Human Albumin Research Articles

Effect of Co-Loaded Vitamin D3 on Intravenous Injectable Raloxifene Delivery System

Owing to its promising advantages, including improved drug bioavailability and therapeutic efficiency at low doses and frequency, increased patient convenience and compliance, and prolonged storage life, nanomedicine has received heightened attention over conventional pharmaceuticals. Human serum albumin (HSA)-based nanoparticles have been used as drug carriers in injectable formulations, with great success and versatility. In this study, raloxifene and vitamin D3 were co-encapsulated in HSA-based nanoparticles (Ral/VitaD/HSA/PSS NPs) as an intravenously injected pharmaceutical formulation in order to enhance their availability in the body. The lyophilization–hydration method was utilized to develop the Ral/VitaD/HSA/PSS NPs. In addition, the characteristics and stability of the NP and the effect of the co-loading of vitamin D3 on raloxifene release in vitro and in vivo were discussed. The raloxifene and vitamin D3 molecules were successfully encapsulated and well dispersed in an amorphous state within Ral/VitaD/HSA/PSS NPs. The prepared Ral/VitaD/HSA/PSS NPs were lyophilized for long-term storage and were both biocompatible and hemocompatible, enhancing alkaline phosphtase activity in osteoblasts. Delivered via intravenous injection, Ral/VitaD/HSA/PSS NPs addressed the low bioavailability of raloxifene and vitamin D3 caused by oral administration, and improved their compatibility and residence time in the body. Overall, the established raloxifene–vitamin D3-co-loaded NPs may be a potential nanomedicine contender for treating postmenopausal osteoporosis.

Hyperphosphorylated Tau Targeting Human Serum Albumin Fusion Protein as Therapeutics for Alzheimer’s Diseases.

Hyperphosphorylated Tau Targeting Human Serum Albumin Fusion Protein as Therapeutics for Alzheimer’s Diseases.

99mTc-GSA scintigraphy and modified albumin–bilirubin score can be complementary to ICG for predicting posthepatectomy liver failure

BackgroundPosthepatectomy liver failure (PHLF) remains a severe complication after liver resection. This retrospective study investigated the correlation of three hepatic functional tests and whether 99mTc-galactosyl human serum albumin (99mTc-GSA) scintigraphy and modified albumin–bilirubin (ALBI) score are useful for predicting PHLF.MethodsThis retrospective cohort study included 413 consecutive patients undergoing hepatectomies between January 2017 and December 2020. To evaluate preoperative hepatic functional reserve, modified ALBI grade, indocyanine green clearance (ICG-R15), and 99mTc-GSA scintigraphy (LHL15) were examined before scheduled hepatectomy. Based on a retrospective chart review, multivariable logistic regression analysis adjusted for confounding factors was performed to confirm that mALBI, ICG-R15, and LHL15 are independent risk factors for PHLF.ResultsICG-R15 and LHL15 were moderately correlated (r = − 0.61) but this correlation weakened when ICG-R15 was about ≥ 20. Weak correlations were observed between LHL15 and ALBI score (r = − 0.269) and ALBI score and ICG-R15 (r = 0.339). Of 413 patients, 66 (19%) developed PHLF (20 grade A, 44 grade B, 2 grade C). Multivariable logistic regression analyses, major hepatectomy (P < 0.001), mALBI grade (P = 0.01), ICG-R15 (P < 0.001), and Esophagogastric varices (P = 0.007) were significant independent risk factors for PHLF. Subgroup analysis showed that ICG-R15 < 19, major hepatectomy, and mALBI grade and ICG-R15 ≥ 19, major hepatectomy, LHL15, and Esophagogastric varices were significant independent risk factors for PHLF (P = 0.033, 0.017, 0.02, 0.02, and 0.001, respectively).ConclusionLHL15, the assessment of Esophagogastric varices, and mALBI grade are complementary to ICG-R15 for predicting PHLF risk.

Design of fluorescent sensors for the detection of human serum albumin structure employing nitrogen-by modulation of molecular containing heterocycles

Design of fluorescent sensors for the detection of human serum albumin structure employing nitrogen-by modulation of molecular containing heterocycles

Twenty-five percent human albumin solution in clinical practice: indications, risks and monitoring protocols.

Human albumin solution is a commonly used therapeutic agent because of its ability to expand plasma volume and improve oncotic pressure in various clinical settings, such as in patients with cirrhosis and sepsis, whose management is a major challenge. Despite the lack of evidence for the superiority of human albumin solutions compared with crystalloids in improving major outcomes, short-term administration of human albumin solution appears to be more effective than both saline and plasmalyte in recovering systemic hemodynamics and achieving a lower daily net fluid balance in patients with cirrhosis and sepsis-induced hypotension. The use of 25% human albumin solution could also effectively manage ascites in patients with cirrhosis, reducing the volume of fluids administered and allowing a faster achievement of the plasma target concentration. This article aims to comprehensively review the indications for the use of human albumin solutions, examine the associated risks, and outline best practices for monitoring patients receiving this treatment, ensuring optimal patient outcomes while minimizing adverse effects.

Enzyme Activity Inhibition of α-Amylase Using Molecularly Imprinted Polymer (MIP) Hydrogel Microparticles.

Molecularly imprinted polymers (MIPs) are a class of synthetic recognition materials that offer a cost-effective and robust alternative to antibodies. While MIPs have found predominant use in biosensing and diagnostic applications, their potential for alternative uses, such as enzyme inhibition, remains unexplored. In this work, we synthesized a range of acrylamide-based hydrogel MIP microparticles (35 μm) specific for the recognition of α-amylase. These MIPs also showed good selectivity toward the target protein with over 96% binding of the target protein, compared with the control nonimprinted polymer (NIP) counterparts. Specificity of the MIPs was determined with the binding of nontarget proteins, trypsin, human serum albumin (HSA), and bovine serum albumin (BSA). The MIPs were further evaluated for their ability to inhibit α-amylase enzymatic activity, showing a significant decrease in activity. These findings highlight the potential of MIPs as enzyme inhibitors, suggesting an innovative application beyond their conventional use.

Evaluation of Thiol Disulfide, Ischemia Modified Albumin, and Prolidase Parameters in Patients With Localized Scleroderma

Introduction: Localized scleroderma is a rare inflammatory skin disease that causes sclerosis in the dermis and subcutaneous tissue. Oxidative stress may play a role in the etiology or be responsible for the chronicity or progression of the disease. Objectives: We aimed to investigate the presence of oxidative stress in patients with localized scleroderma by examining thiol disulfide balance, ischemia-modified albumin (IMA), and prolidase parameters. Methods: Twenty patients over the age of 18, who were diagnosed with localized scleroderma both clinically and histopathologically and 20 control subjects were included in the study. Age, gender, age of disease onset, duration of the disease, and presence of accompanying systemic diseases were questioned and recorded. Lesion type and modified Rodnan and Lossi scores were calculated through dermatological examination. CRP, sedimentation rate, total thiol, native thiol, and disulfide levels indicated by the Erel profile, IMA level, and prolidase levels were measured and compared in both the patient and control groups. Results: Levels of native thiol (p=0.958), total thiol (p=0.979), disulfide (p=0.449), (disulfide/native thiol%) (p=0.368), (disulfide/total thiol%) (p=0.361), (native thiol/total thiol%) (p=0.368), and prolidase (p=0.121) were similar in both patient and control groups. Only IMA was significantly different. No significant relationship was found between the levels of native thiol, total thiol, disulfide, (disulfide/native thiol), (disulfide/total thiol), IMA, prolidase, and Rodnan and Lossi scores. Conclusion: According to the data obtained from this study, we can say that the thiol-disulfide balance is not disrupted and prolidase levels are not affected in localized scleroderma; however, IMA is negatively affected.

Structural, Antioxidant, and Protein/DNA-Binding Properties of Sulfate-Coordinated Ni(II) Complex with Pyridoxal-Semicarbazone (PLSC) Ligand

The pyridoxal-semicarbazone (PLSC) ligand and its transition metal complexes have shown significant biological activity. In this contribution, a novel nickel(II)-PLSC complex, [Ni(PLSC)(SO4)(H2O)2], was obtained, and its structure was determined by X-ray crystallographic analysis, FTIR, and UV-VIS spectroscopy. The sulfate ion is directly coordinated to the central metal ion. The intermolecular stabilization interactions were examined using Hirshfeld surface analysis. The crystal structure was optimized by a B3LYP functional using two pseudopotentials for nickel(II) (LanL2DZ and def2-TZVP) together with a 6-311++G(d,p) basis set for non-metallic atoms. The experimental and theoretical bond lengths and angles were compared, and the appropriate level of theory was determined. The stabilization interactions within the coordination sphere were investigated by the Quantum Theory of Atoms in Molecules (QTAIM). The antioxidant activity towards hydroxyl and ascorbyl radicals was measured by EPR spectroscopy. The interactions between Human Serum Albumin (HSA) and the complex were examined by spectrofluorimetric titration and a molecular docking study. The mechanism of binding to DNA was analyzed by complex fluorescence quenching, potassium iodide quenching, and ethidium bromide displacement studies in conjunction with molecular docking simulations.

New Pd(II)-pincer type complexes as potential antitumor drugs: synthesis, nucleophilic substitution reactions, DNA/HSA interaction, molecular docking study and cytotoxic activity.

Two new complexes of Pd(II), [Pd(L1)Cl]Cl (Pd1) and [Pd(L2)Cl]Cl (Pd2), (where L1 = N2,N6-bis(5-methylthiazol-2-yl)pyridine-2,6-dicarboxamide and L2 = N2,N6-di(benzo[d]thiazol-2-yl)pyridine-2.6-dicarboxamide) were synthesized. Characterization of the complexes was performed using elemental analysis, IR, 1H NMR spectroscopy and MALDI-TOF mass spectrometry. The nucleophilic substitution reactions of complexes with L-Methionine (L-Met), L-Cysteine (L-Cys) and guanosine-5'-monophosphate (5'-GMP) were studied by stopped-flow method at physiological conditions (pH = 7.2 and 37 °C). Complex Pd1 was more reactive than Pd2 in all studied reactions, while the order of reactivity of the selected ligands was: L-Met > L-Cys > 5'-GMP. The interaction of complexes with calf thymus-DNA (CT-DNA) was studied by Uv-Vis absorption and fluorescence emission spectroscopy. Competitive binding studies with intercalative agent ethidium bromide (EB) and minor groove binder Hoechst 33258 were performed as well. Both complexes interacted with DNA through intercalation and minor groove binding, where the latter was preferred. Additionally, the interaction of Pd1 and Pd2 complexes with human serum albumin (HSA) was studied employing fluorescence quenching spectroscopy. The results indicate a moderate binding affinity of complexes, with slightly stronger binding of the Pd1. Fluorescence competition experiments with site-markers (eosin Y and ibuprofen) for HSA were used to locate the binding site of Pd1 to the HSA. Additionally, the interaction with DNA and HSA was studied by molecular docking and the revealed results were in good agreement with the experimentally obtained ones. Pd1 complex exhibited cytotoxicity toward human (HCT116) and mouse cell lines (CT26) of colorectal cancer, mouse (4T1) and human (MDA-MB468) breast cancer lines and non-cancerous mouse mesenchymal stem cells (mMSC). In addition, Pd1 complex demonstrated significant selectivity towards cancer cells over non-cancerous mMSC, indicating a high potential to eliminate malignant cells without affecting normal cells. It induced apoptosis in CT26 cells, effectively arrested the cell cycle in the S phase, and selectively down-regulated cyclin D and cyclin E. Moreover, it can alter the expression of cell cycle regulators by increasing p21 and decreasing p-AKT. These findings confirm its ability to disrupt key tumor cell survival signals and suggest that the Pd1 complex is a potent candidate for effective cancer treatment.

Isolation of antibodies to hypochlorite-modified low-density lipoproteins from human serum and study of their specificity

BACKGROUND: Modified low-density lipoproteins have immunogenic properties and induce the production of antibodies. In this case, HOCl promotes the formation of subsequent active halogen-containing compounds interacting with proteins and lipid parts of low-density lipoproteins, which leads to their modification and the production of antibodies to them. AIM: The aim of this work is to isolate antibodies to hypochlorite modified low-density lipoproteins from human blood sera and study their specificity. MATERIALS AND METHODS: Malondialdehyde, acetic anhydride and sodium hypochlorite were used to obtain modified low-density lipoproteins. IgG antibodies to hypochlorite modified low-density lipoproteins were isolated by affinity chromatography. The total IgG fraction antibodies was previously isolated from human blood serum using MabSelect Xtra. The specific antibodies to hypochlorite modified low-density lipoproteins were isolated from this IgG pool by affinity chromatography. CNBr-Sepharose 4B conjugated with human serum albumin modified with NaOCl was used as a sorbent. The specificity of antibodies against hypochlorite modified low-density lipoproteins was tested using a competitive enzyme-linked immunosorbent assay. The competitors were hypochlorite modified low-density lipoproteins, acetic anhydride modified low-density lipoproteins and malondialdehyde modified low-density lipoproteins in concentrations (1–250 μg/ml). RESULTS: IgG antibodies against hypochlorite-modified proteins that interact with hypochlorite modified low-density lipoproteins were detected in human blood. According to ELISA date the binding of the isolated antibodies to hypochlorite modified low-density lipoproteins was almost completely inhibited only by appropriately modified low-density lipoproteins, that is, hypochlorite modified low-density lipoproteins, but not native low-density lipoproteins or acetic anhydride modified low-density lipoproteins. Malondialdehyde modified low-density lipoproteins also showed some competitive activity, but much weaker than hypochlorite modified low-density lipoproteins. Hypochlorite modified low-density lipoproteins itself and, to a lesser extent, malondialdehyde modified low-density lipoproteins competed for binding with antibodies of human serum to hypochlorite modified low-density lipoproteins. Acetic anhydride modified low-density lipoproteins and native low-density lipoproteins did not reduce the efficiency of antibody binding to their antigen. CONCLUSIONS: Hypochlorite modified low-density lipoproteins forms epitopes independent of other low-density lipoproteins modifications studied. These epitopes are responsible for the formation of specific antibodies.

Evaluation of pregnancy toxemia in goats: Metabolic profile, hormonal findings, and redox balance

Pregnancy toxemia entails the development of hyperketonemia due to the negative energy balance that occurs in the last trimester of pregnancy in dairy goats. There are a limited number of studies on new diagnostic biomarkers and the pathophysiology of pregnancy toxemia in goats. This study assessed the hormones spexin and irisin and redox biomarker and metabolic profile changes in goats with pregnancy toxemia. The study included 36 hair goats, with 12 in the subclinical pregnancy toxemia (SPT) group, 12 in the clinical pregnancy toxemia (CPT) group, and 12 in the control group (CG). Spexin, irisin, and insulin hormone concentrations were determined by ELISA, while metabolic profile parameters were evaluated with an automatic chemical analyzer and redox balance by spectroscopy. In the goats with pregnancy toxemia, serum levels of spexin, irisin, insulin, and glucose were significantly lower than those of CG goats. The SPT group had significantly higher ischemia-modified albumin concentrations than CG goats, while the CPT group had significantly lower native thiol concentrations compared to CG animals. The concentrations of beta-hydroxybutyric acid and non-esterified fatty acids in the groups with pregnancy toxemia were significantly higher than those of control animals. In the diagnosis of pregnancy toxemia, spexin had sensitivity of 90 %, specificity of 95 %, and an area under the curve value of 0.988, while irisin had sensitivity of 90 %, specificity of 91 %, and an AUC value of 0.979. In this study, both spexin and irisin hormones showed excellent performance in the diagnosis of pregnancy toxemia. In addition, pregnancy toxemia was found to cause increased oxidative stress and significant changes in metabolic and endocrine metabolism in goats. Measuring these biomarkers in both healthy dairy goats and those with pregnancy toxemia may contribute significantly to the management and diagnosis of herd health.

Non-Palpable Breast Cancer: A Targeting Challenge–Comparison of Radio-Guided vs. Wire-Guided Localization Techniques

Background: The incidence of non-palpable breast cancer is increasing due to widespread screening and neo-adjuvant therapies. Among the available tumor localization techniques, radio-guided occult lesion localization (ROLL) has largely replaced wire-guided localization (WGL). The aim of this study was to compare the ROLL and WGL techniques in terms of the effectiveness of isotopic marking of axillary sentinel lymph nodes and to assess patient perspectives along with surgeon and radiologist preferences. Methods: A single-center, prospective, randomized study enrolled 110 patients with non-palpable breast lesions (56 ROLL, 54 WGL). Breast type, tumor volume, location, histological and radiological features, and localization/surgical duration were evaluated in the context of sentinel lymph node marking using isotope (technetium-99m-labeled human serum albumin) and blue dye. Statistical analysis was performed with significance set at p &lt; 0.05 and strong significance at p &lt; 0.01. Results: A single-center, prospective, randomized study enrolled 110 patients with non-palpable breast lesions (56 ROLL, 54 WGL). Breast type, tumor volume, location, histological and radiological features, and localization/surgical duration were evaluated in the context of sentinel lymph node marking using isotope (technetium-99m-labeled human serum albumin) and blue dye. Statistical analysis was performed with significance set at p &lt; 0.05 and strong significance at p &lt; 0.01. Conclusions: While ROLL provided advantages in terms of patient comfort and logistical simplicity, WGL was superior for axillary sentinel lymph node marking, particularly in inner quadrant tumors, suggesting that WGL may be preferred in these cases.

Modulation of Albumin Esterase Activity by Warfarin and Diazepam.

Data are accumulating on the hydrolytic activity of serum albumin towards esters and organophosphates. Previously, with the help of the technology of proton nuclear magnetic resonance (1H NMR) spectroscopy, we observed the yield of acetate in the solution of bovine serum albumin and p-nitrophenyl acetate (NPA). Thus, we showed that albumin possesses true esterase activity towards NPA. Then, using the methods of molecular docking and molecular dynamics, we established site Sudlow I as the catalytic center of true esterase activity of albumin. In the present work, to expand our understanding of the molecular mechanisms of albumin pseudoesterase and true esterase activity, we investigated-in experiments in vitro and in silico-the interaction of anticoagulant warfarin (WRF, specific ligand of site Sudlow I) and benzodiazepine diazepam (DIA, specific ligand of site Sudlow II) with albumins of different species, and determined how the binding of WRF and DIA affects the hydrolysis of NPA by albumin. It was found that the characteristics of the binding modes of WRF in site Sudlow I and DIA in site Sudlow II of human (HSA), bovine (BSA), and rat (RSA) albumins have species differences, which are more pronounced for site Sudlow I compared to site Sudlow II, and less pronounced between HSA and RSA compared to BSA. WRF competitively inhibits true esterase activity of site Sudlow I towards NPA and does not affect the functioning of site Sudlow II. Diazepam can slow down true esterase activity of site Sudlow I in noncompetitive manner. It was concluded that site Sudlow I is more receptive to allosteric modulation compared to site Sudlow II.

Splicing by Overlap Extension PCR for the Production of Fusion Proteins.

Fusion proteins are valuable molecules to meet different demands related to the development of biopharmaceuticals and bioprocesses. In human therapy, they are used to improve the half-life of biologics by modifying the biophysical properties of the proteins. In biotechnology, the design of fusion proteins can standardize the establishment of production clones and the purification process. Analytical detection capabilities of the fusion partner and binding to affinity ligands play a crucial role. For the generation of the recombinant cell line, the maturation of the protein and the secretion are also crucial factors, which can be significantly influenced by the fusion partner and candetermine the final yield of the bioprocess. Here we present a protocol to recombine the human extracellular domain of CD19 with the human serum albumin domain 2 resulting in a fusion protein CD19-AD2 including a flexible linker sequence in the interface between the C-terminus of CD19 and the N-terminus of HSA-D2 and a terminal His12-tag. The two fragments are independently amplified with primers allowing to genetically connect the two fragments in the next step by overlap extension PCR. By this strategy, the linker sequence as well as the albumin fragment can be chosen individually to be flexible in the fine-tuning of the final protein. The amplified product is then cloned into a mammalian expression vector suitable to generate a recombinant transient or stable cell culture. This workflow can be applied to any protein sequence by adapting the specific primer sequences.

Mechanistic insights into the interaction of anxiolytic drugs with human serum albumin in a ternary system utilizing spectroscopic and molecular modeling approaches

In recent years, buspirone has been co-administered with sertraline to resolve sexual disorders caused by sertraline. Therefore, the present study was conducted to investigate the interaction effect of two antidepressants and anxiolytic drugs, sertraline and buspirone, on human serum albumin (HSA) using spectroscopic and molecular docking techniques. Fluorescence emission spectroscopy and molecular docking were used to calculate the binding affinity and determine the best binding sites for these two drugs. Additionally, UV-visible and circular dichroism spectroscopy were performed to investigate the effect of these drugs on the conformational changes of HSA. The results showed that both drugs have a strong ability to quench the fluorescence of HSA through a static mechanism, and cause structural changes in HSA. It was also found that binding of sertraline and buspirone to HSA is spontaneous (ΔG° <) and hydrophobic interactions, van der Waals forces and hydrogen bonds play a significant role in these interactions in the ternary system. In addition, molecular docking data showed that both drugs bind with high affinity to the Trp residue in subdomain IIA. The binding constants (Kb) for (HSA-SRH)-BSH and (HSA-BSH)-SRH were equal to 6.30 and 3.99, respectively, at 298 K. This study demonstrates that the presence of the second drug (buspirone/sertraline) affects the interaction and binding affinity of the first drug (sertraline/buspirone) to human serum albumin.

Validation of Albumin Prescription in Vali Asr and Ayatollah Musavi Zanjan Hospitals

Background: Human serum albumin (HSA) is a versatile protein exclusively produced by hepatocyte cells in the liver, constantly released into the bloodstream. Substantial quantities of HSA are employed to ameliorate a variety of clinical conditions. The purpose of this study was to assess the accuracy of albumin serum administration as recorded in the patient files of Valiasr and Ayatollah Mousavi Hospitals in Zanjan, Iran Methods: his study aimed to assess the accuracy of albumin prescriptions in adult departments of Ayatollah Mousavi and Valiasr hospitals from March 2013 to March 2019. Data on albumin consumption and patient information were collected by reviewing the medical records of patients, resulting in a selection of 316 cases. The study developed a reference framework for assessing albumin administration accuracy. A scoring mechanism was used to categorize prescriptions into appropriate, inappropriate, questionable, and ambiguous classes. Statistical analysis was conducted using SPSS software. Results: The findings indicated that the average patient age was 62.2 years. Among 316 patients, 60.4% were male. The mean serum albumin level was measured at 3.14 g/dL. The collective volume of albumin administered to patients across both hospitals was 5016 units, averaging 15.77 units per patient, and this was utilized over a total of 2253 days. Among the studied patients, 197 passed away during treatment, 110 were discharged, and nine were transferred to other wards. Based on the established reference, it was observed that 5.5% of prescriptions were accurate, 51.9% were inaccurate, 26.4% were debatable, and 0.6% were undetermined. The total cost of prescribing this quantity of albumin in both hospitals amounted to 9,274,584,000 Rials, distributed as 8,347,125,600 Rials and 927,458,400 Rials in their respective proportions. Conclusion: Ultimately, the study highlighted that physician-prescribed albumin, guided by provided instructions, contained numerous errors necessitating vigilant and ongoing oversight. After a comprehensive review of all the data presented, it is apparent that there is no conclusive evidence supporting the existence of a formalized strategy for a consistent reduction in albumin consumption within the hospitals.

Evaluation Of The Frailty Index And Thiol-Disulphide Levels In Geriatric Orthopedic Injuries

Backround: One of the concepts recently discussed about old age is frailty. Frailty was found to be important in determining weakness and indulgence in the elderly. Frail older people are more likely to fall and experience related orthopedic trauma. Free oxygen radicals are known to cause oxidative stress in trauma patients. The aim of this study is to report the levels of frailty and thiol disulphide homeostasis and related factors in patients with geriatric orthopedic injury who presented to the emergency department.Methods: This study included 82 patients aged 65 and over who were admitted to the Emergency Department of XXX City Hospital in 2020 due to orthopedic trauma, and 38 people who presented for other reasons in a control group. FRAIL Frailty scale was used to evaluate frailty. In samples from patients' venous blood, native thiol and total thiol were analyzed.Results: The average age of the patients was78.48 ±7.86(min: 65-max: 99). Of the patients, 30.8% were in the prefrail group and56.7% were in the frail group. In patient and control group comparisons, total thiol values ​​in the patient group were significantly lower, and disulphide, ischemia-modified albumin, index 1 and index 2 values ​​were significantly higher in the patient group compared with the control group. There were significantly more prefrail individuals(41.5%) among orthopedic trauma patients, and frail individuals (81.6%) in the control group. There was a significant weak negative correlation between body mass index and native thiol and total thiol values.Conclusion: Oxidative stress is increased in patients with geriatric orthopedic injuries.

Comparative analysis of purity of human albumin preparations for clinical use

BackgroundAlbumin is the most prevalent plasma protein and serves numerous physiological roles, both in body fluid management and in various other capacities. In many diseases, a deficiency of albumin has been observed, and in certain conditions, albumin substitution has been demonstrated to improve outcome in comparison to plasma expansion using crystalloid or other colloid solutions. The favourable effects of using albumin in patients with liver cirrhosis are likely associated with the non-oncotic functions of albumin. Albumin for clinical use is obtained through fractionation of pooled donor plasma. The production procedures are optimized to ensure pure, chemically uncompromised and native protein. ResultsWe have extensively analysed commercial preparations of human albumin for clinical use from six different providers. Parameters that must correspond to the requirements of international pharmacopoeias were assessed (aluminium, ethanol, sodium, the presence of dimers and oligomers) and found to conform in all cases. In addition, we used for the first time nuclear magnetic resonance (NMR) as an additional analytical approach for investigating in greater depth the quality of a biological remedy gained from human plasma. We applied both 1H NMR and 13C-HSQC for confirming the identity of the albumin preparations, which also conformed in all cases. Moreover, we utilized T2-filtered 1H NMR and 13C-HSQC measurements to identify the presence of small molecules in the preparations. This demonstrated similar patterns of additional substances present, but also unveiled certain differences in purity in the products of the different providers. SignificanceOur analyses confirmed that albumin preparations in clinical use conform to the requirements. We furthermore demonstrate that NMR measurements can provide further depth in identity and purity measurements of biologicals. Despite largely standardized protocols in pharmaceutical albumin production, our in-depth analyses revealed differences in purity. Some samples exhibited lower levels of components other than albumin. We discuss possible causes of these observations and their potential implications for clinical therapy.

Triggered ferroptotic albumin-tocopherol nanocarriers for treating drug-resistant breast cancer.

Ferroptosis is considered an effective method to overcome drug-resistant tumors. This study aims to use three FDA-approved biological materials, human serum albumin, D-α-tocopherol succinate, and indocyanine green, to construct a novel biocompatible nanomaterial named HTI-NPs, exploring its effect in drug-resistant breast cancer (MCF-7/ADR cells). The research results indicate that HTI-NPs can selectively inhibit the proliferation of MCF-7/ADR cells in vitro, accompanied by upregulating transferrin receptor, generating reactive oxygen species, and downregulating glutathione peroxidase 4. Under laser irradiation, HTI-NPs can promote ferroptosis by inhibiting glutathione expression through photodynamic therapy. Notably, HTI-NPs exhibit good inhibitory effects on MCF-7/ADR xenograft tumors in vivo. In conclusion, HTI-NPs represent a biocompatible nanomaterial that induces ferroptosis, providing new insights and options for treating drug-resistant breast cancer.

Human epidermal growth factor receptor 2(Her2)-targeted pH-responsive MR/NIRF bimodal imaging-mediated nano-delivery system for the diagnosis and treatment of undifferentiated thyroid cancer.

Undifferentiated thyroid cancer (ATC) is highly malignant and does not respond well to sorafenib (SRF) treatment owing to the lack of specificity of SRF targeting. Drug delivery nanosystems can improve the efficiencies of drug in treating various cancer types. However, many conventional drug delivery nanosystems lack targeting and exhibit unresponsive drug release. Therefore, we developed a pH-responsive nano-targeted drug delivery systems using human serum albumin (HSA) as a carrier to generate manganese dioxide (MnO2)@HSA nanoparticles (NPs), then encapsulated SRF and the fluorescent dye indocyanine green (ICG) and finally modifyed the targeting antibody pertuzumab in the outer layer of the nano complexes, resulting in SRF/ICG/MnO2@HSA-pertuzumab (HISMP) NPs. This system targets human epidermal growth factor receptor 2 on the cell membrane surface of thyroid cancer cells and is designed to accumulate at tumor sites. Then, pH-responsive release of divalent manganese ions, ICG, and SRF enables magnetic resonance/fluorescence (MR/NIRF) dual-modality imaging and precise drug delivery for diagnostic and therapeutic integration. Various characterization analyses including transmission electron microscopy, Fourier infrared spectroscopy, and particle size analysis confirm that we successfully synthesized HISMP NPs with a diameter of 150.709nm. The results of CCK8 cytotoxicity and apoptosis assays show that HISMP NPs exhibited high cytotoxicity and induce apoptosis in thyroid cancer cells. In vivo MR/NIRF imaging experiments confirmed that the HISMP NPs specifically aggregated at tumor sites and have good in vivo MR/NIRF imaging ability and effective anti-tumor activity. The nano-delivery system is expected to provide a theoretical foundation for the efficient ATC diagnosis and therapy.