Vital Organ Function Research Articles

Advancements in Extracorporeal Therapies for Managing Sepsis: A Comprehensive Review

Sepsis remains a critical condition associated with high morbidity and mortality rates despite advances in medical care. The dysregulated host response to infection leads to systemic inflammation and multi-organ dysfunction, often exacerbated by a cytokine storm involving both proinflammatory and anti-inflammatory mediators. Extracorporeal therapies have emerged as potential adjuncts in sepsis management, aiming to mitigate the inflammatory response and support vital organ function. These therapies include various modalities such as adsorption of inflammatory mediators, removal of endotoxins and cytokine clearance using specialised filters and devices. This review explores the principles, mechanisms and clinical evidence surrounding extracorporeal therapies in sepsis, highlighting their potential benefits and current limitations. Key devices discussed include polymyxin B haemoperfusion, CytoSorb haemoadsorption, high-volume hemofiltration and novel technologies such as the oXiris membrane and Seraph-100 Microbind Affinity Blood Filter. Clinical trials and studies assessing these therapies provide insights into their efficacy in improving haemodynamics, organ function and mortality outcomes in septic patients. Despite promising results in certain trials, variability in patient responses and conflicting evidence necessitate further research to refine treatment protocols and optimise patient selection criteria for extracorporeal therapies in sepsis.

Cardiovascular Diseases, Vital Organ Fibrosis, and Chronic Inflammation Associated with High-Intensity and/or High-Volume Exercise Training: Double-Edged Sword Effects of Vigorous Physical Activity in Elderly People and/or in Middle-Age Cancer-Therapy-Treated Patients.

Cardiotoxicity, cardiovascular diseases (CVDs), hypertension, hepatotoxicity, and respiratory problems occurring several months to several years post-chemotherapy and/or radiotherapy are increasingly documented by scientists and clinicians. Anthracyclines, for example, were discovered in the late 1960s to be dose-dependently linked to induced cardiotoxicity, which frequently resulted in cardiomyopathy and heart failure. Most of those changes have also been associated with aging. While it is well known that exercise can slow down cellular aging processes, lessen the effects of chemotherapy, improve the effectiveness of cancer treatments, and prevent health problems in the general population, it remains unclear how exercise volume or intensity may affect the overall benefits of physical activity on health. For instance, higher rates of sudden cardiac arrest or coronary artery calcification have been found in marathon and ultra-marathon runners. Several additional pathological consequences have also been reported recently on many organs of those athletes. This review reports the most recent evidence suggesting that excessive intensity and/or volume may have deleterious effects on health. These findings are in clear contrast with the popular belief that all forms of physical activity can generally reduce the pathological changes associated with aging or cancer therapies. In conclusion, high-intensity training (HIT) and/or high-volume training (HVT) should not be recommended for middle-age and elderly people who have had cancer therapies or not in order to avoid an exacerbation of the consequences of aging or long-term cancer treatment effects on vital organ structures and functions.

Peran Orang Tua dalam Mencegah Paparan Asap Rokok pada Anak Usia Dini

Children as the next generation of the nation require special attention to health aspects to ensure optimal growth and development. One of the worrying health threats is the high exposure of children to cigarette smoke, which contains dangerous chemicals such as nicotine, tar, and carbon monoxide. Exposure to cigarette smoke can damage the respiratory system, interfere with brain development, and affect the function of vital organs, especially in early childhood whose body systems are still vulnerable. The impacts include an increased risk of respiratory tract infections, asthma, and various other health problems that can have long-term impacts. The role of parents is very important in efforts to prevent exposure to cigarette smoke, starting from setting an example by not smoking to creating an environment free from cigarette smoke. In addition, education about the dangers of cigarette smoke needs to be given to children from an early age to increase their awareness of the importance of maintaining health. The active role of parents in building a healthy environment and educating children about the risks of cigarette smoke is an essential step in creating a healthier generation free from exposure to cigarette smoke.

Safety and efficacy of oral edible bird’s nest supplementation: Anti-inflammatory and immunomodulatory benefits for Arabian race stallions during exercise

Background and Aim: Exercise-induced oxidative stress and inflammation adversely affect the health and performance of athletic horses. This study aimed to evaluate the safety of edible bird’s nest (EBN) supplementation and its potential anti-inflammatory and immunomodulatory effects in Arabian race stallions during exercise. Key objectives included assessing EBN’s impact on hepatic and renal function, hematological profiles, and sialic acid (SA) levels. Materials and Methods: Two experiments were conducted on 18 Arabian stallions. In Experiment 1, six healthy stallions were divided into control (n = 2) and EBN-supplemented groups (n = 4) to assess safety. The treatment group received 10 g of EBN daily for 12 days. Vital signs, hematological parameters, and organ function markers were monitored. In Experiment 2, 12 stallions were divided into three groups: EBN (n = 3), Premier E® (n = 3), and control (n = 6). The exercise regimen included a daily 10-min walk, 10-min canter (30 km/h), and 10-min walk for 30 days. Blood samples were analyzed for hematological indices and SA levels pre- and post-exercise. Results: In Experiment 1, EBN supplementation demonstrated no adverse effects, maintaining normal hematological and vital parameters. Kidney and liver function tests revealed significantly reduced creatine kinase, total bilirubin, and aspartate aminotransferase levels in the EBN group. Experiment 2 showed higher SA levels post-exercise in the EBN group (p < 0.05) compared to Premier E® and control groups, suggesting enhanced anti-inflammatory response. Hematological indices, including mean corpuscular volume, red cell distribution width, and platelet counts, were significantly improved in the EBN group, indicating potential immunomodulatory benefits. Conclusion: EBN supplementation is safe and offers anti-inflammatory and immunomodulatory effects in Arabian race stallions, reducing exercise-induced hepatic and muscular stress markers while enhancing recovery. These findings support EBN as a valuable dietary supplement for performance horses. Further studies should explore long-term effects and molecular mechanisms to optimize its use in equine sports. Keywords: anti-inflammatory, arabian race stallions, edible bird’s nest, exercise stress, immunomodulatory.

Machine learning methods for spectrally-resolved imaging analysis in neuro-oncology

To reduce the frequency of relapses after surgical removal a brain tumor, it is critically important to completely remove all affected areas of the brain without disrupting the functionality of vital organs. Therefore, intraoperative differential diagnostics of micro-areas of tumor tissue with their subsequent removal or destruction is an urgent task that determines the success of the operation as a whole. Optical spectroscopy has shown its advantages over the past decade when used as a tool for intraoperative metabolic navigation. And one of the most promising options for the development of this technology is spectrally-resolved imaging. Currently, methods of spectrally-resolved imaging in diffusely reflected light have been developed, for example, mapping the degree of hemoglobin oxygen saturation, as well as fluorescence visualization systems, for both endogenous fluorophores and special fluorescent markers. These systems allow rapid analysis of tissue by the composition of chromophores and fluorophores, which allows the neurosurgeon to differentiate tumor and normal tissues, as well as functionally significant areas, during surgery. No less mandatory are the methods of using spectrally resolved visualization based on mapping characteristics obtained from Raman spectra, but due to the smaller cross-section of the process, these methods are used ex vivo, as a rule, for urgent analysis of fresh tissue samples. In this paper, we focus on both the physical foundations of such methods and a very important aspect of their application – machine learning (ML) methods for image processing and tissues’ classification.

Ailanthone blocks mitophagy to promote mtDNA leakage through BAX-BAK1 pores and suppress hepatocellular carcinoma cell proliferation.

Hepatocellular carcinoma (HCC), the third leading cancer mortality worldwide, shows rising incidence. The mitochondria in HCC cells are prone to damage from metabolic stress and oxidative stress, necessitating heightened mitophagy for mitochondrial homeostasis and cell survival. Thus, mitophagy inhibition is a promising HCC therapy. The traditional Chinese medicinal herb ailanthone have proved promote mitochondrial dysfunction and inhibits HCC. However, the underlying mechanism remains unclear. CCK8 assay was applied to detect the proliferation. JC-1, MitoTracker Red/Green and MitoSOX staining were applied to detect the mitochondrial homeostasis. Inflammatory factors were analysed via ELISA and WB assay. Mitochondria and cytoplasm separation, genome extraction and qPCR were used to detect mitochondrial DNA (mtDNA) leakage. Mitochondria ultrastructure was detected by transmission electron microscopy. WB and IHC experiments were applied to detect protein expression. Protein-protein interactions detected by immunoprecipitation and immunofluorescence imaging. The in vivo antitumor effect was validated by the xenograft mouse model. In this study, we demonstrated the potent anti-HCC properties of ailanthone and revealed its molecular mechanism. In vitro studies demonstrated that ailanthone effectively inhibited PINK1-PRKN mediated mitophagy and promoted BAX-BAK1 mitochondrial pores formation through PRKN inhibition. This process led to the mitochondrial mtDNA leakage into the cytoplasm, which subsequently triggered the induction of inflammatory factors. The inhibition of mitophagy and the activation of inflammatory response ultimately led to HCC proliferation inhibition. In vivo studies demonstrated that ailanthone exhibited stronger anti-HCC activity than 5-Fluorouracil (5-FU), with no significant adverse effects on animal body weight or the physiological functions of vital organs. This study highlighted the efficacy of ailanthone against HCC and elucidated its underlying molecular mechanisms, suggesting the promising therapeutic potential of ailanthone for HCC.

Metabolic acidosis and sudden infant death syndrome: overlooked data provides insight into SIDS pathogenesis.

Decades of mainstream SIDS research based on the Triple Risk Model and neuropathological findings have failed to provide convincing evidence for a primary CNS-based mechanism behind putative secondary dyshomeostasis (respiratory or cardiac) or impaired arousal. Newly revealed data indicate that severe metabolic acidosis (and severe hyperkalemia) is a common accompaniment in SIDS. This supports the direct effect of sepsis on vital-organ function and occurrence of secondary CNS changes accompanied by the dyshomeostasis leading to SIDS. Using PubMed and Google Scholar literature searches, this paper examines how metabolic acidosis and sepsis might contribute to the underlying pathophysiologic mechanisms in SIDS. The discovery of a series of non-peer-reviewed publications provided the basis for a serious examination of the role of metabolic acidosis and sepsis in SIDS. Most SIDS risk factors relate directly or indirectly to infection. This consequently elevated the position of septic or superantigenic shock and viremia in causing secondary organ failure leading to SIDS. The latter could include diaphragmatic failure, as evidenced by peripheral respiratory (muscle) arrests in experimental septic shock, as well as infectious myositis and diaphragm myopathy in sudden unexpected deaths, including SIDS. In addition, just as acidosis lowers the threshold for ventricular fibrillation and sudden cardiac arrest, it could also contribute to similarly unstable diaphragm excitation states leading to respiratory failure. This paper uniquely reveals compelling evidence for a connection between metabolic acidosis, sepsis, viral infections, and sudden unexpected child deaths and provides a solid basis for further work to define which pathway (or pathways) lead to the tragedy of SIDS. It is recommended that all autopsies in sudden unexpected deaths should include pH, bicarbonate, lactate, and electrolyte measurements, as well as diaphragm histology.

Assessment of the organ function as the primary intention of clinical reasoning applied to the critically ill patient.

This article examines how clinical reasoning about the critical patient is currently treated and draws attention to some critical issues already often highlighted in the literature. Traditional approaches to clinical reasoning, even when applied to critical patients, prioritize identifying structured diseases. In contrast, the critical care setting demands an alternative approach that aligns with the intensivist's goal of supporting or substituting vital organ functions. In this manuscript, we emphasized the reasons that make it primary for intensivists to obtain a diagnosis of function in order to act therapeutically. Moreover, we highlighted the challenges posed by diagnostic errors, often attributed to cognitive biases and shortcomings in clinical reasoning, which can adversely affect patient outcomes and resource utilization. We also discussed the complexities of clinical decision-making in emergency medical services, where physicians must perform rapid actions in the face of incomplete information and high uncertainty. We underscore the limitations of traditional information technology tools in facilitating practical clinical reasoning, advocating for the integration of relevant data that directly informs on organ function and pathophysiological mechanisms. This discourse emphasizes a deep understanding of physiology and pathophysiology as foundational for practical clinical reasoning in critical care. Finally, we propose a structured assessment method that prioritizes pinpointing the compromised organ function, elucidating the pathophysiological mechanism responsible, hypothesizing potential causes, and testing these hypotheses to guide therapeutic interventions. This approach aligns clinical reasoning with the intensivist's goal: supporting and restoring vital functions in the critically ill patient.

The impact of ulinastatin on lymphocyte apoptosis and autophagy in sepsis patients

This study aimed to assess the influence of ulinastatin (UTI) on lymphocyte apoptosis and autophagy in sepsis patients, as well as its effect on inflammatory factors and vital organ function, with the goal of providing insights for improved clinical management of sepsis. A total of 40 sepsis patients were randomly assigned to the UTI group or the control group. The UTI group received standard treatment plus intravenous UTI, while the control group received standard treatment alone. Peripheral blood samples were collected at multiple time points for analysis of lymphocyte apoptosis, autophagy, inflammatory markers, and organ function. Various experimental techniques including Hoechst staining, transmission electron microscopy, and Western blot analysis were utilized to assess lymphocyte apoptosis, autophagy, and related protein expression levels. The study revealed that UTI treatment significantly inhibited lymphocyte apoptosis and promoted autophagy in sepsis patients. The levels of autophagy-related proteins LC3-II and Beclin-1 were substantially elevated, while the ratio of anti-apoptotic Bcl-2 to pro-apoptotic Bax was increased following UTI treatment. Furthermore, the levels of inflammatory markers IL-6, procalcitonin, and C-reactive protein were markedly reduced in the UTI group compared to the control group. Additionally, UTI treatment led to improved liver, kidney and cardiac function as evidenced by reduced levels of liver enzymes and creatinine, and cardiac enzymes. The findings of this study demonstrate that UTI exerts a protective effect on septic patients by inhibiting lymphocyte apoptosis, promoting autophagy, and attenuating systemic inflammation. Moreover, UTI treatment was associated with improved liver, kidney, and cardiac function in septic patients. These results contribute to a better understanding of the clinical management of sepsis and underscore the potential of UTI as a therapeutic intervention in septic patients.

Assessment of Bilirubin, Alkaline Phosphatase, Aspartate and Alanine Transaminases of Domestic Gas Factory Workers

Gasoline station workers are regularly exposed to many hazardous toxins vapors which can cause abnormal alterations in the functioning of many vital organs and they are associated with increased risk of liver dysfunction. This study was carried out to evaluate the Alkaline phosphatase (ALP), Aspartate Aminotransferase (AST), Alanine aminotransferase (ALT) and Bilirubin in domestic cooking gas factory workers in Benin City, Edo State. ALT, AST and ALT were determined enzymatically, while bilirubin was determined using Chemical Pathology semi-autoanalyzer. Statistical analysis was done using one-way analysis of variance (ANOVA) and the student’s t-test. Significant difference was accepted at p<0.05. The results presented in mean ± standard deviation showed that the total bilirubin (mg/dl) of the subjects and control group was 1.12±0.33 and 0.52±0.18, conjugated bilirubin (mg/dl) was 0.44±0.12 and 0.28±0.13, AST (U/L) was 10.33±2.35 and 6.97±2.14, ALT (U/L) was 8.43±2.37 and 5.50±2.05, while ALP (U/L) was 74.83±19.51 and 37.37±17.23 respectively. Total bilirubin, conjugated bilirubin, AST, ALT and ALP were significantly higher (p<0.05) in domestic gas factory workers compared with control group. The total bilirubin (mg/dl) of male and female subjects was 1.25±0.36 and 0.97±0.15, conjugated bilirubin (mg/dl) was 0.45±0.11 and 0.41±0.12, AST (U/L) was 10.83±2.33 and 9.33±1.92, ALT (U/L) was 8.79±2.32 and 7.58±2.10, while ALP (U/L) was 79.91±17.56 and 64.17±19.61 respectively. The total bilirubin (mg/dl) of domestic gas factor workers who have worked for less than 1 year, between 1 – 5 years and for more than 5 years was 0.94±0.22, 1.14±0.25 and 1.54±0.24, conjugated bilirubin (mg/dl) was 0.38±0.09, 0.43±0.09 and 0.57±0.08, AST (U/L) was 8.43±1.16, 10.50±1.60 and 12.91±1.81, ALT (U/L) was 6.50±1.95, 8.79±1.42 and 10.45±1.81, while ALP (U/L) was 57.71±16.73, 78.28±10.40 and 93.55±11.04 respectively. The study concludes that exposure to gasoline by domestic gas factory workers showed increase liver function test parameters. This study observed that the domestic gas factory workers are at risk of developing biochemical alterations in the hepatic enzymes and liver function tests. Long term exposure to gasoline should be monitored, thus calling for collaboration between the health workers and gas factory management to ensure frequent monitoring of their workers health.

The Relationship Between Chronic Energy Deficiency and Anemia in Pregnant Women at The Madandan Community Health Center Rantetayo District Tana Toraja Regency

Chronic Energy Deficiency in pregnant women negatively impacts maternal health and fetal development, leading to weight loss, fatigue, weakness, and reduced immunity. CED also increases the risk of anemia, which can decrease oxygen supply and disrupt vital organ function. Anemia in pregnant women can cause fatigue, reduced productivity, and a higher risk of pregnancy and childbirth complications. This quantitative cross-sectional study aimed to analyze the relationship between CED and anemia in 40 pregnant women out of a total population of 64 at the Madandan Community Health Center, Tana Toraja. Data collection was carried out using a questionnaire, and the analysis employed a chi-square test. The results of Fisher's Exact Test indicated a significant association (p 0.000 < 0.05) between Chronic Energy Deficiency and anemia among pregnant women seeking treatment at the Madandan Community Health Center. The study recommends that community health centers enhance education on balanced nutrition for pregnant women through prenatal clinics, including up-to-date nutritional information, regular health monitoring, and provision of appropriate supplements to reduce the risk of anemia.

The Potential Health Risks of Catha edulis Forsk (Khat) Consumption on Some Vital Organs

Abstract Introduction/Objective Introduction: Catha edulis Forsk (Khat) leaves are widely chewed by adults in the Arabian Peninsula and the Horn of Africa for their mild stimulating properties. Objectives To investigate the impact of an aqueous extract of Catha edulis Forsk leaves on the proper functioning of vital organs. Methods/Case Report Methods: Materials and methods: Twenty-five female albino rats were divided into two groups: a control group and a treated group which received a daily gavage of 1 ml of aqueous Khat extract with a concentration of 700 mg/kg body weight for four weeks. The effects of this treatment on selected organs, including the brain, hippocampus, heart, and ovaries, were assessed using various measurements and analyses. Results (if a Case Study enter NA) Results: Results: The antioxidant evaluation showed a significant increase in MDA levels in the khat group and a significant decrease in GSH, SOD, and CAT levels compared to the control group. There was a significant decrease in IL-4 and a significant increase in TNF-α and TGF-β1 compared to the control group. In contrast, the cardiac enzymes; Troponin, CK, CPK, and GOT showed a significant increase compared to the control group. The results of the hormonal assay indicated a significant increase in LH, FSH, and testosterone levels, along with a significant decrease in estrogen in the khat group compared to the control group. Furthermore, the histological investigations revealed significant changes in tissue architecture in the studied organs. In the heart, the treated group exhibited an intact, thick pericardium, along with markedly apoptotic cardiac muscle fibers and others with pyknotic nuclei and mildly congested blood vessels and capillaries. The examination of brain tissues in the treated group showed thick meninges with mild inflammatory infiltrate, marked astrogliosis with degenerated neurons in the cerebral cortex, inflammatory infiltrate with abscess formation and mildly congested blood vessels and eosinophilic plaque-like area in the deep cortex, and scattered degenerated neurons and some neurons with nuclear vacuoles and average glial cells in the white matter. In the ovaries, sections showed primary, secondary, and antral follicles, scattered cystically dilated follicles with atrophied lining, and multiple corpora lutea in the edematous stroma with scattered apoptotic stromal cells. Conclusion Based on these findings, long-term use of khat as a chewing material may harm vital organs.

Providing Education on Basic Life Support to Increase Student Knowledge

Background: Basic Life Support (BLS) is an essential first aid action performed on individuals experiencing cardiac or respiratory arrest. The primary goal of BLS is to restore and maintain vital organ function through interventions like chest compressions and respiratory support. Knowledge, which arises from experience and observation, is enhanced through education. This process aims to improve understanding and, consequently, decision-making abilities. Purpose: The aim of this Community Service (PkM) project is to increase the knowledge of students at MAN 1 Banyumas regarding Basic Life Support. Method: The methods used in this PkM included lectures and discussions. The students' knowledge was assessed before and after the educational intervention using a structured knowledge questionnaire. Findings: The participants of this PkM were predominantly middle adolescents aged 15-17 years, with 29 participants (96.7%) falling within this age range. The majority were female, comprising 26 participants (86.7%). Most of the participants were in grade 11, accounting for 22 participants (73.3%). Before the educational intervention, the knowledge levels were as follows: Good: 2 participants (6.7%), Sufficient: 12 participants (40.0%), Poor: 16 participants (53.3%). After the BLS education, there was a marked improvement in knowledge, with all 30 participants (100%) achieving a "Good" level of knowledge. Conclusions: Education on basic life support at MAN 1 Banyumas significantly improved students' knowledge, with a higher percentage achieving a good understanding after the training.

Urinary proteomic signature of mineralocorticoid receptor antagonism by spironolactone: evidence from the HOMAGE trial

ObjectiveHeart failure (HF) is characterised by collagen deposition. Urinary proteomic profiling (UPP) followed by peptide sequencing identifies parental proteins, for over 70% derived from collagens. This study aimed to refine...

Cannabis sativa (Linnaeus, 1753): The use of its extract against Rhipicephalus linnaei (Audouin, 1826) ticks

To minimize the damage caused by synthetic acaricides to non-target organisms, the use of bioactives compounds extracted from plants has been considered. In this study, semi-engorged females of Rhipicephalus linnaei ticks were exposed to Cannabis sativa flower extract (submersion for 5 minutes in different concentrations diluted in ethanol 30 %) evaluated alterations in the integument and salivary glands. The results demonstrated that lower concentrations of the extract caused damage to both the integument and salivary glands, affecting the cuticular epithelial cells responsible for synthesizing all layers of the cuticle. The concentration of 2.5 mg/mL caused more extensive damage than 5.0 mg/mL, and 40 mg/mL completely disrupted the epithelium. Exposure of the salivary glands showed that at 2.5 ug/mL dose the glandular acini was disrupted, leaving only a heterogeneous mass with some nuclei of acinar cells, leading to acinar rupture. These findings indicate that the extract from Cannabis sativa flowers irreversibly alters the morphology and consequently, interferes with the functionality of different vital organs.

Role of Excessive Mitochondrial Fission in Seawater Immersion Aggravated Hemorrhagic Shock-Induced Cardiac Dysfunction and the Protective Effect of Mitochondrial Division Inhibitor-1.

Aims: Seawater immersion significantly aggravated organ dysfunction following hemorrhagic shock, leading to higher mortality rate. However, the effective treatment is still unavailable in clinic. Mitochondria were involved in the onset and development of multiple organ function disorders; whether mitochondria participate in the cardiac dysfunction following seawater immersion combined with hemorrhagic shock remains poorly understood. Hence, we investigated the role and possible mechanism of mitochondria in seawater immersion combined with hemorrhage shock-induced cardiac dysfunction. Results: Mitochondrial fission protein dynamin-related protein 1 (Drp1) was activated and translocated from the cytoplasm to mitochondria in the heart following seawater immersion combined with hemorrhagic shock, leading to excessive mitochondrial fission. Excessive mitochondrial fission disrupted mitochondrial function and structure and activated mitophagy and apoptosis. At the same time, excessive mitochondrial fission resulted in disturbance of myocardial structure and hemodynamic disorders and ultimately provoked multiple organ dysfunction and high mortality. Further studies showed that the mitochondrial division inhibitor mitochondrial division inhibitor-1 can significantly reverse Drp1 mitochondrial translocation and inhibit mitochondrial fragmentation, reactive oxygen species (ROS) accumulation, mitophagy, and apoptosis and then protect circulation and vital organ functions, prolonging animal survival. Innovation: Our findings indicate that Drp1-mediated mitochondrial fission could be a novel therapeutic targets for the treatment of seawater immersion combined with hemorrhagic shock. Conclusion: Drp1 mitochondrial translocation played an important role in the cardiac dysfunction after seawater immersion combined with hemorrhage shock. Drp1-mediated excessive mitochondrial fission leads to cardiac dysfunction due to the mitochondrial structure and bioenergetics impairment.

The mitochondrial division inhibitor Mdivi-1 protected organ function and extended the treatment window in rats with uncontrolled haemorrhagic shock.

To elucidate whether the application of the mitochondrial division inhibitor Mdivi-1 can protect organ function and prolong the treatment window for traumatic hemorrhagic shock. Before definitive haemostasis treatment, Mdivi-1 (0.25 mg/kg, 0.5 mg/kg and 1 mg/kg) was administered to uncontrolled haemorrhagic shock (UHS) model rats. Lactate Ringer's solution plus hydroxyethyl starch (130/0.4) was used as a control. The effects of Mdivi-1 on blood loss, fluid demand, survival time, vital organ function, myocardial mitochondrial structure, and mitochondrial function of the heart, liver, kidney and intestine, and oxidative stress at 1 hour after hypotensive resuscitation (50-60 mmHg) were investigated. In addition, we investigated the effect of varying doses of Mdivi-1 on the maintenance time of hypotensive resuscitation without definitive haemostasis and the beneficial effect of Mdivi-1 after prolonging the duration of hypotensive resuscitation to 2 hours. Compared to conventional resuscitative fluid, Mdivi-1 significantly reduced blood loss and fluid demand, improved important organ functions during hypotensive resuscitation, improved animal survival and reduced the incidence of early death. Mdivi-1 significantly alleviated oxidative stress injury, reduced mitochondrial damage and restored myocardial mitochondrial structure and mitochondrial function of the heart, liver, kidney and intestine. In addition, Mdivi-1 increased the maintenance time of hypotensive resuscitation and improved rat survival after the duration of hypotensive resuscitation was prolonged to 2 h. Mdivi-1 significantly prolonged the treatment window for traumatic hemorrhagic shock to 2 hours in UHS model rats. The underlying mechanism may be that Mdivi-1 inhibits excessive mitochondrial fission and oxidative stress and improves the structure and function of mitochondria.

Comparison of the In Vivo Efficacy of Cuban (Raydel®) and Chinese (BOC Science) Policosanol in Alleviating Dyslipidemia and Inflammation via Safeguarding Major Organs and Reproductive Health in Hyperlipidemic Zebrafish: A Twelve-Week Consumption Study.

Policosanol is a blend of long-chain aliphatic alcohols (LCAAs) and is well-known for several health-beneficial activities; however, the functionality of policosanol varied substantially based on the composition of LCAAs. In this study, two distinct policosanols, Raydel® (extracted from Cuban sugarcane wax) and BOC Sciences (extracted from Chinese sugarcane wax), were dietarily supplemented (0.1% w/w) for 12 weeks in hyperlipidemic zebrafish to examine their influence on the blood lipid profile and functionality of the liver, kidney, and reproductive organs. The results demonstrated a noteworthy impact of both policosanols on preventing high-cholesterol diet (HCD, 4% w/w)-induced dyslipidemia by decreasing total cholesterol (TC) and triglyceride (TG) levels in the plasma. However, compared to BOC Sciences, the Raydel® policosanol exhibited a significantly (p < 0.05) higher efficacy in reducing HCD-induced TC and TG levels. A substantial effect was observed exclusively with the Raydel® policosanol in mitigating HCD-impaired low-density-lipoprotein cholesterol (LDL-C) and high-density-lipoprotein cholesterol (HDL-C) levels. Hepatic histology and immunohistochemistry (IHC) analysis revealed the higher efficacy of Raydel® policosanol over BOC Sciences policosanol to prevent HCD-provoked fatty liver changes, cellular senescence, oxidative stress, and interleukin (IL)-6 production. Consistently, a significantly higher effect of Raydel® over BOC Sciences policosanol was observed on the protection of kidney, testis, and ovary morphology hampered by HCD consumption. In addition, Raydel® policosanol exhibited a notably stronger effect (~2-fold, p < 0.05) on the egg-laying ability of the zebrafish compared to policosanol from BOC Sciences. Furthermore, Raydel® policosanol plays a crucial role in improving embryo viability and mitigating developmental defects caused by the intake of an HCD. Conclusively, Raydel® policosanol displayed a substantially higher efficacy over BOC Sciences policosanol to revert HCD-induced dyslipidemia, the functionality of vital organs, and the reproductive health of zebrafish.

Systemic inflammation in midlife is associated with late-life functional limitations

Systemic inflammation generally coexists with functional limitations that seriously affect quality of life. This study aimed to investigate the association between systemic inflammation in midlife and the risk of functional limitations in late-life. A total of 10,044 participants with an average age of 53.9 ± 5.7 years at baseline were included in a cohort study. At the last follow-up, the prevalence of impaired activities of daily living (ADLs), instrumental activities of daily living (IADLs), and lower extremity function (LEF) was 14.7%, 21.6%, and 50.3%, respectively. The values of four inflammatory biomarkers were used to calculate the inflammation composite score. Compared with the participants in the lowest quartile of the inflammation composite score (Q1), those in the highest quartile (Q4) exhibited an odds ratio (OR) of 1.589 and a 95% confidence interval (CI) of 1.335–1.892 for impaired ADLs, an OR of 1.426 and a 95% CI of 1.228–1.657 for impaired IADLs, and an OR of 1.728 and a 95% CI of 1.526–1.957 for impaired LEF. The association between systemic inflammation and functional limitations was partly mediated by cardiac and brain function. The present study provides evidence that systemic inflammation in midlife is associated with a higher risk of late-life functional limitations. Protecting vital organ functions in midlife may have a positive impact on reducing the risk of future functional limitations.Trial registration: www.clinicaltrials.gov; Unique identifier: NCT00005131.

Acute Management of Sepsis beyond 24 Hours.

Sepsis manifests as a dysregulated immune response to an infection, leading to tissue damage, organ failure, and potentially death or long-term health issues. Sepsis remains a major health challenge globally, causing approximately 50 million cases and 11 million deaths annually. Early management of sepsis focuses on source control, antimicrobial treatment, and supporting vital organ function. Subsequent care includes metabolic, nutritional, and immune therapies to address the complex needs of septic patients. Metabolic management is based on obtaining moderate glucose targets. Nutritional support aims to mitigate hypercatabolism and muscle wasting, but aggressive early nutrition does not improve outcomes and could even be harmful. Immune modulation is crucial due to the dual nature of sepsis-induced immune responses. Corticosteroids have shown benefits in shock and organ dysfunction reversal and in mortality reduction with current guidelines recommending them in vasopressor therapy-dependent patients. In conclusion, sepsis management beyond the initial hours requires a multifaceted approach, focusing on metabolic, nutritional, and immune system support tailored to individual patient needs to enhance survival and recovery.