Tissue Hypoxia Research Articles

Macrophage Membrane-Camouflaged Nanozymes for Combating the Oxidative Stress-Microvascular Perfusion Negative Feedback in Ischemia-Reperfusion Induced Acute Kidney Injury.

Oxidative stress plays a critical role in the pathogenesis of ischemia-reperfusion injury (IRI)-induced acute kidney injury (AKI), driving necrosis of proximal tubule cells, inflammation, and capillary rarefaction. Inadequate perfusion resulting from capillary rarefaction can, in turn, induce chronic tissue hypoxia and exacerbate ischemic acute tubular necrosis, leading to an "oxidative stress-microvascular perfusion" negative feedback that further aggravate kidney damage. In this study, a macrophage membrane-camouflaged manganese-based antioxidant nanozyme (MB@LM) is developed for targeted delivery and oxidative stress relief in AKI therapy. By inheriting macrophage surface proteins, MB@LM selectively targets damaged renal tissues that overexpress adhesion molecules like intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), facilitating enhanced accumulation at the injury site. The manganese-based nanozyme core provides antioxidant enzyme-mimicking activities, effectively reducing oxidative stress and inhibiting apoptosis. In IRI-induced AKI mouse model, MB@LM treatment significantly reduces renal damage, restores renal microvascular perfusion as assessed by ultrasound imaging, and alleviated inflammation, demonstrating remarkable therapeutic efficacy. Overall, MB@LM represents a promising targeted therapy for AKI, offering precise delivery, potent antioxidant protection, and anti-inflammatory effects to support renal recovery and improve outcomes for AKI.

Anemia and retinopathy of prematurity: A narrative review

ABSTRACTRetinopathy of prematurity (ROP) and anemia are often comorbid in preterm and low birth weight infants in the United States. However, the relationship between ROP and anemia in infants is unclear across prospective and retrospective studies due to confounding from other comorbidities of prematurity and variable study designs. Molecular mechanisms that may underlie this association include tissue hypoxia, oxidative stress, inflammation, and the timing of onset of anemia relative to the phase of ROP. Furthermore, maternal or neonatal disruptions in iron homeostasis, leading to either iron deficiency or accumulation, have been associated with ROP. Further studies, including randomized clinical trials, are needed to better elucidate the association between ROP and anemia, as well as the impact of the timing of the onset of anemia.

Development of hemoglobin microbubbles for acoustic blood oxygen sensing: A study on PEGylation and gas core modification for in vivo applications.

The creation of innovative ultrasound contrast agents (UCAs) with the ability to monitor oxygen levels in real-time holds immense potential for advancing early diagnosis of various medical conditions such as hypoxic/reperfusion injury. In this study, we propose the development of oxygen sensitive UCAs using microbubbles composed of hemoglobin (HbMBs), which can function as sensors for blood oxygen levels. Previously, we performed a study highlighting the initial proof-of-concept efficacy of air-filled HbMBs in detecting oxygenation changes in vitro, offering a promising tool for clinically detecting tissue hypoxia. Nevertheless, a significant drawback of this approach is the potential for immune reactions and toxicity when hemoglobin is outside its natural red blood cell environment. Moreover, in vitro, HbMBs had low stability, with more than 90% decrease in their concentration after 120 minutes. Therefore, careful consideration of the surface properties and the gas core of HbMBs is crucial. Here, we formulated PEGylated HbMBs (PHbMBs), and investigated their stability, immunogenicity, and their acoustic response in oxygenated and deoxygenated media in vitro. We optimized PEGylated HbMBs (PHbMBs), showing a 42% reduction in immunogenicity and significantly improved stability in vitro, while maintaining their oxygen-binding and acoustic response. In vivo, PHbMBs demonstrated similar contrast enhancement to that of non-PEGylated MBs, demonstrating that PEGylation does not decrease HbMBs' acoustic signaling. Finally, changing the gas core from air to PFB increased PHbMBs' mean circulation time more than 11-fold, without diminishing their responsiveness to oxygen. Overall, the proposed oxygen sensitive PHbMBs offer a promising avenue for real-time acoustic detection of blood oxygen levels, paving the way for potential clinical applications in monitoring critically ill patients. STATEMENT OF SIGNIFICANCE: This research explores the emergent field of Acoustic Oxygen Imaging in vivo using hemoglobin-based microbubbles. This innovative contrast agent approach involves imaging using crosslinked biomaterial comprised of the hemoglobin protein, aiming to transform the way we monitor blood oxygen levels with ultrasound. This work fundamentally addresses central concerns of improving bubble stability and circulation life for eventual clinical use, while minimizing toxicity. Importantly, we demonstrate that PEGylation of hemoglobin microbubbles enhances their stability, reduces immunogenicity, and maintains acoustic responsiveness. The incorporation of perfluorobutane into the bubble core increases the longevity of these microbubbles in circulation, while sustaining their oxygen sensitivity. Favorable in vivo results highlight the potential of this technology in real-time acoustic detection of blood oxygen levels.

Electroacupuncture normalized tumor vasculature by downregulating glyoxalase-1 to polarize tumor-associated macrophage to M1 phenotype in triple-negative breast cancer.

Triple-negative breast cancer is a particularly aggressive type of breast cancer that is closely associated with abnormal vascularization within the tumor. However, traditional anti-VEGF therapies and other treatments have limited efficacy. Tumor-associated macrophages (TAMs) induce and regulate tumor angiogenesis. In recent years, regulating TAMs polarization has become a hot topic for research with objectives to normalize tumor vasculature and improve drug delivery and the tumor microenvironment. Our previous studies have found that peritumoral electroacupuncture (EA) can regulate tumor angiogenesis, but the underlying mechanism remains unclear. In this study, we examined the phenotype of TAMs and inflammatory factors to observe the effect of peritumoral electroacupuncture on the phenotypic polarization of TAMs. Based on this, we evaluated the structure and function of tumor vasculature. Finally, we conducted a preliminary exploration of the mechanism underlying the regulation of TAMs phenotypic polarization by peritumoral electroacupuncture. In this study, we found that peritumoral electroacupuncture could promote the phenotypic polarization of TAMs toward the M1 type, thereby reducing microvascular density in tumor tissue, increasing pericyte coverage, improving the stability of the basement membrane, promoting vascular maturation, and enhancing perfusion while reducing tissue hypoxia. Peritumoral electroacupuncture can promote the phenotypic polarization of TAMs toward the M1 type, leading to normalization of tumor vascular structure and function. The mechanism may be related to the downregulation of glyoxalase-1 and subsequent activation of the MGO-AGEs/RAGE axis.

Enhanced porphyrin-based hypoxia imaging by temporal oversampling of delayed fluorescence signal.

Protoporphyrin IX (PpIX) delayed fluorescence (DF) is inversely related to the oxygen present in tissues and has potential as a novel biomarker for surgical guidance and real-time tissue metabolism assessment. Despite the unique promise of this technique, its successful clinical translation is limited by the low intensity emitted. We developed a systematic study of ways to increase the PpIX DF signal through acquisition sampling changes, allowing optimized imaging at video rates. To accomplish signal increase, time-gating signal compression was achieved through changes in pulse frequency and power density, using sampling rates that are faster than the decay rate of the signal. The increased signal yield was tested and validated in vitro and then demonstrated in vivo, with comparison to settings that sample the full lifetime emission decay. Results in vitro and in vivo demonstrated that optimized timing could increase the detected intensity by a factor of 7. The images showed results that were superior than when sampling the full DF lifetime decay. The proposed timing optimization enhances PpIX-based DF real-time imaging of tissue hypoxia. By increasing sampling frequency and adjusting the acquisition gate and pulse width, the collected signal intensity improved sevenfold, demonstrated both in vitro and in vivo. The technique was shown to enable better visualization of small and anatomically challenging hypoxic structures. The improved target-to-background ratio and compatibility with pressure-enhanced sensing of tissue oxygen technique were demonstrated.

Intracardiac abscess in the clinical course of infective endocarditis complicated by acute heart failure

Background. Infective endocarditis (IE) remains a serious condition with a high incidence rate, ranging from 2.6 to 7 cases per 100,000 people, and has been increasing over recent decades. Intracardiac abscess (ICA) is one of the most severe complications of infective endocarditis, occurring in 30–40 % of cases involving native heart valves. Heart failure, the most common complication, is observed in 19–73 % of patients and often requires urgent surgical intervention. Objective: to determine the optimal diagnostic and treatment algorithm for patients with infective endocarditis complicated by acute heart failure (AHF) and intracardiac abscess. Materials and methods. From 2010 to 2023, at the Amosov National Institute of Cardiovascular Surgery of the National Academy of Medical Sciences of Ukraine, 473 surgeries were performed for active infectious endocarditis complicated by intracardiac abscesses, accounting for 15 % of all cases of IE. A comprehensive approach was used, including autopericardial patches, abscess debridement, reconstruction of the heart chambers, fibrous ring repair, valve replacement, and methods for preventing recurrences. Results. The patients were divided into two groups: ICA with AHF (N = 135, 28.5 %) and ICA without AHF (N = 338, 71.5 %). The average age of participants was 49.2 ± 1.2 years. In the overall group, procalcitonin and C-reactive protein levels were evaluated to characterize the inflammatory process. The inflammatory markers included leukocyte count, elevated erythrocyte sedimentation rate, and levels of C-reactive protein and procalcitonin. High levels of these markers indicate signs of persistent infection syndrome, immunosuppression, and catabolism. Increased blood lactate levels suggest tissue hypoxia and organ dysfunction. Acute heart failure was characterized by elevated levels of NT-proBNP, troponin, and creatine phosphokinase-MB. One hundred and thirty-five (28.5 %) infective endocarditis patients with ICA and signs of AHF at the preoperative stage of IV FC formed the study group. Conclusions. Successful treatment of IE depends on early surgical intervention and effective antibiotic therapy. Early detection of complications such as AHF and intracardiac abscesses is critically important. Autopericardial patches and modern surgical techniques significantly improve patient outcomes. Elevated markers such as NT-proBNP, troponin, C-reactive protein, procalcitonin, and lactate indicate the severity of the condition.

Targeting lung heme iron by aerosol hemopexin adminstration in sickle cell disease pulmonary hypertension.

Lung tissue from human patients and murine models of sickle cell disease pulmonary hypertension (SCD-PH) show perivascular regions with excessive iron accumulation. The iron accumulation arises from chronic hemolysis and extravasation of hemoglobin (Hb) into the lung adventitial spaces, where it is linked to nitric oxide depletion, oxidative stress, inflammation, and tissue hypoxia, which collectively drive SCD-PH. Here, we tested the hypothesis that intrapulmonary delivery of hemopexin (Hpx) to the deep lung is effective at scavenging heme-iron and attenuating the progression of SCD-PH. Herein, we evaluated in a murine model of hemolysis driven SCD-PH, if intrapulmonary Hpx administration bi-weekly for 10 weeks improves lung iron deposition, exercise tolerance, cardiovascular function, and multi-omic indices associated with SCD-PH. Data shows Hpx delivered with a micro-sprayer deposits Hpx in the alveolar regions. Hpx extravasates into the perivascular compartments but does not diffuse into the circulation. Histological examination shows Hpx therapy decreased lung iron deposition, 4-HNE, and HO-1 expression. This was associated with improved exercise tolerance, cardiopulmonary function, and multi-omic profile of whole lung and RV tissue. Our data provides proof of concept that treating lung heme-iron by direct administration of Hpx to the lung attenuates the progression of PH associated with SCD.

End-tidal carbon dioxide-guided extracorporeal cardiopulmonary resuscitation improves neurological prognosis in patients: a single-center retrospective cohort study.

Extracorporeal Cardiopulmonary Resuscitation (ECPR) is an effective intervention for restoring adequate circulatory perfusion after cardiac arrest. Ensuring high-quality Cardiopulmonary Resuscitation (CPR) before initiating Extracorporeal Membrane Oxygenation (ECMO) is critical to mitigate tissue hypoxia and ischemia. This study aimed to evaluate the effect of End-Tidal Carbon Dioxide (ETCO2) Goal-Directed CPR (GDCPR) on neurological function before ECMO using a retrospective case-control analysis. The medical records of all patients who received ECPR treated at Zhongshan City People's Hospital were collected between January 2020 and March 2023. In this retrospective cohort study, the patients were divided into Conventional CPR (CCPR) and ETCO2-GDCPR groups based on whether ETCO2 was used as a guide for CPR. A total of 71 patients were included, of whom 46 comprised the CCPR group and 25 comprised the GDCPR group. Approximately 37% of patients who received ECPR had good cerebral function at discharge, with a higher rate in the GDCPR group (52%) compared with the CCPR group (28%) (p = 0.047). Multivariate analysis showed that the Highest Interleukin-6 (H-IL6) levels after ECMO (Odds Ratio [OR = 1.001], 95% Confidence Interval [95% CI 1.000-1.003], p = 0.005) was a risk factor for neurological function at discharge. The other risk factors for poor prognosis in patients who received ECPR included pre-ECMO CPR protocols (OR = 10.74, 95% CI 1.90-60.48, p = 0.007) and IL6 levels after ECMO (OR = 1.002, 95% CI 1.001-1.003, p = 0.005). ECMO duration (OR = 0.83, 95% CI 0.74-0.94, p = 0.002) was identified as a protective factor. Patients with short ECMO duration have a poor prognosis. The area under the curve for ECMO duration was 0.86 (0.77-0.94, p < 0.01), while that for H-IL6 was 0.19 (0.09-0.29, p < 0.01). ETCO2-guided ECPR is associated with improved neurological prognosis and patient outcomes. Therefore, monitoring ETCO2 levels should be considered a crucial component of evaluating resuscitation efficacy during CPR.

Rod‐Shaped Microgel Scaffolds with Interconnective Pores and Oxygen‐generating Functions Promote Skin Wound Healing and Alleviate Hypertrophic Scar Formation

AbstractThe processes of skin wound healing and scar formation are complex, often involving hypoxia and inflammation, which create a pathological microenvironment that impedes normal healing. Improving wound oxygenation and reducing inflammation are crucial for accelerating healing and reducing scarring. Traditional dressings like sponges, gauze, and hydrogels struggle to balance moisture retention, breathability, and exudate absorption. To address these challenges, rod‐shaped microgel scaffolds with larger surface areas and interconnected porous structures are explored to enhance gas transport, promoting wound oxygenation and moisture retention, thus accelerating healing and reducing scarring. Nanoparticles (NPs) are used to mediate the formation of microgels‐assembled scaffold and to load catalase (CAT) for enhanced bioactivity. In vitro experiments showed that this material alleviated oxidative stress and reduced the activity of hypoxia‐inducible factor‐1α (HIF‐1α), nuclear factor kappa B (NF‐κB), and the downstream transforming growth factor‐β1 (TGF‐β)/Smad pathway in fibroblasts. The incorporation of CAT showed a significant promotion of M2‐phenotype macrophage polarization. In vivo studies on rat and rabbit wounds demonstrated that the microgel scaffolds significantly improved exudate absorption and breathability, maintaining a moist and oxygenated environment. These scaffolds reduced tissue hypoxia, accelerated wound healing, and decreased hypertrophic scar formation in vivo. This innovative method leveraged the unique properties of microgels to effectively enhance skin tissue regeneration.

Mountain sickness: physiological challenges, diagnosis and treatment

INTRODUCTION. The first descriptions of altitude sickness were made in (1540-1600). Nowadays, different cities in the world are at high altitude, for example Qinghai-Tibetan Plateau in China occupies an area of almost 2.5 million inhabitants km2, with an average elevation of over 4,500 m. Altitude sickness should be a major concern for anyone who normally resides at sea level. METHOD. A search for information was carried out in the period August-December 2024 in the SciELO, LILACS, Scopus, PubMed-MedLine databases, the Google Scholar search engine, as well as in the ClinicalKeys services. RESULTS AND DISCUSSION. The partial pressure of arterial oxygen (PaO2 ) decreases with altitude, which produces progressive tissue hypoxia. The normal compensatory response to hypobaric hypoxia is called acclimatization. Its main characteristic is increased ventilation. The ability to acclimatize varies widely among individuals and depends on many factors, including the degree of hypoxic stress (rate of ascent, altitude reached), the intrinsic ability of the individual to compensate for the decrease in PaO2, and extrinsic factors. Progressive ascent produces greater hypoxic stress, requiring greater degrees of physiological and behavioral adaptations to preserve function. The more rapid the ascent and the higher the altitude, the greater the stress. Below 1500 m, symptoms of high altitude illness are generally not manifest. From approximately 1500 to 2500 m, symptoms are generally mild, if experienced at all. From approximately 2500 m, mild to moderate symptoms become quite common among unacclimatized visitors after a rapid ascent. As a general rule, people who normally reside below 1500 m should avoid an abrupt ascent to altitudes above 2800 m for sleeping. Sedative-hypnotics should be avoided during acclimatization. Abstinence from alcohol is safest

A high fraction of inspired oxygen does not mitigate atelectasis-induced lung tissue hypoxia or injury in experimental acute respiratory distress syndrome

Although alveolar hyperoxia exacerbates lung injury, clinical studies have failed to demonstrate the beneficial effects of lowering the fraction of inspired oxygen (FIO2) in patients with acute respiratory distress syndrome (ARDS). Atelectasis, which is commonly observed in ARDS, not only leads to hypoxemia but also contributes to lung injury through hypoxia-induced alveolar tissue inflammation. Therefore, it is possible that excessively low FIO2 may enhance hypoxia-induced inflammation in atelectasis, and raising FIO2 to an appropriate level may be a reasonable strategy for its mitigation. In this study, we investigated the effects of different FIO2 levels on alveolar tissue hypoxia and injury in a mechanically ventilated rat model of experimental ARDS with atelectasis. Rats were intratracheally injected with lipopolysaccharide (LPS) to establish an ARDS model. They were allocated to the low, moderate, and high FIO2 groups with FIO2 of 30, 60, and 100%, respectively, a day after LPS injection. All groups were mechanically ventilated with an 8 mL/kg tidal volume and zero end-expiratory pressure to induce dorsal atelectatic regions. Arterial blood gas analysis was performed every 2 h. After six hours of mechanical ventilation, the rats were euthanized, and blood, bronchoalveolar lavage fluid, and lung tissues were collected and analyzed. Another set of animals was used for pimonidazole staining of the lung tissues to detect the hypoxic region. Lung mechanics, ratios of partial pressure of arterial oxygen (PaO2) to FIO2, and partial pressure of arterial carbon dioxide were not significantly different among the three groups, although PaO2 changed with FIO2. The dorsal lung tissues were positively stained with pimonidazole regardless of FIO2, and the HIF-1α concentrations were not significantly different among the three groups, indicating that raising FIO2 could not rescue alveolar tissue hypoxia. Moreover, changes in FIO2 did not significantly affect lung injury or inflammation. In contrast, hypoxemia observed in the low FIO2 group caused injury to organs other than the lungs. Raising FIO2 levels did not attenuate tissue hypoxia, inflammation, or injury in the atelectatic lung region in experimental ARDS. Our results indicate that raising FIO2 levels to attenuate atelectasis-induced lung injury cannot be rationalized.

Evaluation of Hypoxia Markers in Critically Ill Patients Categorized by Their Burden of Organ Dysfunction: A Novel Approach to Detect Pathophysiological and Clinical Relevance in a Secondary Analysis of a Prospective Observational Study.

In critically ill patients, compromised microcirculation causes tissue hypoxia, organ failure, and death. These pathophysiological processes occur particularly in patients with high illness severity, so reliable hypoxia biomarkers should reflect this in their occurrence. This secondary analysis of a prospective study categorized patients by their burden of organ dysfunction (BOD) using the cohort's median initial sequential organ failure assessment (SOFA) score of 8 as a cutoff. The kinetic parameters of the hypoxia markers lactate and S-adenosylhomocysteine (SAH) were analyzed for correlation with organ dysfunction severity and mortality prediction. In low BOD patients, neither marker correlated with SOFA. In high BOD patients, lactate showed a moderate correlation and SAH showed a strong correlation. Lactate correlated with organ dysfunction in survivors but not in non-survivors, while SAH correlated strongly in non-survivors but not in survivors. In univariate logistic regression, lactate predicted mortality moderately in low BOD (areas under the receiver operating characteristic curves (AUROCs) 0.7-0.8) but poorly in high BOD patients (AUROCs 0.5-0.7). SAH's prediction improved from poor to excellent (AUROCs 0.8-0.9) with higher BOD. Thus, SAH appears superior to lactate in the detection of organ dysfunction severity and mortality prediction in high BOD patients.

Ultra-small curcumin-ruthenium coordination polymer nanodots prevent renal ischemia-reperfusion injury and the progression to chronic kidney disease.

Renal ischemia-reperfusion (IR) induces tissue hypoxia, resulting in disrupted energy metabolism and heightened oxidative stress. These factors contribute to tubular cell damage, which is a leading cause of acute kidney injury (AKI) and can progress to chronic kidney disease (CKD). The excessive generation of reactive oxygen species (ROS) plays a crucial role in the pathogenesis of AKI. This study presents the synthesis of curcumin ultra-small coordination polymer (Ru/Cur) nanodots and their application in scavenging ROS in renal tissues. By adding ruthenium ions to a methanol solution containing the natural product curcumin, ultra-small Ru/Cur nanodots were successfully synthesized. To enhance the dispersibility of these nanoparticles in water, polyvinylpyrrolidone (PVP) was used as a growth aid, resulting in highly stable nanodots with sizes smaller than 10nm. The results indicated that Ru/Cur nanodots effectively eliminated various ROS and demonstrated significant therapeutic effects and biocompatibility in IR-AKI mice, reducing markers of kidney function damage, alleviating renal oxidative stress, and decreasing inflammatory cell infiltration. Ru/Cur nanodots inhibited renal fibrosis by suppressing epithelial-mesenchymal transition and the secretion of transforming growth factor-β1 in the model of IR-AKI to chronic kidney disease (CKD). In summary, our findings confirm that Ru/Cur nanodots mitigate the pathological conditions associated with both AKI and its progression to CKD by reducing IR-induced tubular cell injury.

Effect of ultrasound combined with microbubbles therapy on tumor hypoxic microenvironment.

Tumor tissues exhibit significantly lower oxygen partial pressure compared to normal tissues, leading to hypoxia in the tumor microenvironment and result in resistance to tumor treatments. Strategies to mitigate hypoxia include enhancing blood perfusion and oxygen supply, for example,by decomposing hydrogen peroxide within the tumor. Improving hypoxia in the tumor microenvironment could potentially improve the efficacy of cancer treatments. Previous studies have demonstrated that ultrasound of appropriate intensity when combined with microbubbles, can improve tumor blood perfusion. However, its effects on tumor hypoxia remain unclear. This study aimed to assess the effects of low-frequency non-focused ultrasound combined with microbubbles at different intensities on tumor microenvironment hypoxia and to identify the optimal ultrasound parameters for alleviating tumor hypoxia. Rabbits with VX2 tumors received ultrasound and microbubble treatments at different acoustic pressures and pulse repetition frequencies. The changes in tumor tissue blood perfusion before and after treatment were observed by contrast enhanced ultrasound (CEUS). The changes in tumor tissue hypoxia before and after treatment were observed by measuring oxygen partial pressure directly with in tumor tissue and immunohistochemical staining for hypoxia-inducible factor-1α (HIF-1α). Results indicated that low frequency, non-focused ultrasound at 0.5MPa/20Hz and 0.5MPa/40Hz, when combined with microbubbles, could increase tumor tissue blood perfusion and improve the hypoxia in tumor tissues. This study provides a new method for improving hypoxia in the tumor microenvironment (TME) which could potentially improve the cancer treatments resistance.

Cірководень: механізм токсичної дії, клінічні прояви гострого отруєння, патогістологічні ознаки та стратегія лікування

Hydrogen sulphide (H2S) is a highly toxic gas. Among this group of poisonous substances – causes of death – it is second only to carbon monoxide. The mechanism of its toxicity has not been sufficiently studied and there is currently no specific antidote therapy. This gas is a high-priority chemical threat in industry, as well as a potential terrorist weapon of mass destruction, especially in wartime. Aim. Based on literary data and own researches, to summarize the current concepts of its toxicity mechanisms, clinical manifestations, treatment strategies and pathohistological signs of acute hydrogen sulphide poisoning. Materials and Мethods. Open sources of public information and scientific literature on the research topic were analysed. An analytical review of the publications of scientific online libraries PubMed, Medline, Elsevier was carried out. A retrospective analysis of the medical documentation of two cases with acute poisoning with H2S in combination with other toxic gases was carried out. The first case of acute poisoning with H2S and other sewage gases is in a patient who died in the conditions of a medical institution in the Kyiv region, who fell ill after a 15-minute stay in a household sewage septic tank. In the victim, the data of sectional and microscopic studies of lung tissue were also studied. The second case of acute H2S poisoning in combination with other gases of putrefaction is represented by three victims hospitalized at the clinic of the Research Centre of Preventive Toxicology, Food and Chemical Safety named after L.I. Medved, Ministry of Healthcare of Ukraine after cleaning a deep tank with the remains of rotten sauerkraut. One of the victims died after 6 hours. The methods of system comparative and content analysis were applied. Results. Modern ideas about the mechanism of the toxic effect of H2S indicate that it is a rapidly metabolizing systemic toxicant that affects mitochondria, is the basis for the formation of tissue hypoxia, activation of oxidative stress, inflammatory reactions, and apoptosis. Under the acute effects of H2S, the main target organs are the nervous, bronchopulmonary and cardiovascular systems. Until now, there are no specific antidotes for the treatment of H2S poisoning, so it includes oxygen, symptomatic and supportive therapy. New therapeutic agents – potential antidotes are at the stage of preclinical research, most of which are aimed at binding H2S. There is an urgent need for the development of new therapeutic agents – absorbents (scavengers) of H2S for the prevention and treatment of poisoning, reducing morbidity and mortality. Keywords: hydrogen sulphide, toxicity, acute poisoning, treatment, pathohistological signs.

A Scoping Review of the Association between Hemoglobinopathies and Male Infertility

Worldwide, infertility is a prevalent problem that poses a threat to couples, either the male or female partner, or both spouses, may be the cause of infertility. Numerous elements about the patient's general health or way of life may be to blame. Systemic or gonadal dysfunction may be the cause of the patient's health issues. Hematological factors may be one of the systemic reasons. Thalassemia major (TM) and sickle cell disease (SCD) are the two most prevalent hemoglobinopathies that are suspected to be the cause of infertility, particularly male infertility. Through pathophysiological changes, these two hemoglobinopathies result in male infertility. In particular, they change red blood cells' (RBCs') capacity to carry oxygen, resulting in tissue hypoxia that impacts spermatogenesis and the body's natural process of producing new cells, ultimately leading to infertility. Semen analyses and other systemic blood testing can be used to investigate male infertility. Both hemoglobinopathies can be helped by blood transfusions, which can then alleviate male infertility. This paper aims to explore the relationship between hemoglobinopathies (SCD and TM) and their role in contributing to male infertility, in addition to the role of blood transfusions in addressing male infertility by correcting the root cause.

Enhancing Antituberculosis Treatment Nanoparticles Encapsulated with Catalase and Levofloxacin Under Ultrasound Stimulation: A 3D Spheroid Study.

Tuberculosis (TB) is a chronic infectious disease caused by Mycobacterium tuberculosis (MTB). Tuberculous granuloma is the central and key pathological structure of tuberculosis and is characterized by tissue hypoxia and ineffective drug delivery. To address these issues, this study fabricated a composite nanoparticle loaded with catalase (CAT) and levofloxacin (LEV) (CAT@LEV-NPs) and then combined it with ultrasound (US) to investigate the bactericidal effect and underlying mechanisms using TB spheroids. The TB spheroids were constructed using attenuated Bacillus Calmette-Guérin (BCG) instead of MTB to facilitate operation under general experimental conditions. This study examined the physical properties and oxygen production efficiency of CAT@LEV-NPs. Subsequently, we treated TB spheroids with nanoparticles alone or in combination with US and found that ultrasound significantly increased drug permeability and activated CAT@LEV-NPs to produce a large number of reactive oxygen species (ROS). The combined treatment showed excellent antibacterial effects, resulting in more severe damage to the bacterial structure than other treatments. Additionally, the combined treatment induced a higher M1 polarization of macrophages, increased the apoptosis rate, and improved the anoxic microenvironment in TB spheroids. These factors may be closely related to the enhanced bactericidal effects of combined treatment. In conclusion, our study suggests that US combined with CAT@LEV-NPs could serve as a novel, noninvasive, safe, and effective treatment modality for intractable MTB infections.

Obesity, dietary interventions and microbiome alterations in the development and progression of prostate cancer.

The role of the microbiome in prostate cancer is an emerging subject of research interest. Certain lifestyle factors, such as obesity and diet, can also impact the microbiome, which has been implicated in many diseases, such as heart disease and diabetes. However, this link has yet to be explored in detail in the context of prostate cancer. The purpose of this review is to explore the cross-talk between obesity, dietary interventions, and microbiome alterations in the development and progression of prostate cancer. Many possible mechanisms exist linking obesity and dietary interventions to microbiome alterations and prostate cancer. The gut microbiome produces metabolites that could play a role in prostate cancer oncogenesis, including short-chain fatty acids, cholesterol derivatives, and folic acid. The microbiome also plays a pivotal role in the prostate tumor microenvironment (TME), contributing to inflammation, local tissue hypoxia, and epithelial-mesenchymal transition. A bidirectional relationship exists between obesity and the microbiome, and certain diets can enact changes to the microbiome, its associated metabolites, and prostate cancer outcomes. Cross-talk exists between obesity, dietary interventions, and the role of the microbiome in the development and progression of prostate cancer. To further our understanding, future human studies in prostate cancer should investigate microbiome changes and incorporate an assessment of microbiome-derived metabolites and cellular/immune changes in the TME.

Semaglutide restores astrocyte–vascular interactions and blood–brain barrier integrity in a model of diet-induced metabolic syndrome

IntroductionMetabolic syndrome (MetS) is a metabolic disorder related to obesity and insulin resistance and is the primary determinant of the development of low-intensity chronic inflammation. This continuous inflammatory response culminates in neuroimmune-endocrine dysregulation responsible for the metabolic abnormalities and morbidities observed in individuals with MetS. Events such as the accumulation of visceral adipose tissue, increased plasma concentrations of free fatty acids, tissue hypoxia, and sympathetic hyperactivity in individuals with MetS may contribute to the activation of the innate immune response, which compromises cerebral microcirculation and the neurovascular unit, leading to the onset or progression of neurodegenerative diseases.ObjectiveThis study aimed to evaluate the effects of chronic treatment with a GLP-1 receptor agonist (semaglutide) on cerebral microcirculation and neurovascular unit (NVU) integrity.MethodsC57BL/6 mice were fed a standard normolipidic diet or a high-fat diet (HFD) for 24 weeks and then treated for 4 weeks with semaglutide (HFD SEMA) or saline solution (HFD SAL). At the end of pharmacological treatment, biochemical analyses, immunohistochemistry analysis, and intravital microscopy of the brain microcirculation were carried out to quantify leukocyte–endothelium interactions and to assess structural capillary density, astrocyte coverage on cerebral vessels and microglial activation.ResultsWe observed that SEMA attenuates high-fat diet-induced metabolic alterations in mice fed with HFD for 24 weeks. SEMA also reversed cerebral microcirculation effects of HFD by reducing capillary rarefaction and the interaction of leukocytes in postcapillary brain venules. The HFD-SEMA group exhibited improved astrocyte coverage on vessels. However, SEMA did not reverse microglial activation.ConclusionsSemaglutide can reverse microvascular rarefaction in metabolic syndrome by restoring the integrity of the neurovascular unit. Adverse dietary stimuli can compromise microglial homeostasis that is not reversed by semaglutide.

Effect of bromelain on ischemia-reperfusion injury in the torsion model created in polycystic and normal ovarian tissues.

Due to its increased volume, polycystic ovarian tissue is more prone to torsion than normal ovarian tissue. In treating ovarian torsion, detorsion is applied to ensure oxygenation of hypoxic tissues. However, the resulting oxygen radicals cause tissue damage. Bromelain is a substance obtained from pineapple, and studies in the literature show it is used as an antioxidant. This study aimed to evaluate the damage caused by ischemia-reperfusion (I/R) in the torsion-detorsion model created in normal and polycystic ovarian tissue and investigate the role of bromelain in this damage. Polycystic ovarian tissue was created by applying dihydroepiandrosterone sulfate to rats. Afterward, a torsion-detorsion model was used for all rats. The rats were divided into six groups: the polycystic ovary sham-operated group (P-S), the normal ovary sham-operated group (N-S), the polycystic ovary ischemia/reperfusion group (P-IR), the normal ovary ischemia/reperfusion group (N-IR), the polycystic ovary ischemia/reperfusion group treated with bromelain (P-IRB), and the normal ovary ischemia/reperfusion group treated with bromelain (N-IRB). After the procedure, tissues were collected for histopathological examination, and MDA, TUNEL, and NF-κB levels were measured. This study detected significant decreases in MDA and NF-κB levels and apoptotic cell numbers assessed by TUNEL staining in groups with IR damage and given bromelain compared to the control groups. The number of TUNEL-positive cells was found to be highest in the P-IR group (8.80 ± 2.98) and significantly lower in the bromelain-administered P-IRB (1.04 ± 1.09) and N-IRB (0.52 ± 0.58) groups (p< 0.05). NF-κB expression was also high in P-IR and N-IR groups, while it was significantly decreased in bromelain-treated groups (P-IRB and N-IRB) (p< 0.05). In addition, IR damage was more pronounced in polycystic ovary tissue than in normal ovary tissue. Ischemia perfusion damage may be more pronounced in polycystic ovarian tissue than in normal ovarian tissue. Bromelain may be preferred to prevent I/R injury caused by ovarian torsion. It is also thought that bromelain may function in treating polycystic ovaries, and further studies can be conducted on this subject.