SR) reactions with H2 separation stages to overcome the thermodynamic limit of the conventional SR. The configuration has numerous advantages with respect to the more widely studied and tested membrane reactors, and has been tested during a pilot-scale research project. Although numerous modelling works appeared in the literature, the design features of the material exchanger (in the so-called RMM architecture) of different geometrical configurations have not been developed, and the mass transfer correlations, capable of providing design tools useful for such membrane modules, are not available. The purpose of this work is therefore to apply a physical-mathematical model of the mass transfer, in three different geometries, considering both concentration polarization and membrane permeation, in order to: (i) simulate the cited experimental results; (ii) estimate the scaling-up correlations for the "material exchange modules"; and (iii) identify the mass transfer limiting regime in relation to the gas mass flow rate.

Simulation of a waste incineration process with flue-gas cleaning and heat recovery sections using Aspen Plus.

In the present paper, the modeling of a dual-purpose plant for the production of electrical and thermal energy from the heat treatment of solid wastes is presented. Particularly, the process has been modeled by using the Aspen Plus Shell, with the aim of performing a study about the applicability of this software in the simulation of a solid waste incineration process, which involves complex gas-solid reactions where the solids are referred to as "non-conventional". The model is developed to analyze and quantify the expected benefits associated with refuse derived fuel (RDF) thermal utilization; thus attention is focused on the performance of the energy recovery section.

Las nubes de ceniza del volcán Tungurahua entre octubre 1999 y septiembre 2001

El seguimiento visual de la actividad eruptiva del volcán Tungurahua permitió conocer con mas exactitud la zona de influencia por caída y dispersión de piroclásticos. Así la ceniza, gases y vapor son predominantes llevados y distribuidos al Oeste. Los materiales expulsados por las explosiones, emisiones y/o fuentes de lava no siempre son detectados por los satélites. En este caso es necesario aplicar parámetros volcanológicos. Las relaciones matemáticas del Desplazamiento Reducido (DR, Aki y Koyagani, 1981) con respecto a la Altura de las Columnas de Ceniza (ACC) y pronóstico de la actividad. Así es posible coordinar acciones en el Departamento de Geofísica, Dirección de Aviación Civil, Instituto de Meteorología e Hidrológia, INAMHI y autoridades. (AU)