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TGF-β is widely existed in tumor microenvironment, taking part in tumorigenesis process including angiogenesis, cancer associated fibroblast (CAF) proliferation, and immunosuppression. It inhibited the activation, proliferation, migration and differentiation of T cells, in which way caused a limited therapeutic effects of chimeric antigen receptor T (CAR-T) towards solid tumor such as lymphoma. To targeted block TGF-β at tumor site, we take advantages of nano-techniques to deliver TGF-β inhibitors LY2157299 (LY) towards the tumor sites, in order to help achieve a improved and long-term functions of CAR-T towards lymphoma. Based on amphipathic hydroxyethyl starch-polycaprolactone (HES-PCL), LY and photosensitizer indocyanine green (ICG) were co-loaded in HES-PCL to achieve LY/ICG@HES-PCL nanoparticle. The enhanced function of CAR-T benefited from LY/ICG@HES-PCL were verified through lymphoma Raji cells in vitro and Nod scid gamma mice engrafted with the Raji cells in vivo. LY was targeted transported to tumor site and accelerated release by mild ICG photothermal. Chemokines CXCL9/10/11 ​at the tumor site relevant to CAR-T migration and chemokines receptor CXCR3 of CAR-T could be up-regulated by LY, thus facilitated the enhanced accumulation of CAR-T at lymphoma site. T effector memory cells differentiation could also be accelerated by LY/ICG@HES-PCL. Combined therapy of LY/ICG@HES-PCL and CAR-T achieved 2.4 times higher antitumor activity and 2.7 times higher relapse inhibiting rates than CAR-T alone within 15 days and 11 days, respectively. The results suggested that LY/ICG@HES-PCL facilitated the enhanced therapeutic index of CAR-T cells towards lymphoma simply and safely, it may be further potentiated applied for other solid tumors.

Abstract Background Trauma may be associated with significant to life-threatening blood loss, which in turn may increase the risk of complications and death, particularly in the absence of adequate treatment. Hydroxyethyl starch (HES) solutions are used for volume therapy to treat hypovolemia due to acute blood loss to maintain or re-establish hemodynamic stability with the ultimate goal to avoid organ hypoperfusion and cardiovascular collapse. The current study compares a 6% HES 130 solution (Volulyte 6%) versus an electrolyte solution (Ionolyte) for volume replacement therapy in adult patients with traumatic injuries, as requested by the European Medicines Agency to gain more insights into the safety and efficacy of HES in the setting of trauma care. Methods TETHYS is a pragmatic, prospective, randomized, controlled, double-blind, multicenter, multinational trial performed in two parallel groups. Eligible consenting adults ≥ 18 years, with an estimated blood loss of ≥ 500 ml, and in whom initial surgery is deemed necessary within 24 h after blunt or penetrating trauma, will be randomized to receive intravenous treatment at an individualized dose with either a 6% HES 130, or an electrolyte solution, for a maximum of 24 h or until reaching the maximum daily dose of 30 ml/kg body weight, whatever occurs first. Sample size is estimated as 175 patients per group, 350 patients total (α = 0.025 one-tailed, power 1–β = 0.8). Composite primary endpoint evaluated in an exploratory manner will be 90-day mortality and 90-day renal failure, defined as AKIN stage ≥ 2, RIFLE injury/failure stage, or use of renal replacement therapy (RRT) during the first 3 months. Secondary efficacy and safety endpoints are fluid administration and balance, changes in vital signs and hemodynamic status, changes in laboratory parameters including renal function, coagulation, and inflammation biomarkers, incidence of adverse events during treatment period, hospital, and intensive care unit (ICU) length of stay, fitness for ICU or hospital discharge, and duration of mechanical ventilation and/or RRT. Discussion This pragmatic study will increase the evidence on safety and efficacy of 6% HES 130 for treatment of hypovolemia secondary to acute blood loss in trauma patients. Trial registration Registered in EudraCT, No.: 2016-002176-27 (21 April 2017) and ClinicalTrials.gov, ID: NCT03338218 (09 November 2017).

The article focuses on the impact of varying intravenous fluid volumes on mortality in adults with sepsis. Topics include the comparison of less versus more fluid volumes, the absence of significant differences in clinical outcomes such as mortality and serious adverse events, and the variability in study protocols and definitions.

Hair follicles constitute important drug delivery targets for skin antisepsis since they contain ≈25% of the skin microbiome. Nanoparticles are known to penetrate deeply into hair follicles. By massaging the skin, the follicular penetration process is enhanced based on a ratchet effect. Subsequently, an intrafollicular drug release can be initiated by various trigger mechanisms. Here, we present novel ultraviolet A (UVA)-responsive nanocapsules (NCs) with a size between 400 and 600 nm containing hydroxyethyl starch (HES) functionalized by an o-nitrobenzyl linker. A phase transfer into phosphate-buffered saline (PBS) and ethanol was carried out, during which an aggregation of the particles was observed by means of dynamic light scattering (DLS). The highest stabilization for the target medium ethanol as well as UVA-dependent release of ethanol from the HES-NCs was achieved by adding 0.1% betaine monohydrate. Furthermore, sufficient cytocompatibility of the HES-NCs was demonstrated. On ex vivo porcine ear skin, a strong UVA-induced release of the model drug sulforhodamine 101 (SR101) could be demonstrated after application of the NCs in cyclohexane using laser scanning microscopy. In a final experiment, a microbial reduction comparable to that of an ethanol control was demonstrated on ex vivo porcine ear skin using a novel UVA-LED lamp for triggering the release of ethanol from HES-NCs. Our study provides first indications that an advanced skin antisepsis based on the eradication of intrafollicular microorganisms could be achieved by the topical application of UVA-responsive NCs. [ABSTRACT FROM AUTHOR]

Purpose: To investigate vascular endothelial dysfunction based on glycocalyx impairment in massive hemorrhage and to evaluate fluid therapy. Methods: In this randomized controlled animal study, we withdrew 1.5 mL blood and administered 1.5 mL resuscitation fluid. Mice were divided into six groups according to the infusion type and administration timing: NS-NS (normal saline), NS-HES ([hydroxyethyl starch]130), HES-NS, NS-ALB (albumin), ALB-NS, and C (control) groups. Results: The glycocalyx index (GCXI) of a 40-μm artery was significantly larger in group C than in other groups (P < 0.01). Similarly, the GCXI for a 60-μm artery was significantly higher in group C than in NS-NS (P ≤ 0.05), NS-HES (P ≤ 0.01), and NS-ALB groups (P ≤ 0.05). The plasma syndecan-1 concentration, at 7.70 ± 5.71 ng/mL, was significantly lower in group C than in group NS-NS (P ≤ 0.01). The tetramethylrhodamine-labeled dextran (TMR-DEX40) fluorescence intensity in ALB-NS and HES-NS groups and the fluorescein isothiocyanate-labeled hydroxyethyl starch (FITC-HES130) fluorescence intensity in NS-HES and HES-NS groups were not significantly different from those of group C at any time point. FITC-HES130 was localized on the inner vessel wall in groups without HES130 infusion but uniformly distributed in HES130-treated groups in intravital microscopy. FITC-FITC-HES130 was localized remarkably in the inner vessel walls in group HES-NS in electron microscopy. Conclusions: In an acute massive hemorrhage mouse model, initial fluid resuscitation therapy with saline administration impaired glycocalyx and increased vascular permeability. Prior colloid-fluid administration prevented the progression of glycocalyx damage and improve prognosis. Prior HES130 administration may protect endothelial cell function. [ABSTRACT FROM AUTHOR]

Objective To investigate the effect of 6% hydroxyethyl starch（HES） 130/0.4 on the inflammatory mediators and its signal pathway micro RNA（miR）-146a/Toll-like receptor 4（TLR4）/nuclear factor-κB（NF-κB） in traumatic rabbits.Methods A total of 16 New Zealand male rabbits were selected in April 2022.After anesthesia, the hind limbs of the rabbits were beaten with blunt objects to cause hind limb fractures, and then the fractures were treated with open internal fixation.The skin was prepared and disinfected, the lateral incision of the fracture site was exposed, and the femur fracture site was exposed, after that a suitable domestic four-hole steel plate was placed across the fracture line.A soft tissue defect model was made in the muscle tissue corresponding to the fracture of about 2 cm×2 cm, and at the same time, the muscle tissue of the blood fracture was taken for backup examination（T0）.According to random number table method, the rabbits were divided into the sodium lactate Ringer（LR） group and the HES group, with eight rabbits in each group.The LR group was injected with 10 mL/kg LR,while the HES group was injected 10 mL/kg HES once a day for five days.After the infusion rabbits were anesthetized, the muscle tissue of the injured site was taken for backup examination（T1）.The enzyme-linked immunosorbent assay（ELISA） was used to determine tumor necrosis factor-α（TNF-α）,interleukin-1（IL-1） and IL-6 in blood of rabbits at T0 and T1,and western blotting was used to determine NF-κB P65,TLR4,IL-1 receptor-associated kinase 1（IRAK1）,and TNF receptor-associated factor 6（TRAF6） protein levels in the muscle tissue at T0 and T1.The reverse transcription-polymerase chain reaction was used to determine miR-146a in the rabbit muscle tissue at T0 and T1.Results Compared with T0,the levels of TNF-α,IL-1,IL-6 in blood, and the levels of miR-146a, NF-κB P65,TLR4,IRAK1,and TRAF6 protein in muscle of the two groups were significantly higher at T1,and the differences were statistically significant（P<0.05）.Compared with the LR group, the levels of TNF-α,IL-1 and IL-6 in blood, NF-κB P65,TLR4,IRAK1 and TRAF6 protein in muscle of the rabbits in the HES group were significantly lower at T1,while the level of miR-146a in muscle was significantly higher, with statistical significance differences（P<0.05）.Conclusion HES may upregulate miR-146a, negatively feedback to regulate IRAK1 and TRAF6 in the TLR4 signal pathway, and inhibit the production of inflammatory mediators, thus reducing the inflammatory response of traumatic rabbits. [ABSTRACT FROM AUTHOR]

Although the improving effect of nitric oxide (NO) donors has experimentally been demonstrated in shock, there are still no NO donor medications clinically available. Thiol-nitrosothiol-hydroxyethyl starch (S-NO-HES) is a novel molecule consisting of NO coupled to a thiolated derivative of hydroxyethyl starch (HES). It was aimed to assess the ability of S-NO-HES to serve as an NO donor under a variety of in vitro simulated physiologic conditions, which might be the first step to qualify this molecule as a novel type of NO donor-fluid. We studied the effect of temperature on NO-releasing properties of S-NO-HES in blood, at 34°C, 37°C, and 41°C. Ascorbic acid (Asc) and amylase were also tested in a medium environment. In addition, we evaluated the activity of S-NO-HES in the isolated aortic ring and Langendorff-perfused heart setup. The NO release property of S-NO-HES was found at any temperature. Asc led to a significant increase in the production of NO compared to S-NO-HES incubation (P < 0.05). The addition of amylase together with Asc to the medium further increased the release of NO (P < 0.05). S-NO-HES exerted significant vasodilatory effects on phenylephrine precontracted aortic rings that were dose-dependent (P < 0.01). Furthermore, S-NO-HES significantly increased the heart rate and additionally reduced the duration of the cardiac action potential, as indicated by a reduction of QTc-B values (P < 0.01). We demonstrated for the first time that the S-NO-HES molecule exhibited its NO-releasing effects. The effectiveness of this new NO donor to substitute NO deficiency under septic conditions or in other indications needs to be studied. [ABSTRACT FROM AUTHOR]

Sepsis is one of the most common and deadly syndromes faced in Intensive Care settings globally. Recent advances in bedside imaging have defined the changes in the microcirculation in sepsis. One of the most advocated interventions for sepsis is fluid therapy. Whether or not fluid bolus affects the microcirculation in sepsis has not been fully addressed in the literature. This systematic review of the evidence aims to collate studies examining the microcirculatory outcomes after a fluid bolus in patients with sepsis. We will assimilate the evidence for using handheld intra vital microscopes to guide fluid resuscitation and the effect of fluid bolus on the sublingual microcirculation in patients with sepsis and septic shock. We conducted a systematic search of Embase, CENTRAL and Medline (PubMed) using combinations of the terms "microcirculation" AND "fluid" OR "fluid resuscitation" OR "fluid bolus" AND "sepsis" OR "septic shock". We found 3376 potentially relevant studies. Fifteen studies published between 2007 and 2021 fulfilled eligibility criteria to be included in analysis. The total number of participants was 813; we included six randomized controlled trials and nine non-randomized, prospective observational studies. Ninety percent used Sidestream Dark Field microscopy to examine the microcirculation and 50% used Hydroxyethyl Starch as their resuscitation fluid. There were no clear effects of fluid on the microcirculation parameters. There was too much heterogeneity between studies and methodology to perform meta-analysis. Studies identified heterogeneity of affect in the sepsis population, which could mean that current clinical classifications were not able to identify different microcirculation characteristics. Use of microcirculation as a clinical endpoint in sepsis could help to define sepsis phenotypes. More research into the effects of different resuscitation fluids on the microcirculation is needed. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effectiveness of bromocriptine for prevention of ovarian hyperstimulation syndrome (OHSS). Methods: The retrospective study included women at risk of OHSS who were receiving gonadotropin‐releasing hormone antagonist protocols, including 52 women given 2.5 mg bromocriptine by rectal insertion, 52 women given 500 ml intravenous hydroxyethyl starch (HES), and 40 women who received no intervention. Treatments were administered daily for 5 days beginning on the day of oocyte retrieval. Baseline information and data related to OHSS were compared. Results: No significant differences were found among groups in estradiol concentration on the day of trigger or in number of retrieved oocytes. Incidence of mild OHSS was not significantly different among groups, respectively 13.5%, 15.4%, and 17.5% (P > 0.05). The incidence of moderate to severe OHSS was significantly lower in the bromocriptine and HES groups compared with the control group, respectively 7.7%, 5.8%, and 22.5% (P < 0.05). D‐dimer levels were significantly lower in the bromocriptine and HES groups compared with the control group on Day 5 after oocyte retrieval (P < 0.05). No differences in liver or renal function were found in the three groups. Conclusion: Bromocriptine was apparently as effective as intravenous HES in patients with high risk of OHSS. Synopsis: Prophylactic rectal administration of bromocriptine showed similar effects to intravenous hydroxyethyl starch in patients with high risk of ovarian hyperstimulation syndrome. [ABSTRACT FROM AUTHOR]

Introduction: Optimal intraoperative fluid management guided by central venous pressure (CVP), a traditional intravascular volume status indicator, has improved transplanted graft function during kidney transplantation (KT). Pulse pressure variation (PPV) and stroke volume variation (SVV) – dynamic preload indexes – are robust predictors of fluid responsiveness. This study aimed to compare the accuracy of PPV and CVP against SVV in predicting fluid responsiveness in terms of cost‑effectiveness after a standardised empiric volume challenge in KT patients. Methods: 36 patients undergoing living‑donor KT were analysed. PPV, SVV, CVP and cardiac index (CI) were measured before and after fluid loading with a hydroxyethyl starch solution (7 mL/kg of ideal body weight). Patients were classified as responders (n = 12) or non‑responders (n = 24) to fluid loading when CI increases were ≥10% or <10%, respectively. The ability of PPV, SVV and CVP to predict fluid responsiveness was assessed using receiver operating characteristic (ROC) curves. Results: SVV and CVP measured before fluid loading were correlated with changes in CI caused by fluid expansion (ρ = 0.33, P = 0.049 and ρ = −0.37, P = 0.026) in contrast to PPV (ρ = 0.14, P = 0.429). The ROC analysis showed that SVV and CVP predicted response to volume loading (area under the ROC curve = 0.781 and 0.727, respectively; P < 0.05). Conclusion: Under the conditions of our study, SVV and CVP exhibited similar performance in predicting fluid responsiveness and could inform fluid management during KT as compared with PPV. [ABSTRACT FROM AUTHOR]

It has been documented that hemodynamic disturbances occur in hypovolemic patients. Therefore, the early management of hypovolemia is essential to achieve optimal outcomes. Blood gas, which changes rapidly during hemodynamic instability, can be used as a diagnostic approach for monitoring emergency patients. The objective of the current study was to evaluate the results of resuscitation with hydroxyethyl starch (HES) or lactated Ringer's solution (LR) on venous and arterial blood gas. In addition, the difference between venous and arterial blood gas parameters is investigated to assess the possibility of using venous blood gas analysis as a successor for arterial blood gas analysis in the resuscitation of hypovolemic dogs. Venous and arterial pH, PO2, PCO2, HCO3-, and base excess were analyzed at the end of each study stage as follow: 1) Establishment of anesthesia, 2) Blood collection to an arterial mean pressure of 40-50 mm Hg, 3) Maintaining dogs in a hypovolemic state, 4) Resuscitation with LR (group A) or HES (group B) in four steps, and 5) One hour after the final resuscitation step. Hypovolemia decreased the studied parameters, except venous PCO2, which showed a significant increase (p < 0.05). Fluid resuscitation returned the studied parameters to the control values as venous PCO2 in group A and HCO3- in group B showed a significant change in comparison with the control values (p < 0.05). We found that venous pH, HCO3-, and PCO2 can be used as less invasive and safer alternatives to similar arterial parameters to monitor the fluid resuscitation of hypovolemic dogs. [ABSTRACT FROM AUTHOR]

Background: Resuscitation is the initial step for hemorrhagic shock. However, there is still controversy as to which fluid achieves the best results clinically and experimentally. Aim: It was aimed to investigate the effects of 0.9% NaCl (sodium chloride) and 6% HES (hydroxyethyl starch) on the kidney and blood environment. Methods: Twenty-four male Wistar rats were assigned as control, shock, and resuscitated (colloid: 6% HES and crystalloid: 0.9% NaCl) groups. Besides hemodynamics (mean arterial pressure and shock index) monitoring and kidney function evaluation, hemolysis, oxidative stress, inflammation, and glycocalyx degradation were evaluated in the plasma and kidney. Results: (1) Macrohemodynamics were successfully restored by both fluids. (2) Although 3 times more crystalloid volume was applied compared to the colloid resuscitation, similar hematocrit levels were found in both resuscitation strategies (32.8 ± 2.3 vs. 33.3 ± 1.0). (3) NaCl resuscitation led to increases in the hemolytic index, catalytic iron, and sialic acid compared to control, while HES administration increased the levels of malondialdehyde, ischemia-modified albumin, and sialic acid. (4) However, both fluid resuscitation strategies could inhibit inflammation and oxidative stress in the kidney and restore kidney function parameters. Conclusion: Although both NaCl and HES resuscitation showed protection of the kidney function against oxidative stress and inflammation, these fluids initiated the injury process.

[Display omitted] • Addition of hydroxyethylene starch (HES) significantly enhanced the oxidation stability of polyethyleneimine (PEI) due to efficient hydrogen bonding. • The oxidation stability of supported PEI in the presence of HES was higher compared to other hydroxyl containing polymers. • Co-impregnation of supported PEI with HES gave comparable oxidation stability than the epoxide functionalization, but significantly higher CO 2 uptake. Amine-based adsorbents are widely used for CO 2 capture. However, one of the biggest hurdles for their further development is their limited oxidation stability. Moreover, methods developed to improve the oxidation stability often lead to significant decrease in their CO 2 uptake. Here, we investigated the effect of hydroxyethyl starch (HES) on the CO 2 uptake and oxidation stability of impregnated polyethylenimine (PEI) adsorbents. Performance of HES-PEI co-impregnated materials was evaluated under different oxidation conditions using CO 2 uptake measurements, and mass spectrometry. The effect of HES was compared with other hydroxyl-containing additives such as PVA and PEG, as well as to epoxide functionalization of PEI (EB-PEI). The oxidation stability of PEI upon addition of HES was found to be comparable to EB-PEI containing adsorbent; however, its CO 2 uptake, based on PEI, was twice as high. In addition, oxidation stability of supported HES-PEI was significantly higher than unmodified PEI as well as PVA-PEI and PEG-PEI co-impregnated adsorbents. [ABSTRACT FROM AUTHOR]

The use of hydroxyethyl starch 130/0.4 has been linked to renal injury in critically ill patients, but its impact on surgical patients remains uncertain. A retrospective cohort study. This study was conducted at one tertiary care hospital in China. We evaluated the records of 51,926 Chinese adults who underwent noncardiac surgery from 2013 to 2022. Patients given a combination of hydroxyethyl starch 130/0.4 and crystalloids were propensity-matched at a 1: 1 ratio of baseline characteristics to patients given only crystalloids (11,725 pairs). Eligible patients were divided into those given a combination of hydroxyethyl starch 130/0.4 and crystalloid during surgery and a reference crystalloid group consisting of patients who were not given any colloid. The primary outcome was the incidence of acute kidney injury. Secondarily, acute kidney injury stage, need for renal replacement therapy, intensive care unit transfer rate, and duration of postoperative hospitalization were considered. After matching, hydroxyethyl starch use [8.5 (IQR: 7.5–10.0) mL/kg] did not increase the incidence of acute kidney injury compared with that in the crystalloid group [2.0 vs. 2.2%, OR: 0.90 (0.74–1.08), P = 0.25]. Nor did hydroxyethyl starch use worsen acute kidney injury stage [OR 0.90 (0.75–1.08), P = 0.26]. No significant differences between the fluid groups were observed in renal replacement therapy [OR 0.60 (0.41–0.90), P = 0.02)] or intensive care unit transfers [OR 1.02 (0.95–1.09), P = 0.53] after Bonferroni correction. Even in a subset of patients at high risk of renal injury, hydroxyethyl starch use was not associated with worse outcomes. Hydroxyethyl starch 130/0.4 use was not significantly associated with a greater incidence of postoperative acute kidney injury compared to receiving crystalloid solutions only. • Hydroxyethyl starch 130/0.4 use was not associated with postoperative acute kidney injury. • Postoperative hospitalization slightly longer in hydroxyethyl starch group by median 0.5 days. • No significant difference was found in RRT incidence or ICU transfers. [ABSTRACT FROM AUTHOR]

Abstract Background Hydroxyethyl starch (HES) solutions are used for volume therapy to treat hypovolemia due to acute blood loss and to maintain hemodynamic stability. This study was requested by the European Medicines Agency (EMA) to provide more evidence on the long-term safety and efficacy of HES solutions in the perioperative setting. Methods PHOENICS is a randomized, controlled, double-blind, multi-center, multinational phase IV (IIIb) study with two parallel groups to investigate non-inferiority regarding the safety of a 6% HES 130 solution (Volulyte 6%, Fresenius Kabi, Germany) compared with a crystalloid solution (Ionolyte, Fresenius Kabi, Germany) for infusion in patients with acute blood loss during elective abdominal surgery. A total of 2280 eligible patients (male and female patients willing to participate, with expected blood loss ≥ 500 ml, aged > 40 and ≤ 85 years, and ASA Physical status II–III) are randomly assigned to receive either HES or crystalloid solution for the treatment of hypovolemia due to surgery-induced acute blood loss in hospitals in up to 11 European countries. The dosing of investigational products (IP) is individualized to patients’ volume needs and guided by a volume algorithm. Patients are treated with IP for maximally 24 h or until the maximum daily dose of 30 ml/kg body weight is reached. The primary endpoint is the treatment group mean difference in the change from the pre-operative baseline value in cystatin-C-based estimated glomerular filtration rate (eGFR), to the eGFR value calculated from the highest cystatin-C level measured during post-operative days 1-3. Further safety and efficacy parameters include, e.g., combined mortality/major post-operative complications until day 90, renal function, coagulation, inflammation, hemodynamic variables, hospital length of stay, major post-operative complications, and 28-day, 90-day, and 1-year mortality. Discussion The study will provide important information on the long-term safety and efficacy of HES 130/0.4 when administered according to the approved European product information. The results will be relevant for volume therapy of surgical patients. Trial registration EudraCT 2016-002162-30 . ClinicalTrials.gov NCT03278548

This study reports cross‐linking of hydroxyethyl starch (HES) using citric acid to from cross‐linked HES‐citrate. The HES‐citrate as obtained is characterized using FTIR and 1H NMR. The cross‐linked product HES‐citrate shows remarkable swelling in different media simulated to the physiological systems of human body, i.e., deionized water (DW), pH 6.8 and 7.4, and followed second order swelling kinetics. The HES‐citrate exhibits reversible swelling/deswelling in different combinations of stimuli, i.e., at pH 7.4 and 1.2, in DW and normal saline and in DW and ethanol which makes it a potential candidate for intelligent drug delivery. Therefore, cross‐linked product shows extraordinary stimuli‐responsiveness under different physiological conditions such as in presence electrolytes and solvents and at different temperatures. HES‐citrate‐based aceclofenac tablet is formulated that demonstrates sustained‐release under conditions mimicked to gastrointestinal tract (GIT) in terms of pH and transit time. [ABSTRACT FROM AUTHOR]

In the era of 2019 the most dangerous disease that have affected more than 200 countries is Covid-19 (i.e. corona virus disease 2019) spread by the virus (i.e. novel coronavirus) which is transmitted from susceptible person to survivors in his surroundings. Such an epidemicity occurs first time in the world and number of cases are in excess of normal expectancy for the different areas that's why it is not easy to overcome this pandemic circumstances immediately. However, it is a challenge to develop anti-virus drugs for the suspected patients at global level. The scientists are interested in detailed experiments on Chloroquine (CQ) and Hydroxychloroquine (HCQ) as one of the unique substance used in the manufacturing for an anti virus drugs. For instance the Hydroxychloroquine conjugated molecular structure became an interesting chemical by the scientist. The significance of both substances can be examine by the number of publications which are leading us to introduce an effective treatment. In this paper, we are interested to discussed physcio-chemical properties of Hydroxychloroquine structure and computational work for the specific topological descriptors named as the F-co-index, first Zagreb co-index and first multiplicative Zagreb co-index, second Zagreb co-index and second multiplicative Zagreb co-index. [ABSTRACT FROM AUTHOR]

Hydroxyethyl starch (HES) has been shown to be correlated with increased risk of renal dysfunction. While almost all articles focus on the side effect of HES on glomerular filtration function, it is barely known to us about the effect of HES on renal water reabsorption. The objective of this study is to assess the effect of HES on renal water reabsorption in patients with cardiac shock. In a retrospective cohort-study, 162 patients admitted to the department of cardiology and diagnosed as cardiac shock were randomized into four groups, depending on different treatments of NaCl (NaCl group), HES (HES group), HES and dopamine (HES + DOP group), HES and norepinephrine (HES + NE group). Data collected included age, sex, blood pressure, heart rate, left ventricular ejection fraction, serum creatinine, blood urea nitrogen, urine specific gravity, urine volume, oxygen saturation serum, drug dosage, and so on. Indices related to renal function were recorded before and after the anti-shock treatments. The comparison was performed among four groups at day 0 or at day 3, and indices of the same group were compared between day 0 and day 3. We found that HES and norepinephrine reduced the urine specific gravity in HES group (day 0 vs day 3, 1.019 ± 0.006 vs 1.012 ± 0.005, p < 0.001) and in HES + NE group (day 0 vs day 3, 1.019 ± 0.006 vs 1.011 ± 0.004, p < 0.001). Dopamine increased the urine volume of HES-treated patients at day 3 (p < 0.001), and in the meantime dopamine preserved urine specific gravity during anti-shock treatment at day 3 (p = 0.13). In conclusion, hydroxyethyl starch caused injured function of renal water reabsorption, and dopamine protected renal water reabsorption in HES-treated patients via increased renal blood. [ABSTRACT FROM AUTHOR]

Simple Summary: Critically ill dogs often require intravenous fluid therapy to improve circulation and treat life-threatening shock. Standardly, a balanced electrolyte solution called a crystalloid is prescribed. Some veterinarians also prescribe colloid fluids like hydroxyethyl starch (HES), which are crystalloids that contain large starch molecules, as more of the volume delivered stays in circulation compared to crystalloid. However, there is concern that colloids may impair blood clot formation and increase the risk of serious bleeding. To better understand this risk, this study compared the function of individual clotting components within blood samples collected over time from critically ill dogs that received either crystalloids or HES. The blood samples were saved from a previous clinical trial where critically ill dogs requiring intravenous fluids were randomized to receive HES or crystalloids. Blood was collected before fluid therapy and then 6, 12, and 24 h after the start of the intervention fluid. The results did not provide evidence that HES impaired clotting more than crystalloids. However, considering the small sample size and variability between dogs, this result does not provide evidence that HES is safe. Larger or more targeted studies are required to further assess the effect of HES on blood clotting in dogs. Synthetic colloid fluids containing hydroxyethyl starch (HES) have been associated with impairment of coagulation in dogs. It is unknown if HES causes coagulation impairment in dogs with naturally occurring critical illness. This study used banked plasma samples from a blinded, randomized clinical trial comparing HES and balanced isotonic crystalloid for bolus fluid therapy in 39 critically ill dogs. Blood was collected prior to fluid administration and 6, 12, and 24 h thereafter. Coagulation biomarkers measured at each time point included prothrombin time, activated partial thromboplastin time, thrombin time, fibrinogen concentration, and the activities of coagulation factors V, VII, VIII, IX, and X, von Willebrand factor antigen, antithrombin, and protein C. Given the links between coagulation and inflammation, cytokine concentrations were also measured, including interleukins 6, 8, 10, and 18, keratinocyte-derived chemokine, and monocyte chemoattractant protein-1. Data were analyzed with linear mixed effects models. No significant treatment-by-time interactions were found for any biomarker, indicating that the pattern of change over time was not modified by treatment. Examining the main effect of time showed significant changes in several coagulation biomarkers and keratinocyte-derived chemokines. This study could not detect evidence of coagulation impairment with HES. [ABSTRACT FROM AUTHOR]

Background: The possibility of nephrotoxic effect caused by hydroxy ethyl starch (HES) used as volume therapy in this particular setting is of major clinical concern. We conducted this retrospective study to look for the possible nephrotoxic effects and other systemic adverse effects if any, of 6% HES 130 kD, 0.4 DS used as intraoperative volume expander in the cardiac surgery setting. Aims and Objectives: This study aims to determine whether the infusion of 6% hydroxyethyl starch (130/0.4) harms renal function in cardiac surgical patients. Materials and Methods: The present study was a retrospective study. Sixty-six patients who received crystalloids with hydroxyethyl starch and a matched control of 66 patients based on age and sex and other baseline parameters who received crystalloids only were part of the study. The data extracted from the electronic medical record include patient demographics, details for additive EURO score, and pre-operative data that include details of comorbid illnesses, namely, hypertension and diabetes, plasma hemoglobin, serum creatinine, and eGFR. Results: There is no statistically significant difference in serum creatinine and incidence of post-operative renal dysfunction between the study groups. There was a higher rate of re-exploration and duration of intensive care unit, and hospital stay. Conclusion: In our study, HES 130/0.4 in the dose used as a plasma expander did not adversely affect renal function in cardiac surgical patients undergoing CABG. The study recommends further detailed studies in this area involving multiple centers. [ABSTRACT FROM AUTHOR]

This review presents the analysis of reported data on the current methods for blood hypothermic storage and erythrocyte cryopreservation in dogs. The relevance of designing and improving the techniques for canine erythrocyte cryopreservation, cryobanking, as well as the application of cryopreserved blood components for transfusion were substantiated. The features of canine blood hypothermic storage and specific use of cryoprotectants with various modes of their action were considered. The advantages of applying DMSO and combined cryopreservatives during low temperature storage of canine erythrocytes were specified. [ABSTRACT FROM AUTHOR]

The hydroxethyl starch (HES) is very trending biopolymer in biomedical field. In recent research we have successfully synthesized a novel ester of HES, i.e., HES‐acetate by acetylation of HES followed by investigation of its thermal behavior. The successful acetylation of HES was confirmed by Fourier Transform Infrared (FTIR) and Proton‐Nuclear Magnetic Resonance (1H NMR) spectroscopic techniques. Thermal stability and thermal degradation kinetics of HES‐acetate were investigated by thermo‐gravimetric analysis. Flynn–Waal–Ozawa model was fitted to the thermal data to find the values of thermodynamic triplet (ΔS, ΔG and ΔE). Energy of activation (Ea) values of the major thermal degradation steps were found to be 242.85 and 287.17 kJ mol–1 for HES and HES‐acetate, respectively. The order of degradation, integral procedural decomposition temperature (IPDT) and index of intrinsic thermal stability (ITS) were also taken into account. The results of the thermal analysis reveal that the HES‐acetate gained significant thermal stability as compared to that of HES. This benign polysaccharide‐based material was investigated for its potential in drug release studies by taking caffeine as a model drug. HES‐acetate‐based matrix tablets showed sustained release behavior of the drug indicating its potential for the development of oral delivery systems for sustained drug release. [ABSTRACT FROM AUTHOR]

Microbial transglutaminases (mTGases) or protein‐glutamine γ‐glutamyltransferases are a family of enzymes that catalyze the transamidation of glutamine (Gln) residues of proteins or peptides with various primary amines. mTGase is suitable for site‐specific enzymatic modification of therapeutic proteins. Here, the enzymatic conjugation of recombinant human erythropoietin (rHuEPO) with the semisynthetic starch derivative, hydroxyethyl starch (HES), is studied, using a thermoresistant variant mTGase TG16. An amine‐modified HES (HES‐g‐NH2) is synthesized to act as an acyl acceptor substrate for TG16 and characterized by 1H NMR, 2D NMR, and Fourier transform infrared (FTIR) spectroscopy. Subsequently, HES‐g‐NH2 is labeled with rhodamine B‐isothiocyanate resulting in rhodamine B‐labeled HES‐g‐NH2 (HES‐g‐NH2‐R). Finally, amine‐modified HES before and after labeling is applied for the conjugation reaction with rHuEPO at its transition temperature Tm. Using SDS‐PAGE, high molar mass conjugates as well as aggregates are observed, thus, demonstrating the efficient conjugation of HES with the acyl donor rHuEPO. Importantly, it is shown that this enzymatic method gives easy access to the preparation of rHuEPO‐HES conjugates. [ABSTRACT FROM AUTHOR]

Cancer is a genetic disorder and its treatment usually requires a long time and expensive diagnosis. While chemotherapy is the most conventional approach in treating most cancers, patients often suffer from undesired side effects due to various pharmacokinetic aspects. To address this issue, target-oriented drug-delivery systems (DDS) or pulsatile drug-delivery systems (PDDS) have recently been developed as an alternative tool that takes care of the entire pharmacodynamic activities of drug action. Hydroxyethyl starch (HES) has emerged as an effective clinical tool for delivering anticancer agents into target cells. These systems have demonstrated significant potential as anticancer drug carrier conjugates through their innate pharmacokinetic properties with their safety profile. This review focuses primarily on the structural aspect during the use of HES or HES-based polymers as carriers for delivering well-known anticancer drugs. This review also indicates a perspective on the long-term research needed for the sake of improving modern drug-delivery systems based on HES polymers and in the form of nanocarriers.

Transplantation is lifesaving and the most effective treatment for end-stage organ failure. The transplantation success depends on the functional preservation of organs prior to transplantation. Currently, the University of Wisconsin (UW) and histidine-tryptophan-ketoglutarate (HTK) are the most commonly used preservation solutions. Despite intensive efforts, the functional preservation of solid organs prior to transplantation is limited to hours. In this study, we modified the UW solution containing components from both the UW and HTK solutions and analyzed their tissue-protective effect against ischemic injury. The composition of the UW solution was changed by reducing hydroxyethyl starch concentration and adding Histidine/Histidine-HCl which is the main component of HTK solution. Additionally, the preservation solutions were supplemented with melatonin and glucosamine. The protective effects of the preservation solutions were assessed by biochemical and microscopical analysis at 2, 10, 24, and 72 h after preserving the rat kidneys with static cold storage. Lactate dehydrogenase (LDH) activity in preservation solutions was measured at 2, 10, 24, and 72. It was not detectable at 2 h of preservation in all groups and 10 h of preservation in modified UW+melatonin (mUW-m) and modified UW+glucosamine (mUW-g) groups. At the 72nd hour, the lowest LDH activity (0.91 IU/g (0.63–1.17)) was measured in the mUW-m group. In comparison to the UW group, histopathological damage score was low in modified UW (mUW), mUW-m, and mUW-g groups at 10, 24, and 72 hours. The mUW-m solution at low temperature was an effective and suitable solution to protect renal tissue for up to 72 h. [ABSTRACT FROM AUTHOR]

Objective. This study was aimed at investigating the effects of different types of fluid restriction fluid resuscitation on the immune dysfunction and organ injury of hemorrhagic shock rats under a hypothermic environment. Methods. SD rats were divided into sham operation group (SHAM), hemorrhagic shock model group (HS), crystal liquid limited resuscitation group (CRLLR), colloidal liquid limited resuscitation group (COLLR), and nonlimited resuscitation group (NLR); rats in each group were placed in a low-temperature environment of 0-5°C for 30 min, and then, a hemorrhagic shock rat model was prepared. Sodium lactate Ringer's restricted resuscitation solution, hydroxyethyl starch restricted resuscitation solution, and hydroxyethyl starch were used for resuscitation, and hemodynamic examination was performed. The mortality rate, inflammatory factors, oxidative stress factors, and immune function were detected by ELISA. The dysfunction and injury of the intestinal, lung, liver, and kidney were examined by histological methods. Results. Hemorrhagic shock resulted in decreased immune function and activation of inflammation. Unrestricted fluid infusion further activated the inflammatory response. The crystalloid-restricted fluid infusion performed effectively to regulate inflammatory response, promote antioxidative activity, and reduce the immunosuppressive reaction. Rehydration could regulate the coagulation. The hydroxyethyl starch reduced the expression of platelet glycoproteins Ib and IIb/IIIa and blocked the binding of fibrinogen to activated platelets, thereby inhibiting intrinsic coagulation and platelet adhesion and aggregation. Rats in the CRLLR group showed to relieve the injury of the lung, liver, kidney, and intestine from hemorrhagic shock in low-temperature environment. Conclusion. The early application of restrictive crystalloid resuscitation in hemorrhagic shock rats in hypothermic environment showed the best therapy results. Early LR-restrictive fluid replacement promotes the balance of inflammatory response and the recovery of immunosuppressive state, resists oxidative stress, stabilizes the balance of coagulation and fibrinolysis, improves coagulation function, and relieves organ injury. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the influence of Voluven on the NLRP3 inflammasome-mediated pyroptosis in bone marrow-derived macrophage (BMDM). Separated BMDMs were cultured and treated with different concentration of Voluven (0, 0.1, and 0.5 µg) dissolved in 10 µL 0.9% NaCl solution for 24 h. Both wild-type and nucleotide-binding domain and leucine-rich repeat protein 3 (NLRP3)–/– C57BL/6J mice (n = 18) were intravenously injected with 0.2 mL of 0%, 5%, and 10% Voluven through femoral vein, respectively. Pyroptosis was inspected with flow cytometry. The mRNA levels of NLRP3 and caspase-1 were detected with quantitative real-time polymerase chain reaction (qRT-PCR). The levels of NLRP3, pro-caspase-1, and cleaved caspase-1 (p10) in serum were determined with Western blot. The expression of IL-17A in peripheral blood CD4+ T cells was analyzed with flow cytometry. The expression of cleaved caspase-1 (p10) in mice spleens was inspected with immunofluorescence. Compared with control group, the ratio of pyroptosis in all Voluven-treated groups rose significantly. The levels of NLRP3 and caspase-1 were increased after Voluven treatment. The expression of interleukin (IL)-17A in Voluven-treated CD4+ T cells was also increased, exhibiting a dose-dependent pattern. In wild-type mice, Voluven-treated mice had higher levels of IL-17A, NLRP3, and cleaved caspase-1 (p10) in a dose-dependent manner. The effects of Voluven were diminished in NLRP3–/– mice. [ABSTRACT FROM AUTHOR]

This study is the first report of the preparation of hydroxyethyl starch (HES) hydrogels rapidly crosslinked with divinyl sulfone in a single step and single pot. To develop the physical and chemical features of hydrogels, Graphene oxide (GO) nanoparticles were combined with the crosslinked HES. In addition to swelling studies, structural characterization of the samples was conducted with a scanning electron microscope (SEM) and transmission electron microscope (TEM), Fourier transform infrared (FTIR) spectroscopy, X-ray diffractometry (XRD), Brunauer–Emmett–Teller (BET) analysis and thermogravimetric analysis (TGA). For the removal of malachite green model dye by GO-HES, the effects of GO content, solution concentration, temperature, contact duration, dosage and pH on varying adsorption features were researched. Additionally, adsorption isotherms, kinetic and thermodynamic systematics were analyzed. The maximum adsorption capacity of GO-HES composite hydrogel was found to be 89.3 mg/g for Langmuir isotherm. The possible adsorption mechanism of the composite hydrogels for malachite green dye involved electrostatic, hydrogen bonding, and π–π interactions. In addition to reasonable cost and simple synthesis method, the prepared composite materials have potential use in wastewater treatment as adsorbents for the removal of dye from aqueous solutions due to efficient adsorption capacity. [ABSTRACT FROM AUTHOR]

Objectives: The study aimed to investigate the incidence and risk factors of acute kidney injury (AKI) in elderly patients (aged ≥ 75 years) undergoing major nonvascular abdominal surgery.Methods: The study was a retrospective study that evaluated the incidence of AKI in patients within 48 h after major abdominal surgeries. Patients' preoperative characteristics and intraoperative management, including the use of nephrotoxic medications, were evaluated for associations with AKI using a logistic regression model.Results: A total of 573 patients were included in our analysis. A total of 33 patients (5.76%) developed AKI, and 30 (90.91%), 2 (6.06%) and 1 (3.03%) reached the AKI stages 1, 2 and 3, respectively. Older age (adjusted OR, aOR 1.112, 95% confidence interval, CI 1.020-1.212), serum albumin (aOR 0.900, 95% CI 0.829-0.977), baseline eGFR (aOR 3.401, 95% CI 1.479-7.820), the intraoperative occurrence of hypotension (aOR 3.509, 95% CI 1.553-7.929), and the use of hydroxyethyl starch in combination with nonsteroidal anti-inflammatory drugs (aOR 3.596, 95% CI 1.559-8.292) or furosemide (aOR 5.724, 95% CI 1.476-22.199) were independent risk factors for postoperative AKI.Conclusions: Several risk factors, including intraoperative combined administration of HES and furosemide, are independent factors for AKI during abdominal surgeries. Anesthesiologists and surgeons should take precautions in treating at-risk patients. [ABSTRACT FROM AUTHOR]

Background: Trauma may be associated with significant to life-threatening blood loss, which in turn may increase the risk of complications and death, particularly in the absence of adequate treatment. Hydroxyethyl starch (HES) solutions are used for volume therapy to treat hypovolemia due to acute blood loss to maintain or re-establish hemodynamic stability with the ultimate goal to avoid organ hypoperfusion and cardiovascular collapse. The current study compares a 6% HES 130 solution (Volulyte 6%) versus an electrolyte solution (Ionolyte) for volume replacement therapy in adult patients with traumatic injuries, as requested by the European Medicines Agency to gain more insights into the safety and efficacy of HES in the setting of trauma care.Methods: TETHYS is a pragmatic, prospective, randomized, controlled, double-blind, multicenter, multinational trial performed in two parallel groups. Eligible consenting adults ≥ 18 years, with an estimated blood loss of ≥ 500 ml, and in whom initial surgery is deemed necessary within 24 h after blunt or penetrating trauma, will be randomized to receive intravenous treatment at an individualized dose with either a 6% HES 130, or an electrolyte solution, for a maximum of 24 h or until reaching the maximum daily dose of 30 ml/kg body weight, whatever occurs first. Sample size is estimated as 175 patients per group, 350 patients total (α = 0.025 one-tailed, power 1-β = 0.8). Composite primary endpoint evaluated in an exploratory manner will be 90-day mortality and 90-day renal failure, defined as AKIN stage ≥ 2, RIFLE injury/failure stage, or use of renal replacement therapy (RRT) during the first 3 months. Secondary efficacy and safety endpoints are fluid administration and balance, changes in vital signs and hemodynamic status, changes in laboratory parameters including renal function, coagulation, and inflammation biomarkers, incidence of adverse events during treatment period, hospital, and intensive care unit (ICU) length of stay, fitness for ICU or hospital discharge, and duration of mechanical ventilation and/or RRT.Discussion: This pragmatic study will increase the evidence on safety and efficacy of 6% HES 130 for treatment of hypovolemia secondary to acute blood loss in trauma patients.Trial Registration: Registered in EudraCT, No.: 2016-002176-27 (21 April 2017) and ClinicalTrials.gov, ID: NCT03338218 (09 November 2017). [ABSTRACT FROM AUTHOR]

OBJECTIVE To evaluate the effect of 6% hydroxyethyl starch (HES) 670/0.75 and 6% HES 130/0.4 dilution of canine whole blood on coagulation using dynamic viscoelastic coagulometry (DVC). ANIMALS 56 healthy adult dogs. PROCEDURES 2 blood samples were obtained from each dog and randomized to 1 of 7 groups—undiluted or 2 dilutions (1:3 or 1:10) of 3 different fluids: saline (0.9% NaCl) solution, 6% HES 670/0.75, or 6% HES 130/0.4. Dilutions were calculated to simulate approximately a 10- or 30-mL/kg body weight IV bolus of each fluid. DVC was performed on each sample. Coagulation parameters compared between groups included clot rate (CR), platelet function (PF), and activated clotting time. RESULTS Dilution with saline solution did not significantly affect coagulation, while dilution with HES 670/0.75 and HES 130/0.4 caused a dose-dependent significant decrease in CR (1:3 HES 670/0.75, P = 0.007; 1:10 HES 670/0.75, P = 0.002; 1:3 HES130/0.4, P < 0.0001; and 1:10 HES 130/0.4, P = 0.0003) and PF (1:3 HES 670/0.75, P < 0.0001; 1:10 HES 670/0.75, P < 0.0001; 1:3 HES130/0.4, P < 0.0001; and 1:10 HES 130/0.4, P = 0.0015). CLINICAL RELEVANCE Dilution of canine blood with HES 670/0.75 and HES 130/0.4, at clinically relevant doses (10 and 30 mL/kg), led to significant hypocoagulability beyond dilutional effect. This was, in part, due to impaired PF, which was significantly greater with HES 670/0.75. Further research using DVC to assess the effects of HES on coagulation in dogs, ideally with clinical conditions warranting HES administration, is needed. [ABSTRACT FROM AUTHOR]

Ronghua Tan, Danlei Tian, Jiaoyan Liu, Congcong Wang, Ying Wan National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, People’s Republic of ChinaCorrespondence: Ying Wan Tel +86 27-87792147Fax +86 27-87792234Email ying_wan@hust.edu.cnBackground: Chemotherapeutic drugs used for tumor treatments often show limited efficiency due to their short lifetime, nonspecific delivery, and slow or insufficient intracellular drug release, and also, they can cause severe system or organ toxicity. The development of chemotherapeutic nanomedicines with high efficacy and satisfactory safety still remains a challenge for current tumor chemotherapy.Methods: A novel type of conjugate was synthesized using hydroxyethyl starch (HES) as a carrier while binding doxorubicin (DOX) onto HES backbone through a pH/redox responsive linker containing both disulfide and hydrazone bonds in series. The built conjugates were self-assembled into nanoparticles (NPs) (HES-SS-hyd-DOX NPs) for achieving enhanced antitumor therapy and adequate safety.Results: HES-SS-hyd-DOX NPs had a certain ability for the tumor-orientated drug accumulation and were capable of releasing DOX itself rather than DOX derivatives. It was found that the pH/redox responsive linkage enabled the NPs to achieve fast and sufficient intracellular drug release. Based on the tumor-bearing mouse model, antitumor results demonstrated that these NPs were able to inhibit the growth of the advanced tumors with significantly enhanced efficacy when compared to free DOX, and to those conjugate NPs containing only a single responsive or unresponsive bond. Besides, HES-SS-hyd-DOX NPs also showed adequate safety to the normal organs of the treated mice.Conclusion: The pH/redox responsive linkage in HES-SS-hyd-DOX was found to play a critical role in mediating the drug accumulation and the fast and sufficient intracellular drug release. The HES-exposed surface of HES-SS-hyd-DOX NPs endowed the NPs with long circulation capability and remarkably reduced the DOX-induced side effects.Keywords: hydroxyethyl starch, doxorubicin, conjugate nanoparticles, pH/redox responsive linkage, antitumor therapy

The adaptive antioxidant systems of tumor cells, predominantly glutathione (GSH) and thioredoxin (TRX) networks, severely impair photodynamic therapy (PDT) potency and anti-tumor immune responses. Here, a multistage redox homeostasis nanodisruptor (Phy@HES-IR), integrated by hydroxyethyl starch (HES)-new indocyanine green (IR820) conjugates with physcion (Phy), an inhibitor of the pentose phosphate pathway (PPP), is rationally designed to achieve PDT primed cancer immunotherapy. In this nanodisruptor, Phy effectively depletes intracellular GSH of tumor cells by inhibiting 6-phosphogluconate dehydrogenase (6PGD) activity. Concurrently, it is observed for the first time that the modified IR820-NH 2 molecule not only exerts PDT action but also interferes with TRX antioxidant pathway by inhibiting thioredoxin oxidase (TRXR) activity. The simultaneous weakening of two major antioxidant pathways of tumor cells is favorable to maximize the PDT efficacy induced by HES-IR conjugates. By virtue of the excellent protecting ability of the plasma expander HES, Phy@HES-IR can remain stable in the blood circulation and efficiently enrich in the tumor region. Consequently, PDT and metabolic modulation synergistically induced immunogenic cell death, which not only suppressed primary tumors but also stimulated potent anti-tumor immunity to inhibit the growth of distant tumors in 4T1 tumor-bearing mice. • Phy@HES-IR NPs is a potent immunogenic photodynamic therapy agent. • Phy@HES-IR NPs suppress both glutathione and thioredoxin antioxidant pathways. • It is found for the first time that the modified IR820-NH 2 molecule blocks thioredoxin oxidase activity. [ABSTRACT FROM AUTHOR]

ObjectivesThis study assessed the effect of 2 types of hydroxyethyl starches (HES) on renal integrity and blood transfusion in cardiac surgery patients.DesignRetrospective investigation.SettingPatients from a single tertiary medical center.ParticipantsInclusion criteria included coronary artery bypass graft (CABG) and/or valve surgery that included cardiopulmonary bypass with aortic cross-clamping.InterventionsIntraoperative HES and blood product administration.Measurements and main resultsThe study comprised 1,265 patients who met inclusion criteria. Of these patients, 70% received HES, and of these, 47% received

Efficient management of hemorrhage is vital for preventing hemorrhagic shock and safeguarding wounds against infection. Inspired by the traditional Chinese steamed bread-making process, which involves kneading, foaming, and steaming, we devised a hemostatic sponge by amalgamating an acellular dermal matrix gel, hydroxyethyl starch, and rice hydrolyzed protein. The integration of hydroxyethyl starch bolstered the sponge's mechanical and hemostatic attributes, while the inclusion of rice hydrolyzed protein, acting as a natural foaming agent, enhanced its porosity This augmentation facilitated rapid blood absorption, accelerated clot formation, and stimulated the clotting cascade. Experimental findings underscore the exceptional biocompatibility and physicochemical characteristics of the hemostatic sponge, positioning it on par with commercially available collagen hemostatic sponges for hemorrhage control. Mechanistically, the sponge fosters aggregation and activation of red blood cells and platelets, expediting coagulation kinetics both in vivo and in vitro. Notably, this hemostatic sponge activates the clotting cascade sans crosslinking agents, offering a premium yet cost-effective biomaterial with promising clinical applicability. [ABSTRACT FROM AUTHOR]

Cancer is one of the most lethal diseases all over the world. Despite that many drugs have been developed for cancer therapy, they still suffer from various limitations including poor treating efficacy, toxicity to normal human cells, and the emergence of multidrug resistance. In this study, the amphiphilic LHES polymers were prepared using hydroxyethyl starch (HES) and linoleic acid as starting materials. The content and substitution degree of linoleic acid groups in LHES polymers were analyzed. The LHES polymers were used for fabricating LHES-B nanoparticles carrying a linoleic acid modified berberine derivative (L-BBR). The LHES-B nanoparticles showed high drug loading efficiency (29%) and could quickly release L-BBR under acidic pH condition (pH = 4.5). Biological investigations revealed that LHES-B nanoparticles significantly inhibited the proliferation of HepG2 cells and exhibited higher cytotoxicity than L-BBR. In a transgenic Tg(fabp10:rtTA2s-M2; TRE2:EGFP-kras v12 ) zebrafish model, LHES-B nanoparticles obviously inhibited the expression of kras v12 oncogene. These results indicated that LHES carriers could improve the anticancer activity of L-BBR, and the synthesized LHES-B nanoparticles showed great potential as anticancer drug. [Display omitted] • Starch-based nanoparticles carrying berberine derivative were fabricated. • The nanoparticles showed good sensitivity under acidic pH condition. • The nanoparticles inhibited the expression of kras v12 oncogene in a zebrafish model. [ABSTRACT FROM AUTHOR]

Effective EPR and tumor penetration are bottlenecks in current nanomedicine therapy. Comosol software was utilized to analyze the motion process of nanoparticles (NPs) with different shapes, from blood vessels to tumor tissue, to address this. By calculation, urchin-like NPs experienced higher drag forces than spherical NPs, facilitating their EPR and tumor penetration effects. Thus, urchin-like indocyanine green-loaded hydroxyethyl starch-cholesterol (ICG@HES-CH) NPs were prepared by leveraging the instability of ICG responding to near-infrared light (NIR). Upon NIR exposure, ICG degraded and partly disintegrated ICG@HES-CH NPs, and its morphology transformed from spherical to urchin-like. Vincristine (VC), as a model drug, was loaded in urchin-like ICG@HES-CH NPs for the treatment of lymphoma. A20 lymphoma cells and 3T3-A20 tumor organoids were employed to investigate the influence of shape on NPs' cellular uptake, penetration pathway, and cytotoxicity. It demonstrated that urchin-like ICG@HES-CH NPs mainly transport across the extracellular matrix through intercellular pathways, easily reaching the deep tumor sites and achieving higher cytotoxicity. In vivo VC distribution and anti-tumor results indicated that urchin-like NPs increased VC EPR and penetration ability, lowering VC neurotoxicity and superior anti-tumor effect. Therefore, urchin-like ICG@HES-CH NPs have great translational potential to be used as chemotherapeutic nanocarriers in anticancer therapy. [ABSTRACT FROM AUTHOR]