TNFAIP1 promotes macrophage lipid accumulation and accelerates the development of atherosclerosis through the LEENE/FoxO1/ABCA1 pathway.

Macrophage lipid accumulation is a critical contributor to foam cell formation and atherosclerosis. Tumor necrosis factor-α-induced protein 1 (TNFAIP1) is closely associated with cardiovascular disease. However, its role and molecular mechanisms in atherogenesis remain unclear. TNFAIP1 was knocked down in THP-1 macrophage-derived foam cells and apolipoprotein-deficient (apoE-/-) mice using lentiviral vector. The expression of lncRNA enhancing endothelial nitric oxide synthase expression (LEENE), Forkhead box O1 (FoxO1) and ATP binding cassette transporter A1 (ABCA1) was evaluated by qRT-PCR and/or western blot. Lipid accumulation in macrophage was assessed by high-performance liquid chromatography and Oil red O staining. RNA immunoprecipitation and RNA pull-down assay were performed to verify the interaction between LEENE and FoxO1 protein. Atherosclerotic lesions were analyzed using HE, Oil red O and Masson staining. Our results showed that TNFAIP1 was significantly increased in THP-1 macrophages loaded with oxidized low-density lipoprotein. Knockdown of TNFAIP1 enhanced LEENE expression, promoted the direct interaction of LEENE with FoxO1 protein, stimulated FoxO1 protein degradation through the proteasome pathway, induced ABCA1 transcription, and finally suppressed lipid accumulation in THP-1 macrophage-derived foam cells. TNFAIP1 knockdown also up-regulated ABCA1 expression, improved plasma lipid profiles, enhanced the efficiency of reverse cholesterol transport and attenuated lesion area in apoE-/- mice. Taken together, these results provide the first direct evidence that TNFAIP1 aggravates atherosclerosis by promoting macrophage lipid accumulation via the LEENE/FoxO1/ABCA1 signaling pathway. TNFAIP1 may represent a promising therapeutic target for atherosclerotic cardiovascular disease.

Salidroside Ameliorates Lung Injury Induced by PM 2.5by Regulating SIRT1-PGC-1α in Mice.

Objective: This study aimed to clarify the intervention effect of salidroside (SAL) on lung injury caused by PM 2.5 in mice and illuminate the function of SIRT1-PGC-1ɑ axis. Methods: Specific pathogen-free (SPF) grade male C57BL/6 mice were randomly assigned to the following groups: control group, SAL group, PM 2.5 group, SAL+PM 2.5 group. On the first day, SAL was given by gavage, and on the second day, PM 2.5 suspension was given by intratracheal instillation. The whole experiment consist of a total of 10 cycles, lasting 20 days. At the end of treatment, blood samples and lung tissues were collected and analyzed. Observation of pathological changes in lung tissue using inverted microscopy and transmission electron microscopy. The expression of inflammatory, antioxidants, apoptosis, and SIRT1-PGC-1ɑ proteins were detected by Western blotting. Results: Exposure to PM 2.5 leads to obvious morphological and pathologica changes in the lung of mice. PM 2.5 caused a decline in levels of antioxidant-related enzymes and protein expressions of HO-1, Nrf2, SOD2, SIRT1 and PGC-1ɑ, and an increase in the protein expressions of IL-6, IL-1ß, Bax, caspase-9 and cleaved caspase-3. However, SAL reversed the aforementioned changes caused by PM 2.5 by activating the SIRT1-PGC-1α pathway. Conclusion: SAL can activate SIRT1-PGC-1ɑ to ameliorate PM 2.5-induced lung injury.

Platelet-Rich Plasma in Young and Elderly Humans Exhibits a Different Proteomic Profile.

As people age, their ability to resist injury and repair damage decreases significantly. Platelet-rich plasma (PRP) has demonstrated diverse therapeutic effects on tissue repair. However, the inconsistency of patient outcomes poses a challenge to the practical application of PRP in clinical practice. Furthermore, a comprehensive understanding of the specific impact of aging on PRP requires a systematic investigation. We derived PRP from 6 young volunteers and 6 elderly volunteers, respectively. Subsequently, 95% of high-abundance proteins were removed, followed by mass spectrometry analysis. Data are available via ProteomeXchange with the identifier PXD050061. We detected a total of 739 proteins and selected 311 proteins that showed significant differences, including 76 upregulated proteins in the young group and 235 upregulated proteins in the elderly group. Functional annotation and enrichment analysis unveiled upregulation of proteins associated with cell apoptosis, angiogenesis, and complement and coagulation cascades in the elderly. Conversely, IGF1 was found to be upregulated in the young group, potentially serving as the central source of enhanced cell proliferation ability. Our investigation not only provides insights into standardizing PRP preparation but also offers novel strategies for augmenting the functionality of aging cells or tissues.

Renal-Limited Thrombotic Microangiopathy in a Patient Who Received Gemcitabine, Ramucirumab, and Pembrolizumab: A Case Report and Literature Review.

Cancer drug-induced thrombotic microangiopathy (DITMA) is an important and serious cause of kidney disease in cancer patients. In addition to classical chemotherapy, the increasing use of targeted therapy and immunotherapy has led to more oncotherapy-associated thrombotic microangiopathy (TMA). It is important for clinicians to recognize this potentially life-threatening adverse effect and gain knowledge of the patient's clinical course and treatment response. In this paper, we report a patient with lung cancer, who was treated with three different classes of anti-neoplastic agents, gemcitabine, ramucirumab, and pembrolizumab. This patient subsequently developed renal-limited thrombotic microangiopathy(rTMA) requiring hemodialysis. The varying features of TMA caused by these therapies were discussed. We also described the clinical course, diagnostic challenges, and management of this patient.

dECM restores macrophage immune homeostasis and alleviates iron overload to promote DTPI healing.

Due to its highly insidious and rapid progression, deep tissue pressure injury (DTPI) is a clinical challenge. Our previous study found that DTPI may be a skeletal muscle injury dominated by macrophage immune dysfunction due to excessive iron accumulation. Decellularized extracellular matrix (dECM) hydrogel promotes skeletal muscle injury repair. However, its role in polarizing macrophages and regulating iron metabolism in DTPI remains unclear. Here, porcine dECM hydrogel was prepared, and its therapeutic function and mechanism in repairing DTPI were investigated. The stimulus of dECM hydrogel toward RAW264.7 cells resulted in a significantly higher percentage of CD206+ macrophages and notably decreased intracellular divalent iron levels. In mice DTPI model, dECM hydrogel treatment promoted M1 to M2 macrophage conversion, improved iron metabolism and reduced oxidative stress in the early stage of DTPI. In the remodeling phase, the dECM hydrogel remarkably enhanced revascularization and accelerated skeletal muscle repair. Furthermore, the immunomodulation of dECM hydrogels in vivo was mainly involved in the P13k/Akt signaling pathway, as revealed by GO and KEGG pathway analysis, which may ameliorate the iron deposition and promote the healing of DTPI. Our findings indicate that dECM hydrogel is promising in skeletal muscle repair, inflammation resolution and tissue injury healing by effectively restoring macrophage immune homeostasis and normalizing iron metabolism.

Higher concentration of P7C3 than required for neuroprotection suppresses renal cell carcinoma growth and metastasis.

Background: P7C3 is a novel compound that has been widely applied in neurodegenerative diseases and nerve injury repair. Here, we show that higher concentrations of P7C3 than are required for in vivo neuroprotection have the novel function of suppressing renal cell carcinoma (RCC) proliferation and metastasis. Methods: Colony formation, CCK-8 and EdU assay were applied to evaluate RCC cell proliferation. Wound healing and transwell assay were used to measure RCC cell migration and invasion. Flow cytometry assay was employed to detect RCC cell apoptosis and cell cycle. qRT-PCR assay was carried out to measure ribonucleotide reductase subunit M2 (RRM2) mRNA expression level, while western blot assay was utilized to detect the expression level of target proteins. RCC cell growth in vivo was determined by xenografts in mice. Results: We observed that high concentrations of P7C3 could restrain the proliferation and metastasis of RCC cells and promote cell apoptosis. Mechanistically, this new effect of higher dose of P7C3 was associated with reduced expression of RRM2, and the beneficial efficacy of P7C3 in RCC was blocked when suppression of RRM2 was prevented. When RRM2 suppression was permitted, the cGAS-STING pathway was activated by virtue of RRM2/Bcl-2/Bax signaling. Lastly, intraperitoneal injection of this high level of P7C3 in mice potently inhibited tumor growth. Conclusion: In conclusion, we show here that P7C3 that exerts an anti-cancer effect in RCC. Our study indicated that P7C3 might act as a novel drug for RCC in the future. The regulatory signal pathway RRM2/Bcl-2/BAX/cGAS-STING might present novel insight to the potential mechanism of RCC development.

Genipin inhibits proliferation of gastric cancer cells by inducing ferroptosis: an integrated study of network pharmacology and bioinformatics study.

Ferroptosis has been demonstrated to suppress cancer development and is targeted for cancer therapy. Genipin, an iridoid constituent in Gardeniae Fructus, has been reported to exert anti-cancer abilities. However, whether genipin could induce ferroptosis remains unclear. The purpose of this study is to explore the anti-gastric cancer (GC) effects of genipin by inducing ferroptosis and to identify the potential targets. CCK-8 and colony formation assays were performed to evaluate the anti-GC effects of genipin. Flowcytometry and western blot were used to indicate ferroptosis-inducing ability of genipin. The potential targets of genipin were analyzed by network pharmacology, screened using UALCAN and KM-plotter database and evaluated by molecular docking. The results showed that genipin inhibited cell viability and proliferation of GC cells. Genipin treatment decreased levels of GPX4 and SLC7A11, induced accumulation of lipid peroxidation intracellularly and led to ferroptosis in GC cells. Network pharmacology analysis identified that lipid- and ROS-related pathways involved in ferroptosis ranked high among genipin-GC common targets. Data from UALCAN and KM-plotter database demonstrated that expression levels of ferroptosis-related targets, including AURKA, BCAT2, DHODH, and GPI, increased in GC tissues and the higher levels of the above four targets were related to tumor stage, tumor grade, and poor prognosis. Among these four targets, AURKA, BCAT2, and DHODH were confirmed by molecular docking with binding energies less than - 5. Taken together, our study demonstrates that genipin could exert anti-GC ability by inducing ferroptosis and provides evidence for the potential application of genipin in GC treatment.

Feasibility of Simultaneous Bilateral Endoscopic Surgery in Prone Split-Leg Position for Bilateral Upper Urinary Tract Calculi: A Pilot Study.

INTRODUCTION: We explored the viability of simultaneous bilateral endoscopic surgery (SBES) in the prone split-leg position for managing bilateral calculi. METHODS: We retrospectively reviewed 72 patients who underwent SBES, with procedures involving ureteroscopy (URS) and contralateral percutaneous nephrolithotomy (PNL) simultaneously, in prone split-leg position. RESULTS: Operative times averaged 109.38 ± 30.76 min, with an average hospital stay of 7.79 ± 3.78 days. The bilateral stone-free rate (SFR) was 70.83%, while URS and PNL demonstrated comparable unilateral SFR (83.33% and 79.17%, respectively). Receiver operating characteristics curves for predicting unilateral residual fragments yielded an area under the curve of 0.84 (URS) and 0.81 (PNL) with respective cutoff values of stone diameter of 11.55 mm and 23.52 mm. Fifty-seven (79.17%) and 15 (20.83%) patients encountered grade 0-1/2 complications, with no severe complications (grade 3-5) recorded. No significant changes in blood count or renal function were observed post-SBES. CONCLUSIONS: SBES in the prone split-leg position is a viable option for managing bilateral upper tract urolithiasis. Larger scale studies are needed to further assess safety and efficacy in various positions.

Dysfunctional iron metabolism in pressure injuries is related to aberrant CD163 and Homx-1 signal transduction.

Dysregulation of iron metabolism has been associated with impaired chronic wound healing. However, changes in iron metabolism have yet to be reported in pressure injuries, a type of chronic wound. In this study, we aimed to investigate changes in iron metabolism and associated regulatory mechanisms in pressure injuries. We collected tissue biopsies and data from 20 consenting stage IV-pressure injuries patients and 5 non-pressure injuries patients hospitalised at the Affiliated Hospital of Qingdao University between March 2021 and June 2021. In addition, we measured the iron content by inductively coupled plasma mass spectrometry and Prussian blue staining in deep tissue pressure injury mouse models. An Enzyme-linked immune sorbent assay measured the expression of ferritin, ferroportin-1 and transferrin. Immunofluorescence staining, high-throughput transcriptome sequencing, Western blot and RT-qPCR further analysed the fundamental mechanisms regulating iron metabolism. In this study, we observed numerous inflammatory cells infiltrating the marginal tissues of stage IV pressure injury patients and in deep tissue pressure injury models. The expression levels of pro-inflammatory factors, such as inducible nitric oxide synthase and interleukin-6, were significantly increased (p < 0.05). The iron level was proportional to the degree of progression, with the most significant change appearing on the third day in deep tissue pressure injury models (p < 0.05). Enzyme-linked immune sorbent assay results suggested abnormal gene expression was related to iron metabolism, including a substantial increase in ferritin and a significant decrease in the expression of ferroportin-1 (p < 0.05). In addition, immunofluorescence staining and Western blot showed that the expression of macrophage membrane receptor CD163 was abnormally elevated (p < 0.05). Both high-throughput transcriptome sequencing and qRT-PCR results suggested aberrant expression of the CD163/Homx-1-mediated signalling pathway. Dysfunctional iron metabolism was suggested to be related to the aberrant CD163/Homx-1 signalling pathway in deep tissue pressure injury models.

Clinical outcomes of KRAS-mutant non-small cell lung cancer under untargeted therapeutic regimes in the real world: a retrospective observational study.

Background: Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation seemingly suffered less effective therapeutic regimens in the absence of widely-accepted targeted drugs compared with other mutation types in non-small cell lung cancer (NSCLC). However, whether these non-selective therapy schedules for KRAS mutation matters is still under debate. Correspondingly, we aimed to compare the long term expectancy of indicated therapeutic regimes and further explore the optimal schemes of KRAS mutated NSCLC in the absence of targeted drugs in this retrospective study cohort. Methods: We conducted a single-center retrospective analysis among 66 patients diagnosed with KRAS-mutant advanced NSCLC from November 2018 to December 2020. These enrolled cases were divided into different subgroups in light of mutant isotypes, pathological characteristics, and therapeutic regimes to uncover indicated long-term survival benefits. Additionally, clinical outcomes of treatment schedules and interventional lines to KRAS-mutant NSCLC were described in detail. Results: This cohort enrolled 8 patients with stage IIIB (12.1%) and 58 patients with stage IV (87.9%) with the median age 62 years, ranging from 32 to 91 years old. Genetically, G12C conducted as the most common KRAS mutation type, accounting for 30.3%. Pemetrexed combined with platinum chemotherapy seemed to be a priority (72.7%), and chemotherapy combined with immunotherapy became an alternative (15.2%) in clinic. Performing further analysis of long-term survival of patients receiving different treatment methods indicated that the median overall survival (mOS) in first-line therapy with antiangiogenesis or untreated was 13 and 12 months, respectively (P=0.79). In the first-line regimen, median survival was 17 months for patients who received combined immune checkpoint inhibitors and 12 months for those who did not (P=0.34). The mOS was 20 months for those who had used immune checkpoint inhibitors and 12 months for those who had not (P=0.11). Survival analysis results of NSCLC patients with different KRAS mutation types showed the median survival time of patients with G12C mutation type and patients without with nonG12C mutation type was 19 and 12 months, respectively (P=0.37). Conclusions: In the absence of KRAS targeted drugs, available treatment plans failed to benefit KRAS mutant sufferers regardless of isotypes, making the KRAS-targeted drugs urgent.

Potential targeting of the tumor microenvironment to improve cancer virotherapy.

In 2015, oncolytic virotherapy was approved for clinical use, and in 2017, recombinant adeno-associated virus (AAV) delivery was also approved. However, systemic administration remains challenging due to the limited number of viruses that successfully reach the target site. Although the US Food and Drug Administration (FDA) permits the use of higher doses of AAV to achieve greater rates of transduction, most AAV still accumulates in the liver, potentially leading to toxicity there and elsewhere. Targeting the tumor microenvironment is a promising strategy for cancer treatment due to the critical role of the tumor microenvironment in controlling tumor progression and influencing the response to therapies. Newly discovered evidence indicates that administration routes focusing on the tumor microenvironment can promote delivery specificity and transduction efficacy within the tumor. Here, we review approaches that involve modifying viral surface features, modulating the immune system, and targeting the physicochemical characteristics in tumor microenvironment to regulate therapeutic delivery. Targeting tumor acidosis presents advantages that can be leveraged to enhance virotherapy outcomes and to develop new therapeutic approaches that can be integrated with standard treatments.

SASH1: A Novel Eph Receptor Partner and Insights into SAM-SAM Interactions.

The Eph (erythropoietin-producing human hepatocellular) receptor family, the largest subclass of receptor tyrosine kinases (RTKs), plays essential roles in embryonic development and neurogenesis. The intracellular Sterile Alpha Motif (SAM) domain presents a critical structural feature that distinguishes Eph receptors from other RTKs and participates in recruiting and binding downstream molecules. This study identified SASH1 (SAM and SH3 domain containing 1) as a novel Eph receptor-binding partner through SAM-SAM domain interactions. Our comprehensive biochemical analyses revealed that SASH1 selectively interacts with Eph receptors via its SAM1 domain, displaying the highest affinity for EphA8. The high-resolution crystal structure of the EphA8-SASH1 complex provided insights into the specific intermolecular interactions between these proteins. Cellular assays confirmed that EphA8 and SASH1 co-localize and co-precipitate in mammalian cells, with cancer mutations (EphA8 R942H or G978D) impairing this interaction. We demonstrated that SAM-SAM interaction is critical for SASH1-mediated regulation of EphA8 kinase activity, shedding new light on the Eph signaling pathway and expanding our understanding of the molecular basis of the tumor suppressor gene SASH1.

Alsobacter ponti sp. nov., a novel denitrification and sulfate reduction bacterium isolated from Pearl River sediment.

A Gram-staining negative, aerobic, motile, and short rods strain, designated SYSU M60028T, was isolated from a Pearl River sediment sample in Guangzhou, Guangdong, China. The isolate could be able to grow at pH 6.0-8.0 (optimum, pH 7.0), 25-37 °C (optimum, 28 °C) and in the presence of 0-2% (w/v) NaCl (optimum, 0% NaCl). The cellular polar lipids of this strain were phosphatidylethanolamine, diphosphatidylglycerol, phosphatidylglycerol, phosphatidylcholine, one unidentified aminolipid and three unidentified lipids. The respiratory quinone of SYSU M60028T was found to be Q-10. The major fatty acids (> 5% of total) were summed feature 8, C16:0, and C18:1 ω7c 11-methy1. The genomic DNA G + C content was 69.9%. Phylogenetic analyses based on 16S rRNA gene sequences and core genes indicated that strain SYSU M60028T belonged to the genus Alsobacter and had the highest sequences similarities to Alsobacter metallidurans SK200a-9T (96.87%) and Alsobacter soli SH9T (96.87%). Based on the phenotypic, genotypic, and phylogenetic data, strain SYSU M0028T should be considered to represent a novel species of the genus Alsobacter, for which the name Alsobacter ponti sp. nov. is proposed. The type strain is SYSU M60028T (= CGMCC 1.19341T = KCTC 92046T).

Self-healing hydrogel as an injectable implant: translation in brain diseases.

Tissue engineering biomaterials are aimed to mimic natural tissue and promote new tissue formation for the treatment of impaired or diseased tissues. Highly porous biomaterial scaffolds are often used to carry cells or drugs to regenerate tissue-like structures. Meanwhile, self-healing hydrogel as a category of smart soft hydrogel with the ability to automatically repair its own structure after damage has been developed for various applications through designs of dynamic crosslinking networks. Due to flexibility, biocompatibility, and ease of functionalization, self-healing hydrogel has great potential in regenerative medicine, especially in restoring the structure and function of impaired neural tissue. Recent researchers have developed self-healing hydrogel as drug/cell carriers or tissue support matrices for targeted injection via minimally invasive surgery, which has become a promising strategy in treating brain diseases. In this review, the development history of self-healing hydrogel for biomedical applications and the design strategies according to different crosslinking (gel formation) mechanisms are summarized. The current therapeutic progress of self-healing hydrogels for brain diseases is described as well, with an emphasis on the potential therapeutic applications validated by in vivo experiments. The most recent aspect as well as the design rationale of self-healing hydrogel for different brain diseases is also addressed.

Tuning the Organ Tropism of Polymersome for Spleen-Selective Nanovaccine Delivery to Boost Cancer Immunotherapy.

The past few decades have witnessed explosive development in drug delivery systems. However, in vivo delivery suffers from non-specific distribution in non-targeted organs or tissues, which may cause undesired side effects and even genotoxicity. Here, a general strategy that enables tuning the tropism of polymersomes for liver- and spleen-selective delivery is reported. By using a library screening approach, spleen-targeted polymersome PH9-Aln-8020 and liver-targeted polymersome PA9-ZP3-5050 are identified accordingly. Meanwhile, the second near-infrared (NIR-II) fluorescence imaging allows for in vivo dynamic evaluation of their spatial and temporal accumulation in specific tissues. O ur findings indicate that both polymer composition and protein corona on the surface are essential to determine the in vivo fate of polymersomes and tendency for specific organs. Importantly, PH9-Aln-8020 is employed as a systemic nanocarrier to co-deliver the antigen and adjuvant, which remarkably boost splenic immune responses in acute myeloid leukemia, melanoma, and melanoma lung metastasis mouse models. This study may open a new frontier for polymersomes in organ-selective delivery and other biomedical applications.

A self-healing hydrogel and injectable cryogel of gelatin methacryloyl-polyurethane double network for 3D printing.

Three-dimensional (3D) printing of soft biomaterials facilitates the progress of personalized medicine. The development for different forms of 3D-printable biomaterials can promotes the potential manufacturing for artificial organs and provides biomaterials with the required properties. In this study, gelatin methacryloyl (GelMA) and dialdehyde-functionalized polyurethane (DFPU) were combined to create a double crosslinking system and develop 3D-printable GelMA-PU biodegradable hydrogel and cryogel. The GelMA-PU system demonstrates a combination of self-healing ability and 3D printability and provides two distinct forms of 3D-printable biomaterials with smart functions, high printing resolution, and biocompatibility. The hydrogel was printed into individual modules through an 80 µm or larger nozzle and further assembled into complex structures through adhesive and self-healing abilities, which could be stabilized by secondary photocrosslinking. The 3D-printed hydrogel was adhesive, light transmittable, and could embed a light emitting diode (LED). Furthermore, the hydrogel laden with human mesenchymal stem cells (hMSCs) was successfully printed and showed cell proliferation. Meanwhile, 3D-printed cryogel was achieved by printing on a subzero temperature platform through a 210 µm nozzle. After secondary photocrosslinking and drying, the cryogel was deliverable through a 16-gage (1194 µm) syringe needle and can promote the proliferation of hMSCs. The GelMA-PU system extends the ink pool for 3D printing of biomaterials and has potential applications in tissue engineering scaffolds, minimally invasive surgery devices, and electronic wound dressings. STATEMENT OF SIGNIFICANCE: The 3D-printable biomaterials developed in this work are GelMA-based ink with smart funcitons and have potentials for various customized medical applications. The synthesized GelMA-polyurethane double network hydrogel can be 3D-printed into individual modules (e.g., 11 × 11 × 5 mm3) through an 80 µm or larger size nozzle, which are then assembled into a taller structure over five times of the initial height by self-healing and secondary photocrosslinking. The hydrogel is adhesive, light transmittable, and biocompatible that can either carry human mesenchymal stem cells (hMSCs) as bioink or embed a red light LED (620 nm) with potential applications in electronic skin dressing. Meanwhile, the 3D-printed highly compressible cryogel (e.g., 6 × 6 × 1 mm3) is deliverable by a 16-gage (1194 µm) syringe needle and supports the proliferation of hMSCs also.

Antiviral and Antibacterial Sulfated Polysaccharide-Chitosan Nanocomposite Particles as a Drug Carrier.

Drug delivery system (DDS) refers to the method of delivering drugs to the targeted sites with minimal risk. One popular strategy of DDS is using nanoparticles as a drug carrier, which are made from biocompatible and degradable polymers. Here, nanoparticles composed of Arthrospira-derived sulfated polysaccharide (AP) and chitosan were developed and expected to possess the capabilities of antiviral, antibacterial, and pH-sensitive properties. The composite nanoparticles, abbreviated as APC, were optimized for stability of morphology and size (~160 nm) in the physiological environment (pH = 7.4). Potent antibacterial (over 2 µg/mL) and antiviral (over 6.596 µg/mL) properties were verified in vitro. The pH-sensitive release behavior and release kinetics of drug-loaded APC nanoparticles were examined for various categories of drugs, including hydrophilic, hydrophobic, and protein drugs, under different pH values of the surroundings. Effects of APC nanoparticles were also evaluated in lung cancer cells and neural stem cells. The use of APC nanoparticles as a drug delivery system maintained the bioactivity of the drug to inhibit the proliferation of lung cancer cells (with ~40% reduction) and to relieve the growth inhibitory effect on neural stem cells. These findings indicate that the pH-sensitive and biocompatible composite nanoparticles of sulfated polysaccharide and chitosan well keep the antiviral and antibacterial properties and may serve as a promising multifunctional drug carrier for further biomedical applications.

Bioactive self-healing hydrogel based on tannic acid modified gold nano-crosslinker as an injectable brain implant for treating Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) is one of the most common long-term neurodegenerative diseases. Current treatments for PD are mostly based on surgery and medication because of the limitation and challenges in selecting proper biomaterials. In this study, an injectable bioactive hydrogel based on novel tannic acid crosslinker was developed to treat PD. METHODS: The oxidized tannic acid modified gold nano-crosslinker was synthesized and used to effectively crosslink chitosan for preparation of the bioactive self-healing hydrogel. The crosslinking density, conductivity, self-healing ability, and injectability of the hydrogel were characterized. Abilities of the hydrogel to promote the proliferation and differentiation of neural stem cells (NSCs) were assessed in vitro. Anti-inflammatory property was analyzed on J774A.1 macrophages. The hydrogel was injected in the PD rat model for evaluation of the motor function recovery, electrophysiological performance improvement, and histological repair. RESULTS: The hydrogel exhibited self-healing property and 34G (~ 80 µm) needle injectability. NSCs grown in the hydrogel displayed long-term proliferation and differentiation toward neurons in vitro. Besides, the hydrogel owned strong anti-inflammatory and antioxidative capabilities to rescue inflamed NSCs (~ 90%). Brain injection of the bioactive hydrogel recovered the motor function of PD rats. Electrophysiological measurements showed evident alleviation of irregular discharge of nerve cells in the subthalamic nucleus of PD rats administered with the hydrogel. Histological examination confirmed that the hydrogel alone significantly increased the density of tyrosine hydroxylase positive neurons and fibers as well as reduced inflammation, with a high efficacy similar to drug-loaded hydrogel. CONCLUSION: The new bioactive hydrogel serves as an effective brain injectable implant to treat PD and a promising biomaterial for developing novel strategies to treat brain diseases.

Development of a Sensitive Enzyme-Linked Immunosorbent Assay with Three Amplification Antibodies to Detect Low-Abundant Mouse Antibodies in the Mouse Central Nervous System.

Recombinant Abs are gaining increasing importance for the treatment of certain cancers or immunological or neurologic disorders. The ELISA is one of the most used analytical tools for detecting and quantifying Abs of interest. However, the performance of ELISAs often varies because of nonstandard experimental procedures as well as inadequate data analysis. In our study, we standardized a procedure and statistical analysis for a highly sensitive ELISA of a mouse Ab in mouse (C57BL/6J) CNS tissue. The following steps are of crucial importance: 1) calculation of the limit of detection based on control tissue lysate samples in the same testing buffer as the testing samples; 2) calculation of the limit of quantification as measured with acceptable accuracy and precision; and 3) a five-parameter logistic regression model to interpolate the symmetric and asymmetric standard curves. We also show that three amplification Abs can significantly increase the sensitivity of the ELISA compared with a two amplification Ab setup. This standardized procedure may be a valuable tool to increase the sensitivity, reproducibility, and precision of ELISA studies in basic science and translational research.

Donor-Derived Infection's Prevention and Control in Kidney Transplantation.

BACKGROUND: The study aimed to summarize the experience of donor selection and recipient therapy in the face of potential donor-derived infections and improve the quality of donor organ utilization, which would help reduce the risk of infection after recipient operation and decrease the risk of loss or even death of recipient kidney transplantation. METHODS: In this study, 132 kidneys from 70 donors and their recipients who underwent surgery between July 2017 and January 2021 were studied to perform a retrospective analysis of their etiologic examination results and treatment process. RESULTS: In the 70 donors, only 25 had negative etiologic examination results, accounting for 35.71%. Among the 132 recipients, 31.82% had positive culture results, 3 (2.27%) experienced donor-derived infections, and one died. CONCLUSIONS: Although infection in the donor before the donation is quite common, the incidence of donor-derived infections is relatively low. The targeted and preventive application of adequate sensitive antibiotics in the whole course of therapy was the cornerstone for treating recipients at potential risk of potential donor-derived infection. The changes in infection indicators in the recipient should be closely monitored, which would guide medication adjustments timely. These measures could, to a great degree, ensure the prognosis of the recipient, in turn reducing the adverse events caused by donor-derived infections.