Low Oxygen Levels Research Articles

Genetic and Functional Modifications Associated with Ovarian Cancer Cell Aggregation and Limited Culture Conditions.

The aggregation of cancer cells provides a survival signal for disseminating cancer cells; however, the underlying molecular mechanisms have yet to be elucidated. Using qPCR gene arrays, this study investigated the changes in cancer-specific genes as well as genes regulating mitochondrial quality control, metabolism, and oxidative stress in response to aggregation and hypoxia in our progressive ovarian cancer models representing slow- and fast-developing ovarian cancer. Aggregation increased the expression of anti-apoptotic, stemness, epithelial-mesenchymal transition (EMT), angiogenic, mitophagic, and reactive oxygen species (ROS) scavenging genes and functions, and decreased proliferation, apoptosis, metabolism, and mitochondrial content genes and functions. The incorporation of stromal vascular cells (SVF) from obese mice into the spheroids increased DNA repair and telomere regulatory genes that may represent a link between obesity and ovarian cancer risk. While glucose had no effect, glutamine was essential for aggregation and supported proliferation of the spheroid. In contrast, low glucose and hypoxic culture conditions delayed adhesion and outgrowth capacity of the spheroids independent of their phenotype, decreased mitochondrial mass and polarity, and induced a shift of mitochondrial dynamics towards mitophagy. However, these conditions did not reduce the appearance of polarized mitochondria at adhesion sites, suggesting that adhesion signals that either reversed mitochondrial fragmentation or induced mitobiogenesis can override the impact of low glucose and oxygen levels. Thus, the plasticity of the spheroids' phenotype supports viability during dissemination, allows for the adaptation to changing conditions such as oxygen and nutrient availability. This may be critical for the development of an aggressive cancer phenotype and, therefore, could represent druggable targets for clinical interventions.

Bioprospecting of Actinobacterial Diversity and Antibacterial Secondary Metabolites from the Sediments of Four Saline Lakes on the Northern Tibetan Plateau.

The Tibetan Plateau, known as the "Roof of the World" and "The Third Pole", harbors numerous saline lakes primarily distributed in the Northern Tibetan Plateau. However, the challenging conditions of high altitude, low oxygen level, and harsh climate have limited investigations into the actinobacteria from these saline lakes. This study focuses on investigating the biodiversity and bioactive secondary metabolites of cultivable actinobacteria isolated from the sediments of four saline lakes on the Northern Tibetan Plateau. A total of 255 actinobacterial strains affiliated with 21 genera in 12 families of 7 orders were recovered by using the pure culture technique and 16S rRNA gene phylogenetic analysis. To facilitate a high-throughput bioactivity evaluation, 192 isolates underwent OSMAC cultivation in a miniaturized 24-well microbioreactor system (MATRIX cultivation). The antibacterial activity of crude extracts was then evaluated in a 96-well plate antibacterial assay. Forty-six strains demonstrated antagonistic effects against at least one tested pathogen, and their underlying antibacterial mechanisms were further investigated through a dual-fluorescent reporter assay (pDualrep2). Two Streptomyces strains (378 and 549) that produce compounds triggering DNA damage were prioritized for subsequent chemical investigations. Metabolomics profiling involving HPLC-UV/vis, UPLC-QTOF-MS/MS, and molecular networking identified three types of bioactive metabolites belonging to the aromatic polyketide family, i.e., cosmomycin, kidamycin, and hedamycin. In-depth analysis of the metabolomic data unveiled some potentially novel anthracycline compounds. A genome mining study based on the whole-genome sequences of strains 378 and 549 identified gene clusters potentially responsible for cosmomycin and kidamycin biosynthesis. This work highlights the effectiveness of combining metabolomic and genomic approaches to rapidly identify bioactive chemicals within microbial extracts. The saline lakes on the Northern Tibetan Plateau present prospective sources for discovering novel actinobacteria and biologically active compounds.

The expression of hypoxia inducible factor-1 alpha in diffuse large B-cell lymphoma (DLBCL) patients: a cross-sectional study in Indonesia.

Hypoxia fuels cancer growth by supporting blood vessel formation, suppressing immune response, and helping cancer cells adapt to harsh surroundings. This happens when cancer cells react to low oxygen levels by activating hypoxia inducible factor-1 alpha (HIF-1α). High levels of HIF-1α can indicate an aggressive form of cancer and resistance to treatment in diffuse large B-cell lymphoma (DLBCL) patients. This study aimed to identify which factors are linked to HIF-1α distribution using immunohistochemistry in DLBCL patients. This study conducted at a hospital in Indonesia between 2020 and 2022 aimed to investigate factors associated with HIF-1α expression in DLBCL patients. Newly diagnosed DLBCL patients were categorized into two groups based on HIF-1α distribution (<40% and ≥40%). Various factors were analyzed between the two groups using statistical tests such as χ2, Mann-Whitney U, and Spearman correlation tests. In this study, 40 participants diagnosed with DLBCL were divided into two groups based on their HIF-1α distribution. The group with HIF-1α distribution greater than or equal to 40% had a higher incidence of extranodal involvement, including primary extranodal disease, compared to the group with less than 40% distribution. This difference was statistically significant. The authors also found that haemoglobin level statistically significant (P=0.041) in this research. The Spearman test analysis showed negative correlation between haemoglobin (P = <0.05, r = -0.44) and positive correlation of soluble interleukin-2 receptor (sIL-2R) (P = <0.05, r = 0.5) with vascular endothelial growth factor (VEGF), as well as between tumour volume (P = <0.05, r = 0.37) with sIL-2R. Additionally, there was a positive correlation between VEGF and sIL-2R (P = <0.05, r= 0.5). Patients with higher HIF-1α expression (≥40%) had more extranodal involvement and primary extranodal disease in this study of 40 DLBCL patients. Haemoglobin level, sIL-2R, and VEGF were also identified as potential biomarkers.

State of the Art and Contribution to the Documentation on Fishing, Aquaculture and on the Microbiological Profile of Clarias Gariepinus and Oreochromis Niloticus Two Species of Fish Reared in the Whedos of the Upper Ouémé Delta in the Republic of Benin

Fish is an important source of animal protein in Africa and is used in the composition of several national dishes. This literature review examines fishing, aquaculture and fish reared in the whèdos of the upper Ouémé delta in Benin. It addresses socio-economic aspects, nutritional importance and traditional fish preservation technology. The sources of information used are publications, books, reports of dissertations and theses and technical notes. It was found that Clarias gariepinus and Oreochromis niloticus, among others, are two species of fish most often raised in the whèdos of the Ouémé River in Benin. These fish adapt to large variations of ecological factors of the aquatic environment found everywhere in Africa and reproduce easily in captivity, which favors their breeding in ponds. These species present multiple fish farming qualities: resistance to high densities, resistance to diseases and low oxygen levels, easy adaptation to artificial feeding and high growth. Microbiological contamination of fish flesh occurs only after capture and can be endogenous or exogenous contamination. Generally, several processes are used to overcome this problem of contamination of fish. Hot smoking and drying are very often used. The lack of hygiene in the traditional technology of smoking fish sometimes favor a considerable microbial contamination of the obtained products. Thus, contaminated fish can be the cause of foodborne diseases such as food poisoning. Most of the pathogenic strains responsible for these diseases are resistant to certain antibiotics.

Pairing combustion experiments and thermogravimetric analysis to uncover timescales controlling cellulose ignition and burnout in a Hencken burner

Solid biomass fuels are potential components of several industrial and power-generation decarbonization pathways. Despite considerable literature that documents the fuel properties of lignocellulosic biomass, the fundamental combustion characteristics of biomass constituents are not well understood. We tackle this knowledge gap by analyzing the combustion properties of cellulose (a key biomass component) in a Hencken burner across various temperature and oxygen mole fractions of the oxidizer gases. Combustion data are compared with results from thermogravimetric analysis (TGA) and scaling analyses to reveal two rate-controlling timescales in the ignition of cellulose: devolatilization time and volatile ignition delay time. TGA shows that the devolatilization time is only a function of temperature and occurs on a considerably shorter timescale than oxidation. Hencken burner experiments show that ignition delay time is highly sensitive to temperature; at very low levels of oxygen in the oxidizer gas (mole fractions of 0.01–0.04), the ignition delay time is sensitive to oxygen mole fraction, but this sensitivity disappears at higher oxygen levels. Burnout time is the least sensitive parameter investigated. The combination of experiments and chemical kinetic simulations begins to explain the ignition behavior of the volatiles from cellulose decomposition and lays groundwork for future research to address uncertainties in quantifying the kinetics of cellulose ignition. Finally, this combined combustion-fuel science study raises serious doubts about the use of combustion indices and TGA-calculated properties to predict the true combustion behavior of biomass.

HIF‑1α and RACGAP1 promote the progression of hepatocellular carcinoma in a mutually regulatory way.

Hypoxia, a condition characterized by low oxygen levels, serves an important role in the progression of hepatocellular carcinoma (HCC). However, the precise molecular mechanisms underlying hypoxia‑induced HCC progression are yet to be fully elucidated. The present study assessed the involvement of two key factors, hypoxia‑inducible factor‑1α (HIF‑1α) and Rac GTPase activating protein 1 (RACGAP1), in HCC development under hypoxic conditions. HIF‑1α and RACGAP1 genes were overexpressed and knocked down in Hep3B and Huh7 cells using lentiviral transduction and the levels of HIF‑1α and RACGAP1 in the cells were assessed using quantitative PCR, western blotting and immunofluorescence. Co‑immunoprecipitation experiments were performed to evaluate the interaction between HIF‑1α and RACGAP1. Subsequently, the proliferation, apoptosis, migration and invasion of Hep3B and Huh7 cells were assessed using the Cell Counting Kit‑8 assay, flow cytometry, Transwell assay and migration experiments. The expression levels of HIF‑1α and RACGAP1 in normal and HCC tumor samples were analyzed utilizing the Gene Expression Profiling Interactive Analysis database. Furthermore, correlations between HIF‑1α/RACGAP1 gene expression levels and patient survival outcomes were evaluated using the Kaplan‑Meier plotter. Knockdown of HIF‑1α resulted in a significant decrease in RACGAP1 expression, whilst overexpression of HIF‑1α resulted in a significant increase in RACGAP1 expression. Moreover, overexpression and knockdown of RACGAP1 had the same effect on HIF‑1α expression. Additionally, it was demonstrated that HIF‑1α and RACGAP1 interacted directly within a complex. Overexpression of HIF‑1α or RACGAP1 significantly increased proliferation, invasion and migration, and significantly decreased the proportion of apoptotic Hep3B and Huh7 cells. Conversely, knockdown of HIF‑1α or RACGAP1 significantly decreased proliferation, invasion and migration, and significantly increased the proportion of apoptotic Hep3B and Huh7 cells. In addition, the combined knockdown or overexpression of HIF‑1α and RACGAP1 had a more pronounced effect on HCC cell migration compared with knockdown of HIF‑1α alone. Furthermore, there was a significant positive correlation between the expression levels of HIF‑1α and RACGAP1 in HCC tissues and patients with HCC and upregulation of both HIF‑1α and RACGAP1 demonstrated a lower overall survival probability. In conclusion, HIF‑1α and RACGAP1 may synergistically contribute to the development of HCC, highlighting their potential as valuable targets for HCC therapy.

Influence of oxygen regimes of water on the physiological state of fish (review)

Breeding of sturgeon fish species in recirculating water supply systems is one of the most promising areas in modern aquaculture. With proper operation of recirculation systems and compliance with the requirements for fish breeding, it becomes possible to reduce anthropogenic pressure on fish populations living in natural reservoirs, as well as provide the country’s population with highquality fish products. The use of recirculating water supply systems for sturgeon breeding has many advantages, such as: a smaller number of compound feeds, automation of the process, saving water used and building a small plant in places near settlements, etc. The only exceptions are the two main disadvantages that cause stress in fish — a low level of oxygen dissolved in water and an increased stocking density of bred individuals. Due to the fact that the issue of stocking density regulation is quite well studied, the issue of oxygen effects on physiological changes in fish is very relevant. The aim of the work was to analyze domestic and foreign literature, which describes the effect of different levels of saturation of the aquatic environment with dissolved oxygen on the viability of sturgeons bred in recirculating water supply systems. This review reflects the existing data on the norms of consumption by sturgeons of oxygen dissolved in the aquatic environment, critical and threshold concentrations that affect the body of aquatic organisms and cause them physiological manifestations with concomitant pathologies. This review also summarizes information describing the current requirements for maintaining the oxygen regime when breeding sturgeons in recirculating water supply installations, the effect of different concentrations of oxygen dissolved in water on the pathophysiological state of aquatic organisms, depending on their weight and age. The article deals with the issue of physiological abnormalities that manifest themselves under hyper- and hypoxic exposure. The consequences of hypoxic exposure with increased planting density in containers intended for keeping aquatic organisms are described.

Exploring the Role of Drug Repurposing in Bridging the Hypoxia-Depression Connection.

High levels of oxidative stress are implicated in hypoxia, a physiological response to low levels of oxygen. Evidence supports a connection between this response and depression. Previous studies indicate that tryptophan hydroxylase can be negatively affected in hypoxia, impairing serotonin synthesis and downstream pathways. Some studies also hypothesize that increasing hypoxia-inducible factor-1 (HIF-1) levels may be a new therapeutic modality for depression. Hence, this study delved into the influence of hypoxia on the cellular response to drugs designed to act in depression. By the induction of hypoxia in SH-SY5Y cells through a hypoxia incubator chamber or Cobalt Chloride treatment, the effect of Mirtazapine, an antidepressant, and other drugs that interact with serotonin receptors (TCB-2, Dextromethorphan, Ketamine, Quetiapine, Scopolamine, Celecoxib, and Lamotrigine) on SH-SY5Y cellular viability and morphology was explored. The selection of drugs was initially conducted by literature search, focusing on compounds with established potential for employment in depression therapy. Subsequently, we employed in silico approaches to forecast their ability to traverse the blood-brain barrier (BBB). This step was particularly pertinent as we aimed to assess their viability for inducing potential antidepressant effects. The effect of these drugs in hypoxia under the inhibition of HIF-1 by Echinomycin was also tested. Our results revealed that all the potential repurposed drugs promoted cell viability, especially when hypoxia was chemically induced. When combined with Echinomycin, all drugs decreased cellular viability, possibly by the inability to interact with HIF-1.

Role of hypoxic exosomes and the mechanisms of exosome release in the CNS under hypoxic conditions.

Hypoxia is characterized by low oxygen levels in the body or environment, resulting in various physiological and pathological changes. The brain, which has the highest oxygen consumption of any organ, is particularly susceptible to hypoxic injury. Exposure to low-pressure hypoxic environments can cause irreversible brain damage. Hypoxia can occur in healthy individuals at high altitudes or in pathological conditions such as trauma, stroke, inflammation, and autoimmune and neurodegenerative diseases, leading to severe brain damage and impairments in cognitive, learning, and memory functions. Exosomes may play a role in the mechanisms of hypoxic injury and adaptation and are a current focus of research. Investigating changes in exosomes in the central nervous system under hypoxic conditions may aid in preventing secondary damage caused by hypoxia. This paper provides a brief overview of central nervous system injury resulting from hypoxia, and aimed to conduct a comprehensive literature review to assess the pathophysio-logical impact of exosomes on the central nervous system under hypoxic conditions.

Oxygen Imaging of a Rabbit Tumor Using a Human-Sized Pulse Electron Paramagnetic Resonance Imager.

Spatial heterogeneity in tumor hypoxia is one of the most important factors regulating tumor growth, development, aggressiveness, metastasis, and affecting treatment outcome. Most solid tumors are known to have hypoxia or low oxygen levels (pO2 ≤10 torr). Electron paramagnetic resonance oxygen imaging (EPROI) is an emerging oxygen mapping technology. EPROI utilizes the linear relationship between the relaxation rates of the injectable OX071 trityl spin probe and the partial oxygen pressure (pO2). However, most of the EPROI studies have been limited to mouse models of solid tumors because of the instrument-size limitations. The purpose of this work was to develop a human-sized 9-mT (250 MHz resonance frequency, 60 cm bore size) pulse EPROI instrument and evaluate its performance with rabbit VX-2 tumor oxygen imaging. A New Zealand white rabbit with a 3.2-cm VX-2 tumor in the calf muscle was imaged using the human-sized EPROI instrument and a 2.25-in. ID volume coil. The animal received a ~8-min intravenous injection of OX071 (5.2 mL total volume at 72 mM concentration) and, after 75 min, an intratumoral injection (120 μL total at 5 mM OX071 concentration) and underwent EPROI. At the end of the experiments, MRI was performed using a preclinical 9.4-T MRI system to outline the tumor boundaries. For the first time, a human-sized pulse EPROI instrument with a 60-cm bore size/250-MHz frequency was built and evaluated using rabbit tumor oxygen imaging. For the first time, the systemic IV injection of the oxygen-sensitive trityl OX071 spin probe was used for an animal of this size. The resulting EPROI image from the IV injection showed complete tumor coverage. The image obtained after intratumoral injection showed localized coverage in the upper lobe of the tumor, demonstrating the need for improved intratumoral injection protocol. This study demonstrates the performance of the world's first human-sized pulse EPROI instrument. It also demonstrates that the EPROI of larger animals can be performed using the systemic injection of a manageable amount of the spin probe. This brings EPROI one step closer to clinical applications in cancer therapies. Oxygen imaging is a platform technology, and the instrument and techniques developed here will also be useful for other clinical applications.

Impaired Functions of Human Granulosa Cell Line COV434 under Hypoxic and Inflammatory Conditions

Premature ovarian insufficiency (POI) affects 1% of women under 40 years old and represents one of the main causes of infertility in females of childbearing age. POI is a primary ovarian defect resulting from follicular depletion and/or ovarian dysfunction caused by a compromised ovarian somatic cell compartment. Etiologically, ovarian dysfunction could be caused by certain diseases, including infections and autoimmune disorders. There could also be iatrogenic factors such as chemotherapy, radiation, or surgery. The related surgical risks are due to the possibility of disrupting the blood supply to the ovary and/or a subsequent inflammatory reaction. To date, it is unclear whether and how the impaired oxygen delivery and inflammatory environment may influence the basic functions of human ovarian somatic cells. In this study, we used an immortalized human granulosa cell line (COV434) as a model to investigate the effect of exposure to low oxygen levels (hypoxia) and inflammatory conditions on granulosa cell proliferation, apoptosis, and steroidogenesis. The results showed that both hypoxia (5% O2) and proinflammatory cytokine treatment (a combination of TNF-α, IL-1β, IFN-γ and IL-6) significantly increased apoptosis, suppressed proliferation, and affected estradiol secretion in COV434 cells. Our data suggest that granulosa cells could be particularly sensitive to changes in the local environment caused by oxygen deprivation and chronic inflammation.

Intramacrophage lipid accumulation compromises T cell responses and is associated with impaired drug therapy against visceral leishmaniasis.

Under perturbing conditions such as infection with Leishmania, a protozoan parasite living within the phagosomes in mammalian macrophages, cellular and organellar structures, and metabolism are dynamically regulated for neutralizing the pressure of parasitism. However, how modulations of the host cell metabolic pathways support Leishmania infection remains unknown. Herein, we report that lipid accumulation heightens the susceptibility of mice to L. donovani infection and promotes resistance to first-line anti-leishmanial drugs. Despite being pro-inflammatory, the in vitro generated uninfected lipid-laden macrophages (LLMs) or adipose-tissue macrophages (ATMs) display lower levels of reactive oxygen and nitrogen species. Upon infection, LLMs secrete higher IL-10 and lower IL-12p70 cytokines, inhibiting CD4+ T cell activation and Th1 response suggesting a key modulatory role for intramacrophage lipid accumulation in anti-leishmanial host defence. We, therefore, examined this causal relationship between lipids and immunomodulation using an in vivo high-fat diet (HFD) mouse model. HFD increased the susceptibility to L. donovani infection accompanied by a defective CD4+ Th1 and CD8+ T cell response. The white adipose tissue of HFD mice displays increased susceptibility to L. donovani infection with the preferential infection of F4/80+ CD11b+ CD11c+ macrophages with higher levels of neutral lipids reserve. The HFD increased resistance to a first-line anti-leishmanial drug associated with a defective adaptive immune response. These data demonstrate that the accumulation of neutral lipids contributes to susceptibility to visceral leishmaniasis hindering host-protective immune response and reducing the efficacy of antiparasitic drug therapies.

Sirturo- a diarylquinoline (bedaquiline): a novel approach for the treatment of MDR-TB and pre-XDR TB

Sirturo (bedaquiline fumarate) is a new antitubercular class of medicine, lately, FDA, approved and indicated for use as a part of an appropriate applicable combination regimen along with other antitubercular medicines (i. e.; 2nd line anti-TB agents) for pulmonary multidrug-resistant tuberculosis (MDR TB) in grown up with age 12 years to less than 18 years of age and weighing at least 30 kg when an alternative treatment regimen cannot be considered for the reasons of resistance or tolerability. Bedaquiline, an enantiomer chemically belongs to the diarylquinoline (DAR) compound, which is nearly related to fluoroquinolones and chloroquine with differences in their side-chain moiety. Amongst all anti-TB medicines that have been approved, bedaquiline has a unique mechanism, which targets energy metabolism i. e.; adenosine triphosphate of mycobacteria, and eventually leads to bacterial cell lysis. ATP is an essential energy-producing molecule required for metabolic actions and survival of Mycobacteria and also for many other cells. Mycobacteria generally invade into well-encapsulated lung cavities and endosomes of macrophages, which can survive even under low oxygen levels leading to resistance against standard TB drugs. Bedaquiline has a spectrum of activity against drug-susceptible TB and MDR TB. Many clinical trials and studies demonstrated that bedaquiline is a crucial component of a combination regimen for multidrug-resistant TB.

Organic matter preservation conditions in the third member of the Shahejie Formation (Dongpu Depression, China)

The third member of the Paleogene Shahejie Formation (Es3) in the Dongpu Depression, China, was studied to interpret its paleoenvironment through a series of trace element proxies, to reveal paleosalinity conditions, to elucidate on the hydrological conditions of the paleolake using carbon and oxygen stable isotopes, and to investigate the effects of paleoredox conditions on organic matter preservation. Most of the redox-sensitive proxies, such as U/Th, V/Cr, Ni/Co, Uauth, (Cu + Mo)/Zn, Cu/Zn, Th/U, and V/Sc, indicate that the Es3 was deposited under predominantly oxic and oxic/suboxic conditions, while V/(V + Ni) and δU and previous studies suggested that the formation was deposited under mainly anoxic conditions. Oxygen levels agreed with the trace element ratios and showed a decrease from the lower to the upper part of the Es3 and an increase in paleoproductivity in the same direction. Salt rocks interbedded within the formation were shown to have overall lower oxygen levels than their neighboring organic-rich layers, black shale, and mudstone intervals, thus have likely altered the paleoredox proxies to oxygen consumption. Although Sr/Ba values point to a saline lake environment, the relative fluctuations seen suggest that the above ratio is not an appropriate indicator of paleosalinity in salt-bearing strata and that the variations in paleoredox conditions in the formation are not a function of paleosalinity. Based on the negative δ13C and δ18O stable isotopic values, it is inferred that the shales in the Es3 were deposited in a hydrologically open lake environment. However, the presence of palynomorphs such as dinoflagellate cysts that are typically found in middle to outer neritic and open marine environments reinforces the assumption of a sea level transgression and inundation of the lake basin and mixing with freshwater algae and rare terrigenous phytoclasts such as cuticles, wood fragments, and suberin. The higher paleoproductivity and lower oxygen levels in the upper Es3 have contributed to greater OM preservation conditions in the absence of any variations in salinity or freshwater influx. The study also demonstrates that many of the paleoredox proxies and thresholds established are not valid to properly characterize certain formations deposited in lacustrine lake paleoenvironments such as the Shahejie, thus their applicability in certain situations must be re-evaluated.

The effect of curcumin on hypoxia in the tumour microenvironment as a regulatory factor in cancer.

Hypoxia can lead to different responses from cancer cells, including cell death or survival, partially depending on how long it is exposed. Patients with cancer and under hypoxic tumour conditions have a poorer prognosis and are at greater risk of metastasis. Physiological response to low oxygen levels is controlled by hypoxia-inducible factor (HIF)-1. Curcumin, the major component of the rhizomes of Curcuma longa L., reduces HIF-1 levels and function, inhibiting the production of vascular endothelial growth factor (VEGF). In addition, curcumin efficiently inhibits the angiogenesis of vascular endothelial cells triggered by hypoxia. One of the most compelling features that drive continued interest in curcumin is the molecules' modulation of initiation, promotion, and progression stages of cancer while concomitantly acting as a radiosensitizer and chemosensitizer for tumours. In this review, we discuss the role of curcumin in modulating hypoxia and investigate the mechanisms and regulatory factors of hypoxia in tumour tissues.

E46 Viruses reactivating each other’s!

Abstract Introduction COVID-19 is known to cause an immunocompromised state. This condition was associated with reactivation of quiescent viruses. Objectives Describe a case of HHV-6 reactivation in a patient diagnosed with MIS-C syndrome. Methods The diagnosis of MIS-C syndrome associated to SARS-CoV-2 was done by following the criteria established by the World Health Organization (WHO). The reactivation of HHV6 was confirmed by positivity of RT-PCR in blood and presence of IgG in serology. Results A four years old girl, with no medical history who presented to emergency room with high fever associated with conjunctival injection, cheilitis, cervical adenopathy and rash since four days. She developed a generalized tonic-clonic seizure then a vasoplegic shock two days later. Thus, she was admitted in ICU. Clinical examination on admission showed polypnea, a low blood oxygen level, tachycardia, a low blood pressure (28/15mmhg), a hepatomegaly, a maculopapular rash in pelvic region and a bilateral eyelid swelling. Biology showed lymphopenia (660 109/l), hepatic cytolysis, low prothrombin test (19%), an acute renal failure, a biological inflammatory syndrome with an elevated C-reactive protein (274 mg/l), an elevated ferritin, increased d-dimers (1µg/ml) and fibrinogen level which suggest activation of the coagulation cascade with a prothrombotic state and elevated lactatemia (6.4 mmol/l). The chest X-ray was normal. She had a low ejection fraction (39%) showed on echocardiogram. A rapid SARS-CoV-2 test was negative but serology was positive. Since MIS-C syndrome was not known to give severe hepatitis, other diagnoses was proposed. RT-PCR in serum associated to RT-PCR in cutaneous lesion’s biopsy was positive for HHV6. The hepatitis A serology was negative. She has an anterior immunity to varicella-zoster (VZV). She was intubated. She received vasoactive medications, intravenous immunoglobulin (IVIG) and steroids. Course was marked by hemolytic anaemia, which was associated to immunoglobulin (IVIG). Our patient become rapidly afebrile. Vital signs and laboratory parameters of inflammation, CRP, lymphopenia, markers of cardiac injury, transaminases and renal function parameters all normalized. On day 28 of hospital stay, she was discharged with full dose of steroids and low dose of aspirin. Conclusion HHV6 reactivation needs a state of immunosuppression and was reported with acquired immunodeficiency syndrome (AIDS) and a variety of lymphoproliferative disorders. It leads to fever, cutaneous eruption as well as more serious complication such as hepatitis, which is the case with our patient. Ethics No conflicts of interest.

Discovery of indolinone-bearing benzenesulfonamides as new dual carbonic anhydrase and VEGFR-2 inhibitors possessing anticancer and pro-apoptotic properties

In the current medical era, the utilization of a single small molecule to simultaneously target two distinct molecular targets is emerging as a highly effective strategy in the battle against cancer. Carbonic Anhydrase (CA) and Vascular-Endothelial Growth Factor (VEGF) are genes that are activated in response to low oxygen levels (hypoxia) and play a role in the development and progression of tumors in hypoxic conditions. Herein we report the design, synthesis, and biological assessment of a series of novel indolinone-based benzenesulfonamides (8a-k, 11a-d, 15a-d, and 16) as potential dual inhibitors for cancer-associated hCA IX/XII and VEGFR-2. All the synthesized sulfonamides were assessed for their inhibitory effect against four CA isoforms I, II, IX, and XII where they displayed varying degrees of hCA inhibition. The most effective and selective hCA IX and XII inhibitors 8g, 8j and 15b were chosen to be tested for their in vitro inhibitory impact against VEGFR-2 as well as their antiproliferative impact against VEGFR-2 overexpressing MDA-MB-231 and MCF-7 breast cancer cells. Furthermore, molecular docking studies were conducted within the hCA IX, XII, and VEGFR-2 active sites to explain the observed inhibitory results.

Prognostic impact of the combination of HIF‑1α and GLUT1 in patients with oesophageal squamous cell carcinoma.

Oesophageal squamous cell carcinoma (ESCC) is a common type of carcinoma. Hypoxia is associated with chemo- and radio-resistance, which may lead to a poor prognosis. Hypoxia-inducible factor-1α (HIF-1α) is the main transcriptional regulator of the cellular response to low oxygen levels. Moreover, it can trigger the expression of critical genes, including glucose transporter protein type 1 (GLUT1). The aim of the present study was to evaluate the roles of HIF-1α and GLUT1 in ESCC and their usefulness as prognostic markers. HIF-1α and GLUT1 were measured in four ESCC cell lines, namely Eca109, KYSE150, TE-1 and TE-10, by western blotting following culture under normoxic and hypoxic conditions. In addition, xenograft tumors were established in mice using normoxic and hypoxic Eca109 cells and the chemosensitivity of the xenografts to 5-fluorouracil (5-FU) was evaluated. Furthermore, HIF-1α and GLUT1 were analysed by immunochemistry in the tumor tissues of patients with ESCC and the associations of their expression levels with clinicopathological parameters were investigated. The results revealed that HIF-1α and GLUT1 protein expression was weak in all four cell lines under a normoxic atmosphere but increased following culture in a hypoxic environment. In vivo, 5-FU inhibited tumor growth more strongly in normoxic Eca109 ×enografts than hypoxic Eca109 ×enografts. Higher levels of apoptosis were also detected in the normoxic Eca109 ×enografts via western blotting and TUNEL analysis. In patients with ESCC, HIF-1α expression was associated with advanced ESCC while GLUT1 expression was associated with the sex of the patients. Multivariate analysis demonstrated that HIF-1α and GLUT1 were negatively associated with progression-free survival (PFS) and overall survival (OS). Additionally, a combination of HIF-1α and GLUT1 expression was a predictor of RFS and OS in patients with ESCC without lymph node metastasis but not those with lymph node metastasis. The study demonstrated that HIF-1α and GLUT1 were strongly expressed in vitro and in xenograft models when cells were exposed to hypoxia. The simultaneous high expression of HIF-1α and GLUT1 was associated with poorer survival, and may play an important role in ESCC chemoresistance and the prognosis of ESCC.

Detección de Yersinia ruckeri en truchas arcoíris (Oncorhynchus mykiss Walbaum, 1792) infectadas naturalmente en criaderos de truchas en Anatolia, Turquía

The present study aimed to detect Yersinia ruckeri bacteria in fish samples collected from the rainbow trout (Oncorhynchus mykiss, Walbaum, 1792) farms in the South Eastern Anatolia Region of Turkey through bacteriological culturing and polymerase chain reaction. Separate visits were made to trout farming facilities in Diyarbakır, Adıyaman, Şanlıurfa, and Batman in January and February 2021, and 30 fish with an average live weight of 200–250 g were collected from each facility. A total of 1,200 samples were taken from 40 trout farms. Liver, spleen, kidney, and tissue specimens were collected from rainbow trout. Yersinia ruckeri was isolated from the kidney, liver and muscle tissue of fish on McConkey Agar for bacteriological examinations. Isolated strains were identified by MALDİ–TOF and PCR. It was detected the bacteria in the liver, kidney, and muscle tissue samples of fish from 23 out of 40 farms. In conclusion, these bacteria were detected in local farms. These farms must implement vaccination, minimize stress factors affecting the fish, and avoid overstocking. The best methods to protect against infection include avoiding overstocking, low oxygen levels, and underqualified labor force.

Microaerobic degradation of crude oil and long chain alkanes by a new Rhodococcus strain from Gulf of Mexico

Bacterial degradation of crude oil is a promising strategy for reducing the concentration of hydrocarbons in contaminated environments. In the first part of this study, we report the enrichment of two bacterial consortia from deep sediments of the Gulf of Mexico with crude oil as the sole carbon and energy source. We conducted a comparative analysis of the bacterial community in the original sediment, assessing its diversity, and compared it to the enrichment observed after exposure to crude oil in defined cultures. The consortium exhibiting the highest hydrocarbon degradation was predominantly enriched with Rhodococcus (75%). Bacterial community analysis revealed the presence of other hydrocarbonoclastic members in both consortia. In the second part, we report the isolation of the strain Rhodococcus sp. GOMB7 with crude oil as a unique carbon source under microaerobic conditions and its characterization. This strain demonstrated the ability to degrade long-chain alkanes, including eicosane, tetracosane, and octacosane. We named this new strain Rhodococcus qingshengii GOMB7. Genome analysis revealed the presence of several genes related to aromatic compound degradation, such as benA, benB, benC, catA, catB, and catC; and five alkB genes related to alkane degradation. Although members of the genus Rhodococcus are well known for their great metabolic versatility, including the aerobic degradation of recalcitrant organic compounds such as petroleum hydrocarbons, this is the first report of a novel strain of Rhodococcus capable of degrading long-chain alkanes under microaerobic conditions. The potential of R. qingshengii GOMB7 for applications in bioreactors or controlled systems with low oxygen levels offers an energy-efficient approach for treating crude oil-contaminated water and sediments.