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Background: Beetroot juice (BRJ) supplementation has been shown to increase sports performance under hypoxic conditions and to improve athletes’ recovery. Objectives: In the present study, we aimed to investigate the effect of acute BRJ supplementation on slalom (SL) run performance and muscle soreness (MS) in Alpine skiers at moderate to high altitudes. Methods: Ten male Alpine skiers received 220 mL of BRJ (8.9 mmol/L nitrate) or placebo (PLA) in 2 sessions with a 7-d wash out interval in a randomized, crossover, PLA-controlled, double-blind study. The 90-s box jump (BJ90), agility hexagonal obstacle jump (Hex Jump), and wall-sit tests were measured before on-hill SL runs in both sessions. After the functional tests, SL run performance was measured by time to complete 2 runs on the SL course; immediately after each SL run, the rating of perceived exertion (RPE) was recorded. In addition, perceived MS was recorded using the visual analog scale at 12, 24, and 48 h after the SL runs. Results: The data were meticulously analyzed using 2-way repeated measures analysis of variance and paired t tests with significance set at P < 0.05. The findings were significant, indicating that compared with PLA, BRJ notably improved wall-sit and BJ90 performances (P < 0.05), while a substantial reduction was observed in RPE, Hex Jump, and MS (P < 0.05). A 1.74% shorter time to complete SL runs was observed in the BRJ group compared with the PLA group; however, there were no significant differences between the PLA and BRJ groups (P > 0.05). Conclusions: These results underscore the potential of BRJ supplementation to enhance sports performance and reduce MS in Alpine skiers under hypoxic conditions.

Adipose-derived mesenchymal stem cells (ASCs) have the potential to differentiate into bone, cartilage, fat, and neural cells and promote tissue regeneration and healing. It is known that they can have variable responses to hypoxic conditions. In the present study, we aimed to explore diverse changes in the cells and secretome of ASCs under a hypoxic environment over time and to present the possibility of ASCs as therapeutic agents from a different perspective. The expression differences of proteins between normoxic and hypoxic conditions (6, 12, or 24 h) were specifically investigated in human ASCs using 2-DE combined with MALDI-TOF MS analysis, and secreted proteins in ASC-derived conditioned media (ASC-derived CM) were examined by an adipokine array. In addition, genetic and/or proteomic interactions were assessed using a DAVID and miRNet functional annotation bioinformatics analysis. We found that 64 and 5 proteins were differentially expressed in hypoxic ASCs and in hypoxic ASC-derived CM, respectively. Moreover, 7 proteins among the 64 markedly changed spots in hypoxic ASCs were associated with bone-related diseases. We found that two proteins, cathepsin D (CTSD) and cathepsin L (CTSL), identified through an adipokine array independently exhibited significant efficacy in promoting osteocyte differentiation in bone-marrow-derived mesenchymal stem cells (BM-MSCs). This finding introduces a promising avenue for utilizing hypoxia-preconditioned ASC-derived CM as a potential therapeutic approach for bone-related diseases. [ABSTRACT FROM AUTHOR]

Hypoxic environment is known as one of the critical factors in various physiological/pathological processes. It is imperative to recapitulate oxygen level in microscale for human physiology/pathology induced by hypoxia. Herein, we propose an oxygen-regulating system that can be applied to in vitro tissue models. We fabricated a microdevice with a gas-permeable membrane, allowing oxygen diffusion without direct contact to cells. We verified the formation of oxygen level less than 2% O₂ concentration inside the device through computational simulation and experiments. H9c2 heart myoblasts were exposed to hypoxic condition in the device, and their cell viability were investigated. We anticipate that our system will be integrated with a platform to study hypoxia-induced human physiology and pathology as an efficient oxygen-regulating system.

Hypoxic environment is known as one of the critical factors in various physiological/pathological processes. It is imperative to recapitulate oxygen level in microscale for human physiology/pathology induced by hypoxia. Herein, we propose an oxygen-regulating system that can be applied to in vitro tissue models. We fabricated a microdevice with a gas-permeable membrane, allowing oxygen diffusion without direct contact to cells. We verified the formation of oxygen level less than 2% O₂ concentration inside the device through computational simulation and experiments. H9c2 heart myoblasts were exposed to hypoxic condition in the device, and their cell viability were investigated. We anticipate that our system will be integrated with a platform to study hypoxia-induced human physiology and pathology as an efficient oxygen-regulating system.

Availability of oxygen plays an important role in tissue organization and cell-type specific metabolism. It is, however, difficult to analyze hypoxia-related adaptations in vitro because of inherent limitations of experimental model systems. In this study, we establish a microfluidic tissue culture protocol to generate hypoxic gradients in vitro, mimicking the conditions found in the liver acinus. To accomplish this, four microfluidic chips, each containing two chambers, were serially connected to obtain eight interconnected chambers. HepG2 hepatocytes were uniformly seeded in each chamber and cultivated under a constant media flow of 50 µL/h for 72 h. HepG2 oxygen consumption under flowing media conditions established a normoxia to hypoxia gradient within the chambers, which was confirmed by oxygen sensors located at the inlet and outlet of the connected microfluidic chips. Expression of Hif1α mRNA and protein was used to indicate hypoxic conditions in the cells and albumin mRNA and protein expression served as a marker for liver acinus-like zonation. Oxygen measurements performed over 72 h showed a change from 17.5% to 15.9% of atmospheric oxygen, which corresponded with a 9.2% oxygen reduction in the medium between chamber1 (inlet) and 8 (outlet) in the connected microfluidic chips after 72 h. Analysis of Hif1α expression and nuclear translocation in HepG2 cells additionally confirmed the hypoxic gradient from chamber1 to chamber8. Moreover, albumin mRNA and protein levels were significantly reduced from chamber1 to chamber8, indicating liver acinus zonation along the oxygen gradient. Taken together, microfluidic cultivation in interconnected chambers provides a new model for analyzing cells in a normoxic to hypoxic gradient in vitro. By using a well-characterized cancer cell line as a homogenous hepatocyte population, we also demonstrate that an approximate 10% reduction in oxygen triggers translocation of Hif1α to the nucleus and reduces albumin production. [ABSTRACT FROM AUTHOR]

The hypoxic environment is a substantial factor in maintenance, proliferation, and differentiation of the cell cultures. Low oxygen is known as a potent chondrogenesis stimulus in stem cells that is important for clinical application and engineering of functional cartilage. Hypoxia can potentially induce angiogenesis process by secretion of cytokines. This systematic review goal is to discover the effect of hypoxic condition on tendon/ ligament culture and the best oxygen level of hypoxia for in vitro and in vivo studies. We included 21 articles. A comprehensive review of this database confirms that the hypoxic condition is a substantial factor in the maintenance, proliferation, and differentiation of ligament/tendon cultures. Cell proliferation in the severe hypoxic (oxygen concentration of 1%) group at 24 h postcultivation was considered significant, but cell proliferation was markedly inhibited in the severe hypoxic group after 48 h.

Abstract Background Improved chondrogenic differentiation of mesenchymal stem cells (MSCs) by genetic regulation is a potential method for regenerating articular cartilage. MiR-127-5p has been reported to promote cartilage differentiation of rat bone marrow MSCs (rMSCs); however, the regulatory mechanisms underlying hypoxia-stimulated chondrogenic differentiation remain unknown. Methods rMSCs were induced to undergo chondrogenic differentiation under normoxic or hypoxic conditions. Expression of lncRNA DNM3OS, miR-127-5p, and GREM2 was detected by quantitative real-time PCR. Proteoglycans were detected by Alcian blue staining. Western blot assays were performed to examine the relative levels of GREM2 and chondrogenic differentiation related proteins. Luciferase reporter assays were performed to assess the association among DNM3OS, miR-127-5p, and GREM2. Results MiR-127-5p levels were upregulated, while DNM3OS and GREM2 levels were downregulated in rMSCs induced to undergo chondrogenic differentiation, and those changes were attenuated by hypoxic conditions (1% O2). Further in vitro experiments revealed that downregulation of miR-127-5p reduced the production of proteoglycans and expression of chondrogenic differentiation markers (COL1A1, COL2A1, SOX9, and ACAN) and osteo/chondrogenic markers (BMP-2, p-SMAD1/2). MiR-127-5p overexpression produced the opposite results in rMSCs induced to undergo chondrogenic differentiation under hypoxic conditions. GREM2 was found to be a direct target of miR-127-5p, which was suppressed in rMSCs undergoing chondrogenic differentiation. Moreover, DNM3OS could directly bind to miR-127-5p and inhibit chondrogenic differentiation of rMSCs via regulating GREM2. Conclusions Our study revealed a novel molecular pathway (DNM3OS/miR-127-5p/GREM2) that may be involved in hypoxic chondrogenic differentiation.

Neuronal death is the main cause of nerve function impairment after spinal cord injury (SCI). Exosome-based therapy has become a novel strategy for tissue injury repair. We designed a method to treat SCI using exosomes secreted by adipose tissue–derived stromal cells (ADSCs) under hypoxic conditions. We established a neuronal oxygen-glucose deprivation and reperfusion (OGD/R) model in vitro to simulate the hypoxic environment after SCI. We observed that exosomes derived from hypoxia-conditioned ADSCs (Hypo-exo) significantly reduced neuronal apoptosis after OGD. By establishing a rat SCI model, we found that Hypo-exo can significantly reduce the formation of cavities in the injured area and improve the functional recovery of the hindlimbs of rats after injury. To explore the molecular mechanism, we conducted microRNA sequencing analysis of exosomes. Through real-time polymerase chain reaction, dual luciferase reporter assays and signaling pathway chip analysis, we determined that miR-499a-5p regulates the JNK3/c-jun-apoptotic signaling pathway by targeting JNK3. Further, we verified the expression of the key proteins in the JNK3/c-jun-apoptotic signaling pathway by immunofluorescence and Western blotting. These results support the hypothesis that Hypo-exo can reduce neuronal apoptosis after SCI and may provide new methods to treat SCI. [ABSTRACT FROM AUTHOR]

To control asparagus harvest timing, we investigated the effects of short-term low (5%) oxygen (O2) treatment in the cultivation area on asparagus growth and yield using a closed cultivation system. During 120 days of cultivation, low O2 treatments were initiated at 0 to 4, 20 to 24, and 40 to 44 days after planting (DAP). The sprouting spears and control crown yield gradually decreased with increasing DAP. However, low O2 treatment at 0 to 4 DAP significantly delayed the decrease until 80 DAP, although the total yield did not change during cultivation. In contrast, low O2 treatments at 20 to 24 and 40 to 44 DAP did not affect yield performance. Taken together, short-term low O2 treatment immediately after planting can change the harvest timing of white asparagus and can be used for effective asparagus culturing in a closed system, such as a plant factory.

The hypoxic condition in solid tumors induces therapy resistance, limited therapeutic efficacy, and tumor recurrence, especially for chemotherapy and aerobic photodynamic therapy (PDT). To address this matter, an O 2 regulator (SNP@Ato) is designed for breaking chemoresistance and enhancing PDT, which is constructed by loading Atovaquone (Ato) through self-assembly and host-guest interaction between β-cyclodextrin functionalized tetraphenylporphyrin (TPP-CD 4 ) and thioketal-linked camptothecin/azobenzene (Azo-TK-CPT). Specifically, the porphyrin units in SNP@Ato are in "Off state" due to the photoinduced electron transfer (PET) effect between the porphyrin units and azobenzene. After encountering the hypoxic condition in solid tumors, SNP@Ato is dissociated by the cleaved azobenzene on account of over-expressed azo-reductase. Then the mitochondrial respiratory of cancer cells would be suppressed with the participation of Ato, generating a local hypoxia relief for sensitized chemotherapy and enhanced PDT. Accompanied by efficient PDT, the TK linker is broken by ROS, and the CPT is released from the prodrugs. Compared with the SNP group without oxygen-regulator, SNP@Ato exhibits a remarkable improvement of the therapeutic effect against hypoxic tumors in vitro and in vivo. This work proposes a novel paradigm for overcoming hypoxia-induced therapeutic resistance., (© 2024 Wiley‐VCH GmbH.)

The hypoxic environment is a substantial factor in maintenance, proliferation, and differentiation of the cell cultures. Low oxygen is known as a potent chondrogenesis stimulus in stem cells that is important for clinical application and engineering of functional cartilage. Hypoxia can potentially induce angiogenesis process by secretion of cytokines. This systematic review goal is to discover the effect of hypoxic condition on tendon/ ligament culture and the best oxygen level of hypoxia for in vitro and in vivo studies. We included 21 articles. A comprehensive review of this database confirms that the hypoxic condition is a substantial factor in the maintenance, proliferation, and differentiation of ligament/tendon cultures. Cell proliferation in the severe hypoxic (oxygen concentration of 1%) group at 24 h postcultivation was considered significant, but cell proliferation was markedly inhibited in the severe hypoxic group after 48 h. [ABSTRACT FROM AUTHOR]

Background: Improved chondrogenic differentiation of mesenchymal stem cells (MSCs) by genetic regulation is a potential method for regenerating articular cartilage. MiR-127-5p has been reported to promote cartilage differentiation of rat bone marrow MSCs (rMSCs); however, the regulatory mechanisms underlying hypoxia-stimulated chondrogenic differentiation remain unknown. Methods: rMSCs were induced to undergo chondrogenic differentiation under normoxic or hypoxic conditions. Expression of lncRNA DNM3OS, miR-127-5p, and GREM2 was detected by quantitative real-time PCR. Proteoglycans were detected by Alcian blue staining. Western blot assays were performed to examine the relative levels of GREM2 and chondrogenic differentiation related proteins. Luciferase reporter assays were performed to assess the association among DNM3OS, miR-127-5p, and GREM2. Results: MiR-127-5p levels were upregulated, while DNM3OS and GREM2 levels were downregulated in rMSCs induced to undergo chondrogenic differentiation, and those changes were attenuated by hypoxic conditions (1% O2). Further in vitro experiments revealed that downregulation of miR-127-5p reduced the production of proteoglycans and expression of chondrogenic differentiation markers (COL1A1, COL2A1, SOX9, and ACAN) and osteo/chondrogenic markers (BMP-2, p-SMAD1/2). MiR-127-5p overexpression produced the opposite results in rMSCs induced to undergo chondrogenic differentiation under hypoxic conditions. GREM2 was found to be a direct target of miR-127-5p, which was suppressed in rMSCs undergoing chondrogenic differentiation. Moreover, DNM3OS could directly bind to miR-127-5p and inhibit chondrogenic differentiation of rMSCs via regulating GREM2. Conclusions: Our study revealed a novel molecular pathway (DNM3OS/miR-127-5p/GREM2) that may be involved in hypoxic chondrogenic differentiation. [ABSTRACT FROM AUTHOR]

Declining oxygen concentrations in aquatic habitats represent extreme conditions that threaten benthic life. Hypoxia has recently become an important research topic, as areas affected by these phenomena are spreading globally. Omura Bay is one of the most highly enclosed seas in Japan, and severely hypoxic conditions occur at the bottom every summer. We conducted a preliminary study in the center of the bay to evaluate how seasonal hypoxia affects the abundance and community composition of benthic meiofauna, with particular reference to copepods. The copepod densities and their nauplii differed significantly among seasonal categories (before, during, and after hypoxia). Furthermore, the degree of the seasonal decline in copepods during hypoxia seemed much more severe than that in nematodes, the most abundant meiofauna. The assemblages of adult copepods had the simplest composition during hypoxia, when harpacticoid copepods in the family Cletodidae, which have smaller and slender bodies, occurred at significantly higher frequencies (a contribution of 84% to the mean similarity among seasons). After hypoxia, the relative abundance of copepods in the families Ectinosomatidae and Longipediidae increased, which may likely be attributed to their higher swimming abilities and rapid recruitment via specific planktonic nauplius stages, respectively. High frequencies of copepods in the Cletodidae family have also been observed under hypoxic conditions in the Mediterranean Sea, suggesting that similar processes affect benthic copepod communities, which work to the advantage of cletodid species with small and slender forms in the subtidal sediment bottom under severe hypoxia in Omura Bay and other regions. [ABSTRACT FROM AUTHOR]

Abstract Background Treatment with bone marrow mesenchymal stem cells (BM-MSCs) has been demonstrated to be an excellent cellular-based therapeutic strategy for treating myocardial infarction (MI). However, most of the patients suffering with MI are elderly. Hypoxic conditions can cause apoptosis of BM-MSCs, and this type of apoptosis is more prevalent in aged BM-MSCs. Decreased autophagy is one of the mechanisms underlying aging. The aim of this study is to uncover whether the increased hypoxic injury of aged BM-MSCs is due to autophagy and whether reducing autophagy diminishes the tolerance of hypoxia in aged BM-MSCs. Methods Young and aged BM-MSCs were isolated from male young and aged GFP/Fluc transgenic C57BL/6 mice respectively and then exposed to hypoxia and serum deprivation (H/SD) injury. The apoptosis level induced by H/SD was measured by terminal deoxynucleotidy transferase-mediated dUTP nick end-labeling (TUNEL) assay. Additionally, autophagy was analyzed via transfection with plasmids encoding green fluorescent protein-microtubule-associated protein lightchain3 (GFP-LC3), and autophagic vacuoles were visualized with transmission electron microscopy. Meanwhile, protein expression was measured by western blot analysis. Autophagic activity was manipulated by the administration of IGF-1 (insulin-like growth factor siRNA) and 3-methyladenine (3MA). Furthermore, young, aged, and the IGF-1 siRNA-transfected aged BM-MSCs were transplanted to myocardial infarcted adult C57BL/6 mice respectively. In vivo longitudinal in vivo bioluminescence imaging (BLI) of transplanted BM-MSCs was performed to monitor the survival of transplanted BM-MSCs in each groups. Results Aged BM-MSCs exhibited a higher rate of apoptosis compared with young BM-MSCs under hypoxic conditions. Additionally, the level of autophagy was lower in aged BM-MSCs compared with young BM-MSCs under normoxic and hypoxic conditions. Meanwhile, hypoxia decreased the activity of the protein kinase B (Akt) and mammalian target of rapamycin (mTOR) signaling pathway in young and aged BM-MSCs, but aged BM-MSCs exhibited a relatively stronger Akt/mTOR activity compared with young BM-MSCs. In addition, IGF-1 knockdown significantly decreased the level of apoptosis in aged BM-MSCs under normoxic and hypoxic conditions. IGF-1 knockdown also decreased the activity of the Akt/mTOR signaling pathway and increased the level of autophagy in aged BM-MSCs under hypoxic condition. Furthermore, IGF-1 knockdown protected aged BM-MSCs from hypoxic injury by increasing the level of autophagy, thereby promoting the survival of aged BM-MSCs after myocardial infarction transplantation. Conclusion This study demonstrates that reducing autophagy decreases the hypoxia tolerance of aged BM-MSCs. Maintaining optimal levels of autophagy may serve as a new strategy in treating MI by BM-MSC transplantation in aged patients.

The Effect of Intermittent Hypoxic Breathing on Blood Pressure and Nitric Oxide in Hypertensive Patients with Excess Weight. JEPonline 2020;23(3):63- 76. The purpose of this study was to investigate the effect of intermittent hypoxic exposure (IHE) on blood pressure (BP), nitric oxide metabolites (NOx), malondialdehyde (MDA) levels and the 6-min walk distance (6MWD) test in hypertensive patients with excess weight. Twenty-seven patients on medications with a BMI of 25 to 31.6 kg·m-2 were randomized into the Control Group (CON) or the IHE Group. The IHE Group was exposed to 8 sets of a 3-min on-off of hypoxic gas (FIO2 = 0.14) interspersed with normoxic gas (FIO2 = 0.21) for 48 min·d-1, 2 d·wk-1 for 6 wks during rest; whereas, the patients in the CON Group had no intervention. All the parameters were measured before and after the experimental period. Relative to the CON Group, the IHE Group showed a significant decrease in all BP values [systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure, (MAP)] and plasma MDA levels, and an increase in plasma NOx levels and 6MWD. The findings suggest that IHE during rest revealed substantial improvement in BP levels. The mechanisms behind the changes may relate to NO elevation and MDA reduction. This training program helped improve exercise capacity in patients with excess weight and hypertension. [ABSTRACT FROM AUTHOR]

Long non-coding RNA (lncRNA) anti-differentiation non-coding RNA (ANCR) has been reported to participate in numerous types of malignancies. The present study aimed to investigate the function of lncRNA ANCR in cervical squamous cell carcinoma (CSCC). The expression of ANCR in the cervical tissues (tumor tissues in patients with CSCC) and serum of patients with CSCC in addition to healthy female controls was detected using reverse transcription-quantitative polymerase chain reaction. Diagnostic values of ANCR expression in cervical tissue and serum for CSCC were determined using receiver operating characteristic curve analysis. LncRNA ANCR and hypoxia-inducible factor 1α (HIF-1α) expression vectors were constructed and transfected into CSCC cell lines, and cell proliferation under normal O2 and hypoxic conditions (8% O2) was detected using a Cell Counting kit-8 assay. Expression of HIF-1α was determined using western blot analysis. It was observed that ANCR was downregulated in human papillomavirus (HPV)-negative patients with CSCC compared with in normal female cases and HPV-positive patients with CSCC in cervical tissues and in the serum, and the downregulation of ANCR effectively distinguished HPV-negative patients with CSCC from healthy controls. ANCR overexpression inhibited the proliferation of HPV-negative CSCC cells under hypoxic conditions, whilst HIF-1α overexpression reversed this effect. ANCR overexpression inhibited HIF-1α expression in HPV-negative CSCC cells, while HIF-1α overexpression exhibited no significant effect on ANCR expression. It was therefore concluded that ANCR may inhibit the growth of HPV-negative cervical squamous cell carcinoma under hypoxic conditions by downregulating HIF-1α. [ABSTRACT FROM AUTHOR]

This study shows vanadate (V(V)) reduction in a methane (CH4) based membrane biofilm batch reactor when the concentration of dissolved oxygen (O2) was extremely low. V(IV) was the dominant products formed from V(V) bio-reduction, and majority of produced V(IV) transformed into precipitates with green color. Quantitative polymerase chain reaction and Illumina sequencing analysis showed that archaea methanosarcina were significantly enriched. Metagenomic predictive analysis further showed the enrichment of genes associated with reverse methanogenesis pathway, the key CH4-activating mechanism for anaerobic methane oxidation (AnMO), as well as the enrichment of genes related to acetate synthesis, in archaea. The enrichment of aerobic methanotrophs Methylococcus and Methylomonas implied their role in CH4 activation using trace level of O2, or their participation in V(V) reduction. [ABSTRACT FROM AUTHOR]

Hypoxia is a constant feature of the synovial microenvironment. How synovial mesenchymal stem cells (SMSCs) proliferate and differentiate in a hypoxic environment over a long period of time has aroused the interest of researchers. The aim of the present study was to explore the effects of hypoxia-inducible factor-1α (HIF-1α) on the proliferation and apoptosis of human SMSCs. SMSCs were harvested and cultured under different concentration of oxygen, normoxia (21% O2), hypoxia (5% O2) and severe hypoxia (0.5% O2) to determine its effect on the expression of HIF-1α. Then, the cells were collected and cell proliferation and apoptosis were detected at severe hypoxia (0.5% O2) and hypoxia (5% O2) conditions following HIF-1α siRNA transfection. There were no significant changes in cellular proliferation or apoptosis when cultured in normoxia (21% O2), hypoxia (5% O2) or severe hypoxia (0.5% O2). However, the mRNA and protein expression of HIF-1α were markedly upregulated in the hypoxic conditions. Further experiments suggested that the proliferation of SMSCs was obviously suppressed and apoptosis was markedly increased under severe hypoxic (0.5%) and hypoxic (5% O2) conditions following HIF-1α siRNA transfection. In conclusion, HIF-1α effectively improved the tolerance of SMSCs to hypoxia, which may promote cellular proliferation and prevent the apoptosis of SMSCs under hypoxic conditions. [ABSTRACT FROM AUTHOR]

Scrippsiella trochoidea produces a calcareous walled cyst with spines during its life history. It has been recently reported that the calcareous wall can be decalcified under acidified conditions in coastal areas linked to hypoxia caused by bacterial activities. In this study, in order to determine whether the calcareous cysts can be a biological tool for indicating an in situ hypoxic environment, the morphology of S. trochoidea cysts in the surface sediments of Ise Bay, Japan, was examined in relation to dissolved oxygen concentrations in the bottom water. The surface sediments were collected from the inner to outer parts of the bay in May 2014 and June 2018. The living cysts of S. trochoidea were counted separately into two morphotypes: cyst with calcareous wall (calcareous walled-type cyst) and without the wall (naked-type cyst). The proportions (%) of naked-type cyst abundance in the total living cyst population showed an increasing tendency in the hypoxic environment of the inner and central parts of Ise Bay, but not in the normoxic environment at the mouth. This result supports the supposition that the naked-type cyst of S. trochoidea can be used as a biological indicator for the assessment of hypoxia in coastal areas. [ABSTRACT FROM AUTHOR]

The entomopathogenic fungi encounter hypoxic conditions in both nature and artificial culture. Alcohol dehydrogenases (ADHs) are a group of oxidoreductases that occur in many organisms. Here we demonstrate that an alcohol dehydrogenase I, MaADH1, in the locust-specific fungal pathogen, Metarhizium acridum, functions in acetaldehyde detoxification mechanism under hypoxic conditions in growth and sporulation. The MaADH1 was highly expressed in sporulation stage under hypoxic conditions. Compared with a wild-type strain, the ΔMaADH1 mutant showed inhibited growth and sporulation under hypoxic conditions, but no impairment under normal conditions. Under hypoxic conditions, ΔMaADH1 mutant produced significant decreased alcohol, but significant increased acetaldehyde compared to wild type. M. acridum was sensitive to exogenous acetaldehyde, exhibiting an inhibited growth and sporulation with acetaldehyde added in the medium. MaADH1 did not affect virulence. Our results indicated that the MaADH1 was critical to growth and sporulation under hypoxic stress by detoxification of acetaldehyde in M. acridum.

Diabetes mellitus (DM) is a group of diseases characterized by abnormally high levels of glucose in the blood stream. In developing a potential therapy for diabetic patients, pancreatic cells transplantation has drawn great attention. However, the hinder of cell transplantation for diabetes treatment is insufficient sources of insulin-producing cells. Therefore, new cell based therapy need to be developed. In this regard, human embryonic stem cells (hESCs) may serve as good candidates for this based on their capability of differentiation into various cell types. In this study, we designed a new differentiation protocol that can generate hESC-derived insulin-producing cells (hES-DIPCs) in a hypoxic condition. We also emphasized on the induction of definitive endoderm during embryoid bodies (EBs) formation. After induction of hESCs differentiation into insulin-producing cells (IPCs), the cells obtained from the cultures exhibited pancreas-related genes such as Pdx1, Ngn3, Nkx6.1, GLUT2, and insulin. These cells also showed positive for DTZ-stained cellular clusters and contained ability of insulin secretion in a glucose-dependent manner. After achievement to generated functional hES-DIPCs in vitro, some of the hES-DIPCs were then encapsulated named encapsulated hES-DIPCs. The data showed that the encapsulated cells could possess the function of insulin secretion in a time-dependent manner. The hES-DIPCs and encapsulated hES-DIPCs were then separately transplanted into STZ-induced diabetic mice. The findings showed the significant blood glucose levels regulation capacity and declination of IL-1β concentration in all transplanted mice. These results indicated that both hES-DIPCs and encapsulated hES-DIPCs contained the ability to sustain hyperglycemia condition as well as decrease inflammatory cytokine level in vivo. The findings of this study may apply for generation of a large number of hES-DIPCs in vitro. In addition, the implication of this work is therapeutic value in type I diabetes treatment in the future. The application for type II diabetes treatment remain to be investigated.

The entomopathogenic fungi encounter hypoxic conditions in both nature and artificial culture. Alcohol dehydrogenases (ADHs) are a group of oxidoreductases that occur in many organisms. Here we demonstrate that an alcohol dehydrogenase I, MaADH1 , in the locust-specific fungal pathogen, Metarhizium acridum , functions in acetaldehyde detoxification mechanism under hypoxic conditions in growth and sporulation. The MaADH1 was highly expressed in sporulation stage under hypoxic conditions. Compared with a wild-type strain, the Δ MaADH1 mutant showed inhibited growth and sporulation under hypoxic conditions, but no impairment under normal conditions. Under hypoxic conditions, Δ MaADH1 mutant produced significant decreased alcohol, but significant increased acetaldehyde compared to wild type. M. acridum was sensitive to exogenous acetaldehyde, exhibiting an inhibited growth and sporulation with acetaldehyde added in the medium. MaADH1 did not affect virulence. Our results indicated that the MaADH1 was critical to growth and sporulation under hypoxic stress by detoxification of acetaldehyde in M. acridum. [ABSTRACT FROM AUTHOR]

Abstract: A hypoxic condition is known to contribute to pluripotency. In the present article, the effects of transcription factors were first assessed regarding the proliferation and differentiation of human induced pluripotent stem (iPS) cells under hypoxic conditions using cell morphology and real‐time polymerase chain reaction (RT‐PCR). Morphology evaluations and RT‐PCR revealed that the colony formation was promoted and the expression of pluripotent markers was increased under hypoxic conditions. In addition, the function of hypoxia inducible factors (HIFs) in human iPS cells under hypoxic conditions was evaluated in relation to the morphology and the expression of pluripotency markers by siRNA and RT‐PCR. The HIF‐2α silencing group showed a reduction in the colony size of human iPS cells and a statistically significant reduction in the expression of undifferentiation markers compared to the control group. Furthermore, the expression of HIF‐2α was decreased when signal transducer and activator of transcription 3 (STAT3) was suppressed by its inhibitor, Stattic or S31 201. The inhibition using Stattic did not produce colony formation. The expression of pluripotent markers was also decreased using Stattic or S31 201. This study indicates that the HIF‐2α expression in human iPS cells was activated under hypoxic conditions, similarly to that in murine iPS cells, and that HIF‐2α among HIFs is the most effective compound for maintaining the pluripotency of human iPS cells. Furthermore, the STAT3 signal pathway regulates the expression of HIF‐2α. [ABSTRACT FROM AUTHOR]

Tissue engineering scaffolds with oxygen generating elements have shown to be able to increase the level of oxygen and cell survivability in specific conditions. In this study, biphasic calcium phosphate (BCP) scaffolds with the composition of 60% hydroxyapatite (HA) and 40% beta-tricalcium phosphate (β-TCP), which have shown a great potential for bone tissue engineering applications, were fabricated by a direct-write assembly (robocasting) technique. Then, the three-dimensional (3D)-printed scaffolds were coated with different ratios of an oxygen releasing agent, calcium peroxide (CPO), which encapsulated within a polycaprolactone (PCL) matrix through dip-coating, and used for in situ production of oxygen in the implanted sites. The structure, composition and morphology of the prepared scaffolds were characterized by different techniques. The oxygen release kinetics and biological investigations of the scaffolds were also studied in vitro . The results showed that oxygen release behaviour was sustained and dependant on the concentration of CPO encapsulated in the PCL coating matrix. It was also demonstrated that the coated scaffolds, having 3% CPO in the coating system, could provide a great potential for promoting bone ingrowth with improving osteoblast cells viability and proliferation under hypoxic conditions. The findings indicated that the prepared scaffolds could play a significant role in engineering of large bone tissue implants with limitations in oxygen diffusion. [ABSTRACT FROM AUTHOR]

Purpose: The present study was performed to determine the impact of hypoxia on working muscle oxygenation during incremental running, and to compare tissue oxygenation between the thigh and calf muscles.Methods: Nine distance runners and triathletes performed incremental running tests to exhaustion under normoxic and hypoxic conditions (fraction of inspired oxygen = 0.15). Peak pulmonary oxygen uptake ([Formula: see text]) and tissue oxygen saturation (StO2) were measured simultaneously in both the vastus lateralis and medial gastrocnemius.Results: Hypoxia significantly decreased peak running speed and [Formula: see text] (p < 0.01). During incremental running, StO2 in the vastus lateralis decreased almost linearly, and the rate of decrease from warm-up (180 m min-1) to [Formula: see text] was significantly greater than in the medial gastrocnemius under both normoxic and hypoxic conditions (p < 0.01). StO2 in both muscles was significantly decreased under hypoxic compared with normoxic conditions at all running speeds (p < 0.01). The rate at which StO2 was decreased by hypoxia was greater in the vastus lateralis as the running speed increased, whereas it changed little in the medial gastrocnemius.Conclusions: These results suggest that the thigh is more deoxygenated than the calf under hypoxic conditions, and that the effects of hypoxia on tissue oxygenation differ between these two muscles during incremental running. [ABSTRACT FROM AUTHOR]

Hypoxic environment is known as one of the critical factors in various physiological/pathological processes. It is imperative to recapitulate oxygen level in microscale for human physiology/pathology induced by hypoxia. Herein, we propose an oxygen-regulating system that can be applied to in vitro tissue models. We fabricated a microdevice with a gas-permeable membrane, allowing oxygen diffusion without direct contact to cells. We verified the formation of oxygen level less than 2% O2 concentration inside the device through computational simulation and experiments. H9c2 heart myoblasts were exposed to hypoxic condition in the device, and their cell viability were investigated. We anticipate that our system will be integrated with a platform to study hypoxia-induced human physiology and pathology as an efficient oxygen-regulating system.

Even though exercise hemorheology at hypoxic condition has been considered as a good tool to understand clinical hemorheology, there have been limited studies reported. Previous researches showed that hemorheological variables are closely correlated with oxygen delivery capacity during exercise. The present study investigated hypoxic responses including RBC deformability and aggregation, metabolic parameters and complete blood cell counts at various hypoxic conditions during cycling exercise and recovery. Eleven Korean healthy male subjects performed submaximal bike exercise at sea level (20.9% O2) and under various hypoxic conditions (16.5% O2, 14.5% O2, 12.8% O2, and 11.2% O2) in a random order. The submaximal bike exercise intensity of the subjects was 70% maximum heart rate at sea level. All variables were measured at rest, during exercise and recovery 30-minute, respectively. As oxygen partial pressure decreased, arterial blood oxygen saturation decreased but oxygen uptake did not change much. Heart rate and lactate concentration during exercise increased when oxygen partial pressure is less than or equal to 14.5% O2 condition. Red blood cell (RBC) counts, hemoglobin counts, and hematocrit level were not apparently altered with hypoxic conditions. RBC deformability showed significant alterations at 11.2% O2 conditions compared with other hypoxic conditions during exercise or recovery, except at 10 minutes recovery. However, decreases in oxygen partial pressure did not affect red blood cell aggregation. Therefore, we conclude that alterations in RBC deformability may reduce aerobic capabilities at hypoxic condition. [ABSTRACT FROM AUTHOR]

Compost-amended landfill reactors were developed to reduce polychlorinated- p -dioxins and dibenzofurans (PCDD/Fs) in contaminated soils. By periodically recirculating leachate and suppling oxygen, the online monitoring of the oxidation reduction potential confirmed that the reactors were maintained under hypoxic conditions, with redox levels constantly fluctuating between −400 and +80 mV. The subsequent reactor operation demonstrated that PCDD/F degradation in soil could be facilitated by amending compost originating from the cow manure and waste sludge and that the degradation might be affected by the availability of easily degradable substrates in the soil and compost. The pyrosequencing analysis of V4/V5 regions of bacterial 16S rRNA genes suggested that species richness of the soil microbial community was increased by a factor of 1.37–1.61. Although the bacterial community varied with the compost origin and changed markedly during reactor operation, it was dominated by Alphaproteobacteria , Gammaproteobacteria , Actinobacteria , and Firmicutes . The aerotolerant anaerobic Sedimentibacter and Propionibacterium spp., and the uncultured Chloroflexi group could be temporarily induced to a high abundance by amending the cow manure compost; the bacterial growths were associated with the rapid degradation of PCDD/Fs. Overall, the novel bioremediation method for PCDD/F-contaminated soils using hypoxic conditions was effective, simple, energy saving, and thus easily practicable. [ABSTRACT FROM AUTHOR]