Organ Protection Research Articles

A comprehensive organ protection strategy in total arch replacement: a propensity-weighted analysis.

To report the outcomes and determine the effectiveness of a comprehensive organ protection strategy in total arch replacement. A total of 350 patients who underwent total arch replacement were enrolled. 54 patients underwent the comprehensive organ protection strategy with bilateral antegrade cerebral perfusion (bACP) and aortic balloon occlusion (ABO) technique (comprehensive strategy group) and 296 patients underwent the standard strategy with unilateral antegrade cerebral perfusion (standard strategy group). Inverse probability of treatment weighting (IPTW) was used to balance the baseline characteristics. After IPTW, the comprehensive strategy group had lower incidences of 30-day mortality (0.9% vs 4.9%, P = 0.002), continuous renal replacement therapy (CRRT) (0.6% vs 10.3%, P < 0.001), renal failure (4.6% vs 13.7%, P < 0.001), hepatic dysfunction (11.6% vs 21.1%, P = 0.001), and shorter duration of mechanical ventilation [16 (13, 31) vs 20 (14, 48) hours, P = 0.011]. Multivariable logistic analysis showed the comprehensive strategy was an independent protective factor of 30-day mortality (odds ratio (OR): 0.242, 95% confidence interval (CI): 0.068-0.867, P = 0.029), CRRT (OR: 0.045, 95% CI: 0.008-0.264, P = 0.001), renal failure (OR: 0.351, 95% CI: 0.156-0.788, P = 0.011), and mechanical ventilation >20 hours (OR: 0.531, 95% CI: 0.319-0.883, P = 0.015). Kaplan-Meier analysis showed mid-term survival was comparable. The comprehensive organ protection strategy might improve early survival, reduce the use of CRRT, have protective effects on the kidney, and shorten mechanical ventilation time in total arch replacement. This strategy might be considered a viable alternative in total arch replacement.

Anti irradiation nanoparticles shelter immune organ from radio-damage via preventing the IKK/IκB/NF-κB activation

BackgroundNormal tissue and immune organ protection are critical parts of the tumor radiation therapy process. Radiation-induced immune organ damage (RIOD) causes several side reactions by increasing oxidative stress and inflammatory responses, resulting in unsatisfactory curability in tumor radiation therapy. The aim of this study was to develop a novel and efficient anti irradiation nanoparticle and explore its mechanism of protecting splenic tissue from radiation in mice.MethodsNanoparticles of triphenylphosphine cation NIT radicals (NPs-TPP-NIT) were prepared and used to protect the spleens of mice irradiated with X-rays. Splenic tissue histopathology and hematological parameters were investigated to evaluate the protective effect of NPs-TPP-NIT against X-ray radiation. Proteomics was used to identify differentially expressed proteins related to inflammatory factor regulation. In addition, in vitro and in vivo experiments were performed to assess the impact of NPs-TPP-NIT on radiation therapy.ResultsNPs-TPP-NIT increased superoxide dismutase, catalase, and glutathione peroxidase activity and decreased malondialdehyde levels and reactive oxygen species generation in the spleens of mice after exposure to 6.0 Gy X-ray radiation. Moreover, NPs-TPP-NIT inhibited cell apoptosis, blocked the activation of cleaved cysteine aspartic acid–specific protease/proteinase, upregulated the expression of Bcl-2, and downregulated that of Bax. We confirmed that NPs-TPP-NIT prevented the IKK/IκB/NF-κB activation induced by ionizing radiation, thereby alleviating radiation-induced splenic inflammatory damage. In addition, when used during radiotherapy for tumors in mice, NPs-TPP-NIT exhibited no significant toxicity and conferred no significant tumor protective effects.ConclusionsNPs-TPP-NIT prevented activation of IKK/IκB/NF-κB signaling, reduced secretion of pro-inflammatory factors, and promoted production of anti-inflammatory factors in the spleen, which exhibited radiation-induced damage repair capability without diminishing the therapeutic effect of radiation therapy. It suggests that NPs-TPP-NIT serve as a potential radioprotective drug to shelter immune organs from radiation-induced damage.

Pharmacological activity, phytochemistry, and organ protection of lithospermic acid.

Lithospermic acid (LA) is a water-soluble phenolic acid compound extracted and separated from the dried root and the rhizome of Salviamiltiorrhiza Bge (Labiatae), possessing multiple biological activities. Firstly, in terms of pharmacological activities, LA has been proven to possess anti-inflammatory, antioxidant, autophagy activation, and antiapoptotic properties. Secondly, the pharmacokinetic characteristics of LA show rapid and extensive distribution in various tissues after intravenous administration, followed by rapid elimination and excretion. Additionally, potential therapeutic effects of LA have been found in various diseases such as thrombosis, Parkinson's disease, hepatitis B, diabetes, and psoriasis, among others. Particularly, LA has shown promising prospects in the treatment of clinical heart diseases and has been included in new drug formulations for the treatment of chronic angina, demonstrating superior efficacy compared to current cardiovascular drugs. In conclusion, this review comprehensively introduces the pharmacological mechanisms, pharmacokinetics, and protective effects in diseases of LA. These information can lay a theoretical foundation for the future development and new clinical applications of LA.

Urgent hybrid repair of a symptomatic dissection-related type ii thoracoabdominal aortic aneurysms.

Emergency repair of type II thoraco-abdominal aortic aneurysms is burdened by high perioperative morbidity and mortality. We report the case of a symptomatic type II post-dissection thoraco-abdominal aortic aneurysm that was treated by mean of a hybrid technique. The repair was carried out through two stages. In the first stage, we deployed two imbricated stent grafts in the descending thoracic aorta. A left carotid to left subclavian artery by-pass was preemptively performed in order to obtain a proper proximal landing zone and as part of the spinal cord protective maneuvers. The endovascular first stage was effective in obtaining proximal sealing but, as expected, did not prevent distal reperfusion of the aneurysmatic false lumen. Few hours later, we moved on to the second stage in which we repaired the aneurysmal distal thoracic and abdominal aortic segment by mean of a multibranched synthetic graft. The repair was carried out through a left thoracophrenolaparotomy in the VII intercostal space. A left passive arterial by-pass and selective cold renal and warm visceral perfusion were adopted in order to provide organ protection. Technical success was achieved and radiologically confirmed. The patient experienced a mild postoperative paraplegia, which almost completely regressed after a neuro-motor rehabilitation program.

Research progress in the clinical application of inhaled anesthetic sevoflurane.

Sevoflurane has been widely used in clinical anesthesia as an inhalation anesthetic. With the development of medicine, there have been several new applications in recent years, such as daytime surgery, labor analgesia, and combined nerve block for some surgeries. Moreover, as research progresses, it has been found that it not only has potential organ protection effects but can also be used to treat severe asthma and relieve the tracheal spasm state. In addition, local administration can effectively treat vascular ulcers. We briefly review the organ protective effect of sevoflurane, its application in dental treatment, asthma treatment, vascular ulcer treatment and some new progress in clinical application.

The Year in Cardiothoracic Transplant Anesthesia: Selected Highlights From 2022 Part II: Cardiac Transplantation

These highlights focus on the research that has been published in the year 2022 and is divided into preoperative, intraoperative, and postoperative sections. The preoperative section includes research pertaining to the assessment and optimization of candidates for HTX, donor optimization and the use of extended donors, organ protection systems, and donation after circulatory death (DCD) allografts, recipient factors including cannabis use, sex, race, and comorbidities such as obesity, diabetes mellitus, and peripartum cardiomyopathy, the effects of the 2018 heart allocation policy change on waitlist and postoperative mortality, updates on HTX in patients with Covid-19, in pediatric patients, and those who require a bridge to transplant. The intraoperative section includes the use of a multidisciplinary team, a proposed transfusion algorithm, bench surgery on the allograft, and size matching. The postoperative section focuses on the research pertaining to the development and management of tricuspid regurgitation, echocardiography, arrhythmia management, and finally xenotransplantation.

Clinical Application of Equivalent Uniform Dose in Intensity-Modulated Rotational Radiotherapy Based on Eclipse TPS

To investigate the application of equivalent uniform dose (EUD) in intensity-modulated rotational radiotherapy and to explore optimization methods for improving the quality of modulated treatment plans. The impact of the parameter a in the EUD formula on the characteristics of the EUD curve was analyzed using Python. Thirty cases of head and neck tumors, thoracic tumors, and pelvic tumors were randomly selected for treatment planning. Dose optimization for the target area and organs at risk were performed using a physics-based optimization approach or an optimization approach that combines physical constraints with the EUD function. The dose distribution and compliance with constraints of the two groups of plans were compared, while also observing the effect of different values of a on the planning outcomes. The impact of the value of a on the changes in EUD curve characteristics was consistent with its impact on the results of EUD plan optimization. When -15≤ a≤-5, the dose distribution in the target area was more uniform; when 1≤ a≤7, the effect on the uniform dose and low-dose regions in organs at risk was more noticeable; when 10≤ a≤30, the effect of constraining the high-dose regions in organs at risk was more pronounced, with the EUD for the target area and organs at risk exhibiting different expressions under different a values. The study also found that the target dose distribution and the protection of organs at risk in the EUD optimization group were better than those in the physical optimization group only. The a-value has a significant impact on the, the dose distribution in the target area and the organ at risk, providing a reference for the setting of a-value while using EUD to optimize the intensity modulation plan. The using of EUD optimization method can not only achieve excellent dose distribution in the target area, but also significantly reduce the normal tissue dose and the probability of complications, which has certain clinical application value.

Simultaneous integrated boost-intensity modulated radiation therapy (SIBIMRT) planning for pelvic tumours: dose coverage to target volume and normal tissue sparing.

To evaluate the better radiotherapy plan for pelvic tumours that may achieve a high target coverage dose and low normal tissue tolerance dose using simultaneous integrated boost-intensity-modulated radiation therapy technique. The analytical, cross-sectional, descriptive study was conducted from October 2020 to March 2021 at Al- Amal National Hospital for Cancer Treatment, Baghdad, Iraq, and comprised male pelvic cancer patients aged 50-80 years. Computed tomography scans were randomly selected. For each patient, 4 treatment plans (phases Ι and Π) were generated using the simultaneous integrated boost-intensity-modulated radiation therapy technique while keeping all parameters constant except the number of beams, which were 5, 7, 9 and 11. The optimal and safe dose was defined as the one to cover 95% planning target volume. Homogeneity and conformity indices were used to assess the uniformity of dose distribution in the target volume, and various treatment plans in the same patient were compared. Data was analysed using SPSS 24. There were 15 males with mean age 67.12±2.84 years. There was a significant variance in the target volume dose and organ at risk in the 4 different plans generated using the simultaneous integrated boost-intensitymodulated radiation therapy technique (p<0.05). The 9-beam treatment plan was the best for coverage of tumours and protection of healthy organs assessed through homogeneity and conformity indices (p<0.05). The 9-beam treatment plan showed significant tumour coverage, homogeneity and conformity values, and sparing dose for organs at risk.

Normothermic ex vivo kidney perfusion preserves mitochondrial and graft function after warm ischemia and is further enhanced by AP39

We previously reported that normothermic ex vivo kidney perfusion (NEVKP) is superior in terms of organ protection compared to static cold storage (SCS), which is still the standard method of organ preservation, but the mechanisms are incompletely understood. We used a large animal kidney autotransplant model to evaluate mitochondrial function during organ preservation and after kidney transplantation, utilizing live cells extracted from fresh kidney tissue. Male porcine kidneys stored under normothermic perfusion showed preserved mitochondrial function and higher ATP levels compared to kidneys stored at 4 °C (SCS). Mitochondrial respiration and ATP levels were further enhanced when AP39, a mitochondria-targeted hydrogen sulfide donor, was administered during warm perfusion. Correspondingly, the combination of NEVKP and AP39 was associated with decreased oxidative stress and inflammation, and with improved graft function after transplantation. In conclusion, our findings suggest that the organ-protective effects of normothermic perfusion are mediated by maintenance of mitochondrial function and enhanced by AP39 administration. Activation of mitochondrial function through the combination of AP39 and normothermic perfusion could represent a new therapeutic strategy for long-term renal preservation.

Natural hydrogen gas and engineered microalgae prevent acute lung injury in sepsis

BackgroundHydrogen gas and microalgae both exist in the natural environment. We aimed to integrate hydrogen gas and biology nano microalgae together to expand the treatment options in sepsis. MethodsPhosphoproteomics, metabolomics and proteomics data were obtained from mice undergoing cecum ligation and puncture (CLP) and inhalation of hydrogen gas. All omics analysis procedure were accordance with standards. Multi R packages were used in single cell and spatial transcriptomics analysis to identify primary cells expressing targeted genes, and the genes’ co-expression relationships in sepsis related lung landscape. Then, network pharmacology method was used to identify candidate drugs. We used hydrophobic-force-driving self-assembly method to construct dihydroquercetin (DQ) nanoparticle. To cooperate with molecular hydrogen, ammonia borane (B) was added to DQ surface. Then, Chlorella vulgaris (C) was used as biological carrier to improve self-assembly nanoparticle. Vivo and vitro experiments were both conducted to evaluate anti-inflammation, anti-ferroptosis, anti-infection and organ protection capability. ResultsAs a result, we identified Esam and Zo-1 were target phosphorylation proteins for molecular hydrogen treatment in lung. Ferroptosis and glutathione metabolism were two target pathways. Chlorella vulgaris improved the dispersion of DQB and reconstructed morphological features of DQB, formed DQB@C nano-system (size = 307.3 nm, zeta potential = −22mv), with well infection-responsive hydrogen release capability and biosafety. In addition, DQB@C was able to decrease oxidative stress and inflammation factors accumulation in lung cells. Through increasing expression level of Slc7a11/xCT and decreasing Cox2 level to participate with the regulation of ferroptosis. Also, DQB@C played lung and multi organ protection and anti-inflammation roles on CLP mice. ConclusionOur research proposed DQB@C as a novel biology nano-system with enormous potential on treatment for sepsis related acute lung injury to solve the limitation of hydrogen gas utilization in clinics.

Extensive aortic replacement including aortic arch for a mega aorta with chronic aortic dissection via posterolateral thoracotomy

BackgroundMega-aortic syndrome including aortic arch and descending aortic aneurysm is a challenging surgical case. Because the aorta continuously dilates, creating the distal anastomosis sites becomes an issue. Despite the developments in endovascular techniques including frozen elephant trunk, in the case of mega-aortic syndrome or mycotic aneurysm, extensive surgical repair is still a strong armamentarium. Our patient had a mega-aorta with chronic aortic dissection. Herein, we show tips regarding concurrent ascending, aortic arch, and descending aortic replacement via posterolateral thoracotomy for this relatively young patient.Case presentationA 46-year-old man with chronic kidney disease had chronic type A aortic dissection with an extensively dilated thoracic aorta from the distal ascending to the descending aorta measuring 63 mm in diameter and abdominal aorta measuring 50 mm. The short segment of the distal descending aorta was narrowed to 36 mm. The patient underwent a concurrent replacement of the distal ascending aorta, aortic arch, and descending aorta via a posterolateral thoracotomy. The patient was extubated on postoperative day (POD) 1 and discharged home without serious complications such as stroke, respiratory failure, or renal failure on POD 18. The 1-year follow-up computed tomography did not find issues in the anastomosis sites; however, the abdominal aorta enlarged from 50 to 58 mm. The patient underwent a thoracoabdominal aortic replacement and recovered well without any complications.ConclusionsGood exposure and meticulous organ protection methods are key to a safe concurrent replacement of the ascending, aortic arch, and descending aorta via posterolateral thoracotomy.

The mechanism of perioperative intravenous lidocaine in regulating the inflammatory response: A review.

Perioperative inflammatory responses are a series of endogenous immune responses produced by the body following surgical trauma. Excessive inflammatory response weakens the body's ability to repair surgical trauma and reduces the body's defense against the invasion of harmful factors, leading to a series of complications, such as infections, pain, and organ damage, which prolong the length of hospitalization and increase the risk of death. Lidocaine is a classical local anesthetic widely used in clinical practice because of its local anesthetic and antiarrhythmic effects. Several recent studies have shown that lidocaine modulates the body's inflammatory response, and that its anti-inflammatory properties can lead to analgesia, organ protection, and improved postoperative recovery. In this paper, we introduce the mechanism of the modulating effect of lidocaine on the perioperative inflammatory response and its clinical application, to provide a reference for the clinical prevention and treatment of the perioperative inflammatory response.

Effect of sodium–glucose co-transporter-2 inhibitors on survival free of organ support in patients hospitalised for COVID-19 (ACTIV-4a): a pragmatic, multicentre, open-label, randomised, controlled, platform trial

Patients hospitalised for COVID-19 are at risk for multiorgan failure and death. Sodium-glucose co-transporter-2 (SGLT2) inhibitors provide cardiovascular and kidney protection in patients with cardiometabolic conditions and could provide organ protection during COVID-19. We aimed to investigate whether SGLT2 inhibitors can reduce the need for organ support in patients hospitalised for COVID-19. This pragmatic, multicentre, open-label, randomised, controlled, platform trial was conducted across 63 sites in the USA, Spain, Brazil, Italy, and Mexico. Patients aged at least 18 years hospitalised for COVID-19 (moderate or severe illness) were randomly assigned (1:1), via an interactive voice system or web-response system, to receive locally available SGLT2 inhibitor (administered orally, once daily) plus standard-of-care or standard-of-care for 30 days. The primary outcome was organ support-free days evaluated through 21 days, assessed using intention-to-treat approach. This trial is registered on ClinicalTrials.gov, NCT04505774. The first patient was randomly assigned to the SGLT2 inhibitor domain on Dec 3, 2021. On March 31, 2023, at the recommendation of the data and safety monitoring board, enrolment in the SGLT2 inhibitor domain for both moderately and severely ill hospitalised patients was stopped prematurely for futility due to a low likelihood of finding a treatment benefit. The final randomised population consisted of 575 patients (mean age 72 years [SD 13], 242 (42%) female and 154 (27%) Hispanic; 504 in the moderate illness group and 71 in the severe illness group). 573 patients had a known 21-day outcome; 215 (75%) of 285 patients in the SGLT2 inhibitor plus standard-of-care group did not require respiratory or cardiovascular organ support versus 231 (80%) of 288 patients in the standard-of-care group. The adjusted odds ratio (OR) for an SGLT2 inhibitor effect on organ support-free days was 0·74 (95% Credible Interval [CrI] 0·48-1·13; where OR higher than 1 indicated treatment benefit, yielding a posterior probability of futility P(OR <1·2) of 99% and a posterior probability of inferiority P(OR<1·0) of 91%). There were 37 deaths (13%) in the SGLT2 inhibitor plus standard-of-care group and 42 deaths (15%) in the standard-of-care group at 90 days (hazard ratio 0·91 [95% CrI 0·58-1·43], probability of hazard ratio <1 of 66%). No safety concerns were observed with SGLT2 inhibitors, including no cases of ketoacidosis. SGLT2 inhibitors did not significantly increase days free of organ support or reduce mortality in patients hospitalised with COVID-19. SGLT2 inhibitors were well tolerated with no observed safety concerns. Overall, these findings do not support the use of SGLT2 inhibitors as standard care in patients hospitalised with COVID-19. National Institutes of Health.

Looking for the ideal medication for heart failure with reduced ejection fraction: a narrative review.

The main goals of the pharmacological treatment of Heart failure with reduced ejection fraction (HFrEF) are the reduction of mortality and the prevention of hospitalizations. However, other outcomes such as improvements in cardiac remodeling and clinical status, functional capacity and quality of life, should be taken into account. Also, given the significant inter-individual and intra-individual variability of HF, and the fact that patients usually present with comorbidities, an appropriate treatment for HFrEF should exert a clinical benefit in most patient profiles irrespective of their characteristics or the presence of comorbidities, while providing organ protection beyond the cardiovascular system. The aim of this narrative review is to determine which are the proven effects of the guideline-directed treatments for HFrEF on five key clinical outcomes: cardiovascular mortality and hospitalization due to HF, sudden death, reverse cardiac remodeling, renal protection and evidence in hospitalized patients. Publications that fulfilled the pre-established selection criteria were selected and reviewed. Renin-angiotensin system (RAS) inhibitors, namely angiotensin-converting enzyme inhibitors (ACE-I) and angiotensin II receptor blockers (ARBs) or angiotensin receptor-neprilysin inhibitors (ARNI), beta-blockers (BB), mineralocorticoid receptor antagonists (MRA), sodium-glucose co-transporter 2 inhibitors (SGLT2i) show a benefit in terms of mortality and hospitalization rates. ARNI, BB, and MRA have demonstrated a significant positive effect on the incidence of sudden death. ARB, ARNI, BB and SGLT2i have been associated with clear benefits in reverse cardiac remodeling. Additionally, there is consistent evidence of renal protection from ARB, ARNI, and SGLT2i in renal protection and of benefits for hospitalized patients from ARNI and SGLT2i. In conclusion, the combination of drugs that gather most beneficial effects in HFrEF, beyond cardiovascular mortality and hospitalization, would be ideally pursued.

571. A PHASE I/II MULTICENTER STUDY EVALUATING THE EFFICACY AND SAFETY OF INDUCTION IMMUNOCHEMOTHERAPY FOLLOWED BY CONCURRENT IMMUNO-CHEMORADIOTHERAPY IN UNRESECTABLE LA-ESCC

Abstract Background Despite advances in radiotherapy techniques, the prognosis for patients undergoing definite chemoradiotherapy remains suboptimal. There exists an urgent and unmet need to enhance the efficacy of concurrent chemoradiotherapy for patients with unresectable Locally Advanced Esophageal Squamous Cell Carcinoma (LA-ESCC). Immunotherapy, when combined with chemotherapy, has emerged as the established first-line treatment for advanced esophageal cancer. Significant tumor shrinkage and reduced tumor residual observed after induction immunotherapy might provide the potential to enhance locoregional control of radiotherapy as well as better protection of critical organs and circulating lymphocytes. Methods We conducted a multicenter, phase I/II study aiming to assess the efficacy and safety of induction immunochemotherapy followed by immuno-chemoradiotherapy (ICRT) for unresectable LA-ESCC (SCR-ESCC-002, NCT06173986) (Figure 1). Eligible patients will initiate treatment with 2-3 cycles of immunochemotherapy. Within 4 weeks after completing the induction treatment, patients without disease progression will proceed to receive concurrent radiotherapy (45-50Gy in 25 fractions), weekly chemotherapy, and PD-1 inhibitor on day1,22. Following immuno-chemoradiotherapy, patients will continue with immunotherapy maintenance until disease progression or unacceptable toxicity, for a maximum duration of one year. The study's dual primary endpoints are progression-free survival and treatment completion rate. Results As of January 2024, 13 eligible patients were enrolled in our trial, with median follow-up of 7.8 months. Due to tumor shrinkage of induction immunochemotherapy, radiation doses to normal tissues were significantly reduced, particularly for the lungs, heart, and vertebrae. All 13 patients completed the planned induction treatment and radiotherapy, with 8 completing more than 4 weekly chemotherapies. During ICRT, 10 of 13 patients experienced grade 3-4 adverse events. These included lymphopenia (69.23%), myelosuppression (46.15%), hepatitis (7.69%), esophagitis (7.69%), and pneumonitis (7.69%). Nine patients achieved a complete response, and 3 partial response 4 weeks after ICRT according to RECIST v1.1. Conclusion Decreased radiation volumes due to tumor regression brought by induction immunochemotherapy diminish the occurrence of non-hematological adverse events during ICRT. Preliminary analysis suggests that this therapeutic modality exhibits favorable safety profiles and yields a superior clinical complete response rate compared to definitive chemoradiotherapy alone. The trial is presently enrolling participants, and the confirmation of efficacy and survival outcomes necessitates larger sample sizes and extended follow-up durations.

Cardamom Essential Oil-Loaded Nanostructured Lipid Carrier Reduces Obesity and Mitigates Diabetes Mellitus in Rats Fed with High Sugar/High Fat Diet

Background: Obesity is a chronic disease and one of the characteristic features of metabolic syndrome that is associated with severe health problems such as diabetes, hypertension, and cardiovascular diseases. Objective: To assess the effectiveness of the Cardamom Essential Oil-Loaded Nanostructured Lipid Carrier) CEO-NLC) as a potential therapeutic agent to lower blood sugar and an anti-inflammatory, antioxidant, and weight-reducing agent. Methods: A total of 24 male Wistar rats, aged 8–10 weeks and weighing 200–410 g, were used in this study. The rats were divided into four groups: negative control (G1), diabetic control (G2), treatment group (CEO-NLC) (G3), and positive control (Empagliflozin; EMPA) (G4). Diabetes was induced in all groups by injection of Streptozotocin (50 mg/kg) except G1. Then, animals were treated consecutively for four weeks. On day 29, they were sacrificed, and blood/tissue samples were collected for serological and histopathological analysis, respectively. Results: Significant decrease in blood sugar levels on day 28 for both the CEO-NLC group and EMPA versus diabetic control group were seen (250 mg in CEO-NLC, and 300 mg in EMPA, vs 450 mg in the diabetic control group). CEO-NLC achieved a significant effect as a weight-losing agent (p = 0.004). Proinflammatory biomarkers and kidney and liver function tests were enhanced after CEO-NLC treatment. Additionally, substantial histopathological modifications in the CEO-NLC group were also seen compared to the diabetic group and EMPA group. Conclusions: CEO-NLC has potential activity in lowering blood sugar levels, aiding weight loss, and eventually, organ protection ability.

Effects of renal denervation on the incidence and severity of cardiovascular diseases.

Renal denervation (RDN) is a neuromodulation therapy performed in patients with hypertension using an intraarterial catheter. Recent randomized sham-controlled trials have shown that RDN has significant antihypertensive effects that last for more than 3 years. Based on this evidence, the US Food and Drug Administration has approved two devices, the ultrasound-based ReCor ParadiseTM RDN system and the radiofrequency-based Medtronic Symplicity SpyralTM RDN system, as adjunctive therapy for patients with refractory and uncontrolled hypertension. On the other hand, there have been no randomized sham-controlled prospective outcome trials on RDN, and the effects of RDN on cardiovascular events such as myocardial infarction, heart failure, and stroke have not been elucidated. This mini-review summarizes the latest findings focusing on the effects of RDN on organ protection and physiological function and symptoms in both preclinical and clinical studies. Furthermore, the feasibility of using blood pressure as surrogate marker for cardiovascular outcomes is discussed in the context of relevant clinical studies on RDN. A comprehensive understanding of the beneficial effects of RDN on the incidence and severity of cardiovascular diseases with their underlying mechanisms will enhance physicians' ability to incorporate RDN into clinical strategies to prevent cardiovascular events including myocardial infarction, heart failure, and stroke. This mini-review focuses on the effects of RDN on organ protection and physiological function and symptoms in preclinical and clinical studies. RDN is expected to reduce the onset and progression of cardiovascular diseases including myocardial infarction, heart failure, and stroke in clinical practice.LV left ventricular, LVEF left ventricular ejection fraction, VO2max maximal oxygen uptake, VT ventricular tachycardia, VF ventricular fibrillation, 6MWD 6-min walk distance, NT-proBNP N-terminal pro-B-type natriuretic peptide, NYHA New York Heart Association, BBB blood-brain barrier, BP blood pressure.

Green Molecular Reactor Boosting the Photocatalytic Aerobic Oxidation of Sulfides in Clean Solvent

AbstractThe synthesis of sulfoxides has long attracted considerable interest due to their pivotal role in organic synthesis, pharmaceutics and environmental protection. Oxidation of the corresponding sulfides is recognized as the most effective strategy. Traditional oxidation methods, however, fall short of the growing demands of green chemistry. Photocatalytic aerobic oxidation has thus garnered attention, employing the greenest and most sustainable oxidants—oxygen or air—and sunlight as the energy source. Nevertheless, these reactions are typically conducted in potentially pollutive organic solvents rather than in the greenest solvent, water. To facilitate this organic transformation in aqueous phase, molecular reactors that can encapsulate reactants within their confined pores and facilitate photocatalytic reactions have been developed recently. This Concept article summarizes the development of molecular reactors for the photocatalytic oxidation of sulfides and provides perspectives for the design and construction of effective photocatalytic molecular reactors.

Aloperine Attenuates Hepatic Ischemia/Reperfusion-Induced Liver Injury via STAT-3 Signaling in a Murine Model.

Hepatic ischemia/reperfusion (I/R) damage is one of the most common side effects of liver surgery. This pathophysiological process may lead to excessive hepatic damage. Aloperine is an active ingredient isolated from Sophora alopecuroides Linn and has a variety of therapeutic effects, including organ protection. However, the hepatoprotective effect of aloperine against hepatic I/R damage has not yet been determined. C57BL/6 mice were allocated to the sham-operated (sham), hepatic ischemia/reperfusion (I/R), and aloperine groups. The mice were exposed to 30 min of hepatic hilum occlusion. Then a 3-h reperfusion was performed. Mice in the sham group underwent sham surgery. Hepatic injury was evaluated by plasma aspartate aminotransferase (AST) and transaminase alanine aminotransferase (ALT) levels, histological evaluation, cell apoptosis, the number of activated inflammatory cells, and the expression levels of inflammatory cytokines, including tumor necrosis factor-α and interleukin-6. The protein phosphorylation status of the reperfusion-associated survival pathways was evaluated. Mice with hepatic I/R injury presented increased plasma ALT and AST levels, increased hepatic apoptosis, abnormal histological structure, and elevated inflammatory responses. However, aloperine ameliorated hepatic I/R-induced injury. Moreover, aloperine enhanced the level of signal transducer and activator of transcription (STAT)-3 phosphorylation after I/R. Ag490, an agent that inhibits STAT-3 activity, abolished aloperine-induced STAT-3 phosphorylation and liver protection. Aloperine ameliorates hepatic I/R-induced liver injury via a STAT-3-mediated protective mechanism. Patients with hepatic I/R injury may benefit from aloperine treatment. SIGNIFICANCE STATEMENT: Hepatic I/R can cause excessive liver damage. This study revealed that aloperine, an active component isolated from Sophora alopecuroides Linn, ameliorates hepatic I/R injury and related liver damage in vivo. The underlying protective mechanism may involve the STAT-3 signaling pathway. These findings may lead to the development of a novel approach for treating hepatic I/R damage in clinical practice.

Identification of human circulating factors following remote ischemic conditioning (RIC): Potential impact on stroke

Remote ischemic conditioning (RIC) is a procedure consisting of short cycles of ischemia applied in a limb that activates endogenous protection in distant organs, such as the brain. Despite the promising outcomes of RIC, the biochemical factors governing inter-organ communication remain largely unexplored, particularly in humans. A pilot study on 20 healthy humans was performed to identify potential circulating biochemical factors involved in RIC signalling. Blood was collected before and immediately, 4 and 22 h after the end of RIC. To characterize the responses triggered by RIC, a combination of biochemical and proteomic analysis, along with functional in vitro tests in human cells, were performed.RIC did not alter the levels of nitric oxide, bilirubin and cell-free mitochondrial DNA. In contrast, carboxyhaemoglobin levels increased following RIC at all time points and young subset, suggesting endogenous production of carbon monoxide that is a cytoprotective gasotransmitter. Additionally, the levels of glutathione and cysteinylglycine bound to proteins also increased after RIC, while glutathione catabolism decreased. Plasma proteomic analysis identified overall 828 proteins. Several steps of statistical analysis (Student's t-test, repeated measures ANOVA, with Holm corrected pairwise p-values <0.05 threshold and fold change higher or lower than 100 %) leaded to the identification of 9 proteins with altered circulating levels in response to RIC at 4h and 22h. All 9 proteins are from extracellular space or exosomes, being involved in inflammation, angiogenesis or metabolism control. In addition, RIC-conditioned plasma from young subjects protected microglial cell culture against inflammatory stimuli, indicating an anti-inflammatory effect of RIC. Nevertheless, other functional tests in neurons or endothelial cells had no effect. Overall, we present some evidence for RIC-induced anti-inflammatory and antioxidant responses in healthy human subjects, in particular in young subjects. This study is a first step towards the disclosure of signalling factors involved in RIC-mediated inter-organ communication.