Ethanol Extract of Propolis Attenuates Liver Lipid Metabolism Disorder in High-Fat Diet-Fed SAMP8 Mice.

SCOPE: The prevalence of high-fat diet (HFD) consumption is increasing among middle-aged and older adults, which accelerates the aging process of this population and is more likely to induce lipid metabolism disorders. But the alleviation of ethanolic extract of propolis (EEP) on lipid metabolism disorders during aging remains unclear. METHODS AND RESULTS: This study assesseed the impact of EEP intervention (200 mg kg-1 bw) on aging and lipid metabolism disorders in HFD-fed senescence accelerate mouse prone 8 (SAMP8) mice. Findings indicate that EEP ameliorates hair luster degradation and weight gain, reduces systemic inflammation and metabolism levels, enhances hepatic antioxidant enzyme activities, and improves the hepatic expression of senescence-associated secretory phenotype and aging-related genes in HFD-fed SAMP8 mice. Histological staining demonstrates that EEP improves hepatic lipid deposition and inflammatory cell infiltration. Transcriptomic and lipidomic analysis reveal that EEP promotes fatty acid ß-oxidation by activating PPAR pathway, resulting in reduced hepatic lipid deposition, and attenuates bile acid (BA) accumulation by improving BA metabolism, which were ensured through qPCR validation of key genes and immunoblot validation of key proteins. CONCLUSIONS : EEP can regulate lipid metabolic dysregulation during aging accompanied by an HFD, potentially delaying the onset and progression of age-related diseases. This provides new approach for supporting healthy aging.

Machine learning analysis of oxidative stress-related phenotypes for specific gene screening in ovarian cancer.

BACKGROUND: Oxidative stress serves a crucial role in tumor development. However, the relationship between ovarian cancer and oxidative stress remains unknown. We aimed to create an oxidative stress-related prognostic signature to enhance the prognosis prediction of CC patients using bioinformatics. METHODS: The genes differentially expressed and associated with oxidative stress were extracted with the help of "limma" packages. The model for prognosis was created using Multivariate Cox regression analysis to determine the risk related to the genes related to oxidative stress. Patients were categorized as low-risk or high-risk based on the median score. The receiver operation characteristic (ROC) and survival curves were used to evaluate the predictive effect of the prognostic signature. We utilized quantitative real-time PCR to assess the expression levels of key genes associated with oxidative stress in ovarian cancer cell lines (SKOV3, OVCAR3, and HeyA8) and normal ovarian epithelial cells (HOSEpiC). RESULTS: A signature comprising seven genes associated with oxidative stress was developed to prognosticate patients with ovarian cancer. Overall survival (OS) of the patient having CC was determined using Kaplan-Meier analysis. It was found that patient with a higher risk score had lower OS than the low-risk score. The signature of genes associated with oxidative stress was found to be independently prognostic for 1, 2, and 3 years. Further research found that the expression levels of nine hub genes had a strong association with patient outcomes. Our analysis revealed a higher expression of CX3CR1 in ovarian cancer cell lines compared with normal cells. CONCLUSIONS: To deploy a novel oxidative stress-related prognostic signature as an independent biomarker in cervical cancer, we developed and validated it.

ACOT7 positively regulated by CREB1 promotes the progression of cutaneous melanoma.

Cutaneous melanoma (cM) is a prevalent invasive cancer resulting from the malignant transformation of melanocytes. At present, the primary treatment for melanoma is surgical resection, which is not appropriate for patients with metastasis. Therefore, it is necessary to identify effective therapeutic targets for the early diagnosis and treatment of metastatic melanoma. Acyl-CoA thioesterase 7 (ACOT7) has been reported to be involved in the progression of multiple cancer, while its role in melanoma has not been extensively researched. Through gain-of-function and loss-of-function experiments, ACOT7 was identified as a tumor promoter that facilitates the progression of melanoma cells. Cell proliferation was promoted by overexpressing ACOT7 in M14 cells, and was suppressed by silencing ACOT7 in MeWo cells. Knockdown of ACOT7 induced cell cycle arrest by increasing the expressions of cyclin dependent kinase inhibitor 1B (P27) and cyclin dependent kinase inhibitor 1 A (P21), while simultaneously reducing proliferating cell nuclear antigen (PCNA) expression. Upregulation of ACOT7 promoted the cell cycle of melanoma cells. Additionally, apoptosis was induced by the absence of ACOT7 through activating caspase-3 and poly (ADP-ribose) polymerase (PARP). The metastatic and invasive capacity of melanoma cells was significantly enhanced by the overexpression of ACOT7 and inhibited by the downregulation of ACOT7. Moreover, the cAMP responsive element binding protein 1 (CREB1) positively regulates ACOT7 expression by binding to its promoter region. A decrease of cell proliferation, migration and invasion, as well as an increase of cell apoptosis induced by silencing CREB1 were obviously reversed by ACOT7. In summary, ACOT7 transcriptionally activated by CREB1 elevates the progression of cM.

The development and application of a novel E-commerce recommendation system used in electric power B2B sector.

The advent of the digital era has transformed E-commerce platforms into critical tools for industry, yet traditional recommendation systems often fall short in the specialized context of the electric power industry. These systems typically struggle with the industry's unique challenges, such as infrequent and high-stakes transactions, prolonged decision-making processes, and sparse data. This research has developed a novel recommendation engine tailored to these specific conditions, such as to handle the low frequency and long cycle nature of Business-to-Business (B2B) transactions. This approach includes algorithmic enhancements to better process and interpret the limited data available, and data pre-processing techniques designed to enrich the sparse datasets characteristic of this industry. This research also introduces a methodological innovation that integrates multi-dimensional data, combining user E-commerce activities, product specifics, and essential non-tendering information. The proposed engine employs advanced machine learning techniques to provide more accurate and relevant recommendations. The results demonstrate a marked improvement over traditional models, offering a more robust and effective tool for facilitating B2B transactions in the electric power industry. This research not only addresses the sector's unique challenges but also provides a blueprint for adapting recommendation systems to other industries with similar B2B characteristics.

AI-based digital pathology provides newer insights into lifestyle intervention-induced fibrosis regression in MASLD: An exploratory study.

BACKGROUND AND AIMS: Lifestyle intervention is the mainstay of therapy for metabolic dysfunction-associated steatohepatitis (MASH), and liver fibrosis is a key consequence of MASH that predicts adverse clinical outcomes. The placebo response plays a pivotal role in the outcome of MASH clinical trials. Second harmonic generation/two-photon excitation fluorescence (SHG/TPEF) microscopy with artificial intelligence analyses can provide an automated quantitative assessment of fibrosis features on a continuous scale called qFibrosis. In this exploratory study, we used this approach to gain insight into the effect of lifestyle intervention-induced fibrosis changes in MASH. METHODS: We examined unstained sections from paired liver biopsies (baseline and end-of-intervention) from MASH individuals who had received either routine lifestyle intervention (RLI) (n = 35) or strengthened lifestyle intervention (SLI) (n = 17). We quantified liver fibrosis with qFibrosis in the portal tract, periportal, transitional, pericentral, and central vein regions. RESULTS: About 20% (7/35) and 65% (11/17) of patients had fibrosis regression in the RLI and SLI groups, respectively. Liver fibrosis tended towards no change or regression after each lifestyle intervention, and this phenomenon was more prominent in the SLI group. SLI-induced liver fibrosis regression was concentrated in the periportal region. CONCLUSION: Using digital pathology, we could detect a more pronounced fibrosis regression with SLI, mainly in the periportal region. With changes in fibrosis area in the periportal region, we could differentiate RLI and SLI patients in the placebo group in the MASH clinical trial. Digital pathology provides new insight into lifestyle-induced fibrosis regression and placebo responses, which is not captured by conventional histological staging.

Quantitative susceptibility mapping of subcortical iron deposition in Parkinson disease and multiple system atrophy: clinical correlations and diagnostic implications.

Background: Parkinson disease (PD) and multiple system atrophy (MSA) are neurodegenerative disorders characterized by the accumulation of alpha-synuclein. Distinguishing between these conditions remains a significant challenge. This study thus employed quantitative susceptibility mapping (QSM) to evaluate subcortical iron deposition and its clinical implications in patients with PD or MSA and a group of healthy controls (HCs). Methods: The study included 26 patients with MSA, 40 patients with PD, and 35 HCs. We used magnetic resonance imaging (MRI)-based QSM to measure iron accumulation in the substantia nigra pars compacta (SNc), substantia nigra pars reticulata (SNr), and globus pallidus internus (GPi). We assessed differences between groups, examined correlations with clinical scores, and conducted receiver operating characteristic (ROC) curve analysis. Results: Compared to those with PD, patients with MSA showed more severe motor and nonmotor impairment. QSM analysis indicated a significant increase in iron levels in the SNc, SNr, and GPi regions in patient groups compared to HCs. In patients with MSA, a notable positive correlation was found between SNc QSM values and Non-Motor Symptoms Scale scores (r=0.4; P=0.043). In patients with PD, a positive association was observed between iron levels in the SNc and Unified Parkinson's Disease Rating Scale Part III (UPDRS-III) (r=0.395; P=0.012) and Hamilton Depression Rating Scale scores (r=0.313; P=0.049). Furthermore, iron content in the GPi inversely correlated with rapid-eye movement sleep behavior disorder questionnaire-Hong Kong scores (r=-0.342; P=0.031). The SNr region demonstrated the best ability to discriminate between MSA and PD with an area under the curve (AUC) of 0.67, followed by the GPi (AUC =0.64) and SNc (AUC =0.57). Conclusions: QSM effectively quantified subcortical iron deposition in the PD, MSA, and HC groups. The correlations found between iron levels and clinical manifestations provide insights into the pathophysiological processes of these disorders, highlighting the potential of QSM as a diagnostic tool for differentiation.

Development of a Preoperative Prediction Model Based on Spectral CT to Evaluate Axillary Lymph Node With Macrometastases in Clinical T1/2N0 Invasive Breast Cancer.

OBJECTIVES: To develop a prediction model based on spectral computed tomography (CT) to evaluate axillary lymph node (ALN) with macrometastases in clinical T1/2N0 invasive breast cancer. METHODS: A total of 217 clinical T1/2N0 invasive breast cancer patients who underwent spectral CT scans were retrospectively enrolled and categorized into a training cohort (n = 151) and validation cohort (n = 66). These patients were classified into ALN nonmacrometastases (stage pN0 or pN0 [i+] or pN1mi) and ALN macrometastases (stage pN1-3) subgroups. The morphologic criteria and quantitative spectral CT parameters of the most suspicious ALN were measured and compared. Least absolute shrinkage and selection operator (Lasso) was used to screen predictive indicators to build a logistic model. The receiver operating characteristic (ROC) curve and decision curve analysis (DCA) were used to evaluate the models. RESULTS: The combined arterial-venous phase spectral CT model yielded the best diagnostic performance in discrimination of ALN nonmacrometastases and ALN macrometastases with the highest AUC (0.963 in the training cohort and 0.945 in validation cohorts). Among single phase spectral CT models, the venous phase spectral CT model showed the best performance (AUC = 0.960 in the training cohort and 0.940 in validation cohorts). There was no significant difference in AUCs among the 3 models (DeLong test, P > .05 for each comparison). CONCLUSION: A Lasso-logistic model that combined morphologic features and quantitative spectral CT parameters based on contrast-enhanced spectral imaging potentially be used as a noninvasive tool for individual preoperative prediction of ALN status in clinical T1/2N0 invasive breast cancers.

Research progress on roles of iron metabolism in the occurrence and development of periodontitis. / é“ä»£è°¢åœ¨æ ¢æ€§ç‰™å‘¨ç‚Žå‘ç”Ÿå‘å±•ä¸­çš„ä½œç”¨ç ”ç©¶è¿›å±•.

Iron metabolism refers to the process of absorption, transport, excretion and storage of iron in organisms, including the biological activities of iron ions and iron-binding proteins in cells. Clinical research and animal experiments have shown that iron metabolism is associated with the progress of periodontitis. Iron metabolism can not only enhance the proliferation and toxicity of periodontal pathogens, but also activate host immune- inflammatory response mediated by macrophages, neutrophils and lymphocytes. In addition, iron metabolism is also involved in regulating the cellular death sensitivity of gingival fibroblasts and osteoblasts and promoting the differentiation of osteoclasts to play a regulatory role in the regeneration and repair of periodontal tissue. This article reviews the research progress on the pathogenesis of periodontitis from the perspective of iron metabolism, aiming to provide new ideas for the treatment of periodontitis.

A quick method to customize pictorial blood assessment tools towards better measurement: Method development and validation.

OBJECTIVE: Identification of heavy menstrual bleeding (HMB) cases in primary care settings is often done by using pictorial blood assessment charts (PBAC). The study aims to highlight the challenge of assessing blood loss, to develop a standardized method to efficiently customize a patient-reported pictorial chart, to validate the tool produced with our proposed method, and to demonstrate the feasibility of using PBACs in settings where resources are scarce. MATERIALS AND METHODS: Using blood samples and feedback from 21 women aged 30-51 years, we followed guidelines suggested in the literature, developed a method to produce PBACs for regular, long and night sizes, and had 9 participants testuse them. Linear regression analysis was performed to determine the correlation between participants' scores and menstrual blood weight. RESULTS: The study demonstrated the feasibility of customizing product-sensitive and size-specific pictorial charts by adopting essential steps including collecting menstrual blood with menstrual cups, employing fluid application techniques, and using sanitary pads as icons for easy identification. Linear regression analyses of score versus blood weight showed that the recorded blood weight was around 95% of the scored values (R2 = 0.9428, 0.947, and 0.9508, respectively; p < 0.001). CONCLUSION: Valid patient-reported PBACs created by the proposed method provides an innovative women's healthcare solution to assist HMB identification and reduce health expenditure by preventing risks for HMB related complications in varying economic and technological contexts. Women's participation in tracking menstrual abnormalities may improve health literacy.

Association of Dietary Selenium Intake with Type 2 Diabetes in Middle-Aged and Older Adults in China.

The relationship between distinct dietary selenium intake and type 2 diabetes (T2D) is still a topic of uncertainty. This study examined the relationship between dietary selenium intake and T2D risk among middle-aged and older Chinese adults. Dietary selenium intake was assessed through three 24 h recalls, using data from the China Health and Nutrition Survey. To investigate the relationship and the potential dose-response pattern between selenium intake and the likelihood of developing T2D, we employed both the restricted cubic spline analysis and the Cox proportional hazards model as our analytical tools. A cohort of 5970 participants aged ≥ 50 years was followed for an average of 5.44 years. The results revealed a V-shaped correlation between selenium intake and T2D risk, with the lowest risk observed at approximately 45 µg/day. Below this level, the risk decreased with an increasing selenium intake, while the risk increased between 45 and 100 µg/day. No significant association was found beyond 100 µg/day. These findings suggest that both low and high selenium consumption may increase T2D risk, highlighting the importance of maintaining a balanced selenium intake for T2D prevention.

MAZ-mediated up-regulation of BCKDK reprograms glucose metabolism and promotes growth by regulating glucose-6-phosphate dehydrogenase stability in triple-negative breast cancer.

Tumour metabolic reprogramming is pivotal for tumour survival and proliferation. Investigating potential molecular mechanisms within the heterogeneous and clinically aggressive triple-negative breast cancer (TNBC) subtype is essential to identifying novel therapeutic targets. Accordingly, we investigated the role of branched-chain α-keto acid dehydrogenase kinase (BCKDK) in promoting tumorigenesis in TNBC. We analysed The Cancer Genome Atlas dataset and immunohistochemically stained surgical specimens to investigate BCKDK expression and its prognostic implications in TNBC. The effects of BCKDK on tumorigenesis were assessed using cell viability, colony formation, apoptosis, and cell cycle assays, and subsequently validated in vivo. Metabolomic screening was performed via isotope tracer studies. The downstream target was confirmed using mass spectrometry and a co-immunoprecipitation experiment coupled with immunofluorescence analysis. Upstream transcription factors were also examined using chromatin immunoprecipitation and luciferase assays. BCKDK was upregulated in TNBC tumour tissues and associated with poor prognosis. BCKDK depletion led to reduced cell proliferation both in vitro and vivo. MYC-associated zinc finger protein (MAZ) was confirmed as the major transcription factor directly regulating BCKDK expression in TNBC. Mechanistically, BCKDK interacted with glucose-6-phosphate dehydrogenase (G6PD), leading to increased flux in the pentose phosphate pathway for macromolecule synthesis and detoxification of reactive oxygen species. Forced expression of G6PD rescued the growth defect in BCKDK-deficient cells. Notably, the small-molecule inhibitor of BCKDK, 3,6-dichlorobenzo(b)thiophene-2-carboxylic acid, exhibited anti-tumour effects in a patient-derived tumour xenograft model. Our findings hold significant promise for developing targeted therapies aimed at disrupting the MAZ/BCKDK/G6PD signalling pathway, offering potential advancements in treating TNBC through metabolic reprogramming.

Development of an all-in-one real-time PCR assay for simultaneous detection of spotted fever group rickettsiae, severe fever with thrombocytopenia syndrome virus and hantaan virus prevalent in central China.

Central China has been reported to be one of the most important endemic areas of zoonotic infection by spotted fever group rickettsiae (SFGR), severe fever with thrombocytopenia syndrome virus (SFTSV) and hantaan virus (HTNV). Due to similar clinical symptoms, it is challenging to make a definite diagnosis rapidly and accurately in the absence of microbiological tests. In the present study, an all-in-one real-time PCR assay was developed for the simultaneous detection of nucleic acids from SFGR, SFTSV and HTNV. Three linear standard curves for determining SFGR-ompA, SFTSV-L and HTNV-L were obtained within the range of 101-106 copies/µL, with the PCR amplification efficiencies ranging from 93.46% to 96.88% and the regression coefficients R2 of >0.99. The detection limit was 1.108 copies/µL for SFGR-ompA, 1.075 copies/µL for SFTSV-L and 1.006 copies/µL for HTNV-L, respectively. Both the within-run and within-laboratory coefficients of variation on the cycle threshold (Ct) values were within the range of 0.53%-2.15%. It was also found there was no statistical difference in the Ct values between single template and multiple templates (PSFGR-ompA = 0.186, PSFTSV-L = 0.612, PHTNV-L = 0.298). The sensitivity, specificity, positive and negative predictive value were all 100% for determining SFGR-ompA and SFTSV-L, 97%, 100%, 100% and 99.6% for HTNV-L, respectively. Therefore, the all-in-one real-time PCR assay appears to be a reliable, sensitive, rapid, high-throughput and low cost-effective method to diagnose the zoonotic infection by SFGR, SFTSV and HTNV.

Remote coupling of electrical and mechanical cues by diurnal photothermal irradiation synergistically promotes bone regeneration.

Recapitulating the natural extracellular physical microenvironment has emerged as a promising method for tissue regeneration, as multiple physical interventions, including ultrasound, thermal and electrical therapy, have shown great potential. However, simultaneous coupling of multiple physical cues to highly bio-mimick natural characteristics for improved tissue regeneration still remains formidable. Coupling of intrinsic electrical and mechanical cues has been regarded as an effective way to modulate tissue repair. Nevertheless, precise and convenient manipulation on coupling of mechano-electrical signals within extracellular environment to facilitate tissue regeneration remains challengeable. Herein, a photothermal-sensitive piezoelectric membrane was designed for simultaneous integration of electrical and mechanical signals in response to NIR irradiation. The high-performance mechano-electrical coupling under NIR exposure synergistically triggered the promotion of osteogenic differentiation of stem cells and enhances bone defect regeneration by increasing cellular mechanical sensing, attachment, spreading and cytoskeleton remodeling. This study highlights the coupling of mechanical signals and electrical cues for modulation of osteogenesis, and sheds light on alternative bone tissue engineering therapies with multiple integrated physical cues for tissue repair.

Application of Antioxidant Compounds in Bone Defect Repair.

Bone defects caused by trauma, tumor resection, and infections are significant clinical challenges. Excessive reactive oxygen species (ROS) usually accumulate in the defect area, which may impair the function of cells involved in bone formation, posing a serious challenge for bone repair. Due to the potent ROS scavenging ability, as well as potential anti-inflammatory and immunomodulatory activities, antioxidants play an indispensable role in the maintenance and protection of bone health and have gained increasing attention in recent years. This narrative review aims to give an overview of the main research directions on the application of antioxidant compounds in bone defect repair over the past decade. In addition, the positive effects of various antioxidants and their biomaterial delivery systems in bone repair are summarized to provide new insights for exploring antioxidant-based strategies for bone defect repair.

Circadian clock disruption stimulates bone loss via regulatory T cell-Mediated regulation of IL-10 expression.

Circadian rhythms play a crucial role in regulating various physiological processes, including specific immune functions that enhance the body's ability to anticipate and respond to threats effectively. However, research on the impact of circadian rhythms on osteoimmunology remains limited. Our study uncovered that circadian disruption leads to bone mass loss by reducing the population of Treg cells in the bone marrow. Furthermore, we observed a significant decrease in serum IL-10 cytokine levels in jet lagged mice. In our current investigation, we explored the anti-osteoclastogenic effects of IL-10 and found that IL-10 inhibits RANKL-induced osteoclastogenesis in a dose-dependent manner. Our findings suggest that the diminished anti-osteoclastogenic properties of Tregs under circadian disruption are mediated by IL-10 cytokine production. Moreover, our discoveries propose that administration of IL-10 or butyrate could potentially reverse bone mass loss in individuals experiencing jet lag.

THRIVE, ASTRAL, and iScore scales for predicting prognosis of mechanical thrombectomy in patients with acute ischemic stroke.

OBJECTIVE: To validate the predictive performance of the THRIVE, ASTRAL, and iScore scales for clinical functional outcomes following mechanical thrombectomy (MT) for acute ischemic stroke (AIS). METHODS: A total of 111 patients meeting the inclusion criteria were included in this study, with 59 (53.2%) having a good prognosis and 52 (46.8%) having a poor prognosis. MedCalc software was applied to plot receiver operating characteristic (ROC) curves, calculate the area under the curve (AUC), and compare the predictive efficacy of the three scales two by two using Delong text. Statistical significance was defined as Pc < 0.05. RESULTS: Logistic binary regression multifactorial analysis revealed that iScore is one of the poor predictors of prognosis in patients with MT. The AUC values for the THRIVE, ASTRAL, and iScore scales in predicting prognosis after MT were found to be 0.713, 0.738, and 0.820, respectively. CONCLUSION: The iScore is a reliable tool for assessing the poor prognosis of MT in patients with AIS.

Modified roll envelope technique combined with apically repositioned flap (MRARF) for peri-implant soft tissue augmentation---A case series.

AIMS: In the present case series, we performed implant surgery using a modified roll envelope technique and an apically repositioned flap (MRARF). To improve patients' peri-implant soft tissue phenotypes, they underwent dental implantation following the buccal contour concavities, inadequate keratinized tissue width, and soft tissue thickness simultaneously. MATERIALS AND METHODS: This case series includes four patients treated between July 2021 and February 2022 who received dental implants and GBR treatment six months earlier and were to be taken up for second-stage surgery. They were eligible for the MRARF technique if each implant site showed a labial and buccal deficiency and a reduced keratinized mucosa width than the adjacent teeth. Sutures were removed two weeks after surgery, and a provisional restoration was delivered. A final impression was taken at six weeks to produce the definitive implant-supported restoration. RESULTS: All surgery sites healed uneventfully, and no postoperative pain or excessive swelling was reported. The modified flap design allowed for increasing the width and thickness of keratinized mucosa with a minimally invasive technique. A harmonious color, texture, and mucogingival junction position that matched the surrounding tissue and adjacent teeth was achieved, and all patients were satisfied with the final results. CONCLUSIONS: MRARF at second-stage implant surgery could obtain satisfactory results regarding vertical and horizontal aesthetic gingival contours and an adequate width and thickness of keratinized mucosa around the implants.

Development of a Humanized Antibody Targeting Extracellular HSP90α to Suppress Endothelial-Mesenchymal Transition-Enhanced Tumor Growth of Pancreatic Adenocarcinoma Cells.

Extracellular HSP90α (eHSP90α) is a promoter of tumor development and malignant progression. Patients with malignancies, including pancreatic ductal adenocarcinoma (PDAC), have generally shown 5~10-fold increases in serum/plasma eHSP90α levels. In this study, we developed a humanized antibody HH01 to target eHSP90α and evaluated its anticancer efficacy. HH01, with novel complementarity-determining regions, exhibits high binding affinity toward HSP90α. It recognizes HSP90α epitope sites 235AEEKEDKEEE244 and 251ESEDKPEIED260, with critical amino acid residues E237, E239, D240, K241, E253, and K255. HH01 effectively suppressed eHSP90α-induced invasive and spheroid-forming activities of colorectal cancer and PDAC cell lines by blocking eHSP90α's ligation with the cell-surface receptor CD91. In mouse models, HH01 potently inhibited the tumor growth of PDAC cell grafts/xenografts promoted by endothelial-mesenchymal transition-derived cancer-associated fibroblasts while also reducing serum eHSP90α levels, reflecting its anticancer efficacy. HH01 also modulated tumor immunity by reducing M2 macrophages and reinvigorating immune T-cells. Additionally, HH01 showed low aggregation propensity, high water solubility, and a half-life time of >18 days in mouse blood. It was not cytotoxic to retinal pigmented epithelial cells and showed no obvious toxicity in mouse organs. Our data suggest that targeting eHSP90α with HH01 antibody can be a promising novel strategy for PDAC therapy.