Mitochondria-rich Cells Research Articles

SLC26A4-AP-2 mu2 interaction regulates SLC26A4 plasma membrane abundance in the endolymphatic sac.

Decreased presence or activity of human SLC26A4 at the plasma membrane is a common cause of hearing loss. SLC26A4 (Pendrin) is necessary for normal reabsorption of endolymph, the fluid bathing the inner ear. We identified the μ2 subunit of adaptor protein 2 (AP-2) complex required for clathrin-mediated endocytosis as a protein-partner of SLC26A4 involved in regulating its plasma membrane abundance. We showed that, in the endolymphatic sac, where fluid reabsorption occurs, SLC26A4 is localized along the apical microvilli of mitochondria-rich cells, in contact with the endolymph, and associated with clathrin-coated pits where μ2 and AP-2 are present. Based on SLC26A4 structure, the elements involved in SLC26A4-μ2 interaction were identified and validated experimentally, allowing modeling of this interaction at the atomic level. Pharmacological inhibition of clathrin-mediated endocytosis led to an increased plasma membrane abundance of hemagglutinin-tagged SLC26A4 virally or endogenously expressed in mitochondria-rich cells. These results indicate that the SLC26A4-μ2 interaction regulates SLC26A4 abundance at the apical surface of mitochondria-rich cells.

Hypoxia induces reversible gill remodeling in largemouth bass (Micropterus salmoides) through integrins-mediated cell adhesion

Gill remodeling is an important strategy for fish to cope with hypoxia, and many of the teleost possess this ability, but the underlying mechanism is not well understood. To investigate the mechanism of hypoxia-induced gill remodeling, largemouth bass (Micropterus salmoides) exposed to hypoxia (dissolved oxygen level: 2.0 ± 0.2 mg L−1) for 7 days, followed by 7 days of reoxygenation. Hypoxia tests were also performed on primary gill cells from largemouth bass. We found that hypoxia-induced gill remodeling increased the respiratory surface area of the gills. This change in gill morphology was reversible and recovered after reoxygenation. A reduction in the number of mucous cells and rearrangement of mitochondria-rich cells (MRCs) were observed during gill remodeling. After 7 days of reoxygenation, the number of mucous cells and the position of the MRCs were restored. Hypoxia resulted in a 2.92-fold increase in the number of primary gill cells that underwent migration over a 12-h period. The mRNA levels of nine integrin subunits (α1, α2, α5, α7, α8, α10, αL, β1 and β2) were significantly up-regulated after 12 h of hypoxia in vivo, and the changes in the expression of these subunits were consistent with the HIF-1α trend. Immunohistochemistry showed that integrin β1 protein levels were significantly increased and were abundantly expressed in the interlamellar cell mass after exposure to hypoxia. Taken together, the results of the present study demonstrated that changes in mucosal cells and MRCs play an important role in hypoxia-induced gill remodeling in largemouth bass and that these changes are regulated by integrins.

Multi-Biomarkers' Responses in Gills of Oreochromis niloticus Exposed to Glyphosate and Polyethylene Microplastic, Isolated and in Mixture.

Microplastics (MPs) and glyphosate-based herbicides (GBH) are among the most common contaminants in aquatic environments. In Brazilian rivers, both contaminants were found in elevated levels, leading to a high probability of their association, which can alter their individual effects and potentially intensify their toxicity. This study evaluated the isolated and combined effects of polyethylene microplastics (PE-MPs) and GBH on Oreochromis niloticus using multi-biomarkers of toxicity. The fish were subjected to a 96-h exposure period, with concentrations set based either isolated, PE-MPs group (5 mg L-1), GBH group (5 mg L-1), or in a group of associated contaminants (GAC), PE-MP + GBH (5 mg L-1 + 5 mg L-1). Toxicity effects were evaluated using biochemical, cytogenetic, hematological, and histopathological biomarkers. We observed change in erythrocyte parameters leading to macrocytic normochromic anemia in GAC. Leukocyte parameters indicate a nonspecific immunosuppression caused by the exposure of associated contaminants, besides the attempts to repair damage caused by PE-MPs. Histopathological markers indicate damage to tissues exposed to contaminants. Besides, there were morphophysiological adjustments on gills, with proliferation and hypertrophy of mitochondria-rich cells on GBH and GAC, besides epithelium ruptures, which were mostly present in the exposed groups. Therefore, this study indicates that PE-MPs and GBHs present toxic effects in O. niloticus with the used concentrations, intensified by the association of contaminants. Thus, multi-biomarkers were useful key to verify toxicity, providing data to the investigation of high levels of contaminant's mixture toxicity present in aquatic environments.

Effects of saline and alkaline stresses on the survival, growth, and physiological responses in juvenile mandarin fish (Siniperca chuatsi)

Saline-alkaline water is widely distributed and abundant worldwide. It plays a critical role in the advancement of the aquaculture and the comprehensive utilization of saline-alkaline resources. The mandarin fish (Siniperca chuatsi), a freshwater species with high economic value, and has potential for cultivation in such environments. We evaluated its tolerance to acute salinity and alkalinity, and investigated the growth and physiological changes under chronic saline and alkaline stress. Initially, the effects of acute salinity and alkalinity were estimated on mandarin fish (4.33 ± 0.31 g), and found that the LC50 for 96 h of salinity and alkalinity was 13.91 ppt and 13.45 mmol/L, respectively. Subsequently, over a 60-day period, we measured the survival, growth performance, and physiological responses in mandarin fish (22.53 ± 0.60 g) reared in freshwater (FW, the control group), saline water (SW; fixed salinity of 5 ppt) and alkaline water (AW; carbonate alkalinity of 8 mmol/L). The results indicated that neither SW nor AW group adversely affected survival rates, and growth performance in SW group was significantly superior to the FW group. Additionally, compared to the FW group， the AW group had a lower hepatosomatic index, while the SW group exhibited significantly higher meat content. In terms of physiological responses, the AW group showed elevated V-H+-ATPase (VHA) activity, whereas the SW group had decreased prolactin (PRL) levels. Furthermore, the mitochondria-rich cells (MRCs) in mandarin fish underwent morphological adaptations to saline and alkaline stress, indicating their role in osmoregulation and acid-base balance. Our results suggested that the mandarin fish demonstrated good tolerance to both salinity and alkalinity, indicating suitability for breeding in low saline and alkaline water. This research contributes to a broader understanding of saline and alkaline tolerance in aquaculture species and provides theoretical support for the cultivation of mandarin fish in saline-alkaline water. Moreover, the results of this study suggested that saline-alkaline areas and agricultural irrigation water in the world could be successfully utilized for sustainable aquaculture.

Morphological, Genetic, and Physiological Effects of Nutrient Manipulation on a Colonial Marine Hydroid.

AbstractThe availability of environmental nutrients is an existential constraint for heterotrophic organisms and is thus expected to impact numerous biochemical and physiological features. The continuously proliferative polyp stage of colonial hydroids provides a useful model to study these features, allowing genetically identical replicates to be compared. Two groups of colonies of Eirene sp., defined by different feeding treatments, were grown by explanting the same founder colony onto cover glass. Colonies of both treatments were allowed to grow continuously by explanting them onto new cover glass as they reached the edge of the existing surface. The nutrient-abundant polyps grew faster and produced more clumped or "sheet-like" colonies. Compared to the founder colony, the nutrient-abundant colonies exhibited more mutations (i.e., single-nucleotide polymorphisms) than the nutrient-scarce colonies. Nevertheless, these differences were not commensurate with the differences in growth. Using a polarographic electrode, we found that the nutrient-abundant colonies exhibited lower rates of oxygen uptake relative to total protein. The probe 2',7'-dichlorodihydrofluorescein diacetate and fluorescent microscopy allowed visualization of the mitochondrion-rich cells at the base of the polyps and showed that the nutrient-abundant colonies exhibited greater amounts of reactive oxygen species than the nutrient-scarce colonies. Parallels to the Warburg effect-aerobic glycolysis, diminished oxygen uptake, and lactate secretion-found in human cancers and other proliferative cells may be suggested. However, little is known about anaerobic metabolism in cnidarians. Examination of oxygen uptake suggests an anaerobic threshold at a roughly 1-mg/L oxygen concentration. Nutrient-abundant colonies may respond more dramatically to this threshold than nutrient-scarce colonies.

Osmoregulatory and immunological role of new canceled cells: Mitochondrial rich cells and its future perspective: A concise review.

Mitochondrial-rich cells (MRCs) are one of the most significant canceled type of epithelial cells. Morphologically these cells are totally different from other epithelial cells. These cells primarily implicated in sea-water and fresh-water adaptation, and acid-base regulation. However, in this review paper, we explored some of the most intriguing biological and immune-related functional developmental networks of MRCs. The main pinpoint, MRCs perform a dynamic osmoregulatory and immunological functional role in the gut and male reproductive system. The Na+/K+_ATPase (NKA) and Na+/K+/2Cl cotransporter (NKCC) are key acidifying proteins of MRCs for the ion-transporting function for intestinal homeostasis and maintenance of acidifying the luminal microenvironment in the male reproductive system. Further more importantly, MRCs play a novel immunological role through the exocrine secretion of nano-scale exosomes and multivesicular bodies (MVBs) pathway, which is very essential for sperm maturation, motility, acrosome reaction, and male sex hormones, and these an essential events to produce male gametes with optimal fertilizing ability. This effort is expected to promote the novel immunological role of MRCs, which might be essential for nano-scale exosome secretion.

What a Neurosurgeon Should Know about the Endolymphatic Sac: Part 1–Anatomy and Physiology

Abstract Objective To describe the microsurgical anatomy and the physiology of the endolymphatic sac (ES) that a neurosurgeon should know. Methods Review of previous studies from 1927 to 2021, from basic and translational research using human and animal ES tissue or cells, as well as previous reviews about the subject. The present article is divided into three parts. In this first part, we review the microsurgical anatomy and physiology of the ES. Results The ES is a structure situated in the inner ear, together with the cochlea, the vestibular system, and other structures. Differently from its adjacent structures, the ES does not have a specialized epithelium; instead, it has mitochondria-rich cells and ribosomal-rich cells, which are responsible for ionic transportation and secretory activity. Apart from these functions, the ES is also responsible for homeostasis regulation of the inner ear, endolymphatic fluid volume control, immune response, elimination of inner ear cellular debris and floating otoconia, regulation of membranous labyrinth pressure, acid/basic transport, and secretion of substances. Its anatomy is not very variable, since in most studies no more than 20mm separates the location of the ES in the samples, in any direction. Conclusion The human ES has vital functions in the inner ear, and its anatomy is rarely variable. Knowing that, and the importance of this area for neurosurgery, the present study elucidates the exact location of the ES and the lost functions that a lesion in this structure must cause.

Morphological Changes and Ionic Regulations in Gills of Euryhaline Fish during Osmoregulation: A Review

Euryhaline fish can thrive in both freshwater habitat and saltwater conditions. The migration from one salinity range to another involves the use of various organs like gills, kidneys and intestine which are all osmoregulatory in function. Among them, gills are considered to be the most important osmoregulatory organ with multiple functions and various ion transporters which helps the fish to survive the adverse environmental conditions. The gills have various cells involved in osmoregulation and mainly the MR (Mitochondria Rich) cells which have many transporters for intake and excretion of ions according to the environmental salinity. This review briefs the studies of various researchers on the morphological changes and the ionic variations in the fish gills which helps in acclimating them to different salinities.

Glucocorticoid Receptor Mediates Cortisol Regulation of Glycogen Metabolism in Gills of the Euryhaline Tilapia (Oreochromis mossambicus)

In this study, we investigated the effects of cortisol on the regulation of the glycogen metabolism biomarkers glycogen synthase (GS) and glycogen phosphorylase (GP) in the glycogen-rich cells of the gills of tilapia (Oreochromis mossambicus). In the gills of tilapia, GP, GS, and glycogen were immunocytochemically colocalized in a specific group of glycogen-rich cells adjacent to the gills’ main ionocytes and mitochondria-rich cells. Cortisol plays a vital role in the regulation of physiological functions in animals, including energy metabolism, respiration, immune response, and ion regulation. However, no studies have elucidated the mechanisms regulating cortisol and glycogen-rich cells in the gills. Therefore, we treated tilapia larvae with exogenous cortisol and a glucocorticoid receptor (GR) antagonist to investigate the regulatory mechanisms between cortisol and glycogen-rich cells in the gills. Our results showed that cortisol promoted the expression of gill glycogen phosphorylase isoform (GPGG) mRNA via GR, whereas the GS gene expression remained unaffected. We also found that GR mRNA was colocalized with some glycogen-rich cells in the gills, further confirming our hypothesis that cortisol directly acts on glycogen-rich cells in the gills of tilapia and regulates glycogen metabolism by promoting GPGG mRNA expression.

Transcriptomic profile comparison reveals conservation of ionocytes across multiple organs

Single-cell RNA sequencing has recently led to the identification of a flurry of rare, new cell types, such as the CFTR-high ionocytes in the airway epithelium. Ionocytes appear to be specifically responsible for fluid osmolarity and pH regulation. Similar cells exist in multiple other organs and have received various names, including intercalated cell in the kidney, mitochondria-rich cell in the inner ear, clear cell in the epididymis, and ionocyte in the salivary gland. Here, we compare the previously published transcriptomic profile of cells expressing FOXI1, the signature transcription factor expressed in airway ionocytes. Such FOXI1+ cells were found in datasets representing human and/or murine kidney, airway, epididymis, thymus, skin, inner ear, salivary gland, and prostate. This allowed us to assess the similarities between these cells and identify the core transcriptomic signature of this ionocyte ‘family’. Our results demonstrate that, across all these organs, ionocytes maintain the expression of a characteristic set of genes, including FOXI1, KRT7, and ATP6V1B1. We conclude that the ionocyte signature defines a class of closely related cell types across multiple mammalian organs.

Effects of sublethal concentrations of cypermethrin on the gills of Lake Van Fish (Alburnus tarichi)

ABSTRACT Cypermethrin is one of the most commonly used pesticides in the Lake Van Basin of Turkey. In this study, the effects of a sublethal dose (0.05 µg/L) of cypermethrin for 96 h on the gills of Lake Van fish (Alburnus tarichi), the only vertebrate species living in Lake Van, were investigated. Levels of heat shock protein 70 (HSP70), Na,K-ATPase, and DNA damage (8-OHdG) were determined immunohistochemically in the gills. In addition, changes in gill mucous cells and histopathological changes in gill tissues after 96 h were investigated. At the end of the cypermethrin administration, an increase was observed in the numbers of mitochondria-rich cells, HSP70-positive cells, and 8-OHdG-positive cells in the gills. A decrease in both the number and volume of mucous cells was detected. The expansion of blood vessels, aneurysms, lamellar lifting, hypertrophy, lamellar fusion, and necrosis were observed in gill tissues. It was concluded that the 96-h sublethal application of cypermethrin caused stress, deterioration of osmoregulation, DNA damage, and histopathological damage in the gills of Lake Van fish.

Single-cell transcriptomic analysis of neuroepithelial cells and other cell types of the gills of zebrafish (Danio rerio) exposed to hypoxia

The fish gill is a multifunctional organ involved in numerous physiological processes, such as gas exchange and sensing of hypoxia by respiratory chemoreceptors, called neuroepithelial cells (NECs). Many studies have focused on zebrafish (Danio rerio) to investigate the structure, function and development of the gills, yet the transcriptomic profile of most gill cells remains obscure. We present the results of a comprehensive transcriptomic analysis of the gills of zebrafish using single-cell RNA sequencing (scRNA‐seq). Gill cells from ETvmat2:EGFP zebrafish were individually labelled before scRNA‐seq library construction using 10× Genomics Chromium technology. 12,819 cells were sequenced with an average depth of over 27,000 reads per cell. We identified a median of 485 genes per cell and 16 cell clusters, including NECs, neurons, pavement cells, endothelial cells and mitochondrion-rich cells. The identity of NECs was confirmed by expression of slc18a2, encoding the vesicular monoamine transporter, Vmat2. Highly differentially-expressed genes in NECs included tph1a, encoding tryptophan hydroxylase, sv2 (synaptic vesicle protein), and proteins implicated in O2 sensing (ndufa4l2a, cox8al and epas1a). In addition, NECs and neurons expressed genes encoding transmembrane receptors for serotonergic, cholinergic or dopaminergic neurotransmission. Differential expression analysis showed a clear shift in the transcriptome of NECs following 14 days of acclimation to hypoxia. NECs in the hypoxia group showed high expression of genes involved in cell cycle control and proliferation. The present article provides a complete cell atlas for the zebrafish gill and serves as a platform for future studies investigating the molecular biology and physiology of this organ.

Increased level of free-circulating MtDNA in maintenance hemodialysis patients: Possible role in systemic inflammation.

BackgroundMitochondrial DNA (MtDNA) exposed to the extracellular space due to cell death and stress has immunostimulatory properties. However, the clinical significance of circulating MtDNA in maintenance hemodialysis (MHD) patients and the precise mechanism of its emergence have yet to be investigated.MethodsThis cross‐sectional study consisted of 52 MHD patients and 32 age‐ and sex‐matched healthy controls. MHD patients were further categorized into high and low circulating cell‐free MtDNA (ccf‐MtDNA) groups based on the median value. Copy number of MtDNA was quantified using TaqMan‐based qPCR. Plasma cytokines were measured using ELISA kits. Reactive oxygen species (ROS) and mitochondrial membrane potential (Δψm) in peripheral blood mononuclear cells (PBMCs) were detected using DCFH‐DA or JC‐1 staining.ResultsThe copy numbers of ccf‐MtDNA in patients with MHD were higher than those in healthy controls, and these alterations were correlated with changes of cytokines TNF‐α and IL‐6. Adjusted model in multivariate analysis showed that the presence of anuria and longer dialysis vintage were independently associated with higher levels of ccf‐MtDNA. Meanwhile, although not statistically significant, an inverse correlative trend between urinary MtDNA and ccf‐MtDNA was observed in patients with residual urine. Afterward, using PBMCs as surrogates for mitochondria‐rich cells, we found that patients in the high ccf‐MtDNA group exhibited a significantly higher ROS production and lower Δψm in cells.ConclusionsOur data suggested that changes in ccf‐MtDNA correlate with the degree of inflammatory status in MHD patients, and that the excessive MtDNA may be caused by mitochondrial dysfunction and reduced urinary MtDNA excretion.

Altered levels of circulating mitochondrial DNA in elderly people with sarcopenia: Association with mitochondrial impairment.

Age-related chronic inflammatory process is often referred to as "inflammaging", which had been described in several human disorders, including sarcopenia. Recently, mitochondrial DNA (MtDNA) has moved into the spotlight as a "damage-associated molecular pattern" (DAMP) agent that can potentially elicit inflammation. Yet, the roles of this mitochondrial DAMP have never been investigated in sarcopenia. Cross-sectional study. From January 2021 to June 2021, elderly outpatients ≥65years and able to finish a comprehensive geriatric assessment were recruited in our study. Participants were divided into sarcopenia group and non-sarcopenia group according to the DXA scans and grip strength. Genomic DNA was extracted from plasma and peripheral blood mononuclear cells (PBMCs), and changes in MtDNA copies were quantified using qPCR. Plasma levels of inflammatory cytokines were measured using ELISA kits. Loss of mitochondrial membrane potential (Δψm) in PBMCs was analyzed using the fluorescent probe JC-1. Participants with sarcopenia were significantly older, more likely to be physically inactive, and had higher levels of circulating cell-free MtDNA (ccf-MtDNA) (all p<0.05). After adjusting for potential confounders, ccf-MtDNA was independently associated with increased odds of sarcopenia (adjusted odds ratio (AOR), 1.576; p=0.009). Furthermore, ROC curve analysis showed that ccf-MtDNA had an area under the curve (AUC) of 0.726 (95% CI: 0.607-0.844; p<0.05) for distinguishing elderly subjects from sarcopenia. Compared with non-sarcopenia subjects, plasma interleukin (IL)-6 and IL-8 were significantly higher in sarcopenia subjects (both p<0.05). By performing a correlation test, it was found that the level of IL-6 was positively correlated with ccf-MtDNA (r=0.301; p<0.05). Then, PBMCs were used as surrogates for mitochondria-rich cells, and the results showed that the relative amplification of MtDNA in PBMCs was significantly reduced (p<0.05), whereas the depolarization of Δψm was significantly increased in sarcopenia subjects (p<0.05). Taken together, our data suggested that circulating MtDNA might be a novel and important source of inflammatory stimuli potentially relevant for sarcopenia in elderly people, and this would provide an attractive therapeutic target to improve this disease.

FOXI1 Promotes Expression of V‐ATPase and GPR116 in M‐1 Cells

G protein‐coupled receptors (GPCRs) are a diverse family of integral membrane proteins that have significant roles in numerous physiological systems. We previously reported that GPR116 (ADGRF5), an adhesion‐class GPCR, is a critical regulator of vacuolar‐type H+‐ATPase (V‐ATPase) surface expression in A‐type intercalated cells (AICs) in mouse kidney cortical collecting ducts. The V‐ATPase is a multi‐subunit proton pump that localizes to the plasma membrane in specialized acid‐secreting epithelial cells. FOXI1 is a transcription factor that regulates V‐ATPase expression in ICs and other mitochondria‐rich cells. Recently, FOXI1 was identified as a key regulator of CFTR‐rich pulmonary ionocytes which express both V‐ATPase and GPR116. Therefore, we hypothesized that FOXI1 is a transcription factor in AICs that upregulates V‐ATPase as well as GPR116. To test this hypothesis, we cloned FOXI1 from whole mouse kidney into a pME18s expression vector (pFOXI1). Transfection with pFOXI1 significantly increased GPR116 expression (qPCR) in M‐1 mouse cortical collecting duct cells (n=3, ΔCt ±SEM: untransfected = 13.8±0.6, pFoxi1 = 10.7±0.2, p&lt;0.05), but not in HEK293T cells (n=3, not significant). RNA‐scope hybridization on murine kidney sections and pFOXI1‐transfected M‐1 cells revealed colocalization of FOXI1 and GPR116 mRNA in the same cell. Treating pFOXI1‐transfected M‐1 cells with a synthetic agonist peptide for GPR116 results in an increase of [Ca2+]iin a subset of cells (n=3, ΔF340/380 ±SEM: pFoxi1 = 0.296±0.017). Internal calcium mobilization is never seen with the agonist peptide in untransfected control cells, indicating that pFOXI1 is sufficient for the production of physiologically responsive GPR116 on the cell surface (n=3, ΔF340/380±SEM: untransfected = 0 ±0.0009). Moreover, only M‐1 cells transfected with pFOXI1 express GPR110 (ADGRF1), an adhesion‐GPCR with unknown function in the kidney, as well as three V‐ATPase subunits, ATP6V1B1, ATP6V1G3, ATP6V0D2, indicating a larger transcriptional program initiated by pFOXI1 (n=3, untransfected: Ct ~ 40 for all genes, pFoxi1 ΔCt±SEM: ADGRF1 = 13.2±0.21, ATP6V1B1 = 11.4±0.3, ATP6V1G3 = 10±0.1, ATP6V0D2 = 12.1±0.03). Additionally, these pFOXI1 cells also upregulate the expression of SLC26A4 (pendrin), a known marker of B‐type intercalated cells, suggesting that FOXI1‐driven regulation is upstream of AIC fate determination (n=3, ΔCt ± SEM: untransfected = 19.3±0.7, pFoxi1 = 16.1±0.2, p&lt;0.01). These data reveal that FOXI1 upregulates both GPR116 and V‐ATPase in M‐1 cells, generating IC‐like cells. Finally, our study suggests that GPR116 may be a universal and genetically‐coded regulator of V‐ATPase surface expression in FOXI1‐positive cells.

Renal Toxicity of Tenofovir: Narrative Review

Tenofovir is a reverse-transcriptase inhibitor based on acyclic nucleotide analogs. Tenofovir is a drug that is often used in treating HIV infection and has also been approved for treating infection by the hepatitis B virus. Despite the fact that its renal safety has been demonstrated in cell culture and clinical trials, clinical use and in vivo animal studies have shown its association with a low, but important, risk of kidney injury. Tenofovir accumulation in these mitochondria-rich cells is explained by proximal tubular cell secretion. Proximal tubular cell dysfunction is a symptom of Tenofovir nephrotoxicity, which might be the leading cause of acute renal injury or chronic diseases of the kidney. A review of articles is performed using keywords related to the topic in the databases of Google Scholar and PubMed, and 54 papers have been included, which were case studies, cross-sectional studies, and in vivo animal studies from 2004 up to 2021. The review aims at explaining the interaction of Tenofovir with kidney tubules, an association of genetic polymorphism, clinical features of Tenofovir-induced renal toxicity, potential mechanisms of Tenofovir-induced renal toxicity, its predisposing conditions and factors, and finally, some proposed strategies and agents to monitor and manage Tenofovir-induced nephrotoxicity.

Transcriptome profiles revealed high- and low-salinity water altered gill homeostasis in half-smooth tongue sole (Cynoglossus semilaevis)

Salinity is an important environmental factor that affects fish growth, development, and reproduction. As euryhaline fish, half-smooth tongue sole (Cynoglossus semilaevis) are a suitable species for deciphering the salinity adaptation mechanism of fish; however, the molecular mechanisms underlying low- and high-salinity responses remain unclear. In this study, RNA-seq was applied to characterize the genes and regulatory pathways involved in C. semilaevis gill responses to high- (32 ppt), low- (8 ppt), and control-salinity (24 ppt) water. Gills were rich in mitochondria-rich cells (MRCs) in high salinity. Compared with control, 2137 and 218 differentially expressed genes (DEGs) were identified in low and high salinity, respectively. The enriched functions of most DEGs were metabolism, ion transport, regulation of cell cycle, and immune response. The DEGs involved in oxidative phosphorylation, citrate cycle, and fatty acid metabolism were down-regulated in low salinity. For ion transport, high and low salinity significantly altered the expressions of prlr, ca12, and cftr. In cell cycle arrest and cellular repair, gadd45b, igfbp5, and igfbp2 were significantly upregulated in high and low salinity. For immune response, il10, il34, il12b, and crp increased in high and low salinity. Our findings suggested that alterations in material and energy metabolism, ions transport, cell cycle arrest, cellular repair, and immune response, are required to maintain C. semilaevis gill homeostasis under high and low salinity. This study provides insight into the divergence of C. semilaevis osmoregulation mechanisms acclimating to high and low salinity, which will serve as reference for the healthy culture of C. semilaevis.

Uncovering the molecular identity of cardiosphere-derived cells (CDCs) by single-cell RNA sequencing

Cardiosphere-derived cells (CDCs) generated from human cardiac biopsies have been shown to have disease-modifying bioactivity in clinical trials. Paradoxically, CDCs’ cellular origin in the heart remains elusive. We studied the molecular identity of CDCs using single-cell RNA sequencing (sc-RNAseq) in comparison to cardiac non-myocyte and non-hematopoietic cells (cardiac fibroblasts/CFs, smooth muscle cells/SMCs and endothelial cells/ECs). We identified CDCs as a distinct and mitochondria-rich cell type that shared biological similarities with non-myocyte cells but not with cardiac progenitor cells derived from human-induced pluripotent stem cells. CXCL6 emerged as a new specific marker for CDCs. By analysis of sc-RNAseq data from human right atrial biopsies in comparison with CDCs we uncovered transcriptomic similarities between CDCs and CFs. By direct comparison of infant and adult CDC sc-RNAseq data, infant CDCs revealed GO-terms associated with cardiac development. To analyze the beneficial effects of CDCs (pro-angiogenic, anti-fibrotic, anti-apoptotic), we performed functional in vitro assays with CDC-derived extracellular vesicles (EVs). CDC EVs augmented in vitro angiogenesis and did not stimulate scarring. They also reduced the expression of pro-apoptotic Bax in NRCMs. In conclusion, CDCs were disclosed as mitochondria-rich cells with unique properties but also with similarities to right atrial CFs. CDCs displayed highly proliferative, secretory and immunomodulatory properties, characteristics that can also be found in activated or inflammatory cell types. By special culture conditions, CDCs earn some bioactivities, including angiogenic potential, which might modify disease in certain disorders.

Physiological, morphological and transcriptomic responses of Tibetan naked carps (Gymnocypris przewalskii) to salinity variations

Gymnocypris przewalskii is a native cyprinid fish that dwells in the Lake Qinghai with salinity of 12–13‰. It migrates annually to the freshwater rivers for spawning, experiencing the significant changes in salinity. In the present study, we performed the physiological, morphological and transcriptomic analyses to understand the osmoregulation in G. przewalskii. The physiological assay showed that the osmotic pressure of G. przewalskii was almost isosmotic to the brackish lake water. The low salinity reduced its ionic concentrations and osmotic pressure. The plasticity of gill microstructure was linked to the salinity variations, including the presence of mucus and intact tight junctions in brackish water and the development of the mitochondria-rich cells and the loosened tight junctions in freshwater. RNA-seq analysis identified 1926 differentially expressed genes, including 710 and 1216 down- and up-regulated genes in freshwater, which were enriched in ion transport, cell-cell adhesion, and mucus secretion. Genes in ion uptake were activated in low salinity, and mucus pathways and tight junction showed the higher transcription in brackish water. The isosmoticity between the body fluid and the environment suggested G. przewalskii was in the metabolic-saving condition in the brackish water. The decreased salinity disrupted this balance, which activated the ion uptake in freshwater to maintain osmotic homeostasis. The gill remodeling was involved in this process through the development of the mitochondria-rich cells to enhance ion uptake. The current finding provided insights into the potential mechanisms of G. przewalskii to cope with salinity alteration.

Renal Oncocytoma: The Diagnostic Challenge to Unmask the Double of Renal Cancer.

Renal oncocytoma represents the most common type of benign neoplasm that is an increasing concern for urologists, oncologists, and nephrologists due to its difficult differential diagnosis and frequent overtreatment. It displays a variable neoplastic parenchymal and stromal architecture, and the defining cellular element is a large polygonal, granular, eosinophilic, mitochondria-rich cell known as an oncocyte. The real challenge in the oncocytoma treatment algorithm is related to the misdiagnosis due to its resemblance, at an initial radiological assessment, to malignant renal cancers with a completely different prognosis and medical treatment. Unfortunately, percutaneous renal biopsy is not frequently performed due to the possible side effects related to the procedure. Therefore, the majority of oncocytoma are diagnosed after the surgical operation via partial or radical nephrectomy. For this reason, new reliable strategies to solve this issue are needed. In our review, we will discuss the clinical implications of renal oncocytoma in daily clinical practice with a particular focus on the medical diagnosis and treatment and on the potential of novel promising molecular biomarkers such as circulating microRNAs to distinguish between a benign and a malignant lesion.