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1.
Front Public Health ; 12: 1226239, 2024.
Article in English | MEDLINE | ID: mdl-38414890

ABSTRACT

Background: Aging is an inevitable process of life development. These physical changes can cause a decline in the functional adaptability and health status of older adult individuals. Aims: The purpose of this study was to investigate the association of lower-limb muscle strength performance with static and dynamic balance control among older adults in Taiwan. Methods: We conducted a cross-sectional study and reviewed data derived from the National Physical Fitness Survey in Taiwan 2015-2016. A total of 20,846 Taiwanese older adult individuals aged 65 years old or older were recruited as study participants. Demographic characteristics, anthropometric assessments, lifestyle habits, and health-related physical fitness measurements from this dataset were analyzed using the chi-square test, one-way analysis of variance, and linear regression analysis. Lower-limb muscle strength performance was classified into 4 groups based on quartile (Quartile 1 [Q1], Quartile 2 [Q2], Quartile 3 [Q3], and Quartile 4 [Q4]) values. Results: Increased lower-limb muscle strength levels were significantly associated with static balance in men (Q2: ß = 2.539, p < 0.0001; Q3: ß = 4.590, p < 0.0001; Q4: ß = 7.700, p < 0.0001) and women (Q2: ß = 2.022, p < 0.0001; Q3: ß = 4.179, p < 0.0001; Q4: ß = 6.920, p < 0.0001) after adjusting for potential confounders. In addition, we observed that increased lower-limb muscle strength levels were significantly associated with dynamic balance in men (Q2: ß = -1.661, p < 0.0001; Q3: ß = -2.434, p < 0.0001; Q4: ß = -3.091, p < 0.0001) and women (Q2: ß = -1.660, p < 0.0001; Q3: ß = -2.548, p < 0.0001; Q4: ß = -3.196, p < 0.0001) after adjusting for potential confounders. Conclusion: Lower-limb muscle strength was the most important factor, as it was an improved method for static and dynamic balance control in both genders.


Subject(s)
Aging , Physical Fitness , Humans , Male , Female , Aged , Taiwan , Cross-Sectional Studies , Aging/physiology , Physical Fitness/physiology , Muscle Strength/physiology
2.
Med Sci Monit ; 29: e940959, 2023 Aug 01.
Article in English | MEDLINE | ID: mdl-37525452

ABSTRACT

BACKGROUND Hyperparathyroidism poses significant risks for patients prior to kidney transplantation. However, the outcomes of patients who undergo parathyroidectomy before renal transplantation compared to those without such a procedure remain uncertain. This real-world data study aimed to examine the clinical outcomes of both patient groups. MATERIAL AND METHODS Using the Taiwan National Health Insurance Research Database, we conducted a retrospective cohort study on patients who underwent renal transplantation between January 2005 and December 2015. The patients were divided into two groups: a case group (n=294) with parathyroidectomy and a control group (n=588) without the need for parathyroidectomy before kidney transplantation. The groups were matched based on age, sex, dialysis vintage, and baseline characteristics at a 1:2 ratio. Hazard ratios (HR) were estimated using the Cox regression model. The main outcomes assessed were graft failure, mortality, and major adverse cardiovascular events (MACE) recorded until December 2019. RESULTS During a mean follow-up period of 6 years, a significant difference was observed in graft failure (HR 1.40; 95% confidence interval 1.10-1.79, p=0.007) between the two groups. After further adjustment, graft failure remained significant (HR 1.52; 95% CI 1.07-2.15, p=0.019). Additionally, machine learning-based feature selection identified the importance of parathyroidectomy (ranked 9 out of 11) before kidney transplantation in predicting subsequent graft failure. CONCLUSIONS Our study demonstrates that severe hyperparathyroidism requiring parathyroidectomy before kidney transplantation may contribute to poor post-transplant graft outcomes compared to patients who do not require parathyroidectomy.


Subject(s)
Hyperparathyroidism , Kidney Transplantation , Humans , Kidney Transplantation/methods , Retrospective Studies , Parathyroidectomy/adverse effects , Hyperparathyroidism/surgery , Hyperparathyroidism/etiology , Renal Dialysis , Graft Survival
3.
Sci Transl Med ; 15(711): eadd9990, 2023 08 30.
Article in English | MEDLINE | ID: mdl-37647386

ABSTRACT

Myeloid cells in the tumor microenvironment (TME) can exist in immunosuppressive and immunostimulatory states that impede or promote antitumor immunity, respectively. Blocking suppressive myeloid cells or increasing stimulatory cells to enhance antitumor immune responses is an area of interest for therapeutic intervention. Triggering receptor expressed on myeloid cells-1 (TREM1) is a proinflammatory receptor that amplifies immune responses. TREM1 is expressed on neutrophils, subsets of monocytes and tissue macrophages, and suppressive myeloid populations in the TME, including tumor-associated neutrophils, monocytes, and tumor-associated macrophages. Depletion or inhibition of immunosuppressive myeloid cells, or stimulation by TREM1-mediated inflammatory signaling, could be used to promote an immunostimulatory TME. We developed PY159, an afucosylated humanized anti-TREM1 monoclonal antibody with enhanced FcγR binding. PY159 is a TREM1 agonist that induces signaling, leading to up-regulation of costimulatory molecules on monocytes and macrophages, production of proinflammatory cytokines and chemokines, and enhancement of T cell activation in vitro. An antibody against mouse TREM1, PY159m, promoted antitumor efficacy in syngeneic mouse tumor models. These results suggest that PY159-mediated agonism of TREM1 on tumoral myeloid cells can promote a proinflammatory TME and offer a promising strategy for immunotherapy.


Subject(s)
Monocytes , Myeloid Cells , Animals , Mice , Antibodies, Monoclonal/pharmacology , Antibodies, Monoclonal/therapeutic use , Disease Models, Animal , Immunosuppressive Agents , Macrophages , Triggering Receptor Expressed on Myeloid Cells-1
4.
J Mater Chem A Mater ; 11(28): 15329-15335, 2023 Jul 18.
Article in English | MEDLINE | ID: mdl-37469657

ABSTRACT

In the search for novel solid polymer electrolytes (SPEs), primarily targeting battery applications, a range of different polymers is currently being explored. In this context, the non-coordinating poly(vinylidene fluoride-co-hexafluoropropylene) (PVdF-HFP) polymer is a frequently utilized system. Considering that PVdF-HFP should be a poor solvent for cation salts, it is counterintuitive that this is a functional host material for SPEs. Here, we do an in-depth study of the salt dissolution properties and ionic conductivity of PVdF-HFP-based electrolytes, using two different fabrication methods and also employing a low-molecular-weight solvent analogue. It is seen that PVdF-HFP is remarkably poor as an SPE host, despite its comparatively high dielectric constant, and that the salt dissolution properties instead are controlled by fluorophilic interactions of the anion with the polymer.

5.
Tzu Chi Med J ; 35(2): 143-147, 2023.
Article in English | MEDLINE | ID: mdl-37261302

ABSTRACT

Key management schemes for hierarchical access control enable users who have hierarchical relationships with each other to manage their secret keys efficiently. In these schemes, the users are divided into several groups, and all groups have their own central authorities. Each central authority is responsible for setting parameters and generating user's secret keys in a hierarchical structure such that all users efficiently derive their secret keys and solve dynamic access control problems. Several key management schemes with Health Insurance Portability Accountability Act regulations were recently proposed for hierarchical access control in e-medicine systems. However, these schemes either are insecure or require a large amount of storage and heavy computations. Therefore, this study reviews and discusses hierarchical access control schemes with privacy/security regulations for medical record databases.

6.
Healthcare (Basel) ; 11(6)2023 Mar 08.
Article in English | MEDLINE | ID: mdl-36981455

ABSTRACT

As technology continues to evolve, vast amounts of diverse digital data are becoming more easily generated and collected [...].

7.
Cell Genom ; 3(3): 100272, 2023 Mar 08.
Article in English | MEDLINE | ID: mdl-36950379

ABSTRACT

Estrogen and progesterone have been extensively studied in the mammary gland, but the molecular effects of androgen remain largely unexplored. Transgender men are recorded as female at birth but identify as male and may undergo gender-affirming androgen therapy to align their physical characteristics and gender identity. Here we perform single-cell-resolution transcriptome, chromatin, and spatial profiling of breast tissues from transgender men following androgen therapy. We find canonical androgen receptor gene targets are upregulated in cells expressing the androgen receptor and that paracrine signaling likely drives sex-relevant androgenic effects in other cell types. We also observe involution of the epithelium and a spatial reconfiguration of immune, fibroblast, and vascular cells, and identify a gene regulatory network associated with androgen-induced fat loss. This work elucidates the molecular consequences of androgen activity in the human breast at single-cell resolution.

8.
Environ Toxicol ; 38(4): 857-866, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36629037

ABSTRACT

Parkinson's disease (PD), a chronic and progressive neurodegenerative disease, can reduce the population of dopaminergic neurons in the substantia nigra. The cause of this neuronal death remains unclear. 1-Methyl-4-phenylpyridinium ion (MPP+) is a potent neurotoxin that can destroy dopaminergic (DA) neurons and promote PD. Garcinol, a polyisoprenylated benzophenone derivative, was extracted from Garcinia indica and is an important active compound it has been used as an anticancer, antioxidant, and anti-inflammatory, agent and it can suppress reactive oxygen species (ROS) mediated cell death in a PD model. Human neuroblastoma (SH-SY5Y) cells (1 × 105 cells) were treated with MPP+ (1 mM) for 24 h to induce cellular ROS production. The formation of ROS was suppressed by pretreatment with different concentrations of garcinol (0.5 and 1.0 µM) for 3 h in SH-SY5Y cells. The present study found that MPP+ treatment increased the formation of reactive oxygen species (ROS), and the increased ROS began to promote cell death in SH-SY5Y cells. However, our natural compound garcinol effectively blocked MPP+-mediated ROS formation by activating the DJ-1/SIRT1 and PGC-1α mediated antioxidant pathway. Further findings indicate that the activated SIRT1 can also regulate p-AMPK-mediated autophagy to protect the neurons from the damage it concludes that garcinol sub-sequential regulates intracellular autophagy in this model, and the productive efficacy of garcinol was confirmed by western blot analysis and MitoSOX DCFDA and MTT assays. The results showed garcinol increased protection due to the prevention of MPP+-induced ROS and the promotion of cell survival.


Subject(s)
Neuroblastoma , Neurodegenerative Diseases , Parkinson Disease , Humans , Antioxidants/metabolism , 1-Methyl-4-phenylpyridinium/pharmacology , Reactive Oxygen Species/metabolism , AMP-Activated Protein Kinases/metabolism , Oxidative Stress , Sirtuin 1/metabolism , Cell Line, Tumor , Cell Death , Autophagy , Cell Survival , Apoptosis
9.
Healthcare (Basel) ; 10(12)2022 Dec 09.
Article in English | MEDLINE | ID: mdl-36554020

ABSTRACT

With the rapid development of medicine and technology, machine learning (ML) techniques are extensively applied to medical informatics and the suboptimal health field to identify critical predictor variables and risk factors. Metabolic syndrome (MetS) and chronic kidney disease (CKD) are important risk factors for many comorbidities and complications. Existing studies that utilize different statistical or ML algorithms to perform CKD data analysis mostly analyze the early-stage subjects directly, but few studies have discussed the predictive models and important risk factors for the stage-III CKD high-risk health screening population. The middle stages 3a and 3b of CKD indicate moderate renal failure. This study aims to construct an effective hybrid important risk factor evaluation scheme for subjects with MetS and CKD stages III based on ML predictive models. The six well-known ML techniques, namely random forest (RF), logistic regression (LGR), multivariate adaptive regression splines (MARS), extreme gradient boosting (XGBoost), gradient boosting with categorical features support (CatBoost), and a light gradient boosting machine (LightGBM), were used in the proposed scheme. The data were sourced from the Taiwan health examination indicators and the questionnaire responses of 71,108 members between 2005 and 2017. In total, 375 stage 3a CKD and 50 CKD stage 3b CKD patients were enrolled, and 33 different variables were used to evaluate potential risk factors. Based on the results, the top five important variables, namely BUN, SBP, Right Intraocular Pressure (R-IOP), RBCs, and T-Cho/HDL-C (C/H), were identified as significant variables for evaluating the subjects with MetS and CKD stage 3a or 3b.

10.
Sensors (Basel) ; 22(20)2022 Oct 18.
Article in English | MEDLINE | ID: mdl-36298289

ABSTRACT

The Tactile Internet enables physical touch to be transmitted over the Internet. In the context of electronic medicine, an authenticated key agreement for the Tactile Internet allows surgeons to perform operations via robotic systems and receive tactile feedback from remote patients. The fifth generation of networks has completely changed the network space and has increased the efficiency of the Tactile Internet with its ultra-low latency, high data rates, and reliable connectivity. However, inappropriate and insecure authentication key agreements for the Tactile Internet may cause misjudgment and improper operation by medical staff, endangering the life of patients. In 2021, Kamil et al. developed a novel and lightweight authenticated key agreement scheme that is suitable for remote surgery applications in the Tactile Internet environment. However, their scheme directly encrypts communication messages with constant secret keys and directly stores secret keys in the verifier table, making the scheme vulnerable to possible attacks. Therefore, in this investigation, we discuss the limitations of the scheme proposed by Kamil scheme and present an enhanced scheme. The enhanced scheme is developed using a one-time key to protect communication messages, whereas the verifier table is protected with a secret gateway key to mitigate the mentioned limitations. The enhanced scheme is proven secure against possible attacks, providing more security functionalities than similar schemes and retaining a lightweight computational cost.


Subject(s)
Computer Security , Telemedicine , Humans , Confidentiality , Touch , Internet
11.
Int J Biol Sci ; 18(10): 4203-4218, 2022.
Article in English | MEDLINE | ID: mdl-35844787

ABSTRACT

Rationale: Triple-negative breast cancer (TNBC) does not respond to anti-estrogen and anti-HER2 therapies and is commonly treated by chemotherapy. TNBC has a high recurrence rate, particularly within the first 3 years. Thus, there is an urgent clinical need to develop more effective therapies for TNBC. Topoisomerase I (TOP1) inhibitors cause DNA damage, making these drugs desirable for TNBC treatment since DNA repair machinery is defective in this subtype of breast cancer. Among the main molecular subtypes of breast cancer, the TNBC cell lines exhibited the highest TOP1 inhibition sensitivity. However, clinically used TOP1 inhibitors, such as topotecan and irinotecan, have shown limited clinical applications and the reasons remain unclear. Understanding the mechanism of differential responses to TOP1 blockade and identifying the predictive markers for cancer cell sensitivity will help further TOP1-targeted therapy for TNBC treatment and improve the clinical use of TOP1 inhibitors. Methods: Viability assays were used to evaluate breast cancer cell sensitivity to topotecan and other TOP1 inhibitors as well as TOP2 inhibitors. An in vitro-derived topotecan-resistant TNBC cell model and TNBC xenograft models were employed to confirm cancer cell response to TOP1 blockade. RNA-seq was used to identify potential predictive markers for TNBC cell response to TOP1 blockade. Western blotting and qRT-PCR were performed to measure the protein levels and RNA expression. ATAC-seq and luciferase reporter assays were used to examine MYC transcriptional regulations. The effects of MYC and JNK in cancer cell response to TOP1 inhibition were validated via loss-of-function and gain-of-function experiments. Results: We observed two distinct and diverging cancer cell responses - sensitive versus resistant to TOP1 inhibition, which was confirmed by TNBC xenograft mouse models treated by topotecan. TNBC cells exhibited bifurcated temporal patterns of ATR pathway activation upon TOP1 inhibitor treatment. The sensitive TNBC cells showed an "up then down" dynamic pattern of ATR/Chk1 signaling, while the resistant TNBC cells exhibited a "persistently up" profile. On the contrary, opposite temporal patterns of induced expression of MYC, a key regulator and effector of DNA damage, were found in TNBC cells treated by TOP1 inhibitors. Mechanistically, we showed that TOP1-induced JNK signaling upregulated MYC expression. Furthermore, pharmacological inhibition of ATR reversed TNBC cell resistance to topotecan, whereas MYC knockdown and JNK inhibition reduced cancer cell sensitivity. Conclusions: Dynamic temporal profiles of induced ATR/Chk1 and JNK activation as well as MYC expression, may predict cancer cell response to TOP1 inhibitors. JNK activation-mediated constitutive elevation of MYC expression may represent a novel mechanism governing cancer cell sensitivity to TOP1-targeting therapy. Our results may provide implications for identifying TNBC patients who might benefit from the treatment with TOP1 inhibitors.


Subject(s)
DNA Topoisomerases, Type I , Triple Negative Breast Neoplasms , Animals , Cell Line, Tumor , Cell Proliferation , DNA Topoisomerases, Type I/metabolism , DNA Topoisomerases, Type I/pharmacology , DNA Topoisomerases, Type I/therapeutic use , Humans , Mice , Proto-Oncogene Proteins c-myc/genetics , Signal Transduction/genetics , Topotecan/pharmacology , Topotecan/therapeutic use , Triple Negative Breast Neoplasms/drug therapy , Triple Negative Breast Neoplasms/genetics , Triple Negative Breast Neoplasms/metabolism
12.
ACS Sens ; 7(7): 1808-1818, 2022 07 22.
Article in English | MEDLINE | ID: mdl-35748570

ABSTRACT

The measurement of oxygen consumption of adherent cells is a profoundly important issue for estimating the bioenergetic health and metabolism activity of cells. The study describes the construction of a microfluidic chip consisting of an open container connected with a position-raised channel and dissolved oxygen (DO)-sensing gold ultramicroelectrodes for quantifying the oxygen consumption rate (OCR) of adherent cells. The microfluidic chip design can reduce the action of shear force on the adherent cells during medium replacement. The residual concentration of analytes in the open container was only 4.4% after solution replacement via the position-raised channel. The DO reduction current measured by ultramicroelectrodes averaged in the range of 40-60 s presented high reproducibility with a 1.1% relative standard deviation suitable for OCR calculation. After short-term (90 min) cultivation, the microfluidic chip can monitor the time-dependent change in the OCR of 3T3-L1 cells for several hours by repeatedly replacing the culture medium or with the stimulation of different mitochondrial inhibitors. The presented microfluidic cell-based chip has great promise for drug screening and chemosensitivity testing by measuring OCR to evaluate the mitochondrial function of adherent cells.


Subject(s)
Oxygen Consumption , Oxygen , Microfluidics , Mitochondria/metabolism , Oxygen/metabolism , Oxygen Consumption/physiology , Reproducibility of Results
13.
Radiology ; 305(1): 219-227, 2022 10.
Article in English | MEDLINE | ID: mdl-35727156

ABSTRACT

Background The added value of preoperative PET/CT for the overall survival of patients with resectable non-small cell lung cancer (NSCLC) is unknown. Purpose To investigate the association of the use of preoperative PET/CT on survival of patients with resectable stage I-IIIB NSCLC. Materials and Methods In this retrospective study, patients with resectable stage I-IIIB NSCLC who underwent thoracic surgery from January 1, 2009, to December 31, 2018, from the Taiwan Cancer Registry were included. The last follow-up date was December 31, 2019. Patients were categorized into two groups according to whether they underwent preoperative metabolic imaging with fluorine 18 fluorodeoxyglucose PET/CT. Patients who did not undergo preoperative imaging were used as the control group. The primary outcome of interest was all-cause mortality. Patients in both groups were propensity score matched at a ratio of 1:1. Matching variables used were sex, age, histologic findings, American Joint Committee on Cancer clinical stage, cT stage, cN stage, current and past smoker history, adjuvant chemotherapy, adjuvant chemoradiation, Charlson comorbidity index, and hospital type. Survival curves were generated using the Kaplan-Meier method and compared using the log-rank test. Results In the matched cohort, 6754 patients (3349 men, mean age ± SD: 64 years ± 11) underwent PET/CT and 6754 did not (3362 men, mean age: 64 years ± 11). In adjusted analysis, patients with stage IIIA or IIIB NSCLC and preoperative PET/CT had a lower risk of death versus those without PET/CT (for stage IIIA: hazard ratio [HR] = 0.90 [95% CI: 0.79, 0.94], P = .02; for stage IIIB: HR = 0.80 [95% CI: 0.71, 0.90], P < .01). There was no improvement in a lower risk of death for patients with stage I-II NSCLC (after multivariable adjustment, the HR was 1.19 [95% CI: 0.89, 1.30], P = .65). Conclusion Use of preoperative PET/CT was associated with lower risk of death in patients with stage IIIA-IIIB non-small cell lung cancer compared with those without preoperative PET/CT. © RSNA, 2022 Online supplemental material is available for this article.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Carcinoma, Non-Small-Cell Lung/diagnostic imaging , Carcinoma, Non-Small-Cell Lung/metabolism , Carcinoma, Non-Small-Cell Lung/surgery , Fluorodeoxyglucose F18 , Humans , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/metabolism , Lung Neoplasms/surgery , Male , Middle Aged , Neoplasm Staging , Positron Emission Tomography Computed Tomography , Retrospective Studies
14.
S Afr J Physiother ; 78(1): 1628, 2022.
Article in English | MEDLINE | ID: mdl-35402743

ABSTRACT

Background: Knee osteoarthritis (OA) affects the quality of life (QOL) and balance control of elderly people; our study explored the balance factors that affected the QOL in patients with knee OA. Objectives: To determine the balance factors that affected the QOL of patients with knee OA who attended general clinics. Method: A total of 30 healthy controls and 60 patients with mild-to-moderate bilateral knee OA, all aged 55-75 years, were enrolled in our cross-sectional study. All participants were interviewed; the Medical Outcomes Study 36-Item Short-Form Health Survey was used to assess their QOL in eight dimensions, and the Balance Master System was used to evaluate their balance control according to six parameters. Descriptive statistics were used to reduce the data; an independent t-test determined differences between the two groups, and a multiple regression analysis was undertaken to establish associations between variables from the balance control test and SH36 physical and mental health components. The level of statistical significance was set at 5%. Results: In the OA group, significant negative correlations were observed between sway velocity and the physical health component (p = 0.003) and between sway velocity and the mental health component (p = 0.006). Thus, sway velocity had a major impact on the QOL of patients with knee OA. Conclusions: The sway velocity at the centre of gravity in balance control was a crucial factor for determining the QOL of patients with bilateral knee OA. Clinical implications: Sway velocity is a key factor affecting the QOL and may provide a basis to formulate preventive actions and design treatment goals for patients with knee OA.

15.
Radiat Oncol ; 17(1): 33, 2022 Feb 12.
Article in English | MEDLINE | ID: mdl-35151355

ABSTRACT

BACKGROUND: To date, no data on the effect of adjuvant postmastectomy radiotherapy (PMRT) on oncologic outcomes, such as all-cause death, locoregional recurrence (LRR), and distant metastasis (DM), are available in women with left-side breast invasive ductal carcinoma (IDC) and heart failure with reduced ejection fraction (HFrEF). PATIENTS AND METHODS: We enrolled 646 women with left-breast IDC at clinical stages I-IIIC and HFrEF receiving radical total mastectomy (TM) followed by adjuvant PMRT or non-adjuvant PMRT. We categorized them into two groups based on their adjuvant PMRT status and compared their overall survival (OS), LRR, and DM outcomes. We calculated the propensity score and applied inverse probability of treatment weighting (IPTW) to create a pseudo-study cohort. Furthermore, we performed a multivariate analysis of the propensity score-weighted population to obtain hazard ratios (HRs). RESULTS: In the IPTW-adjusted model, adjuvant PMRT (adjusted HR [aHR]: 0.52; 95% confidence interval [CI]: 0.37-0.74) was a significant independent prognostic factor for all-cause death (P = 0.0003), and the aHR (95% CI) of LRR and DM for adjuvant PMRT was 0.90 (0.79-0.96; P = 0.0356) and 0.89 (0.54-1.50; P = 0.6854), respectively, compared with the nonadjuvant PMRT group. CONCLUSION: Adjuvant PMRT was associated with a decrease in all-cause death, and LRR in women with left IDC and HFrEF compared with nonadjuvant PMRT.


Subject(s)
Heart Failure/complications , Mastectomy, Simple , Unilateral Breast Neoplasms/complications , Unilateral Breast Neoplasms/mortality , Unilateral Breast Neoplasms/radiotherapy , Adult , Aged , Female , Humans , Middle Aged , Radiotherapy, Adjuvant , Survival Rate , Unilateral Breast Neoplasms/surgery , Young Adult
16.
Clin Transl Med ; 12(2): e606, 2022 02.
Article in English | MEDLINE | ID: mdl-35170261

ABSTRACT

BACKGROUND: Protein disulfide isomerases a4 (Pdia4) is known to be involved in cancer development. Our previous publication showed that Pdia4 positively promotes cancer development via its inhibition of procaspase-dependent apoptosis in cancer cells. However, nothing is known about its role in the cancer microenvironment. RESULTS: Here, we first found that Pdia4 expression in lung cancer was negatively correlated with patient survival. Next, we investigated the impact of host Pdia4 in stromal cells during cancer development. We showed that Pdia4 was expressed at a low level in stromal cells, and this expression was up-regulated akin to its expression in cancer cells. This up-regulation was stimulated by tumour cell-derived stimuli. Genetics studies in tumour-bearing wild-type and Pdia4-/- mice showed that host Pdia4 promoted lung cancer development in the mice via cancer stroma. This promotion was abolished in Rag1-/- mice which lacked T and B cells. This promotion could be restored once T and B cells were added back to Rag1-/- mice. In addition, host Pdia4 positively regulated the number and immunosuppressive function of stromal cells. Mechanistic studies showed that host Pdia4 positively controlled the Stat3/Vegf pathway in T and B lymphocytes via its stabilization of activated Stat3 in a Thioredoxin-like domain (CGHC)-dependent manner. CONCLUSIONS: These findings identify Pdia4 as a possible target for intervention in cancer stroma, suggesting that targeting Pdia4 in cancer stroma is a promising anti-cancer approach.


Subject(s)
Lung Neoplasms/etiology , Protein Disulfide-Isomerases/metabolism , STAT3 Transcription Factor/metabolism , Stromal Cells/metabolism , Animals , Apoptosis , Mice
17.
Cancers (Basel) ; 14(3)2022 Feb 03.
Article in English | MEDLINE | ID: mdl-35159055

ABSTRACT

BACKGROUND: The incidence of female BC among the Eastern and Southeastern Asian populations has gradually increased in recent years. However, epidemiological studies on the relationship between a sedentary lifestyle and female BC are insufficient. In order to determine the association between this lifestyle and the incidence of female BC, we conducted a population-based cohort study on women in Taiwan. METHODS: We followed a prospective cohort of 5879 women aged 30 years and over enrolled in the 2001 National Health Interview Survey (NHIS), who developed female BC over a period of 72,453 person years, and we estimated the hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) using the Cox proportional hazards model. RESULTS: RFs associated with female BC incidence included parity (adjusted HR = 0.63; 95% CI: 0.44-0.91), body mass index (adjusted HR = 1.34; 95% CI: 1.04-1.71), and ≥3 h/day spent sitting (adjusted HR = 1.89; 95% CI: 1.08-3.32). The incidence of female BC in participants who sat for ≥3 h/day and consumed sugary drinks was 2.5 times greater than that in those who sat for <3 h/day and did not consume sugary drinks (adjusted HR = 2.51; 95% CI: 1.01-6.23). CONCLUSIONS: The findings of this study indicate that sedentary behavior and sugary drink intake may increase the risk of developing female BC. These are modifiable RFs; therefore, a healthy lifestyle and diet can reduce the incidence of female BC.

18.
Mol Ther ; 30(2): 672-687, 2022 02 02.
Article in English | MEDLINE | ID: mdl-34274535

ABSTRACT

Triple-negative breast cancer (TNBC) has a high propensity for organ-specific metastasis. However, the underlying mechanisms are not well understood. Here we show that the primary TNBC tumor-derived C-X-C motif chemokines 1/2/8 (CXCL1/2/8) stimulate lung-resident fibroblasts to produce the C-C motif chemokines 2/7 (CCL2/7), which, in turn, activate cholesterol synthesis in lung-colonizing TNBC cells and induce angiogenesis at lung metastatic sites. Inhibiting cholesterol synthesis in lung-colonizing breast tumor cells by pulmonary administration of simvastatin-carrying HER3-targeting nanoparticles reduces angiogenesis and growth of lung metastases in a syngeneic TNBC mouse model. Our findings reveal a novel, chemokine-regulated mechanism for the cholesterol synthesis pathway and a critical role of metastatic site-specific cholesterol synthesis in the pulmonary tropism of TNBC metastasis. The study has implications for the unresolved epidemiological observation that use of cholesterol-lowering drugs has no effect on breast cancer incidence but can unexpectedly reduce breast cancer mortality, suggesting interventions of cholesterol synthesis in lung metastases as an effective treatment to improve survival in individuals with TNBC.


Subject(s)
Triple Negative Breast Neoplasms , Animals , Cell Line, Tumor , Chemokines , Humans , Lung/metabolism , Mice , Neovascularization, Pathologic/drug therapy , Neovascularization, Pathologic/genetics , Triple Negative Breast Neoplasms/drug therapy , Triple Negative Breast Neoplasms/genetics
19.
Planta Med ; 88(3-04): 282-291, 2022 Mar.
Article in English | MEDLINE | ID: mdl-34187059

ABSTRACT

Currently, antibiotics are commonly used to treat coccidiosis, a severe protozoal disease in chickens. However, due to growing concerns about the antibiotic residue in meat and eggs, phytogenic formulations are becoming an attractive approach to manage this disease. In this study, we investigated the anti-coccidial function and mechanism of phytogenic formulations composed of Bidens pilosa, Artemisia indica, and both used in combination. We found that these formulations increased the survival rate and reduced body weight loss, the feed conversion ratio, oocyst excretion, bloody stools, and gut lesions of chickens. Mechanistic studies showed that A. indica, but not B. pilosa, reduced the survival of Eimeria oocysts. Accordingly, they both inhibited oocyst sporulation and sporozoite invasion into Madin-Darby bovine kidney (MDBK) cells. Overall, we demonstrate that these formulations protect chickens against coccidiosis. Moreover, a combination of B. pilosa and A. indica has an additive effect on coccidiosis control and growth performance in chickens compared to either one used alone.


Subject(s)
Artemisia , Bidens , Coccidiosis , Eimeria , Poultry Diseases , Animals , Artemisia/chemistry , Cattle , Chickens , Coccidiosis/drug therapy , Coccidiosis/veterinary
20.
Cell Transplant ; 30: 9636897211067447, 2021.
Article in English | MEDLINE | ID: mdl-34939863

ABSTRACT

Stem cell therapy has been explored for the treatment of cerebral stroke. Several types of stem cells have been investigated to ensure the safety and efficacy in clinical trials.Cryopreserved umbilical cord blood (UCB) mononuclear cells (MNCs) obtained from healthy donors have a more stabilized quality, thereby ensuring a successful therapy. A phase I study was conducted on patients aged 45-80 years who sustained acute ischemic stroke. An UCB unit was obtained from a public cord blood bank based on ABO/Rh blood type, HLA matching score (6/6), and cell dose (total MNC count of 0.5-5 × 107 cells/kg). In addition, to facilitate blood brain barrier penetration of UCB, 4 doses of 100 mL mannitol was administered intravenously after 30 min after UCB transplantation and every 4 h thereafter. The primary outcomes were the number of disease (GVHD) within 100 days after transfusion. The secondary outcomes were changes in the National Institutes of Health Stroke Scale (NIHSS), Barthel index, and Berg Balance Scale scores. A 46-year-old male patient with identical ABO/Rh blood type, HLA matching score of 6/6, and MNC count of 2.63 × 108 cells/kg was enrolled. The patient did not present with serious AEs or GVHD during the 12-month study period. The patient's NIHSS score decreased from 9 to 1. Moreover, the Berg Balance Scale score increased from 0 to 48 and the Barthel index score from 0 to 90. This preliminary study showed that an adult patient with hemiplegia due to ischemic stroke completely recovered within 12 months after receiving allogeneic UCB therapy.


Subject(s)
Cord Blood Stem Cell Transplantation/methods , Monocytes/metabolism , Stroke/therapy , Transplantation, Homologous/methods , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged
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