Acute physiological effects on macromolecule digestion following oral ingestion of the enzyme blend Elevase® in individuals that had undergone an ileostomy, but were otherwise healthy-a randomized, double blinded, placebo-controlled exploratory study.

Digestive enzymes can selectively degrade proteins, carbohydrates and lipids; and their supplementation alongside food may accelerate the breakdown of complex food matrices, facilitate greater nutrient absorption, decrease food sensitivities and aid in the management of certain disease states. Several intrinsic and extrinsic factors govern food digestion and for every individual this phenomenon is unique. This study was conducted as a randomized, crossover, placebo-controlled design where each participant served as their own control. This post-hoc analysis investigated the impact of a dietary enzyme supplementation blend known as Elevase® on dietary macromolecule digestion in samples from otherwise healthy participants that had previously undergone a small bowel resection, resulting in an ileostomy (NCT04489810). This is the first time this study-paradigm has been used for the assessment of in vivo dietary breakdown following enzyme supplementation. Arguably, this technique offers superior data when compared to that generated in artificial gut digestion models, preclinical animal models, or indeed conventional clinical studies using stool analyses, as it allows real-time access to samples in situ in the small intestine where the majority of nutritional absorption takes place. It was demonstrated that after 4 h, Elevase® significantly increased monosaccharide levels (predominantly glucose and fructose) in the ileostomy samples taken from the same individuals on the same diet on a different day. In addition, the bile salt taurohyodeoxycholic acid was also increased, suggesting a physiological host response to the macromolecule digestion induced by the enzymatic blend. Overall, these findings suggest Elevase® could accelerate food digestion and potentially increase nutrient availability from the diet.

Biological macromolecule-based hydrogels with antibacterial and antioxidant activities for wound dressing: A review.

Because of the complex symptoms resulting from metabolic dysfunction in the wound microenvironment during bacterial infections, along with the necessity to combat free radicals, achieving prompt and thorough wound healing remains a significant medical challenge that has yet to be fully addressed. Moreover, the misuse of common antibiotics has contributed to the emergence of drug-resistant bacteria, underscoring the need for enhancements in the practical and commonly utilized approach to wound treatment. In this context, hydrogel dressings based on biological macromolecules with antibacterial and antioxidant properties present a promising new avenue for skin wound treatment due to their multifunctional characteristics. Despite the considerable potential of this innovative approach to wound care, comprehensive research on these multifunctional dressings is still insufficient. Consequently, the development of advanced biological macromolecule-based hydrogels, such as chitosan, alginate, cellulose, hyaluronic acid, and others, has been the primary focus of this study. These materials have been enriched with various antibacterial and antioxidant agents to confer multifunctional attributes for wound healing purposes. This review article aims to offer a comprehensive overview of the latest progress in this field, providing a critical theoretical basis for future advancements in the utilization of these advanced biological macromolecule-based hydrogels for wound healing.

High-performance epoxy resin with flame-retardant, transparent, and ultraviolet shielding properties based on a vanillin-based multifunctional macromolecule.

Flame-retardant epoxy resins with tough, transparent, ultraviolet shielding, and low dielectric properties have fascinating prospects in electronic and electrical applications, but it is still challenging at present. In this work, a bio-based macromolecule was synthesized from vanillin (a lignin derivative), phenyl dichlorophosphate, 9,10-dihydro-9-oxa-10-phosphaphenanthrene 10-oxide (DOPO), and poly(propylene glycol) bis(2-aminopropyl ether). The bio-based macromolecule, namely, MFR, was designed and added to the epoxy resin (EP). The cured EP containing 15 wt% MFR (i.e., EP/MFR15) exhibits excellent flame retardancy with an Underwriter Laboratory 94 (UL-94) V-0 rating and a limiting oxygen index (LOI) of 29.2 %. Furthermore, the peak heat release rate (PHRR) and total heat release rate (THR) are drastically reduced by 59.5 % and 40.7 %, respectively. Meanwhile, EP/MFR15 shows 20.3 % and 43.8 % improvements in tensile strength and toughness, respectively. Moreover, MFR simultaneously endows EP with accessional ultraviolet shielding performance and low dielectric constant without sacrificing transparency. This work provides a promising strategy for fabricating a bio-based macromolecular flame retardant and preparing a high-performance EP composite with versatile properties.

AAV-aMTD-Parkin, a therapeutic gene delivery cargo, enhances motor and cognitive functions in Parkinson's and Alzheimer's diseases.

Neurodegenerative disorders, such as Parkinson's disease (PD) and Alzheimer's disease (AD), have a global prevalence and profoundly impact both motor and cognitive functions. Although adeno-associated virus (AAV)-based gene therapy has shown promise, its application for treating central nervous system (CNS) diseases faces several challenges, including effective delivery of AAV vectors across the blood-brain barrier, determining optimal dosages, and achieving targeted distribution. To address these challenges, we have developed a fusion delivery therapeutic cargo called AAV-aMTD-Parkin, which combines a hydrophobic cell-penetrating peptide sequence with the DNA sequences of AAV and Parkin. By employing this fusion delivery platform at lower dosages compared to zolgensma, we have achieved significant enhancements in cell and tissue permeability, while reducing the occurrence of common pathological protein aggregates. Consequently, motor and cognitive functions were restored in animal models of PD and AD. With its dual functionality in addressing PD and AD, AAV-aMTD-Parkin holds immense potential as a novel class of therapeutic biologics for prevalent CNS diseases.

A Patent Analysis on Nano Drug Delivery Systems.

BACKGROUND: A nano drug delivery system is an effective tool for drug delivery and controlled release, which is used for a variety of medical applications. In recent decades, nano drug delivery systems have been significantly developed with the emergence of new nanomaterials and nanotechnologies. OBJECTIVE: This article aimed to provide insight into the technological development of nano drug delivery systems through patent analysis. METHODS: 3708 patent documents were used for patent analysis after retrieval from the Incopat patent database. RESULTS: The number of patents on nano drug delivery systems has shown a rapid growth trend in the past two decades. At present, China and the United States have obvious contributions to the number of patents. According to the patent data, the nanomaterials used in nano drug delivery system are mainly inorganic nanomaterials, lipid-based nanomaterials, and macromolecules. In recent years, the highly cited patents (≥14) for nano drug delivery systems mainly involve lipid-based nanomaterials, indicating that their technology is mature and widely used. The inorganic nanomaterials in drug delivery have received increasing attention, and the number of related patents has increased significantly after 2016. The number of highly cited patents in the United States is 250, which is much higher than in other countries. CONCLUSION: Even after decades of development, nano drug delivery systems remain a hot topic for researchers. The significant increase in patents since 2016 can be attributed to the large number of new patents from China. However, according to the proportion of highly cited patents in total, China's patented technologies in nano drug delivery systems are not advanced enough compared to developed countries, including the United States, Canada, Germany, and France. In the future, research on emerging nanomaterials for nano drug delivery systems, such as inorganic nanomaterials, may focus on developing new materials and optimising their properties. The lipid-based and polymer- based nanomaterials can be continuously improved for the development of new nanomedicines.

Chandipura viral glycoprotein (CNV-G) promotes Gectosome generation and enables delivery of intracellular therapeutics.

Overexpression of vesicular stomatitis virus G protein (VSV-G) elevates the secretion of EVs known as gectosomes, which contain VSV-G. Such vesicles can be engineered to deliver therapeutic macromolecules. We investigated viral glycoproteins from several viruses for their potential in gectosome production and intracellular cargo delivery. Expression of the viral glycoprotein (viral glycoprotein from the Chandipura virus [CNV-G]) from the human neurotropic pathogen Chandipura virus in 293T cells significantly augments the production of CNV-G-containing gectosomes. In comparison with VSV-G gectosomes, CNV-G gectosomes exhibit heightened selectivity toward specific cell types, including primary cells and tumor cell lines. Consistent with the differential tropism between CNV-G and VSV-G gectosomes, cellular entry of CNV-G gectosome is independent of the Low-density lipoprotein receptor, which is essential for VSV-G entry, and shows varying sensitivity to pharmacological modulators. CNV-G gectosomes efficiently deliver diverse intracellular cargos for genomic modification or responses to stimuli in vitro and in the brain of mice in vivo utilizing a split GFP and chemical-induced dimerization system. Pharmacokinetics and biodistribution analyses support CNV-G gectosomes as a versatile platform for delivering macromolecular therapeutics intracellularly.

Macromolecular Nano-Assemblies for Enhancing the Effect of Oxygen-Dependent Photodynamic Therapy Against Hypoxic Tumors.

In oxygen (O2)-dependent photodynamic therapy (PDT), photosensitizers absorb light energy, which is then transferred to ambient O2 and subsequently generates cytotoxic singlet oxygen (1O2). Therefore, the availability of O2 and the utilization efficiency of generated 1O2 are two significant factors that influence the effectiveness of PDT. However, tumor microenvironments (TMEs) characterized by hypoxia and limited utilization efficiency of 1O2 resulting from its short half-life and short diffusion distance significantly restrict the applicability of PDT for hypoxic tumors. To address these challenges, numerous macromolecular nano-assemblies (MNAs) have been designed to relieve hypoxia, utilize hypoxia or enhance the utilization efficiency of 1O2. Herein, we provide a comprehensive review on recent advancements achieved with MNAs in enhancing the effectiveness of O2-dependent PDT against hypoxic tumors.

Multiparametric exchange protons using Z-spectrum analysis proton (ZAP) and CEST on phantoms and human abdomen.

PURPOSE: This study aims to investigate a multiparametric exchange proton approach using CEST and Z-spectrum analysis protons (ZAP) in human abdominal organs, focusing on tissue differentiation for a potential early biomarker of abnormality. Prior to human studies, CEST and ZAP effects were studied in phantoms containing exchange protons. METHODS: Phantoms composed of iopamidol and iohexol solutions with varying pH levels, along with 12 human subjects, were scanned on a clinical 3T MR scanner. Subsequent ZAP analyses employed a two-Lorentzian pool model to provide free and restricted apparent T 2 f , r ex $$ {\mathrm{T}}_{2\ \mathrm{f},\mathrm{r}}^{\mathrm{ex}} $$ , and their fractions for data acquired across a wide range of offset frequencies (±100 kHz or ± 800 ppm), while a narrower range (±7 ppm or ± 900 Hz) was used for CEST analysis to estimate magnetization transfer ratio asymmetry (MTRAsym) for exchange protons like hydroxyl (-OH), amine (-NH2), and amide (-NH), resonating ˜1, 2, and 3.5 ppm, respectively. Differences in ZAP metrics across various organs were statistically analyzed using one-way analysis of variance (ANOVA). RESULTS: The phantom study differentiated contrast agents based on resonance peaks detected from CEST analysis, while ZAP metrics showed sensitivity to pH variations. In human, ZAP metrics revealed significant differences in abdominal organs, with a subgroup study indicating changes in ZAP metrics due to the presence of gallstones. CONCLUSION: CEST and ZAP techniques demonstrated promise in specific CEST protons and wide range ZAP protons and identifying tissue-specific characteristics. The preliminary findings underscore the necessity for more extensive study involving a broader subject pool to potentially establish biomarkers for diseased states.

Validation of the Absorption-Enhancing Ability of Oligoarginines Grafted onto a Backbone of Hyaluronic Acid through Animal Studies from Rodents to Primates.

The purpose of our research is to develop functional additives that enhance mucosal absorption of biologics, such as peptide/protein and antibody drugs, to provide their non-to-poor invasive dosage forms self-managed by patients. Our previous in vivo and in vitro studies demonstrated that the intranasal absorption of biologics in mice was significantly improved when coadministered with oligoarginines anchored chemically to hyaluronic acid via a glycine spacer, presumably through syndecan-4-mediated macropinocytosis under activation by oligoarginines. The present mouse experiments first revealed that diglycine-L-tetraarginine-linked hyaluronic acid significantly enhanced the intranasal absorption of sulpiride, which is a poor-absorptive organic compound with a low molecular weight. However, similar enhancement was not observed for levofloxacin, which has a similarly low molecular weight but is a well-absorptive organic compound, probably because its absorption was mostly dominated by passive diffusion. The subsequent monkey experiments revealed that there was no species difference in the absorption-enhancing ability of diglycine-L-tetraarginine-linked hyaluronic acid for not only organic compounds but also biologics. This was presumably because the expression levels of endocytosis-associated membrane proteins on the nasal mucosa in monkeys were almost equivalent to those in mice, and poorly membrane-permeable/membrane-impermeable drugs were mainly absorbed via syndecan-4-mediated macropinocytosis, regardless of animal species. Drug concentrations in the brain assessed in mice and monkeys and those in the cerebral spinal fluids (CSFs) assessed in monkeys indicated that drugs would be delivered from the systemic circulation to the central nervous system by crossing the blood-brain and the blood-CSF barriers under coadministration with the hyaluronic acid derivative. In line with our original hypothesis, this new set of data supported that our oligoarginine-linked hyaluronic acid would locally perform on the mucosal surface and enhance the membrane permeation of drugs under its colocalization.

Variation pattern in the macromolecular (cellulose, hemicelluloses, lignin) composition of cell walls in Pinus tabulaeformis tree trunks at different ages as revealed using multiple techniques.

The plant cell wall is a complex, heterogeneous structure primarily composed of cellulose, hemicelluloses, and lignin. Exploring the variations in these three macromolecules over time is crucial for understanding wood formation to enhance chemical processing and utilization. Here, we comprehensively analyzed the chemical composition of cell walls in the trunks of Pinus tabulaeformis using multiple techniques. In situ analysis showed that macromolecules accumulated gradually in the cell wall as the plant aged, and the distribution pattern of lignin was opposite that of polysaccharides, and both showed heterogenous distribution patterns. In addition, gel permeation chromatography (GPC) results revealed that the molecular weights of hemicelluloses decreased while that of lignin increased with age. Two-dimensional heteronuclear single quantum coherence nuclear magnetic resonance (2D-HSQC NMR) analysis indicated that hemicelluloses mainly comprised galactoglucomannan and arabinoglucuronoxylan, and the lignin types were mainly comprised guaiacyl (G) and p-hydroxyphenyl (H) units with three main linkage types: ß-O-4, ß-ß, and ß-5. Furthermore, the C-O bond (ß-O-4) signals of lignin decreased while the C-C bonds (ß-ß and ß-5) signals increased over time. Taken together, these findings shed light on wood formation in P. tabulaeformis and lay the foundation for enhancing the processing and use of wood and timber products.

Harnessing DNA origami's therapeutic potential for revolutionizing cardiovascular disease treatment: A comprehensive review.

DNA origami is a cutting-edge nanotechnology approach that creates precise and detailed 2D and 3D nanostructures. The crucial feature of DNA origami is how it is created, which enables precise control over its size and shape. Biocompatibility, targetability, programmability, and stability are further advantages that make it a potentially beneficial technique for a variety of applications. The preclinical studies of sophisticated programmable nanomedicines and nanodevices that can precisely respond to particular disease-associated triggers and microenvironments have been made possible by recent developments in DNA origami. These stimuli, which are endogenous to the targeted disorders, include protein upregulation, pH, redox status, and small chemicals. Oncology has traditionally been the focus of the majority of past and current research on this subject. Therefore, in this comprehensive review, we delve into the intricate world of DNA origami, exploring its defining features and capabilities. This review covers the fundamental characteristics of DNA origami, targeting DNA origami to cells, cellular uptake, and subcellular localization. Throughout the review, we emphasised on elucidating the imperative for such a therapeutic platform, especially in addressing the complexities of cardiovascular disease (CVD). Moreover, we explore the vast potential inherent in DNA origami technology, envisioning its promising role in the realm of CVD treatment and beyond.

Enhancing stem cell therapy efficacy with functional lignin modified cerium-iron nanozyme through magnetic resonance imaging tracking and apoptosis protection in inflammatory environment.

Stem cell transplantation provides a promising approach for addressing inflammation and functional disorders. Nonetheless, the viability of these transplanted cells diminishes significantly within pathological environments, limiting their therapeutic potential. Moreover, the non-invasive tracking of these cells in vivo remains a considerable challenge, hampering the assessment of their therapeutic efficacy. Transition-metal oxide nanocrystals, known for their unique "enzyme-like" catalytic property and imaging capability, provide a new avenue for clinical application. In this study, the lignin as a biocompatible macromolecule was modified with poly (ethylene glycol) through chain-transfer polymerization, and then it was utilized to incorporate superparamagnetic iron oxide and cerium oxide nanocrystals creating a functional nanozyme. The iron oxide nanocrystals self-assembled into the hydrophobic core of nano system, while the in-situ mineralization of cerium oxide particles was carried out with the assistance of peripheral phenolic hydroxyl groups. The product, cerium­iron core-shell nanozyme, enabled effective stem cells labeling through endocytosis and exhibited catalase and superoxide dismutase activities within the cells. As a result, it could scavenge highly destructive hydroxyl radicals and peroxyl radicals, shielding stem cells from apoptosis in inflammatory environment and maintaining their differentiation ability. Additionally, when these functionalized stem cells were administered to mice with acute inflammation, not only did they alleviate disease symptoms, but they also allowed for the visualization using T2-weighted magnetic resonance imaging. This innovative therapeutic approach provides a new strategy for combatting diseases.

Evaluation of the Glymphatic System in Schizophrenia Spectrum Disorder Using Proton Magnetic Resonance Spectroscopy Measurement of Brain Macromolecule and Diffusion Tensor Image Analysis Along the Perivascular Space Index.

BACKGROUND AND HYPOTHESIS: The glymphatic system (GS), a brain waste clearance pathway, is disrupted in various neurodegenerative and vascular diseases. As schizophrenia shares clinical characteristics with these conditions, we hypothesized GS disruptions in patients with schizophrenia spectrum disorder (SCZ-SD), reflected in increased brain macromolecule (MM) and decreased diffusion-tensor-image-analysis along the perivascular space (DTI-ALPS) index. STUDY DESIGN: Forty-seven healthy controls (HCs) and 103 patients with SCZ-SD were studied. Data included 135 proton magnetic resonance spectroscopy (1H-MRS) sets, 96 DTI sets, with 79 participants contributing both. MM levels were quantified in the dorsal-anterior cingulate cortex (dACC), dorsolateral prefrontal cortex, and dorsal caudate (point resolved spectroscopy, echo-time = 35ms). Diffusivities in the projection and association fibers near the lateral ventricle were measured to calculate DTI-ALPS indices. General linear models were performed, adjusting for age, sex, and smoking. Correlation analyses examined relationships with age, illness duration, and symptoms severity. STUDY RESULTS: MM levels were not different between patients and HCs. However, left, right, and bilateral DTI-ALPS indices were lower in patients compared with HCs (P < .001). In HCs, age was positively correlated with dACC MM and negatively correlated with left, right, and bilateral DTI-ALPS indices (P < .001). In patients, illness duration was positively correlated with dACC MM and negatively correlated with the right DTI-ALPS index (P < .05). In the entire population, dACC MM and DTI-ALPS indices showed an inverse correlation (P < .01). CONCLUSIONS: Our results suggest potential disruptions in the GS of patients with SCZ-SD. Improving brain's waste clearance may offer a potential therapeutic approach for patients with SCZ-SD.

The effect of konjac glucomannan on enzyme kinetics and fluorescence spectrometry of digestive enzymes: An in vitro research from the perspective of macromolecule crowding.

Konjac glucomannan (KGM) can significantly prolong gastrointestinal digestion. However, it is still worth investigating whether the macromolecular crowding (MMC) induced by KGM is correlated with digestion. In this paper, the MMC effect was quantified by fluorescence resonance energy transfer and microrheology, and the digests of starch, protein, and oil were determined. The digestive enzymes were analyzed by enzyme reaction kinetic and fluorescence quenching. The results showed that higher molecular weight (604.85 âˆ¼ 1002.21 kDa) KGM created a larger MMC (>0.8), and influenced the digestion of macronutrients; the digests of starch, protein, and oil all decreased significantly. MMC induced by KGM decreased the Michaelis-Menten constants (Km and Vmax) of pancreatic α-amylase (PPA), pepsin (PEP), and pancreatic lipase (PPL). The larger MMC (>0.8) induced by KGM resulted in the decrease of fluorescence quenching constants (Ksv) in PPA and PPL, and the increase of Ksv in PEP. Therefore, varying degrees of MMC induced by KGM could play a role in regulating digestion and the inhibitory effect on digestion was more significant in a relatively more crowded environment induced by KGM. This study provides theoretical support for the strategies of nutrient digestion regulation from the perspective of MMC caused by dietary fiber.

Near-Infrared Triggered Biodegradable Microneedle Patch for Controlled Macromolecule Drug Release.

Transdermal drug delivery of macromolecule drugs attracts significant attention due to the advantage of convenience and biocompatibility. However, the practical usage of it is limited by the low delivery efficiency and poor drug absorption. To develop an efficient, safe, and controllable transdermal delivery method, the near-infrared (NIR) triggered calcium sulfate and gelatin biodegradable composite microneedle (MN) patches are developed. The MN patches are fabricated by polydimethylsiloxane (PDMS) molds, and the structure data can be adjusted by changing the molds. Such an MN patch can release both macro and micro molecule drugs. After loading with photothermal converter IR780, which can transfer energy of light to heat, the release of macromolecule drugs in MNs can be controlled by applying NIR irradiation. The control effect can be enhanced by spraying 1-tetradecanol (TD) coating and optimizing the ratio (weight) of gelatin and calcium sulfate to 2:6. Besides, the MN patch can deliver drugs through the skin barrier, and the process can be controlled by NIR. Moreover, the insulin-loaded MN patch exhibits some therapeutic effects on healthy mice. This work suggests that biodegradable MNs can achieve controllable drug delivery and potentially be applied in individual treatment via transdermal ingestion.

Releasing Free Radicals in Precursor Triggers the Formation of Closed Pores in Hard Carbon for Sodium-Ion Batteries.

Increasing closed pore volume in hard carbon is considered to be the most effective way to enhance the electrochemical performance in sodium-ion batteries. However, there is a lack of systematic insights into the formation mechanisms of closed pores at molecular level. In this study, a regulation strategy of closed pores via adjustment of the content of free radicals is reported. Sufficient free radicals are exposed by part delignification of bamboo, which is related to the formation of well-developed carbon layers and rich closed pores. In addition, excessive free radicals from nearly total delignification lead to more reactive sites during pyrolysis, which competes for limited precursor debris to form smaller microcrystals and therefore compact the material. The optimal sample delivers a large closed pore volume of 0.203 cm3 g-1, which leads to a high reversible capacity of 350 mAh g-1 at 20 mA g-1 and enhanced Na+ transfer kinetics. This work provides insights into the formation mechanisms of closed pores at molecular level, enabling rational design of hard carbon pore structures.

Recent advances in harnessing biological macromolecules for wound management: A review.

Wound dressings (WDs) are an essential component of wound management and serve as an artificial barrier to isolate the injured site from the external environment, thereby helping to prevent exogenous infections and supporting healing. However, maintaining a moist wound environment, providing protection from infection, good biocompatibility, and allowing for gas exchange, remain a challenge in device design. Functional wound dressings (FWDs) prepared from hybrid biological macromolecule-based materials can enhance efficacy of these systems for skin wound management. This review aims to provide an overview of the state-of-the-art FWDs within the field of wound management, with a specific focus on hybrid biomaterials, techniques, and applications developed over the past five years. In addition, we highlight the incorporation of biological macromolecules in WDs, the emergence of smart WDs, and discuss the existing challenges and future prospects for the development of advanced WDs.

Melanoidin-like carbohydrate-containing macromolecules from Shanxi aged vinegar exert immunoenhancing effects on macrophage RAW264.7 cells.

Bioactive macromolecule mining is important for the functional chemome analysis of traditional Chinese vinegar. In this study, we isolated and characterized carbohydrate-containing macromolecules from Shanxi aged vinegar (CCMSAV) and evaluated their immunomodulatory activity. The isolation process involved ethanol precipitation, deproteinization, decolorization, and DEAE-650 M column chromatography, resulting in the acquisition of four sub-fractions. All sub-fractions exhibited a molecular weight range of 6.92 to 16.71 kDa and were composed of 10 types of monosaccharides. Comparative analysis of these sub-fractions with two melanoidins exhibited similarities in elemental composition, spectral signature, and pyrolytic characteristics. Immunological assays confirmed the significantly enhanced cell viability, phagocytic activity, and secretion of nitric oxide, tumor necrosis factor (TNF)-α and interleukin (IL)-6 in RAW264.7 cells by all four sub-fractions. Further investigation of the immunomodulatory mechanism revealed that SAV-RP70-X, the most potent purified sub-fraction, enhanced aerobic glycolysis in macrophages and activated Toll-like receptor 2 (TLR2), TLR4, mannose receptor (MR), scavenger receptor (SR), and the dendritic cell-associated C-type lectin-1 receptor (Dectin-1). Furthermore, the activation of macrophages was associated with the MyD88/PI3K/Akt/NF-κB signaling pathway. Methylation analysis revealed that 1,4-Xylp was the most abundant glycosidic linkage in SAV-RP70-X.

Inetetamab combined with pyrotinib and chemotherapy in the treatment of breast cancer brain metastasis: A case report.

BACKGROUND: Breast cancer brain metastasis (BCBM) is an advanced breast disease that is difficult to treat and is associated with a high risk of death. Patient prognosis is usually poor, with reduced quality of life. In this context, we report the case of a patient with HER-2-positive BCBM treated with a macromolecular mAb (inetetamab) combined with a small molecule tyrosine kinase inhibitor (TKI). CASE SUMMARY: The patient was a 58-year-old woman with a 12-year history of type 2 diabetes. She was compliant with regular insulin treatment and had good blood glucose control. The patient was diagnosed with invasive carcinoma of the right breast (T3N1M0 stage IIIa, HER2-positive type) through aspiration biopsy of the ipsilateral breast due to the discovery of a breast tumor in February 2019. Immunohistochemistry showed ER (-), PR (-), HER-2 (3+), and Ki-67 (55-60%+). Preoperative neoadjuvant chemotherapy, i.e., the AC-TH regimen (epirubicin, cyclophosphamide, docetaxel-paclitaxel, and trastuzumab), was administered for 8 cycles. She underwent modified radical mastectomy of the right breast in November 2019 and received tocilizumab targeted therapy for 1 year. Brain metastasis was found 9 mo after surgery. She underwent brain metastasectomy in August 2020. Immunohistochemistry showed ER (-) and PR. (-), HER-2 (3+), and Ki-67 (10-20%+). In November 2020, the patient experienced headache symptoms. After an examination, tumor recurrence in the original surgical region of the brain was observed, and the patient was treated with inetetamab, pyrotinib, and capecitabine. Whole-brain radiotherapy was recommended. The patient and her family refused radiotherapy for personal reasons. In September 2021, a routine examination revealed that the brain tumor was considerably larger. The original systemic treatment was continued and combined with intensity-modulated radiation therapy for brain metastases, followed by regular hospitalization and routine examinations. The patient's condition is generally stable, and she has a relatively high quality of life. This case report demonstrates that in patients with BCBM and resistance to trastuzumab, inetetamab combined with pyrotinib and chemotherapy can prolong survival. CONCLUSION: Inetetamab combined with small molecule TKI drugs, chemotherapy and radiation may be an effective regimen for maintaining stable disease in patients with BCBM.