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Cardiovascular diseases pose a significant public health challenge globally, necessitating the development of effective treatments to mitigate the risk of cardiovascular diseases. Recently, circular RNAs (circRNAs), a novel class of non-coding RNAs, have been recognized for their role in cardiovascular disease. Aberrant expression of circRNAs is closely linked with changes in various cellular and pathophysiological processes within the cardiovascular system, including metabolism, proliferation, stress response, and cell death. Functionally, circRNAs serve multiple roles, such as acting as a microRNA sponge, providing scaffolds for proteins, and participating in protein translation. Owing to their unique properties, circRNAs may represent a promising biomarker for predicting disease progression and a potential target for cardiovascular drug development. This review comprehensively examines the properties, biogenesis, and potential mechanisms of circRNAs, enhancing understanding of their role in the pathophysiological processes impacting cardiovascular disease. Furthermore, the prospective clinical applications of circRNAs in the diagnosis, prognosis, and treatment of cardiovascular disease are addressed. [ABSTRACT FROM AUTHOR]

In multicellular tissues, the size and shape of cells are intricately linked with their physiological functions. In the vertebrate auditory organ, the neurosensory epithelium develops as a mosaic of sensory hair cells (HCs), and their glial-like supporting cells, which have distinct morphologies and functional properties at different frequency positions along its tonotopic long axis. In the chick cochlea, the basilar papilla (BP), proximal (high-frequency) HCs, are larger than their distal (low-frequency) counterparts, a morphological feature essential for sound perception. Mitochondrial dynamics, which constitute the equilibrium between fusion and fission, regulate differentiation and functional refinement across a variety of cell types. We investigate this as a potential mechanism for regulating the shape of developing HCs. Using live imaging in intact BP explants, we identify distinct remodelling of mitochondrial networks in proximal compared with distal HCs. Manipulating mitochondrial dynamics in developing HCs alters their normal morphology along the proximal-distal (tonotopic) axis. Inhibition of the mitochondrial fusion machinery decreased proximal HC surface area, whereas promotion of fusion increased the distal HC surface area. We identify mitochondrial dynamics as a key regulator of HC morphology in developing inner ear epithelia. [ABSTRACT FROM AUTHOR]

The vast regenerative potential of stem cells has laid the foundation for stem cell-based therapies. However, certain challenges limit the application of cell-based therapies. The therapeutic use of cell-free therapy can avoid limitations associated with cell-based therapies. Acellular stem cell-based therapies rely on the use of biological factors released by stem cells, including growth factors and extracellular vesicles such as exosomes. Due to their comparable regenerative potential, acellular therapies may provide a feasible and scalable alternative to stem cell-based therapies. Exosomes are small vesicles secreted by various types of cells, including stem cells. Exosomes contain parent cell-derived nucleic acids, proteins, lipids, and other bioactive molecules. They play an important role in intra-cellular communication and influence the biological characteristics of cells. Exosomes inherit the properties of their parent cells; therefore, stem cell-derived exosomes are of particular interest for applications of regenerative medicine. In comparison to stem cell-based therapy, exosome therapy offers several benefits, such as easy transport and storage, no risk of immunological rejection, and few ethical dilemmas. Unlike stem cells, exosomes can be lyophilized and stored off-the-shelf, making acellular therapies standardized and more accessible while reducing overall treatment costs. Exosome-based acellular treatments are therefore readily available for applications in patients at the time of care. The current review discusses the use of exosomes as an acellular therapy. The review explores the molecular mechanism of exosome biogenesis, various methods for exosome isolation, and characterization. In addition, the latest advancements in bioengineering techniques to enhance exosome potential for acellular therapies have been discussed. The challenges in the use of exosomes as well as their diverse applications for the diagnosis and treatment of diseases have been reviewed in detail. [ABSTRACT FROM AUTHOR]

Circular RNA (circRNA) is a type of non-coding RNA with multiple biological functions. Whole circRNA genomes in plants have been identified, and circRNAs have been demonstrated to be widely present and highly expressed in various plant tissues and organs. CircRNAs are highly stable and conserved in plants, and exhibit tissue specificity and developmental stage specificity. CircRNAs often interact with other biomolecules, such as miRNAs and proteins, thereby regulating gene expression, interfering with gene function, and affecting plant growth and development or response to environmental stress. CircRNAs are less studied in plants than in animals, and their regulatory mechanisms of biogenesis and molecular functions are not fully understood. A variety of circRNAs in plants are involved in regulating growth and development and responding to environmental stress. This review focuses on the biogenesis and regulatory mechanisms of circRNAs, as well as their biological functions during growth, development, and stress responses in plants, including a discussion of plant circRNA research prospects. Understanding the generation and regulatory mechanisms of circRNAs is a challenging but important topic in the field of circRNAs in plants, as it can provide insights into plant life activities and their response mechanisms to biotic or abiotic stresses as well as new strategies for plant molecular breeding and pest control. [ABSTRACT FROM AUTHOR]

World Health Organisation data suggest that up to 99% of the global population are exposed to air pollutants above recommended levels. Impacts to health range from increased risk of stroke and cardiovascular disease to chronic respiratory conditions, and air pollution may contribute to over 7 million premature deaths a year. Additionally, mounting evidence suggests that in utero or early life exposure to particulate matter (PM) in ambient air pollution increases the risk of neurodevelopmental impairment with obvious lifelong consequences. Identifying brain‐specific cellular targets of PM is vital for determining its long‐term consequences. We previously established that microglial‐like BV2 cells were particularly sensitive to urban (U)PM‐induced damage including reactive oxygen species production, which was abrogated by a mitochondrially targeted antioxidant. Here we extend those studies to find that UPM treatment causes a rapid impairment of mitochondrial function and increased mitochondrial fragmentation. However, there is a subsequent restoration of mitochondrial and therefore cell health occurring concomitantly with upregulated measures of mitochondrial biogenesis and mitochondrial load. Our data highlight that protecting mitochondrial function may represent a valuable mechanism to offset the effects of UPM exposure in the neonatal brain. Key points: Air pollution represents a growing risk to long‐term health especially in early life, and the CNS is emerging a target for airborne particulate matter (PM).We previously showed that microglial‐like BV2 cells were vulnerable to urban (U)PM exposure, which impaired cell survival and promoted reactive oxygen species production.Here we find that, following UPM exposure, BV2 mitochondrial membrane potential is rapidly reduced, concomitant with decreased cellular bioenergetics and increased mitochondrial fission.However, markers of mitochondrial biogenesis and mitochondrial mass are subsequently induced, which may represent a cellular mitigation strategy.As mitochondria are more vulnerable in the developing brain, exposure to air pollution may represent a greater risk to lifelong health in this cohort; conversely, promoting mitochondrial integrity may offset these risks. [ABSTRACT FROM AUTHOR]

BACKGROUND: Aging is associated with increased susceptibility to cardiovascular disease, and mitochondrial dysfunction plays a key role in the pathogenesis of cardiovascular disease. Regular physical activity is beneficial to cardiovascular health and can prevent and treat chronic heart disease. However, the specific mechanism of mitochondria in the protective effect of exercise on the aging heart has not yet been clarified. OBJECTIVE: To explore the effect of aerobic exercise on cardiac pathological remodeling in aging rats and to investigate the possible mechanism of mitochondrial quality control system. METHODS: Sixty Wistar rats were randomly divided into young sedentary group (6 months old), old sedentary group (20 months old) and old exercise group (20 months old) with 20 rats in each group. Rats in the young sedentary and old sedentary groups were fed in cages for 12 weeks, while those in the old exercise group underwent moderate-intensity aerobic treadmill exercise (60% of the maximal running speed, slope 0°, 60 minute per day, 5 days per week) for 12 weeks. After the experiment, the heart was extracted for relevant indicator tests. RESULTS AND CONCLUSION: Cardiac morphology and myocardial histopathology: compared with the young sedentary group, the rats in the old sedentary group presented with concentric cardiac hypertrophy, myocardial fibrosis, myocardial cell apoptosis and loss, and cardiac diastolic dysfunction (P < 0.05); compared with the old sedentary group, animals in the old exercise group showed reduced myocardial fibrosis and apoptosis rates, increased cell numbers, improved cardiac function (P < 0.05), and a transition in cardiac phenotype from pathological to physiological hypertrophy. Mitochondrial function: compared with the young sedentary group, the generation rate of mitochondrial hydrogen peroxide increased (P < 0.05), respiration rate and respiratory control ratio of state 3 and state 4 decreased (P < 0.05), activities of respiratory chain complexes I, II and IV decreased (P < 0.05), mitochondrial calcium retention capacity decreased (P < 0.05), and mitochondrial permeability transition pore opening increased (P < 0.05) in the old sedentary group. Compared with the old sedentary group, all of the above indicators were significantly improved in the old exercise group (P < 0.05). Mitochondrial quality control: compared with the young sedentary group, mitochondrial biogenesis decreased (P < 0.05), mitophagy activity increased (P < 0.05), mitochondrial fusion reduced (P < 0.05), and fission raised (P < 0.05) in the old sedentary group; compared with the old sedentary group, mitochondrial biogenesis and mitophagy activity increased (P < 0.05), mitochondrial fusion raised (P < 0.05) and fission decreased (P < 0.05) in the old exercise group. To conclude, regular aerobic exercises exert cardioprotective effects in aging rats by regulating the mitochondrial quality control system, thus reversing pathological cardiac remodeling and improving cardiac function. [ABSTRACT FROM AUTHOR]

After an initial positive response to chemotherapy, cancer patients often acquire chemoresistance and tumor relapse, which makes cancer one of the most lethal diseases worldwide. Exosomes are essential mediators of cell-to-cell communication by delivering their cargo, such as proteins, RNAs and DNA, from cell to cell. They participate in cancer progression, metastasis, immune response and therapy resistance. Their ability to shuttle between cells makes them efficient drug delivery systems. As drug transporters, they provide novel strategies for cancer therapy by advancing targeted drug therapy and improving the therapeutic effects of anti-cancer medications. In this review, a comprehensive overview of the potential of exosomes as therapeutic agents and targeted molecules in the treatment of cancer patients is given. The current challenges of preparation of exosomes loaded with drugs and delivering them to the recipient tumor cells as well as a consequent exosome-mediated cancer therapy are also discussed. [ABSTRACT FROM AUTHOR]

Membrane proteins carrying redox cofactors are key subunits of respiratory chain complexes, yet the exact path of their folding and maturation remains poorly understood. Here, using cryo‐EM and structure prediction via Alphafold2, we generated models of early assembly intermediates of cytochrome b (Cytb), a central subunit of complex III. The predicted structure of the first assembly intermediate suggests how the binding of Cytb to the assembly factor Cbp3‐Cbp6 imposes an open configuration to facilitate the acquisition of its heme cofactors. Moreover, structure predictions of the second intermediate indicate how hemes get stabilized by binding of the assembly factor Cbp4, with a concomitant weakening of the contact between Cbp3‐Cbp6 and Cytb, preparing for the release of the fully hemylated protein from the assembly factors. [ABSTRACT FROM AUTHOR]

PIWI-interacting RNAs (piRNAs), a class of small non-coding RNAs (sncRNAs) with 24–32 nucleotides (nt), were initially identified in the reproductive system. Unlike microRNAs (miRNAs) or small interfering RNAs (siRNAs), piRNAs normally guide P-element-induced wimpy testis protein (PIWI) families to slice extensively complementary transposon transcripts without the seed pairing. Numerous studies have shown that piRNAs are abundantly expressed in the brain, and many of them are aberrantly regulated in central neural system (CNS) disorders. However, the role of piRNAs in the related developmental and pathological processes is unclear. The elucidation of piRNAs/PIWI would greatly improve the understanding of CNS development and ultimately lead to novel strategies to treat neural diseases. In this review, we summarized the relevant structure, properties, and databases of piRNAs and their functional roles in neural development and degenerative disorders. We hope that future studies of these piRNAs will facilitate the development of RNA-based therapeutics for CNS disorders. [ABSTRACT FROM AUTHOR]

Exploration and marketable exploitation of coalbed methane (CBM) as cleaner fuel has been started globally. In addition, incidence of methane in coal basins is an imperative fraction of global carbon cycle. Significantly, subsurface coal ecosystem contains methane forming archaea. There is a rising attention in optimizing microbial coal gasification to exploit the abundant or inexpensive coal reserves worldwide. Therefore, it is essential to understand the coalbeds in geo-microbial perspective. Current review provides an in-depth analysis of recent advances in our understanding of how methanoarchaea are distributed in coal deposits globally. Specially, we highlight the findings on coal-associated methanoarchaeal existence, abundance, diversity, metabolic activity, and biogeography in diverse coal basins worldwide. Growing evidences indicates that we have arrived an exciting era of archaeal research. Moreover, gasification of coal into methane by utilizing microbial methanogenesis is a considerable way to mitigate the energy crisis for the rising world population. [ABSTRACT FROM AUTHOR]

Exosomes‐like nanoparticles (ELNs) (exosomes or extracellular vesicles) are vesicle‐like bodies secreted by cells. Plant ELNs (PENs) are membrane vesicles secreted by plant cells, with a lipid bilayer as the basic skeleton, enclosing various active substances such as proteins and nucleic acids, which have many physiological and pathological functions. Recent studies have found that the PENs are widespread within different plant species and their biological functions are increasingly recognized. The effective separation method is also necessary for its function and application. Ultracentrifugation, sucrose density gradient ultracentrifugation, ultrafiltration, polymer‐based precipitation methods, etc., are commonly used methods for plant exosome‐like nanoparticle extraction. In recent years, emerging methods such as size exclusion chromatography, immunoaffinity capture‐based technique, and microfluidic technology have shown advancements compared to traditional methods. The standardized separation process for PENs continues to evolve. In this review, we summarized the recent progress in the biogenesis, components, separation methods, and some functions of PENs. When the research on the separation method of PENs and their unique biological structure is further studied. A brand‐new idea for the efficient separation and utilization of PENs can be provided in the future, which has a very broad prospect. [ABSTRACT FROM AUTHOR]

The etiology of epilepsy is ascribed to the synchronized aberrant neuronal activity within the brain. Circular RNAs (circRNAs), a class of non‐coding RNAs characterized by their circular structures and covalent linkage, exert a substantial influence on this phenomenon. CircRNAs possess stereotyped replication, transience, repetitiveness, and paroxysm. Additionally, MicroRNA (miRNA) plays a crucial role in the regulation of diverse pathological processes, including epilepsy. CircRNA is of particular significance due to its ability to function as a competing endogenous RNA, thereby sequestering or inhibiting miRNA activity through binding to target mRNA. Our review primarily concentrates on elucidating the pathological and functional roles, as well as the underlying mechanisms, of circRNA–miRNA–mRNA networks in epilepsy. Additionally, it explores the potential utility of these networks for early detection and therapeutic intervention. [ABSTRACT FROM AUTHOR]

Mitochondria-Associated Endoplasmic Reticulum Membranes (MAMs) mediate the communication between the Endoplasmic Reticulum (ER) and the mitochondria, playing a fundamental role in steroidogenesis. This study aimed to understand how D-aspartate (D-Asp), a well-known stimulator of testosterone biosynthesis and spermatogenesis, affects the mechanism of steroidogenesis in rat testes. Our results suggested that D-Asp exerts this function through MAMs, affecting lipid trafficking, calcium signaling, ER stress, and mitochondrial dynamics. After 15 days of oral administration of D-Asp to rats, there was an increase in both antioxidant enzymes (SOD and Catalase) and in the protein expression levels of ATAD3A, FACL4, and SOAT1, which are markers of lipid transfer, as well as VDAC and GRP75, which are markers of calcium signaling. Additionally, there was a decrease in protein expression levels of GRP78, a marker of aging that counteracts ER stress. The effects of D-Asp on mitochondrial dynamics strongly suggested its active role as well. It induced the expression levels of proteins involved in fusion (MFN1, MFN2, and OPA1) and in biogenesis (NRF1 and TFAM), as well as in mitochondrial mass (TOMM20), and decreased the expression level of DRP1, a crucial mitochondrial fission marker. These findings suggested D-Asp involvement in the functional improvement of mitochondria during steroidogenesis. Immunofluorescent signals of ATAD3A, MFN1/2, TFAM, and TOMM20 confirmed their localization in Leydig cells showing an intensity upgrade in D-Asp-treated rat testes. Taken together, our results demonstrate the involvement of D-Asp in the steroidogenesis of rat testes, acting at multiple stages of both MAMs and mitochondrial dynamics, opening new opportunities for future investigation in other steroidogenic tissues. [ABSTRACT FROM AUTHOR]

Exosomes are nanoscale extracellular vesicles present in bodily fluids that mediate intercellular communication by transferring bioactive molecules, thereby regulating a range of physiological and pathological processes. Exosomes can be secreted from nearly all cell types, and the biological function of exosomes is heterogeneous and depends on the donor cell type and state. Recent research has revealed that the levels of exosomes released from the endosomal system increase in cells undergoing programmed cell death. These exosomes play crucial roles in diseases, such as inflammation, tumors, and autoimmune diseases. However, there is currently a lack of systematic research on the differences in the biogenesis, secretion mechanisms, and composition of exosomes under different programmed cell death modalities. This review underscores the potential of exosomes as vital mediators of programmed cell death processes, highlighting the interconnection between exosome biosynthesis and the regulatory mechanisms governing cell death processes. Furthermore, we accentuate the prospect of leveraging exosomes for the development of innovative biomarkers and therapeutic strategies across various diseases. [ABSTRACT FROM AUTHOR]

Exosomes are nanoscale extracellular vesicles present in bodily fluids that mediate intercellular communication by transferring bioactive molecules, thereby regulating a range of physiological and pathological processes. Exosomes can be secreted from nearly all cell types, and the biological function of exosomes is heterogeneous and depends on the donor cell type and state. Recent research has revealed that the levels of exosomes released from the endosomal system increase in cells undergoing programmed cell death. These exosomes play crucial roles in diseases, such as inflammation, tumors, and autoimmune diseases. However, there is currently a lack of systematic research on the differences in the biogenesis, secretion mechanisms, and composition of exosomes under different programmed cell death modalities. This review underscores the potential of exosomes as vital mediators of programmed cell death processes, highlighting the interconnection between exosome biosynthesis and the regulatory mechanisms governing cell death processes. Furthermore, we accentuate the prospect of leveraging exosomes for the development of innovative biomarkers and therapeutic strategies across various diseases. [ABSTRACT FROM AUTHOR]

Mitochondria perform a myriad of essential functions that ensure organismal homeostasis, including maintaining bioenergetic capacity, sensing and signalling the presence of pathogenic threats, and determining cell fate. Their function is highly dependent on mitochondrial quality control and the appropriate regulation of mitochondrial size, shape, and distribution during an entire lifetime, as well as their inheritance across generations. The roundworm Caenorhabditis elegans has emerged as an ideal model organism through which to study mitochondria. The remarkable conservation of mitochondrial biology has allowed C. elegans researchers to investigate complex processes that are challenging to study in higher organisms. In this review, we explore the key recent contributions of C. elegans to mitochondrial biology through the lens of mitochondrial dynamics, organellar removal, and mitochondrial inheritance, as well as their involvement in immune responses, various types of stress, and transgenerational signalling. [ABSTRACT FROM AUTHOR]

Extrachromosomal circular DNA (eccDNA) is a circular form of DNA that exists outside of the chromosome. Although it has only been a few decades since its discovery, in recent years, it has been found to have a close relationship with cancer, which has attracted widespread attention from researchers. Thus far, under the persistent research of researchers from all over the world, eccDNA has been found to play an important role in a variety of tumors, including breast cancer, lung cancer, ovarian cancer, etc. Herein, we review the sources of eccDNA, classifications, and the mechanisms responsible for their biogenesis. In addition, we introduce the relationship between eccDNA and various cancers and the role of eccDNA in the generation and evolution of cancer. Finally, we summarize the research significance and importance of eccDNA in cancer, and highlight new prospects for the application of eccDNA in the future detection and treatment of cancer. [ABSTRACT FROM AUTHOR]

Placental extracellular vesicles (EVs) can be found in the maternal circulation throughout gestation, and their concentration, content and bioactivity are associated with pregnancy outcomes, including gestational diabetes mellitus (GDM). However, the effect of changes in the maternal microenvironment on the mechanisms associated with the secretion of EVs from placental cells remains to be fully established. Here, we evaluated the effect of high glucose on proteins associated with the trafficking and release of different populations of EVs from placental cells. BeWo and HTR8/SVneo cells were used as placental models and cultured under 5‐mM D‐glucose (i.e. control) or 25‐mM D‐glucose (high glucose). Cell‐conditioned media (CCM) and cell lysate were collected after 48 h. Different populations of EVs were isolated from CCM by ultracentrifugation (i.e. pellet 2K‐g, pellet 10K‐g, and pellet 100K‐g) and characterised by Nanoparticle Tracking Analysis. Quantitative proteomic analysis (IDA/SWATH) and multiple reaction monitoring protocols at high resolution (MRMHR) were developed to quantify 37 proteins related to biogenesis, trafficking/release and recognition/uptake of EVs. High glucose increased the secretion of total EVs across the pellets from BeWo cells, an effect driven mainly by changes in the small EVs concentration in the CCM. Interestingly, no effect of high glucose on HTR8/SVneo cells EVs secretion was observed. High glucose induces changes in proteins associated with vesicle trafficking in BeWo cells, including Heat Shock Protein Family A (Hsp70) Member 9 (HSPA9) and Member 8 (HSPA8). For HTR8/SVneo, altered proteins including prostaglandin F2α receptor regulatory protein (FPRP), RAB5A, RAB35, RAB5B, and RB11B, STAM1 and TSG101. These proteins are associated with the secretion and trafficking of EVs, which could explain in part, changes in the levels of circulating EVs in diabetic pregnancies. Further, we identified that proteins RAB11B, PDCD6IP, STAM, HSPA9, HSPA8, SDCBP, RAB5B, RAB5A, RAB7A and ERAP1 regulate EV release in response to high and low glucose when overexpressed in cells. Interestingly, immunohistochemistry analysis of RAB7A revealed distinct changes in placental tissues obtained from women with normal glucose tolerance (NGT, n = 6) and those with GDM (n = 6), influenced by diet or insulin treatment. High glucose regulation of proteins involved in intercellular dynamics and the trafficking of multivesicular bodies to the plasma membrane in placental cells is relevant in the context of GDM pregnancies. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the nexus between mitochondrial function and kidney injury by using a dietary-induced obese minipig model. Female Lee-Sung minipigs feeding a high-fat diet (HFD) for 6 months exhibited obesity, hyperglycaemia and dyslipidemia. HFD elevated the levels of plasma biomarkers related to renal injury, including symmetric dimethylarginine, creatinine and urea nitrogen. An extensive structural change in tubules and glomeruli was observed in HFD-fed pigs. A great amount of triacylglycerol was accumulated in HFD kidney compared to control kidney, whereas a reduction of ATP level and antioxidant capacity were exhibited in HFD kidney. Moreover, HFD altered the expressions of mitochondrial-related protein in renal cortex. To conclude, long-term HFD feeding to Lee-Sung minipigs induced obesity and kidney injury accompanied by abnormal mitochondrial functions in the renal cortex, suggesting an interrelationship with renal disease progression. [ABSTRACT FROM AUTHOR]

Summary: CircRNAs exist widely in plants, but the regulatory mechanisms for the biogenesis and function of plant circRNAs remain largely unknown.Using extensive mutagenesis of expression plasmids and genetic transformation methods, we analyzed the biogenesis and anti‐salt functions of a new grape circRNA Vv‐circSIZ1.We identified Vv‐circSIZ1 that is mainly expressed in the cytoplasm of xylem. CircSIZ1 is species‐specific, and genomic circSIZ1‐forming region of seven tested species could be backspliced in Nicotiana benthamiana, but not in Arabidopsis. The retention length of Vv‐circSIZ1 flanking introns was significantly positively correlated with its generation efficiency. The precise splicing of Vv‐circSIZ1 does not depend on its mature exon sequence or internal intron sequences, but on the AG/GT splicing signal sites and branch site of the flanking introns. The spliceosome activity was inversely proportional to the expression level of Vv‐circSIZ1. Furthermore, RNA‐binding proteins can regulate the expression of Vv‐circSIZ1. The overexpression of Vv‐circSIZ1 improved salt tolerance of grape and N. benthamiana. Additionally, Vv‐circSIZ1 could relieve the repressive effect of VvmiR3631 on its target VvVHAc1. Vv‐circSIZ1 also promoted transcription of its parental gene.Overall, these results broaden our understanding of circRNAs in plants. [ABSTRACT FROM AUTHOR]

In prokaryotes, the role of Mo/W enzymes in physiology and bioenergetics is widely recognized. It is worth noting that the most diverse family of Mo/W enzymes is exclusive to prokaryotes, with the probable existence of several of them from the earliest forms of life on Earth. The structural organization of these enzymes, which often include additional redox centers, is as diverse as ever, as is their cellular localization. The most notable observation is the involvement of dedicated chaperones assisting with the assembly and acquisition of the metal centers, including Mo/W-bisPGD, one of the largest organic cofactors in nature. This review seeks to provide a new understanding and a unified model of Mo/W enzyme maturation. [ABSTRACT FROM AUTHOR]

Background: Exosomes are nanosized bio vesicles formed when multivesicular bodies and the plasma membrane merge and discharge into bodily fluids. They are well recognized for facilitating intercellular communication by transporting numerous biomolecules, including DNA, RNAs, proteins, and lipids, and have been implicated in varied diseases including cancer. Exosomes may be altered to transport a variety of therapeutic payloads, including as short interfering RNAs, antisense oligonucleotides, chemotherapeutic drugs, and immunological modulators, and can be directed to a specific target. Exosomes also possess the potential to act as a diagnostic biomarker in cancer, in addition to their therapeutic potential. Conclusion: In this review, the physiological roles played by exosomes were summarized along with their biogenesis process. Different isolation techniques of exosomes including centrifugation-based, size-based, and polymer precipitation-based techniques have also been described in detail with a special focus on cancer therapeutic applications. The review also shed light on techniques of incubation of drugs with exosomes and their characterization methods covering the most advanced techniques. Myriad applications of exosomes in cancer as diagnostic biomarkers, drug delivery carriers, and chemoresistance-related issues have been discussed at length. Furthermore, a brief overview of exosome-based anti-cancer vaccines and a few prominent challenges concerning exosomal delivery have been concluded at the end. [ABSTRACT FROM AUTHOR]

Cancer cells overexpress IF1, the endogenous protein that inhibits the hydrolytic activity of ATP synthase when mitochondrial membrane potential (ΔμH+) falls, as in ischemia. Other roles have been ascribed to IF1, but the associated molecular mechanisms are still under debate. We investigated the ability of IF1 to promote survival and proliferation in osteosarcoma and colon carcinoma cells exposed to conditions mimicking ischemia and reperfusion, as occurs in vivo, particularly in solid tumors. IF1-silenced and parental cells were exposed to the FCCP uncoupler to collapse ΔμH+ and the bioenergetics of cell models were validated. All the uncoupled cells preserved mitochondrial mass, but the implemented mechanisms differed in IF1-expressing and IF1-silenced cells. Indeed, the membrane potential collapse and the energy charge preservation allowed an increase in both mitophagy and mitochondrial biogenesis in IF1-expressing cells only. Interestingly, the presence of IF1 also conferred a proliferative advantage to cells highly dependent on oxidative phosphorylation when the uncoupler was washed out, mimicking cell re-oxygenation. Overall, our results indicate that IF1, by allowing energy preservation and promoting mitochondrial renewal, can favor proliferation of anoxic cells and tumor growth. Therefore, hindering the action of IF1 may be promising for the therapy of tumors that rely on oxidative phosphorylation for energy production. [ABSTRACT FROM AUTHOR]

The study of host–pathogen interactions has increased considerably in recent decades. This intercellular communication has been mediated by extracellular vesicles (EVs) that play an important role during the interaction. EVs are particles of lipid bilayer and described in different types of cells, eukaryotic or prokaryotic. Depending on their biogenesis they are described as exosomes (derived from multivesicular bodies) and microvesicles (derived from the plasma membrane). The EVs carry biomolecules, including nucleic acids, lipids, and proteins that can be released or internalized by other cells in different pathways (endocytosis, macropinocytosis, phagocytosis, or membrane fusion) in the process described as uptake. The balance between biogenesis and uptake of EVs could modify physiological and pathophysiological processes of the cell. This review is focusing on the dynamic roles of release and capture of EVs during host–pathogen interaction. We also do a critical analysis of methodologies for obtaining and analyzing EVs. Finally, we draw attention to critical points to be considered in EV biogenesis and uptake studies. [ABSTRACT FROM AUTHOR]

In rice, various types of non-coding RNA molecules (ncRNAs) exist which are distinguished by their origin, biogenesis, and biological functions. Based on size and structure, ncRNAs are broadly categorized into short non-coding (sncRNAs) and long non-coding RNAs (lncRNAs). Both of the groups have been further split into several subtypes based on their distinct features including biogenesis, length, polarity, and putative functions. In rice and other higher plants, the majority of sncRNAs negatively regulate gene expression through interactions with mRNA. Research evidence has shown that they play a vital role in different developmental processes including growth, phase transition, and against various biotic and abiotic stresses, by mediating endogenous gene silencing in a precise fashion. These molecules act either at the transcriptional level through DNA methylation and repressive modification of histone protein or at the post-transcriptional level by the degradation of mRNA and translational repression. Recent progress in research has revealed that lncRNA is responsible to stabilize alterations in the plant genome and is the key regulator of transcription via interactions with both coding and non-coding RNA molecules as well as transcription factors (TFs). This review article briefly summarizes the important types of ncRNAs in rice and current progress towards the understanding of the biogenesis of ncRNAs and their main biological functions. [ABSTRACT FROM AUTHOR]

Cellular communication depends heavily on the participation of vesicular systems generated by most cells of an organism. Exosomes play central roles in this process. Today, these vesicles have been characterized, and it has been determined that the cargo they transport is not within a random system. In fact, it depends on various molecular signals and the recruitment of proteins that participate in the biogenesis of exosomes. It has also been shown that multiple viruses can recruit these vesicles to transport viral factors such as genomes or proteins. It has been shown that the late domains present in viral proteins are critical for the exosomal selection and biogenesis systems to recognize these viral proteins and introduce them into the exosomes. In this review, the researchers discuss the evidence related to the characterization of these late domains and their role in exosome recruitment during viral infection. [ABSTRACT FROM AUTHOR]

Background & Aims: One of the possible mechanisms for resistance to insulin and type 2 diabetes is dysfunction and impaired mitochondrial biogenesis. Mitochondrial density and function are associated with cardiovascular disease, sarcopenia, insulin resistance and type 2 diabetes, the aging process, and aerobic capacity. Today, a complete understanding of mitochondrial biogenesis is associated with an understanding of various cellular pathological conditions. Mitochondria play a role in increasing mitochondrial function. Quality, mitochondria represent an improvement in mitochondrial biogenesis. In tissues with high oxidative capacity, such as skeletal muscle, activated by gamma receptor joint proliferator, an alpha activated by peroxisome proliferator (AMPK) is considered to be the most important regulator of biogenesis and mitochondrial function. (cytochrome C and AMPK) is a transcription and replication agent for mitochondrial DNA and plays an important role in mitochondrial biogenesis processes. A study by Madrasa (2018) showed that decreased expression of this group of genes is associated with decreased capacity, whole body aerobics in patients with type 2 diabetes and decreased expression of PGC-1α and nuclear genes encoding mitochondria in individuals. Insulin resistance can mean that these people have low levels of aerobic exercise. Exercise can play an important role in accelerating mitochondrial biogenesis, possibly leading to a reduction in mitochondrial dysfunction that occurs during the aging process, metabolic diseases such as type 2 diabetes, and conditions of muscle inactivity resisting fatigue and increasing the quality of life . The method of training is in the form the although metabolic control is available in type2 diabetes effect of aerobic exercise and the chemical drug atrostatin on the expression of genes affecting the mitochondrial biogenesis of cardio myositis in samples with type 2 diabetes has not been studied and because of its importance in controlling mitochondrial function following diabetes. Type 2 is impaired, it is necessary to study it, so the aim of the present study was to investigate the protective effect of continuous and intermittent exercise with atrostatin on some markers of mitochondrial biogenesis signaling myositis (cytochrome C and AMPK) in diabetic elderly rats. Methods: Thirty-five male rats (20 weeks old) weighing between 300 and 350 g were randomly divided into 7 groups. Diabetes was induced in 6 groups. To make diabetic mice, streptozotocin (STZ) was injected intraperitoneally at a dose of 50 mg per kg body weight (26). Atorvastatin was taken orally after a meal at a dose of 2 mg per kg body weight . The first week of continuous training program at a speed of 15 meters per minute for five minutes, the rats started running on the treadmill. Then, every week, increasing the speed by 1 to 2 meters per minute for 1 to 2 minutes increases the running time. The number of continuous training sessions was five times a week. The interval training program consisted of 25-25 minutes of treadmill running on a treadmill at a speed of 15 meters per minute for the first week, with one meter per minute added each week to 22 meters per minute in the eighth week. The duration of the first session was 25 minutes, with one minute added to each session, reaching 64 minutes in the eighth week. 48 hours after the last training session with 10 to 12 hours of night fasting, intraperitoneal injection of a combination of ketamine and xylazine was performed in anesthetized mice and tissue samples were taken. Their heart tissue was isolated and stored at -80 ° C and then transferred to a laboratory for genetic testing. To investigate the significant changes in each of the research changes between different groups, one-way analysis of variance was used and if a statistically significant difference was observed to determine the location of ANOVA, Tukey post hoc test was used. Significance level P <0.05 was considered for all calculations. Results: In the present study, the effect of continuous and intermittent exercise combined with atorvastatin administration (cytochrome C and AMPK) gene expression in cardiac myocytes of elderly diabetic rats was investigated. The first finding of the present study showed that the expression of (cytochrome C and AMPK) gene in cardiac myocytes of rats with type 2 diabetes was significantly reduced compared to the healthy control group, while after 8 weeks of intervention, the mean (cytochrome C and AMPK) to Significantly decreased compared to the healthy control group, while after 8 weeks of intervention, the mean (cytochrome C and AMPK) increased in the exercise and atorvastatin groups, but in the combined intervention group, this increase was significantly greater. It seems that taking atorvastatin with 8 weeks of continuous and intermittent physical activity has been able to make changes beyond taking atorvastatin alone or continuous and intermittent exercise. In this regard, Baghdam et al. (2019) by examining the effect of 8 weeks of aerobic exercise on the expression of PGC-lα gene in heart tissue in diabetic rats, concluded that aerobic exercise significantly increases the concentration of PGC-lα in heart tissue ( 29). However, in contrast to the findings of Chavanel et al. (2017) showed that exercise has no significant effect on the level of PGC-1α mRNA or other mitochondrial biogenesis regulators such as (cytochrome C and AMPK) (30). One of the most important reasons for inconsistency in Chavanel research with the results of the present study may be the age, sex and race of the subjects as well as the type of training protocol. (cytochrome C and AMPK) is one of the most important transcriptional coordinator coagulators that positively regulates the expression of genes associated with metabolic and mitochondrial adaptations, thus influencing cardiac substrate selection, mitochondrial function, ATP production capacity, and species production. Reacts to oxygen (ROS). Physical activity is one of the factors that trigger these messaging pathways. In other words, mitochondrial biogenesis in the cell is induced by environmental stimuli such as physical activity . Another result of the present study was the decrease in (cytochrome C and AMPK) gene expression in cardiac myocytes of elderly diabetic rats compared to the healthy control group, while after 8 weeks of intervention, a significant increase in (cytochrome C and AMPK) gene expression was observed in atorvastatin and combination groups compared to the patient group. This increase was greater in the combination of diabetic + atorvastatin + periodic exercise. It seems that when the volume of training is the same, the intensity of training can be an effective factor in the expression of (cytochrome C and AMPK); Therefore, this study showed that with a constant volume of periodic training is more effective than continuous training in the expression of (cytochrome C and AMPK) gene. The present study showed that intermittent and continuous exercise with atorvastatin increased (cytochrome C and AMPK) in the heart cells of elderly diabetic rats, which decreased due to diabetes and aging. Consistent with the results of the present study, Popo et al. Examined the effect of two months of aerobic exercise on skeletal muscle TFAM in human diabetic specimens and reported a significant increase. Therefore, the effect of the training period is enhanced at higher intensities. Exercise frequency is also one of the effective factors in increasing mitochondrial biogenesis. Chavanel et al. (2017) have shown that exercise has no significant effect on the level of mRNAPGC-1α or other mitochondrial biogenesis regulators including TFAM and cytochrome C and AMPK. One of the most important reasons for inconsistency in Chavanel research with the results of the present study may be in the condition of the subject and the type of muscle fiber as well as the type of training protocol. TFAM is a high-mobility transcription factor group responsible for replication and transcription of mitochondrial DNA. Impairment of the (cytochrome C and AMPK) target specifically in cardiac tissue leads to a significant reduction in electron transport capacity, spontaneous cardiomyopathy, and heart failure. In contrast, increased TFAM expression in cardiac tissue protects against heart failure due to myocardial infarction. Conclusion: Another finding of the present study was the positive and significant effect of atorvastatin on the expression of (cytochrome C and AMPK) genes in mice with type 2 diabetes. Studies show that atorvastatin improves mitochondrial function and prevents apoptosis in myocardial hypertrophy. In the present study, Chen et al. (2018) inhibited the decrease in the expression of (cytochrome C and AMPK) in mice with myocardial insufficiency by treatment with atorvastatin . According to the results obtained in the present study, the effects of atorvastatin may be fundamentally different in different patients and with different races, and also its effects may vary depending on the dose or duration of use and the type of statin used. However, the effect of co-administration of atorvastatin and exercise with (cytochrome C and AMPK) on cardiac tissue has not been investigated. Reduces oxidative stress and inflammation in a variety of metabolic syndrome diseases such as diabetes and therefore improves these diseases by inhibiting mitochondrial damage .The combined use of both has more effective therapeutic effects on type 2 diabetes. The results of this study on improving heart function have been confirmed by previous studies. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS) is a complex, but relatively common endocrine disorder associated with chronic anovulation, hyperandrogenism, and micro-polycystic ovaries. In addition to reduced fertility, people with PCOS have a higher risk of obesity, insulin resistance, and metabolic disease, all comorbidities that are associated with mitochondrial dysfunction. This review summarizes human and animal data that report mitochondrial dysfunction and metabolic dysregulation in PCOS to better understand how mitochondria impact reproductive organ pathophysiology. This in-depth review considers all the elements regulating mitochondrial quantity and quality, from mitochondrial biogenesis under the transcriptional regulation of both the nuclear and mitochondrial genome to the ultrastructural and functional complexes that regulate cellular metabolism and reactive oxygen species production, as well as the dynamics that regulate subcellular interactions that are key to mitochondrial quality control. When any of these mitochondrial functions are disrupted, the energetic equilibrium within the cell changes, cell processes can fail, and cell death can occur. If this process is ongoing, it affects tissue and organ function, causing disease. The objective of this review is to consolidate and classify a broad number of PCOS studies to understand how various mitochondrial processes impact reproductive organs, including the ovary (oocytes and granulosa cells), uterus, placenta, and circulation, causing reproductive pathophysiology. A secondary objective is to uncover the potential role of mitochondria in the transgenerational transmission of PCOS and metabolic disorders. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) are short endogenous non-coding RNAs that regulate gene expression at the post-transcriptional level in a broad range of eukaryotic species. In animals, it is estimated that more than 60% of mammalian genes are targets of miRNAs, with miRNAs regulating cellular processes such as differentiation and proliferation. In plants, miRNAs regulate gene expression and play essential roles in diverse biological processes, including growth, development, and stress responses. Arabidopsis mutants with defective miRNA biogenesis are embryo lethal, and abnormal expression of miRNAs can cause severe developmental phenotypes. It is therefore crucial that the homeostasis of miRNAs is tightly regulated. In this review, we summarize the key mechanisms of plant miRNA biogenesis and stabilization. We provide an update on nuclear proteins with functions in miRNA biogenesis and proteins linking miRNA biogenesis to environmental triggers. [ABSTRACT FROM AUTHOR]

Emerging lines of evidence have shown that the production of the covalently closed single-stranded circular RNAs is not splicing errors, but rather a regulated process with distinct biogenesis and turnover. Circular RNAs are expressed in a cell type- and tissue-specific manner and often localize to specific subcellular regions or organelles for functions. The dysregulation of circular RNAs from birth to death is linked to the pathogenesis and progression of diverse diseases. This review outlines how aberrant circular RNA biogenesis, subcellular location, and degradation are linked to disease progression, focusing on metaflammation and cancers. We also discuss potential therapeutic strategies and obstacles in targeting such disease-related circular RNAs. [ABSTRACT FROM AUTHOR]

The repertoire of regulatory noncoding RNAs (ncRNAs) has been enriched by the inclusion of long noncoding RNA (lncRNA) that are longer than 200 nt. Some of the currently known lncRNAs, were reported in the 1990s before the term lncRNA was introduced. These lncRNAs have diverse regulatory functions including regulation of transcription via interactions with proteins and RNAs, chromatin remodeling, translation, posttranslational protein modification, protein trafficking and cell signaling. Predictably, the dysregulation of lncRNA expression due to exposure to toxicants may precipitate adverse health consequences. Dysregulation of lncRNAs has also been implicated in various adverse human health outcomes. There is an increasing agreement that lncRNA expression profiling data needs to be closely examined to determine whether their altered expression can be used as biomarkers of toxicity as well as adverse human health outcomes. This review summarizes the biogenesis, regulation, function of lncRNA and their emerging significance in toxicology and disease conditions. Because our understanding of the lncRNA-toxicity relationship is still evolving, this review discusses this developing field using some examples. [ABSTRACT FROM AUTHOR]

Extracellular communication, in other words, crosstalk between cells, has a pivotal role in the survival of an organism. This communication occurs by different methods, one of which is extracellular vesicles. Exosomes, which are small lipid extracellular vesicles, have recently been discovered to have a role in signal transduction between cells inside the body. These vesicles contain important bioactive molecules including lipids, proteins, DNA, mRNA, and noncoding RNAs such as microRNAs (miRNAs). Exosomes are secreted by all cells including immune cells (macrophages, lymphocytes, granulocytes, dendritic cells, mast cells) and tumor cells. The tumor microenvironment (TME) represents a complex network that supports the growth of tumor cells. This microenvironment encompasses tumor cells themselves, the extracellular matrix, fibroblasts, endothelial cells, blood vessels, immune cells, and non-cellular components such as exosomes and cytokines. This review aims to provide insights into the latest discoveries concerning how the immune system communicates internally and with other cell types, with a specific focus on research involving exosomal miRNAs in macrophages, dendritic cells, B lymphocytes, and T lymphocytes. Additionally, we will explore the role of exosomal miRNA in the TME and the immunomodulatory effect. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) are a heterogeneous group of lipid membrane-enclosed compartments that contain different biomolecules and are released by almost all living cells, including fungal genera. Fungal EVs contain multiple bioactive components that perform various biological functions, such as stimulation of the host immune system, transport of virulence factors, induction of biofilm formation, and mediation of host–pathogen interactions. In this review, we summarize the current knowledge on EVs of human pathogenic fungi, mainly focusing on their biogenesis, composition, and biological effects. We also discuss the potential markers and therapeutic applications of fungal EVs. [ABSTRACT FROM AUTHOR]

Exosomes are emerging intercellular communicators essential for cellular homeostasis during development and differentiation. The dysregulation in exosome‐mediated communication alters cellular networking leads to developmental defects and chronic diseases. Exosomes are heterogeneous in nature depending on differences in size, membrane protein abundance, and differential cargo load. In this review, we have highlighted the latest developments in exosome biogenesis pathways, heterogeneity, and selective enrichment of various exosomal cargoes including proteins, nucleic acids, and mitochondrial DNA. Furthermore, the recent developments in the isolation techniques of exosome subpopulations have also been discussed. The comprehensive knowledge of extracellular vesicle (EV) heterogeneity and selective cargo enrichment during specific pathology may provide a clue for disease severity and early prognosis possibilities. The release of specific exosome subtypes is associated with the progression of specific disease type and hence a probable tool for therapeutics and biomarker development. [ABSTRACT FROM AUTHOR]

The central dogma of genetics, which outlines the flow of genetic information from DNA to RNA to protein, has long been the guiding principle in molecular biology. In fact, more than three-quarters of the RNAs produced by transcription of the plant genome are not translated into proteins, and these RNAs directly serve as non-coding RNAs in the regulation of plant life activities at the molecular level. The breakthroughs in high-throughput transcriptome sequencing technology and the establishment and improvement of non-coding RNA experiments have now led to the discovery and confirmation of the biogenesis, mechanisms, and synergistic effects of non-coding RNAs. These non-coding RNAs are now predicted to play important roles in the regulation of gene expression and responses to stress and evolution. In this review, we focus on the synthesis, and mechanisms of non-coding RNAs, and we discuss their impact on gene regulation in plants. [ABSTRACT FROM AUTHOR]

Mitochondrial biogenesis and destruction in skeletal muscle are coordinated by distinct signaling pathways that are influenced by internal and exogenous variables including, but not limited to, muscle phenotype, physical activity, dietary composition, or drug administration. Previously we found that long-term resveratrol administration (up to 480 mg/day) ameliorates the slow-to-fast phenotypic shift in soleus muscles and promotes the expression in slow myosin heavy chain in the mixed plantaris muscle of non-human primates consuming a high fat/sugar (HFS) diet. Here, we expand on these earlier findings by examining whether mitochondrial content and the markers that dictate their biogenesis and mitophagy/autophagy are similarly affected by HFS and/or influenced by resveratrol while consuming this diet (HFSR). Compared to controls (n = 9), there was a ~20-25% decrease in mitochondrial content in HFS (n = 8) muscles as reflected in the COX2- and CYTB-to-GAPDH ratios using PCR analysis, which was blunted by resveratrol in HFSR (n = 7) soleus and, to a lesser degree, in plantaris muscles. A ~1.5 and 3-fold increase in Rev-erb-α protein was detected in HFSR soleus and plantaris muscles compared to controls, respectively. Unlike in HFSR animals, HFS soleus and plantaris muscles exhibited a ~2-fold elevation in phosphor-AMPKα (Thr172). HFS soleus muscles had elevated phosphorylated-to-total TANK binding protein-1 (TBK1) ratio suggesting an enhancement in mito/autophagic events. Taken together, resveratrol appears to blunt mitochondrial losses with a high fat/sugar diet by tempering mito/autophagy rather than promoting mitochondrial biogenesis, suggesting that the quantity of daily resveratrol supplement ingested and/or its long-term consumption are important considerations. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) comprise a broad range of secreted cell-derived membrane vesicles. Beyond their more well-characterized role in cell communication, in recent years, EVs have also been shown to play important roles during infection. Viruses can hijack the biogenesis of exosomes (which are small EVs) to promote viral spreading. Additionally, these exosomes are also important mediators in inflammation and immune responses during both bacterial and viral infections. This review summarizes these mechanisms while also describing the impact of bacterial EVs in regulating immune responses. Finally, the review also focuses on the potential and challenges of using EVs, in particular, to tackle infectious diseases. [ABSTRACT FROM AUTHOR]

Lipid droplets (LDs) are ubiquitous, dynamic organelles found in almost all organisms, including animals, protists, plants and prokaryotes. The cell biology of LDs, especially biogenesis, has attracted increasing attention in recent decades because of their important role in cellular lipid metabolism and other newly identified processes. Emerging evidence suggests that LD biogenesis is a highly coordinated and stepwise process in animals and yeasts, occurring at specific sites of the endoplasmic reticulum (ER) that are defined by both evolutionarily conserved and organism- and cell type-specific LD lipids and proteins. In plants, understanding of the mechanistic details of LD formation is elusive as many questions remain. In some ways LD biogenesis differs between plants and animals. Several homologous proteins involved in the regulation of animal LD formation in plants have been identified. We try to describe how these proteins are synthesized, transported to the ER and specifically targeted to LD, and how these proteins participate in the regulation of LD biogenesis. Here, we review current work on the molecular processes that control LD formation in plant cells and highlight the proteins that govern this process, hoping to provide useful clues for future research. [ABSTRACT FROM AUTHOR]

Aim: Myotonic dystrophy type 1 (DM1) is the second most common muscular dystrophy after Duchenne and is the most prevalent muscular dystrophy in adults. DM1 patients that participate in aerobic exercise training experience several physiological benefits concomitant with improved muscle mitochondrial function without alterations in typical DM1‐specific disease mechanisms, which suggests that correcting organelle health is key to ameliorate the DM1 pathology. However, our understanding of the molecular mechanisms of mitochondrial turnover and dynamics in DM1 skeletal muscle is lacking. Methods: Skeletal muscle tissue was sampled from healthy and DM1 mice under sedentary conditions and at several recovery time points following an exhaustive treadmill run. Results: We demonstrate that DM1 patients exhibit an imbalance in the transcriptional apparatus for mitochondrial turnover and dynamics in skeletal muscle. Additionally, DM1 mice displayed elevated expression of autophagy and mitophagy regulators. A single dose of exercise successfully enhanced canonical exercise molecular pathways and skeletal muscle mitochondrial biogenesis despite failing to alter the cellular pathology in DM1 mice. However, treadmill running stimulated coordinated organelle fusion and fission signaling, as well as improved alternative splicing of Optic atrophy 1. Exercise also evoked autophagy and mitophagy pathways in DM1 skeletal muscle resulting in the normalized expression of autophagy‐ and lysosome‐related machinery responsible for the clearance of dysfunctional organelles. Conclusion: Collectively, our data indicate that mitochondrial dynamics and turnover processes in DM1 skeletal muscle are initiated with a single dose of exercise, which may underlie the adaptive benefits previously documented in DM1 mice and patients. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) have various advantageous properties, including a small size, high biocompatibility, efficient cargo loading, and precise cell targeting ability, making them promising tools for therapeutic development. EVs have been increasingly explored for applications like drug delivery. However, due to limited cellular secretion rates of EVs, wide-scale clinical applications are not achievable. Therefore, substantial strategies and research efforts have been devoted to increasing cellular secretion rates of EVs. This review describes various studies exploring different methods to increase the cellular production of EVs, including the application of electrical stimulus, pharmacologic agents, electromagnetic waves, sound waves, shear stress, cell starvation, alcohol, pH, heat, and genetic manipulation. These methods have shown success in increasing EV production, but careful consideration must be given as many of these strategies may alter EV properties and functionalities, and the exact mechanisms causing the increase in cellular production of EVs is generally unknown. Additionally, the methods' effectiveness in increasing EV secretion may diverge with different cell lines and conditions. Further advancements to enhance EV biogenesis secretion for therapeutic development is still a significant need in the field. [ABSTRACT FROM AUTHOR]

Simple Summary: Exosomes are nanometer-sized vesicles released by different cells that are important in the normal functioning of the body. In cancer, exosomes have been found to promote tumor growth and metastasis by carrying functional biomolecules and acting on different target sites in the body. Understanding the mechanism by which cancers modulate exosome secretion is crucial to studying cancer biology and developing new therapeutic approaches. Herein, we summarize the biological processes involved in the generation of exosomes, and the factors affecting the targeting and internalization of exosomes. By outlining the mechanisms regulating exosome dynamics, we link exosome secretion with characteristics of cancer cells and suggest methods for improving future research. Exosomes are mediators of intercellular communication in normal physiology and diseases. While many studies have emerged on the function of exosomal cargoes, questions remain regarding the origin of these exosomes. The packaging and secretion of exosomes in different contexts modify exosomal composition, which may in turn impact delivery, uptake and cargo function in recipient cells. A mechanistic understanding of exosome biology is therefore crucial to investigating exosomal function in complex biological systems and to the development of novel therapeutic approaches. Here, we outline the steps in exosome biogenesis, including endosome formation, MVB formation, cargo sorting and extracellular release, as well as exosome absorption, including targeting, interaction with recipient cells and the fate of internalized exosomes. In addition to providing a framework of exosome dynamics, we summarize current evidence on major pathways and regulatory mechanisms. We also highlight the various mechanisms observed in cancer and point out directions to improve study design in exosome biology. Further research is needed to illuminate the relationship between exosome biogenesis and function, which will aid the development of translational applications. [ABSTRACT FROM AUTHOR]

Membrane lipids play vital roles in small extracellular vesicle (sEV) biogenesis. However, the function of various lipids in the biogenesis of sEVs is still poorly understood. Phosphoinositolphosphates (PIPs), a group of the most critical lipids in vesicle transport, can undergo rapid conversion in response to a variety of cell signals, which in turn influence the generation of vesicles. Due to the challenge in detecting the low amount of PIP content in biological samples, the function of PIPs in sEVs has been insufficiently investigated. Here, we employed an LC‐MS/MS method to detect the levels of PIPs in sEVs. We revealed phosphatidylinositol‐4‐phosphate (PI4P) was the main PI‐monophosphate in macrophage‐derived sEVs. The release of sEVs was regulated in a time‐dependent manner and correlated with the PI4P level during the lipopolysaccharide (LPS) stimulation. In terms of mechanism, within 10 h of LPS treatment, the LPS‐induced production of type I interferon inhibited the expression of PIP‐5‐kinase‐1‐gamma, which increased the PI4P content on multivesicular bodies (MVBs) and recruited RAB10, member RAS oncogene family, to promote sEV generation. When LPS stimulation was extended to 24 h, the heat shock protein family A member 5 (HSPA5) expression level was elevated. PI4P interacted with HSPA5 on the Golgi or endoplasmic reticulum away from MVBs, which disrupted the continuous fast sEV release. In conclusion, the present study demonstrated an inducible sEV release model response to LPS treatment. The inducible release may be due to PI4P regulating the generation of intraluminal vesicles secreted as sEVs. [ABSTRACT FROM AUTHOR]

Although differential transcription drives the development of multicellular organisms, the ultimate readout of a protein-coding gene is ribosome-dependent mRNA translation. Ribosomes were once thought of as uniform molecular machines, but emerging evidence indicates that the complexity and diversity of ribosome biogenesis and function should be given a fresh look in the context of development. This Review begins with a discussion of different developmental disorders that have been linked with perturbations in ribosome production and function. We then highlight recent studies that reveal how different cells and tissues exhibit variable levels of ribosome production and protein synthesis, and how changes in protein synthesis capacity can influence specific cell fate decisions. We finish by touching upon ribosome heterogeneity in stress responses and development. These discussions highlight the importance of considering both ribosome levels and functional specialization in the context of development and disease. [ABSTRACT FROM AUTHOR]

Telomere length is associated with the proliferative potential of cells. Telomerase is an enzyme that elongates telomeres throughout the entire lifespan of an organism in stem cells, germ cells, and cells of constantly renewed tissues. It is activated during cellular division, including regeneration and immune responses. The biogenesis of telomerase components and their assembly and functional localization to the telomere is a complex system regulated at multiple levels, where each step must be tuned to the cellular requirements. Any defect in the function or localization of the components of the telomerase biogenesis and functional system will affect the maintenance of telomere length, which is critical to the processes of regeneration, immune response, embryonic development, and cancer progression. An understanding of the regulatory mechanisms of telomerase biogenesis and activity is necessary for the development of approaches toward manipulating telomerase to influence these processes. The present review focuses on the molecular mechanisms involved in the major steps of telomerase regulation and the role of post-transcriptional and post-translational modifications in telomerase biogenesis and function in yeast and vertebrates. [ABSTRACT FROM AUTHOR]

Circular RNAs (circRNAs) are characterized by a covalent closed-loop structure with an absence of both 5' cap structure and 3' polyadenylated tail. Numerous studies have found that circRNAs play an important role in various diseases and have a variety of biological regulatory mechanisms, including acting as microRNA sponges, interacting with proteins, modulating the expression of related genes and translating into peptides or proteins. CircRNAs have also been used as biomarkers for a number of diseases, which could improve clinical practice. This review summarizes the most recent advances in biogenesis and knowledge of the biological functions of circRNAs as well as the related bioinformatics databases. We specifically describe developments in understanding of circRNA functions in the field of environmental exposure-induced diseases. Finally, we focus on potential clinical implications of circRNAs to facilitate their clinical transformation into disease treatment. [ABSTRACT FROM AUTHOR]

The continued integrity of biological systems depends on a balance between interdependent elements at the molecular, cellular, and organismal levels. This is particularly true for the generation of ribosomes, which influence almost every aspect of cell and organismal biology. Ribosome biogenesis (RiBi) is an energetically demanding process that involves all three RNA polymerases, numerous RNA processing factors, chaperones, and the coordinated expression of 79–80 ribosomal proteins (r-proteins). Work over the last several decades has revealed that the dynamic regulation of ribosome production represents a major mechanism by which cells maintain homeostasis in response to changing environmental conditions and acute stress. More recent studies suggest that cells and tissues within multicellular organisms exhibit dramatically different levels of ribosome production and protein synthesis, marked by the differential expression of RiBi factors. Thus, distinct bottlenecks in the RiBi process, downstream of rRNA transcription, may exist within different cell populations of multicellular organisms during development and in adulthood. This review will focus on our current understanding of the mechanisms that link the complex molecular process of ribosome biogenesis with cellular and organismal physiology. We will discuss diverse topics including how different steps in the RiBi process are coordinated with one another, how MYC and mTOR impact RiBi, and how RiBi levels change between stem cells and their differentiated progeny. In turn, we will also review how regulated changes in ribosome production itself can feedback to influence cell fate and function. [ABSTRACT FROM AUTHOR]

Non-coding RNAs have been excavated as important cardiac function modulators and linked to heart diseases. Significant advances have been obtained in illuminating the effects of microRNAs and long non-coding RNAs. Nevertheless, the characteristics of circular RNAs are rarely mined. Circular RNAs (circRNAs) are widely believed to participate in cardiac pathologic processes, especially in myocardial infarction. In this review, we round up the biogenesis of circRNAs, briefly describe their biological functions, and summarize the latest literature on multifarious circRNAs related to new therapies and biomarkers for myocardial infarction. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) are versatile, post-transcriptional regulators of gene expression. Canonical miRNAs are generated through the two-step DROSHA- and DICER-mediated processing of primary miRNA (pri-miRNA) transcripts with optimal or suboptimal features for DROSHA and DICER cleavage and loading into Argonaute (AGO) proteins, whereas multiple hairpin-structured RNAs are encoded in the genome and could be a source of non-canonical miRNAs. Recent advances in miRNA biogenesis research have revealed details of the structural basis of miRNA processing and cluster assistance mechanisms that facilitate the processing of suboptimal hairpins encoded together with optimal hairpins in polycistronic pri-miRNAs. In addition, a deeper investigation of miRNA–target interaction has provided insights into the complexity of target recognition with distinct outcomes, including target-mediated miRNA degradation (TDMD) and cooperation in target regulation by multiple miRNAs. Therefore, the coordinated or network regulation of both miRNA biogenesis and miRNA–target interaction is prevalent in miRNA biology. Alongside recent advances in the mechanistic investigation of miRNA functions, this review summarizes recent findings regarding the ordered regulation of miRNA biogenesis and miRNA–target interaction. [ABSTRACT FROM AUTHOR]

The human ether-a-go-go-related gene (hERG) K+ channel conducts a rapidly activating delayed rectifier K+ current (IKr), which is essential for normal electrical activity of the heart. Precise regulation of hERG channel biogenesis is critical for serving its physiological functions, and deviations from the regulation result in human diseases. However, the mechanism underlying the precise regulation of hERG channel biogenesis remains elusive. Here, by using forward genetic screen, we found that PATR-1, the Caenorhabditis elegans homolog of the yeast DNA topoisomerase 2-associated protein PAT1, is a critical regulator for the biogenesis of UNC-103, the ERG K+ channel in C. elegans. A loss-of-function mutation in patr-1 down-regulates the expression level of UNC-103 proteins and suppresses the phenotypic defects resulted from a gain-of function mutation in the unc-103 gene. Furthermore, downregulation of PATL1 and PATL2, the human homologs of PAT1, decreases protein levels and the current density of native hERG channels in SH-SY5Y cells and human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). Knockdown of PATL1 and PATL2 elongates the duration of action potentials in hiPSC-CMs, suggesting that PATL1 and PATL2 affect the function of hERG channels and hence electrophysiological characteristics in the human heart. Further studies found that PATL1 and PATL2 interact with TFIIE, a general transcription factor required for forming the RNA polymerase II preinitiation complex, and dual-luciferase reporter assays indicated that PATL1 and PATL2 facilitate the transcription of hERG mRNAs. Together, our study discovers that evolutionarily conserved DNA topoisomerase 2-associated proteins regulate the biogenesis of hERG channels via a transcriptional mechanism. [ABSTRACT FROM AUTHOR]

Lipid droplets, also known as oil bodies or lipid bodies, are plant organelles that compartmentalize neutral lipids as a hydrophobic matrix covered by proteins embedded in a phospholipid monolayer. Some of these proteins have been known for decades, such as oleosins, caleosins, and steroleosins, whereas a host of others have been discovered more recently with various levels of abundance on lipid droplets, depending on the tissue and developmental stage. In addition to a growing inventory of lipid droplet proteins, the subcellular machinery that contributes to the biogenesis and degradation of lipid droplets is being identified and attention is turning to more mechanistic questions regarding lipid droplet dynamics. While lipid droplets are mostly regarded as storage deposits for carbon and energy in lipid-rich plant tissues such as seeds, these organelles are present in essentially all plant cells, where they display additional functions in signaling, membrane remodeling, and the compartmentalization of a variety of hydrophobic components. Remarkable metabolic engineering efforts have demonstrated the plasticity of vegetative tissues such as leaves to synthesize and package large amounts of storage lipids, which enable future applications in bioenergy and the engineering of high-value lipophilic compounds. Here, we review the growing body of knowledge about lipid droplets in plant cells, describe the evolutionary similarity and divergence in their associated subcellular machinery, and point to gaps that deserve future attention. [ABSTRACT FROM AUTHOR]