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This experimental study was performed to investigate the antitumor effect of skin of venenum bufonis (SVB) in NCI-H460 human lung cancer cell xenografted nude mice. NCI-H460 cell lines were cultured and then xenografted into nude mice. Mice were divided into four groups: SVB (0.25 mg/kg) given orally, SVB (0.25 mg/kg) interperitoneally, SVB (0.5 mg/kg) interperitoneally, and the untreated group. Mice were raised and treated for 28 days. Body weight and tumor weight and volumes were measured daily. Absolute organ weight, microhistological observations and biochemical blood analyses were performed on the final day of the study following the sacrificing of these animals. Tumor inhibition rate, mean survival time and percent increase in life span were also calculated. Tumor size decreased in all SVB treated mice. Increasing the dose of SVB attenuated the inhibition rate seen on the 11th day of this experiment. Furthermore, tumor weight and volume in the mice treated with the highest dose of SVB were the smallest. Mice treated with high-dose intraperitoneal SVB gained weight and had significantly smaller spleens compared with untreated mice. Mean survival time and percent increase in life span in the low-dose intraperitoneal SVB treatment group were higher than those of other groups. Biochemical blood analysis revealed that phosphatase and urea nitrogen levels were decreased significantly in 0.25 mg/kg SVB orally treated mice (p < 0.01). Blood level calcium and alanine transaminase significantly decreased with intraperitoneal SVB 0.5 mg/kg (p < 0.05). The findings of this in vivo study suggest that SVB may have potential as a tumor growth inhibitor. Further research that overcomes the limitations of this study to determine the antitumor mechanism of SVB is still required. [ABSTRACT FROM AUTHOR]

PURPOSE: To assess the efficacy of the best case series program methodology as a preliminary evaluation of complementary and alternative programs. SETTING: East-West Cancer Center (EWCC) is a traditional oriental cancer center located in Daejeon, Korea. Cancer patients received Wheel balance therapy (WBT), which focuses on rediscovering homeostatic harmony with dietary therapy, metabolism-activating therapy, antiangiogenesis and immune system therapy, and controlled breathing and psychotherapy. METHODS: Summaries of 6 cases in which patients showed longer survival without progression and were treated with WBT without conventional treatments were submitted for review to the National Cancer Institute (NCI) Office of Cancer Complementary and Alternative Medicine. Each case was then classified by the NCI review panel with pathologic confirmation of disease and radiologic confirmation of complete response or partial response not attributable to conventional treatments. RESULTS: Two of 6 cases were classified as evaluable NCI best cases; the other 4 cases were classified as unevaluable. Except for a patient with squamous cell lung carcinoma, no patient showed further progression as of July 2007. CONCLUSION: The best case series program provides a preliminary evaluation of complementary and alternative medicine programs. But the method will only find treatments that have effects similar to those of conventional methods such as surgery, chemotherapy, and radiation therapy. Therefore, in future studies, BCSP reviewers should additionally consider assessing tumor dormancy and efficacy of combination therapies for Best Case qualification. [ABSTRACT FROM AUTHOR]

PURPOSE. To identify nursing diagnoses, interventions, and outcomes used with patients undergoing abdominal surgery, and the links among them. METHODS. A review of the nursing records of 60 patients undergoing abdominal surgery. Three checklists developed by the researchers were used to document nursing diagnoses made, interventions specified, and outcomes selected. FINDINGS. Pain was the most frequent diagnosis, 'pain management' the most frequent intervention, and Pain Level the most frequent outcome. Further study is needed with various samples and settings. CONCLUSIONS. Most of the suggested NIC-NANDA interventions and NOC-NANDA outcomes listed in NANDA Nursing Diagnoses: Definitions and Classification, 1999-2000, were used in this study, but some additional interventions and outcomes should be considered for inclusion. PRACTICE IMPLICATIONS. This study provides a framework for documenting nurses' work; the results of the study can promote more rapid computerization of nursing records. [ABSTRACT FROM AUTHOR]

Study Design: Case report. Objectives: To report a rare case of complicated paraplegia caused by a spontaneous epidural hematoma following an epidural steroid injection in a patient with unrecognized chronic idiopathic thrombocytopenic purpura (ITP) and to review relevant literature and discuss etiology, pathogenesis, and clinical features. Summary Of Background Data: A spinal epidural hematoma is a rare but potentially catastrophic complication, which could develop in patients without any risk factors. Some patients with chronic ITP are asymptomatic. To our knowledge there has been no previous report of such a complication. Methods: This is a retrospective review of a case seen at our institution. Results: The authors present a case of a 67-year-old woman who received an epidural steroid injection following complaints of lower back pain and bilateral buttock and leg pain. One day later, the patient had right leg numbness and weakness extending to her right knee; she was taken for emergency surgery. An emergency magnetic resonance imaging revealed an epidural hematoma with high-signal intensity on T2 imaging in the lumbar spinal cord and spinal cord compression with subdural hematoma. One week later, she was progressively developing lower extremity paraplegia with an L1 motor level and no sensory or sphincter activity. She was taken from the emergency room at our institution to the operating room for emergency decompression. After an uneventful course for 1 year, the patient presented with progressive bilateral lower extremity paralysis. Conclusion: Epidural steroid therapy is a commonly used conservative therapy; however, complications could develop in patients without any risk factors. Clinicians who plan an epidural steroid injection must perform a rigorous evaluation through a detailed physical examination, simple laboratory tests, and history taking to prevent various risks associated with spinal cord compression. [ABSTRACT FROM AUTHOR]

To provide an advanced therapy for wound recovery, in this study, pasteurized bovine milk-derived exosomes (mEXO) are immobilized onto a polydopamine (PDA)-coated hyaluronic acid (HA)-based electrospun nanofibrous matrix (mEXO@PMAT) via a simple dip-coating method to formulate an mEXO-immobilized mesh as a wound-healing biomaterial. Purified mEXOs (∼82 nm) contain various anti-inflammatory, cell proliferation, and collagen synthesis-related microRNAs (miRNAs), including let-7b, miR-184, and miR-181a, which elicit elevated mRNA expression of keratin5, keratin14, and collagen1 in human keratinocytes (HaCaT) and fibroblasts (HDF). The mEXOs immobilized onto the PDA-coated meshes are gradually released from the meshes over 14 days without burst-out effect. After treatment with HaCaT and HDF, the degree of in vitro cell migration increases significantly in the mEXO@PMAT-treated HaCaT and HDF cells compared to the unmodified or PDA-coated meshes-treated cells. Additionally, the mEXO@PMAT provides significantly faster wound closure in vivo without notable toxicity. Thus, the sustained liberation of bioactive mEXO from the meshes can effectively enhance cell proliferation in vitro and accelerate wound closure in vivo, which could be harnessed mEXO@PMAT as a promising wound-healing biomaterial., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest exist., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Nanotechnology has been increasingly utilized in anticancer treatment owing to its ability of engineering functional nanocarriers that enhance therapeutic effectiveness while minimizing adverse effects. Inorganic nanoparticles (INPs) are prevalent nanocarriers to be customized for a wide range of anticancer applications, including theranostics, imaging, targeted drug delivery, and therapeutics, because they are advantageous for their superior biocompatibility, unique optical properties, and capacity of being modified via versatile surface functionalization strategies. In the past decades, the high adaptation of INPs in this emerging immunotherapeutic field makes them good carrier options for tumor immunotherapy and combination immunotherapy. Tumor immunotherapy requires targeted delivery of immunomodulating therapeutics to tumor locations or immunological organs to provoke immune cells and induce tumor-specific immune response while regulating immune homeostasis, particularly switching the tumor immunosuppressive microenvironment. This review explores various INP designs and formulations, and their employment in tumor immunotherapy and combination immunotherapy. We also introduce detailed demonstrations of utilizing surface engineering tactics to create multifunctional INPs. The generated INPs demonstrate the abilities of stimulating and enhancing the immune response, specific targeting, and regulating cancer cells, immune cells, and their resident microenvironment, sometimes along with imaging and tracking capabilities, implying their potential in multitasking immunotherapy. Furthermore, we discuss the promises of INP-based combination immunotherapy in tumor treatments., Competing Interests: Competing interests: The authors declare that they have no competing interests., (Copyright © 2024 Wei Mao and Hyuk Sang Yoo.)

Background and Objective: To develop a healthcare chatbot service (AI-guided bot) that conducts real-time conversations using large language models to provide accurate health information to patients., Methods: To provide accurate and specialized medical responses, we integrated several cancer practice guidelines. The size of the integrated meta-dataset was 1.17 million tokens. The integrated and classified metadata were extracted, transformed into text, segmented to specific character lengths, and vectorized using the embedding model. The AI-guide bot was implemented using Python 3.9. To enhance the scalability and incorporate the integrated dataset, we combined the AI-guide bot with OpenAI and the LangChain framework. To generate user-friendly conversations, a language model was developed based on Chat-Generative Pretrained Transformer (ChatGPT), an interactive conversational chatbot powered by GPT-3.5. The AI-guide bot was implemented using ChatGPT3.5 from Sep. 2023 to Jan. 2024., Results: The AI-guide bot allowed users to select their desired cancer type and language for conversational interactions. The AI-guided bot was designed to expand its capabilities to encompass multiple major cancer types. The performance of the AI-guide bot responses was 90.98 ± 4.02 (obtained by summing up the Likert scores)., Conclusions: The AI-guide bot can provide medical information quickly and accurately to patients with cancer who are concerned about their health., Competing Interests: Declaration of competing interest The authors have no potential conflicts of interest to disclose., (Copyright © 2024. Published by Elsevier B.V.)

The simultaneous abuse of alcohol-cocaine is known to cause stronger and more unpredictable cellular damage in the liver, heart, and brain. However, the mechanistic crosstalk between cocaine and alcohol in liver injury remains unclear. The findings revealed cocaine-induced liver injury and inflammation in both marmosets and mice. Of note, co-administration of cocaine and ethanol in mice causes more severe liver damage than individual treatment. The metabolomic analysis confirmed that hippuric acid (HA) is the most abundant metabolite in marmoset serum after cocaine consumption and that is formed in primary marmoset hepatocytes. HA, a metabolite of cocaine, increases mitochondrial DNA leakage and subsequently increases the production of proinflammatory factors via STING signaling in Kupffer cells (KCs). In addition, conditioned media of cocaine-treated KC induced hepatocellular necrosis via alcohol-induced TNFR1. Finally, disruption of STING signaling in vivo ameliorated co-administration of alcohol- and cocaine-induced liver damage and inflammation. These findings postulate intervention of HA-STING-TNFR1 axis as a novel strategy for treatment of alcohol- and cocaine-induced excessive liver damage., (© 2024. The Author(s).)

Background: Parkinson's disease (PD) manifests as a wide variety of clinical phenotypes and its progression varies greatly. However, the factors associated with different disease progression remain largely unknown., Methods: In this retrospective cohort study, we enrolled 113 patients who underwent 18 F-FP-CIT PET scan twice. Given the negative exponential progression pattern of dopamine loss in PD, we applied the natural logarithm to the specific binding ratio (SBR) of two consecutive 18 F-FP-CIT PET scans and conducted linear mixed model to calculate individual slope to define the progression rate of nigrostriatal degeneration. We investigated the clinical and dopamine transporter (DAT) availability patterns associated with the progression rate of dopamine depletion in each striatal sub-region., Results: More symmetric parkinsonism, the presence of dyslipidemia, lower K-MMSE total score, and lower anteroposterior gradient of the mean putaminal SBR were associated with faster progression rate of dopamine depletion in the caudate nucleus. More symmetric parkinsonism and lower anteroposterior gradient of the mean putaminal SBR were associated with faster depletion of dopamine in the anterior putamen. Older age at onset, more symmetric parkinsonism, the presence of dyslipidemia, and lower anteroposterior gradient of the mean putaminal SBR were associated with faster progression rate of dopamine depletion in the posterior putamen. Lower striatal mean SBR predicted the development of LID, while lower mean SBR in the caudate nuclei predicted the development of dementia., Discussion: Our results suggest that the evaluation of baseline clinical features and patterns of DAT availability can predict the progression of PD and its prognosis., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

Severe fever with thrombocytopenia syndrome (SFTS) has a high mortality rate compared to other infectious diseases. SFTS is particularly associated with a high risk of mortality in immunocompromised individuals, while most patients who die of SFTS exhibit symptoms of severe encephalitis before death. However, the region of brain damage and mechanisms by which the SFTS virus (SFTSV) causes encephalitis remains unknown. Here, we revealed that SFTSV infects the brainstem and spinal cord, which are regions of the brain associated with respiratory function, and motor nerves in IFNAR1 -/- mice. Further, we show that A1-reactive astrocytes are activated, causing nerve cell death, in infected mice. Primary astrocytes of SFTSV-infected IFNAR1 -/- mice also induced neuronal cell death through the activation of A1-reactive astrocytes. Herein, we showed that SFTSV induces fatal neuroinflammation in the brain regions important for respiratory function and motor nerve, which may underlie mortality in SFTS patients. This study provides new insights for the treatment of SFTS, for which there is currently no therapeutic approach., (© 2024 The Author(s). Journal of Medical Virology published by Wiley Periodicals LLC.)

Age-related macular degeneration (AMD) is a common retinal neurodegenerative disease among the elderly. Neovascular AMD (nAMD), a leading cause of AMD-related blindness, involves choroidal neovascularization (CNV), which can be suppressed by anti-angiogenic treatments. However, current CNV treatments do not work in all nAMD patients. Here we investigate a novel target for AMD. Granzyme B (GzmB) is a serine protease that promotes aging, chronic inflammation and vascular permeability through the degradation of the extracellular matrix (ECM) and tight junctions. Extracellular GzmB is increased in retina pigment epithelium (RPE) and mast cells in the choroid of the healthy aging outer retina. It is further increased in donor eyes exhibiting features of nAMD and CNV. Here, we show in RPE-choroidal explant cultures that exogenous GzmB degrades the RPE-choroid ECM, promotes retinal/choroidal inflammation and angiogenesis while diminishing anti-angiogenic factor, thrombospondin-1 (TSP-1). The pharmacological inhibition of either GzmB or mast-cell degranulation significantly reduces choroidal angiogenesis. In line with our in vitro data, GzmB-deficiency reduces the extent of laser-induced CNV lesions and the age-related deterioration of electroretinogram (ERG) responses in mice. These findings suggest that targeting GzmB, a serine protease with no known endogenous inhibitors, may be a potential novel therapeutic approach to suppress CNV in nAMD., (© 2024. The Author(s).)

The results of depth-resolved multi-contrast in vivo mouse choroidal imaging using a polarization-diversity optical coherence tomography (PD-OCT) system are presented. A selectively chosen depth of focus that was fine-tuned with a sensorless adaptive optics technique and a simple segmentation based on the degree of polarization uniformity signal visualizes the detailed features of a mouse choroid from the OCT angiography images. A comprehensive image analysis of the choroid revealed the distinctive pathological characteristics of the laser-induced choroidal neovascularization mouse.

Age-related macular degeneration (AMD), a prevalent and progressive degenerative disease of the macula, is the leading cause of blindness in elderly individuals in developed countries. The advanced stages include neovascular AMD (nAMD), characterized by choroidal neovascularization (CNV), leading to subretinal fibrosis and permanent vision loss. Despite the efficacy of anti-vascular endothelial growth factor (VEGF) therapy in stabilizing or improving vision in nAMD, the development of subretinal fibrosis following CNV remains a significant concern. In this review, we explore multifaceted aspects of subretinal fibrosis in nAMD, focusing on its clinical manifestations, risk factors, and underlying pathophysiology. We also outline the potential sources of myofibroblast precursors and inflammatory mechanisms underlying their recruitment and transdifferentiation. Special attention is given to the potential role of mast cells in CNV and subretinal fibrosis, with a focus on putative mast cell mediators, tryptase and granzyme B. We summarize our findings on the role of GzmB in CNV and speculate how GzmB may be involved in the pathological transition from CNV to subretinal fibrosis in nAMD. Finally, we discuss the advantages and drawbacks of animal models of subretinal fibrosis and pinpoint potential therapeutic targets for subretinal fibrosis., Competing Interests: Author DG is a Co-Founder and serves as the Chief Scientific Officer for viDA Therapeutics. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Gill, Yoo, Chakravarthy, Granville and Matsubara.)

This study explored the potential of saponins from Korean Red Ginseng to target the PINK1/Parkin mitophagy pathway, aiming to enhance insulin sensitivity in hepatocytes-a key factor in metabolic disorders like metabolic dysfunction-associated steatotic liver disease (MASLD) and type 2 diabetes. Results from both in vitro and in vivo experiments showed increased expression of PINK1 and Parkin, activating mitophagy and reducing oxidative stress through reduction in mitochondrial and total reactive oxygen species. Additionally, improvements in insulin signaling were observed, including the upregulation of phosphorylated IRS and AKT, and downregulation of gluconeogenic enzymes, underscoring the saponins' efficacy in boosting insulin sensitivity. The findings highlighted Korean Red Ginseng-derived saponins as potential treatments for insulin resistance and related metabolic conditions.

Recombinant cytochrome P450 monooxygenases possess significant potential as biocatalysts, and efforts to improve heme content, electron coupling efficiency, and catalytic activity and stability are ongoing. Domain swapping between heme and reductase domains, whether natural or engineered, has thus received increasing attention. Here, we successfully achieved split intein-mediated reconstitution (IMR) of the heme and reductase domains of P450 BM3 both in vitro and in vivo. Intriguingly, the reconstituted enzymes displayed promising properties for practical use. IMR BM3 exhibited a higher heme content (>50 %) and a greater tendency for oligomerization compared to the wild-type enzyme. Moreover, these reconstituted enzymes exhibited a distinct increase in activity ranging from 165 % to 430 % even under the same heme concentrations. The reproducibility of our results strongly suggests that the proposed reconstitution approach could pave a new path for enhancing the catalytic efficiency of related enzymes., Competing Interests: Declaration of competing interest Geun-Joong Kim, Chul-Ho Yun, Dae-Eun Cheong, Su-Kyoung Yoo, and Hye-Ji Choi declare that they have conflict of interest because “recombinant vector and method for producing reconstituted cytochrome P450 oxygenase-reductase fusion protein using the same” has been registered as patents (Korean Patent No. 10-2252056, United States of America Patent No. 11,236,309). Ho-Seok Yoo and Ngoc Anh Nguyen declare no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Bordetella bronchiseptica is a pathogen causing respiratory infections in mammals. With the improving understanding of companion animals' welfare, addressing the side effects of bordetella vaccine gains importance in dogs. Studies on diverse subunit vaccines are actively pursued in humans to safely and effectively control bordetellosis. Therefore, our objective was to develop a canine bordetella vaccine inspired by human vaccine development. We evaluated the immunogenicity of the two bacterial components: the outer membrane proteins (OMPs) and the dermonecrotic toxin (DNT) from a canine isolate of B. bronchiseptica. In-silico analysis identified eight domains of DNT, and Domain 3 was selected as the most promising antigen candidate. Additionally, the OMPs were extracted and examined using SDS-PAGE and Western blot analysis. The distinct immunological characteristic of OMPs and DNT-3 were examined individually and in combination. Gene expression and cytokine production were also evaluated in DH82 cells after stimulation with those antigens. Treatment with OMPs resulted in higher level of Th1 related cytokines, while DNT-3 induced a predominant response associated with Th17 and Th2 in the cytokine production. Synergistic effects were observed exclusively on IL-23, indicating increase of a potential risk of side effects when OMPs and DNT act together. These findings provide valuable insights into the reactogenicity of conventional Bordetella vaccines. Further, the presented preclinical data in this study offer an alternative method of the development for an optimal next-generation Bordetella vaccine for companion animals and humans, replacing the acellular vaccines containing both toxin and protein components., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Proteus mirabilis is a commensal bacterium dwelling in the gastrointestinal (GI) tract of humans and animals. Although New Delhi metallo-β-lactamase 1 (NDM-1) producing P. mirabilis is emerging as a threat, its epidemiology in our society remains largely unknown. LHPm1, the first P. mirabilis isolate harboring NDM-1, was detected from a companion dog that resides with a human owner. The whole-genome study revealed 20 different antimicrobial resistance (AMR) genes against various classes of antimicrobial agents, which corresponded to the MIC results. Genomic regions, including MDR genes, were identified with multiple variations and visualized in a comparative manner. In the whole-genome epidemiological analysis, multiple phylogroups were identified, revealing the genetic relationship of LHPm1 with other P. mirabilis strains carrying various AMR genes. These genetic findings offer comprehensive insights into NDM-1-producing P. mirabilis, underscoring the need for urgent control measures and surveillance programs using a "one health approach"., (© 2024. The Author(s).)

Aims: Sphingolipids are involved in the regulation of insulin signaling, which is linked to the development of insulin resistance, leading to diabetes mellitus. We aimed to study whether modulation of sphingolipid levels by GT-11 may regulate insulin signaling in C2C12 myotubes., Main Methods: We investigated the effects of sphingolipid metabolism on Akt phosphorylation and glucose uptake using C2C12 myotubes. Either GT-11, an inhibitor of dihydroceramide desaturase 1 and S1P lyase, or siRNA targeting Sgpl1, the gene encoding the enzyme, was employed to determine the effect of sphingolipid metabolism modulation on insulin signaling. Western blotting and glucose uptake assays were used to evaluate the effect of treatments on insulin signaling. Sphingolipid metabolites were analyzed by high performance liquid chromatography (HPLC)., Key Findings: Treatment with GT-11 resulted in decreased Akt phosphorylation and reduced glucose uptake. Silencing the Sgpl1 gene, which encodes S1P lyase, mimicked these findings, suggesting the potential for regulating insulin signaling through S1P lyase modulation. GT-11 modulated sphingolipid metabolism, inducing the accumulation of sphingolipids. Using PF-543 and ARN14974 to inhibit sphingosine kinases and acid ceramidase, respectively, we identified a significant interplay between sphingosine, S1P lyase, and insulin signaling. Treatment with either exogenous sphingosine or palmitic acid inhibited Akt phosphorylation, and reduced S1P lyase activity., Significance: Our findings highlight the importance of close relationship between sphingolipid metabolism and insulin signaling in C2C12 myotubes, pointing to its potential therapeutic relevance for diabetes mellitus., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

An approach to 2,3-benzotropone from 1-benzosuberone via palladium(II)-catalyzed aerobic dehydrogenation was developed. This method first provided a catalytic route to various 2,3-benzotropones from their corresponding 1-benzosuberones in good yields. In addition, the reaction could be applied to a one-pot Diels-Alder reaction with maleimide, providing a complex benzobicyclo[3.2.2]nonenone in ≤90% yield. Kinetic analysis supporting our proposed mechanism was also performed, underscoring the robustness of the developed synthetic pathway.

Inflammatory Bowel Disease (IBD) is a chronic and relapsing inflammatory condition characterized by severe symptoms such as diarrhea, fatigue, and weight loss. Growing evidence underscores the direct involvement of the nuclear factor-erythroid 2-related factor 2 (NRF2) in the development and progression of IBD, along with its associated complications, including colorectal cancer. The NRF2 pathway plays a crucial role in cellular responses to oxidative stress, and dysregulation of this pathway has been implicated in IBD. Flavones, a significant subclass of flavonoids, have shown pharmacological impacts in various diseases including IBD, through the NRF2 signaling pathway. In this study, we conducted a screening of compounds with a flavone structure and identified NJK15003 as a promising NRF2 activator. NJK15003 demonstrated potent NRF2 activation, as evidenced by the upregulation of downstream proteins, promoter activation, and NRF2 nuclear translocation in IBD cellular models. Treatment with NJK15003 effectively restored the protein levels of tight junctions in cells treated with dextran sodium sulfate (DSS) and in DSS-treated mice, suggesting its potential to protect cells from barrier integrity disruption in IBD. In DSS-treated mice, the administration of NJK15003 resulted in the prevention of body weight loss, a reduction in colon length shortening, and a decrease in the disease activity index. Furthermore, NJK15003 treatment substantially alleviated inflammatory responses and apoptotic cell death in the colon of DSS-treated mice. Taken together, this study proposes the potential utility of NRF2-activating flavone compounds, exemplified by NJK15003, for the treatment of IBD., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

In this study, stimuli-responsive liberation of an epidermal growth factor fragment (EGFfr) is accomplished using nanofibrous meshes to improve wound healing effects. Electrospun nanofibers are fragmented by mechanical milling, followed by aminolysis to fabricate powdered nanofibrils (NFs). EGFfrs are covalently immobilized on NFs via thioketal linkers (EGFfr@TK@NF) for reactive oxygen species (ROS)-dependent liberation. EGFfr@TK@NF exhibits ROS-responsive liberation of EGFfr from the matrix at hydrogen peroxide (H 2 O 2 ) concentrations of 0-250 mm. Released EGFfr is confirmed to enhance the migration of HaCaT cell monolayers, and keratinocytic gene expression levels are significantly enhanced when H 2 O 2 is added to obtain the released fraction of NFs. An in vivo study on the dorsal wounds of mice reveals that EGFfr-immobilized NFs improve the expression levels of keratin1, 5, and 14 for 2 weeks when H 2 O 2 is added to the wound sites, suggesting that the wounded skin is re-epithelized with the original epidermis. Thus, EGFfrs-immobilized NFs are anticipated to be potential nanotherapeutics for wound treatment in combination with the conventional disinfection process with H 2 O 2 ., (© 2023 Wiley-VCH GmbH.)

Background: Cholesterol is an essential component of the neuronal cell membrane and is crucial for neuronal function; however, the role of cholesterol levels in Parkinson's disease (PD) is debatable. This study investigated the complex relationship between total cholesterol (TC) levels, body mass index (BMI), and cognition in patients with PD., Methods: This study included 321 drug-naïve patients with PD who underwent dopamine transporter (DAT) imaging and baseline neuropsychological tests. Multivariate linear regression and Cox regression models were used to investigate the effect of TC levels on the composite score of each cognitive domain and dementia conversion after adjusting for covariates, respectively. Interaction analyses were performed to examine the interaction effect between TC levels and BMI on baseline cognition and dementia conversion., Results: TC levels and cognition showed no significant relationship after adjusting for potential confounders. A significant interaction effect between TC levels and BMI was observed in frontal/executive function and dementia conversion. Further analyses showed that TC levels were positively associated with frontal/executive function in the under-/normal weight group (β = 0.205, p = 0.013), whereas a negative relationship existed between TC levels and frontal/executive function in the obese group (β =  - 0.213, p = 0.017). Cox regression analyses also showed the differential effects of TC levels on dementia conversion according to BMI (under-/normal weight group: hazard ratio [HR] = 0.550, p = 0.013; obese group: HR = 2.085, p = 0.014)., Conclusions: This study suggests a cross-over interaction between TC levels and BMI on cognitive symptoms in PD., (© 2023. The Author(s).)

Patients with dementia with Lewy bodies (DLB) show widespread brain metabolic changes. This study investigated whether brain hypo- and hypermetabolism in DLB have differential effects on cognition. We enrolled 55 patients with DLB (15 prodromal DLB [MCI-LB] and 40 probable DLB) and 13 healthy controls who underwent 18 F-fluorodeoxyglucose positron emission tomography and detailed neuropsychological tests. Metabolic indices reflecting associated changes in regional cerebral glucose metabolism were calculated as follows: index (-) for hypometabolism [DLB-hypo] and index (+) for hypermetabolism [DLB-hyper]. The effects of DLB-hypo or DLB-hyper on cognitive function were assessed using a multivariate linear regression model. Additionally, a linear mixed model was used to investigate the association between each index and the longitudinal cognitive decline. There was no correlation between DLB-hypo and DLB-hyper in the disease group. The multivariate linear regression model showed that DLB-hypo was associated with language, visuospatial, visual memory, and frontal/executive functions; whereas DLB-hyper was responsible for attention and verbal memory. There was significant interaction between DLB-hypo and DLB-hyper for verbal and visual memory, which was substantially affected by DLB-hyper in relatively preserved DLB-hypo status. A linear mixed model showed that DLB-hypo was associated with longitudinal cognitive outcomes, regardless of cognitive status, and DLB-hyper contributed to cognitive decline only in the MCI-LB group. The present study suggests that DLB-hypo and DLB-hyper may be independent of each other and differentially affect the baseline and longitudinal cognitive function in patients with DLB., (© 2024. The Author(s).)

Background: Lung cancer has the highest mortality rate of all cancers worldwide. Conserving the immune system and reducing the adverse events associated with cancer treatment have become increasingly important. Our study aimed to investigate the immunological effects of herbal medicine (HM) alone, independent of conventional cancer therapies, in patients with non-small cell lung cancer (NSCLC). Methods: We searched 8 databases for articles published until March 2023. Bias risk was assessed using RevMan 5.4. Meta-analyses of CD4+ and CD8+ levels reported in the included RCTs were also performed. Results: A total of 610 patients from 5 RCTs were included in the analysis. Immune markers in the peripheral blood of patients treated with HM alone were compared with those in the control group. As a result of meta-analyses, CD4+ (three studies; mean difference(MD) = 5.21, 95 confidence interval (CI) [3.26, 7.27], I 2  = 61%, n = 428) and CD4+/CD8+ (two studies; MD = 0.22, 95% CI [0.18, 0.26], I 2  = 0%, n = 278) significantly increased in the treatment group, while CD8+ levels (three studies; MD = -3.04, 95% CI [-5.80, -0.29], I 2  = 74%, n = 428) decreased in HM groups compared to comparison groups. In a single trial, IL-1, IL-6, tumor necrosis factor (TNF)-a levels and the number of Tregs in the treatment group significantly decreased, while Th17 levels and the Th17/Treg ratios increased. Conclusion: This study provides a comprehensive and systematic review of the immunological effects of HM in patients with NSCLC. Future studies should explore how the immunological effects of HM correlate with clinical outcomes, such as tumor response and survival rates.PROSPERO registration: CRD42023459., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Lung cancer, especially non-small cell lung cancer (NSCLC), poses a significant health challenge globally due to its high mortality. Afatinib, a second-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), has shown superior efficacy over traditional chemotherapy in NSCLC treatment. However, issues like secondary resistance and adverse effects call for alternative therapies. HAD-B1, comprising 4 herbal medicines, has shown promise in lung cancer treatment in both preclinical and clinical settings. This study assesses the combination of HAD-B1 and Afatinib in advanced NSCLC patients to potentially improve outcomes by addressing the limitations of current EGFR-TKI therapies., Method: A randomized, open-label trial evaluated the efficacy and safety of HAD-B1 with Afatinib in 90 EGFR-mutation-positive NSCLC patients. Participants were divided into treatment and control groups, receiving Afatinib with or without HAD-B1. The study focused on the initial dose maintenance rate and disease control rate (DCR) of Afatinib, alongside secondary outcomes like survival rates and quality of life, under continuous safety monitoring., Results: Among the 90 participants, no significant difference was found in initial dose maintenance (60.98% in the treatment group vs 52.50% in the control, P  = .4414) or DCR (80.49% vs 90.00%, P  = .2283). Secondary outcomes like PFS, TTP, and OS showed no notable differences. However, physical functioning significantly improved in the treatment group ( P  = .0475, PPS group). The control group experienced higher rates of adverse events of special interest and adverse drug reactions ( P  = .01), suggesting HAD-B1 with Afatinib might enhance physical function without increasing adverse effects., Conclusion: Combining HAD-B1 with Afatinib potentially improves quality of life and reduces adverse events in advanced NSCLC patients. Further research is necessary to confirm the long-term benefits of this combination therapy, aiming to advance NSCLC treatment outcomes., Trial Registration: Clinical Research Information Service (CRIS) of the Republic of Korea, https://cris.nih.go.kr/ (ID: KCT0005414)., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: In the era of precision medicine, individual temperature sensitivity has been highlighted. This trait has traditionally been used for cold-heat pattern identification to understand the inherent physical characteristics, which are influenced by genetic factors, of an individual. However, genome-wide association studies (GWASs) on this trait are limited., Methods: Using genotype data from 90 patients with advanced non-small cell lung cancer (NSCLC) and epidermal growth factor receptor mutations, we performed a GWAS to assess the association between single nucleotide polymorphisms (SNPs) and temperature sensitivity, such as cold and heat scores. The score of each participant was evaluated using self-administered questionnaires on common symptoms and a 15-item symptom-based cold-heat pattern identification questionnaire., Results: The GWAS was adjusted for confounding factors, including age and sex, and significant associations were identified for cold and heat scores: SNP rs145814326, located on the intron of SORCS2 at chromosome 4p16.1, had a P -value of 1.86 × 10 -7 ; and SNP rs79297667, located upstream from SEMA4D at chromosome 9q22.2, had a P -value of 8.97 × 10 -8 . We also found that the genetic variant regulates the expression level of SEMA4D in the main tissues, including the lungs and white blood cells, in NSCLC., Conclusions: SEMA4D was found to be significantly associated with temperature sensitivity in patients with NSCLC, suggesting an increased expression of SEMA4D in patients with higher heat scores. The potential role of temperature sensitivity as a prognostic or predictive marker of immune response in NSCLC should be further studied., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Collagen is a major component of the extracellular matrix that supports the epidermal layers of the skin; thus, many strategies have been made to enhance the topical delivery of collagen for antiaging purposes. In addition, our previous study indicated that liposome can help the penetration of active ingredients into the skin., Aims: To produce stable collagen-encapsulated liposomes to improve the topical delivery of collagen., Methods: Collagen-encapsulated liposomes were fabricated using high-pressure homogenization method. The colloidal stability and adhesion ability were confirmed using dynamic light scattering, and spectrofluorophotometer, respectively. Keratinocyte differentiations of 3D skin before and after treatment with collagen-encapsulated liposomes were confirmed by real-time PCR., Results: In comparison with native collagen, collagen-encapsulated liposomes enhanced collagen retention in artificial membranes by twofold, even after repeated washings with water. In addition, real-time PCR results indicated that 3D skin treated with collagen-encapsulated liposomes exhibited higher levels of collagen, keratin, and involucrin, even after ethanol treatment., Conclusion: Liposomes could serve as efficient delivery vehicles for collagen, thereby enhancing its antiaging effects., (© 2023 The Authors. Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Background: Gastric cancer is a common cause of global mortality, with significant challenges during treatment due to side effects and complications. Traditional herbal medicine (THM) has emerged as a potential adjuvant therapy to enhance cancer treatment by reducing side effects and bolstering the immune response. This study conducted a meta-analysis to assess the efficacy and safety of THM as an adjuvant therapy in post-surgical gastric cancer patients., Methods: PubMed, Cochrane Library, EMBASE, CNKI, CiNii, KMBASE, KISS, OASIS, RISS, and ScienceON databases were searched from inception through December, 2021. The outcomes considered in this analysis encompassed tumor response, quality of life (QoL), side effects, and tumor markers. Additionally, a frequency analysis of the most commonly used herbs in the included studies was conducted. A total of 36 randomized controlled trials (RCTs) were included, and data were extracted according to study design. The analysis compared groups receiving chemotherapy alone with those receiving both chemotherapy and THM treatment., Results: The group receiving both chemotherapy and THM showed substantial improvement in tumor response compared to the chemotherapy-only control group (RR 1.25, 95% CI [1.09, 1.45]). QoL also significantly increased in the THM-treated group. Most drug adverse reactions displayed statistical significance, except for platelet reduction. Tumor markers CEA, CA19-9, and CA72-4 exhibited significant improvements, but CA125 did not. The 1, 2, and 3-year survival rates improved, with RR values of 1.08 (95% CI [1.02, 1.14]), 1.32 (95% CI [1.19, 1.47]), and 1.42 (95% CI [1.12, 1.79]) respectively. However, some publication bias was indicated., Conclusion: THM may offer potential benefits as a complementary approach to post-surgical anticancer therapy in gastric cancer patients. Improved tumor response, quality of life, and survival rates were reported. However, it is important to exercise caution due to the possibility of publication bias, and further research is needed to confirm these findings.Registration:PROSPERO CRD 42022354133., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.