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PeerJ 2024Prostate cancer (PCa) is one of the causes of death in men worldwide. Although treatment strategies have been developed, the recurrence of the disease and consequential...
BACKGROUND
Prostate cancer (PCa) is one of the causes of death in men worldwide. Although treatment strategies have been developed, the recurrence of the disease and consequential side effects remain an essential concern. Kurz, a traditional Thai medicine, exhibits diverse therapeutic properties, including anti-cancer activity. However, its anti-cancer activity against prostate cancer has not been thoroughly explored. This study aims to evaluate the anti-cancer activity and underlying mechanisms of the ethyl acetate extract of Kurz (EADR) related to apoptosis induction in the LNCaP human prostate cancer cell line.
METHODS
Ethyl acetate was employed to extract the dried bark of Kurz. The cytotoxicity of EADR on both LNCaP and WPMY-1 cells (normal human prostatic myofibroblast cell line) was evaluated using MTS assay. The effect of EADR on the cell cycle, apoptosis induction, and alteration in mitochondrial membrane potential (MMP) was assessed by the staining with propidium iodide (PI), Annexin V-FITC/PI, and JC-1 dye, respectively. Subsequent analysis was conducted using flow cytometry. The expression of cleaved caspase-3, BAX, and Bcl-2 was examined by Western blotting. The phytochemical profiling of the EADR was performed using gas chromatography-mass spectrometry (GC-MS).
RESULTS
EADR exhibited a dose-dependent manner cytotoxic effect on LNCaP cells, with IC values of 15.43 and 12.35 µg/mL after 24 and 48 h, respectively. Although it also exhibited a cytotoxic effect on WPMY-1 cells, the effect was comparatively lower, with the IC values of 34.61 and 19.93 µg/mL after 24 and 48 h of exposure, respectively. Cell cycle analysis demonstrated that EADR did not induce cell cycle arrest in either LNCaP or WPMY-1 cells. However, it significantly increased the sub-G1 population in LNCaP cells, indicating a potential induction of apoptosis. The Annexin V-FITC/PI staining indicated that EADR significantly induced apoptosis in LNCaP cells. Subsequent investigation into the underlying mechanism of EADR-induced apoptosis revealed a reduction in MMP as evidenced by JC-1 staining. Moreover, Western blotting demonstrated that EADR treatment resulted in the upregulation of BAX, downregulation of BCL-2, and elevation of caspase-3 cleavage in LNCaP cells. Notably, the epilupeol was a prominent compound in EADR as identified by GC-MS.
CONCLUSION
The EADR exhibits anti-cancer activity against the LNCaP human prostate cancer cell line by inducing cytotoxicity and apoptosis. Our findings suggest that EADR promotes apoptosis by upregulating pro-apoptotic BAX, whereas downregulation of anti-apoptotic Bcl-2 results in the reduction of MMP and the activation of caspase-3. Of particular interest is the presence of epilupeol, a major compound identified in EADR, which may hold promise as a candidate for the development of therapeutic agents for prostate cancer.
Topics: Humans; Male; Apoptosis; Prostatic Neoplasms; Cell Line, Tumor; Plant Extracts; Proto-Oncogene Proteins c-bcl-2; bcl-2-Associated X Protein; Caspase 3; Diospyros; Mitochondria; Membrane Potential, Mitochondrial; Antineoplastic Agents, Phytogenic
PubMed: 38966207
DOI: 10.7717/peerj.17637 -
F1000Research 2023Gastrointestinal bleeds (GIB) are associated with high morbidity and mortality, with upper GIB accounting for 20,000 deaths annually in the United States of America....
Gastrointestinal bleeds (GIB) are associated with high morbidity and mortality, with upper GIB accounting for 20,000 deaths annually in the United States of America. Accurate risk stratification is essential in determining and differentiating high-risk low-risk patients, as low-risk patients have an overall better prognosis. Patients taking antithrombotics to reduce the risk of thromboembolic events have a 4% chance of developing a GIB. This then places physicians in a difficult position as they must perform a risk-and-benefit analysis of whether to reinstate antithrombotics after a major GIB. This systematic review aims to assess the general trends in time for resuming anticoagulation in the setting of upper GI bleed. A literary search of three different databases was performed by three independent reviewers. The research databases included PubMed, ScienceDirect, and ProQuest. Specific keywords were used to narrow the search and articles were screened based on inclusion and exclusion criteria. Our initial search generated 11,769 potential articles and 22 articles were ultimately used for this review using specific inclusion and exclusion criteria. There is an increase in thrombotic events following a GIB if anticoagulants are not resumed. We also found that the best time to resume therapy was 15-30 days post-GIB. Therefore, the decision to resume anticoagulation therapy should consider the patients' medical history and should fall within 15-30 days post-GIB.
Topics: Humans; Anticoagulants; Gastrointestinal Hemorrhage; Platelet Aggregation Inhibitors
PubMed: 38966192
DOI: 10.12688/f1000research.135132.1 -
Frontiers in Bioengineering and... 2024Artificial vertebral implants have been widely used for functional reconstruction of vertebral defects caused by tumors or trauma. However, the evaluation of their...
BACKGROUND AND OBJECTIVE
Artificial vertebral implants have been widely used for functional reconstruction of vertebral defects caused by tumors or trauma. However, the evaluation of their biomechanical properties often neglects the influence of material anisotropy derived from the host bone and implant's microstructures. Hence, this study aims to investigate the effect of material anisotropy on the safety and stability of vertebral reconstruction.
MATERIAL AND METHODS
Two finite element models were developed to reflect the difference of material properties between linear elastic isotropy and nonlinear anisotropy. Their biomechanical evaluation was carried out under different load conditions including flexion, extension, lateral bending and axial rotation. These performances of two models with respect to safety and stability were analyzed and compared quantitatively based on the predicted von Mises stress, displacement and effective strain.
RESULTS
The maximum von Mises stress of each component in both models was lower than the yield strength of respective material, while the predicted results of nonlinear anisotropic model were generally below to those of the linear elastic isotropic model. Furthermore, the maximum von Mises stress of natural vertebra and reconstructed system was decreased by 2-37 MPa and 20-61 MPa, respectively. The maximum reductions for the translation displacement of the artificial vertebral body implant and motion range of whole model were reached to 0.26 mm and 0.77°. The percentage of effective strain elements on the superior and inferior endplates adjacent to implant was diminished by up to 19.7% and 23.1%, respectively.
CONCLUSION
After comprehensive comparison, these results indicated that the finite element model with the assumption of linear elastic isotropy may underestimate the safety of the reconstruction system, while misdiagnose higher stability by overestimating the range of motion and bone growth capability.
PubMed: 38966191
DOI: 10.3389/fbioe.2024.1305837 -
Journal of Experimental Orthopaedics Jul 2024To determine whether scapular morphology could predict isolated supraspinatus tendon tear propagation after exercise therapy. We hypothesised that a larger critical...
PURPOSE
To determine whether scapular morphology could predict isolated supraspinatus tendon tear propagation after exercise therapy. We hypothesised that a larger critical shoulder angle (CSA) and type III acromial morphology predict a positive change in tear size.
METHODS
Fifty-nine individuals aged 40-70 years with isolated symptomatic high-grade partial or full-thickness supraspinatus tendon tears were included. Individuals participated in a structured, individualised 12-week exercise therapy programme and underwent ultrasound to measure tear size at baseline and 12 months following therapy. Computed tomography images were segmented to create three-dimensional subject-specific bone models and reviewed by three trained clinicians to measure CSA and to determine acromion morphology based on the Bigliani classification. A binary logistic regression was performed to determine the predictive value of CSA and acromion morphology on tear propagation.
RESULTS
The CSA was 30.0 ± 5.4°. Thirty-one individuals (52.5%) had type II acromial morphology, followed by type III and type I morphologies (25.4% and 22.0%, respectively); 81.4% experienced no change in tear size, four (6.8%) individuals experienced tear propagation and seven (11.9%) individuals had a negative change in tear size. No significant difference in tear propagation rates based on CSA or acromion morphology (not significant [NS]) was observed. The model predicted tear size status in 81.4% of cases but only predicted tear propagation 8.3% of the time. Overall, CSA and acromion morphology only predicted 24.3% ( = 0.243) of variance in tear propagation (NS).
CONCLUSIONS
CSA and acromion morphology were NS predictors of tear propagation of the supraspinatus tendon 12 months following an individualised exercise therapy programme.
LEVEL OF EVIDENCE
II.
PubMed: 38966184
DOI: 10.1002/jeo2.12072 -
Exploration of Targeted Anti-tumor... 2024There is limited data on prognostic value of baseline plasma cell free DNA (cfDNA) in advanced squamous non-small cell lung cancer (sq-NSCLC). This prospective...
AIM
There is limited data on prognostic value of baseline plasma cell free DNA (cfDNA) in advanced squamous non-small cell lung cancer (sq-NSCLC). This prospective observational study aimed to assess change in plasma cfDNA levels in locally-advanced/metastatic sq-NSCLC with chemotherapy and its correlation with symptom-scores and radiological-responses.
METHODS
Chemotherapy-naive patients with stages-IIIB/IIIC/IV sq-NSCLC ( = 59), smokers with chronic obstructive pulmonary disease [COPD, COPD-controls (CC); = 27] and healthy-controls ( = 25) were enrolled. Respiratory symptom burden (RSB) and total symptom burden (TSB) were calculated from mean visual-analog-scores (VAS) of dyspnoea, cough, chest pain, hemoptysis RSB, anorexia and fatigue (all six for TSB). cfDNA was isolated from peripheral blood. All patients received platinum-doublet chemotherapy. RSB/TSB/cfDNA assessment and contrast-enhanced computed tomography (CECT)-thorax scans were done at baseline and post-chemotherapy.
RESULTS
At baseline, 13/59 (22%) sq-NSCLC, 3/27 (11%) CC and none (0%) healthy-controls had detectable cfDNA. All three CC were heavy smokers with no evidence of malignancy and undetectable cfDNA levels on repeat testing. In sq-NSCLC group, majority were males (95%), current-smokers (88%), heavy-smokers (70%), had metastatic disease (59%) with median age of 65 years. Eastern Co-operative Oncology Group (ECOG) performance status (PS) was 0-1 (56%) and 2 (42%). Median RSB- and TSB-scores were 9 [interquartile range (IQR) = 5-14] and 16 (IQR = 9-23), respectively. Of the 59 patients, 54 received ≥ 1 cycle while 27 underwent post-C4 evaluation with detectable cfDNA levels in 18/27 (66.7%). No baseline characteristic correlated with cfDNA detectability. Median overall survival (OS) and progression-free survival (PFS) were 262 days and 167 days, respectively. ECOG PS ≥ 2, RSB-score > 9 and TSB-score > 16 were all associated with worse OS and PFS as was cfDNA detectability [median OS = 97 days 298 days and median PFS = 97 days 197 days; = 0.025; hazard ratio (HR) = 2.17].
CONCLUSIONS
Baseline cfDNA detectability is independently associated with poor OS and PFS in patients with advanced sq-NSCLC on chemotherapy.
PubMed: 38966173
DOI: 10.37349/etat.2024.00232 -
Acta Medica Philippina 2024This study examined the association between irrational beliefs and psychological distress among female office workers in Bali, and formulate general equation to predict...
OBJECTIVES
This study examined the association between irrational beliefs and psychological distress among female office workers in Bali, and formulate general equation to predict psychological distress from the irrational belief scores.
METHODS
A cross-sectional study was conducted among 111 female office workers in Bali. The irrational beliefs were measured by the Smith Irrational Belief Inventory (SIBI) questionnaire and the psychological distress was assessed by a questionnaire quoted from the Brief Job Stress Questionnaire (BJSQ). Multivariable linear regression was performed to evaluate the role of irrational beliefs on psychological distress scores.
RESULTS
There was a moderate, positive correlation between irrational beliefs and psychological distress, which was statistically significant (r = 0.451, n = 111, p = 0.000). The R squared was 0.205, indicating that 20.5% of psychological distress variance can be explained by irrational beliefs. The F-ratio in the ANOVA test shows that the independent variables statistically significantly predict the dependent variable, F(3,107) = 9.187, p < 0.0005. The general form of the equation to predict psychological distress from irrational belief scores is: Predicted psychological distress (Y) = 17.909 + (0.392 x Irrational belief scores).
CONCLUSION
Irrational beliefs are significantly associated with psychological distress among female office workers in Gianyar, Bali. This finding suggests the need for strategies anticipating better health and productivity among female workers.
PubMed: 38966157
DOI: 10.47895/amp.vi0.5527 -
Acta Medica Philippina 2024People from rural communities are not spared from COVID-19. But implementing preventive measures and strategies can be made to control the spread.
BACKGROUND
People from rural communities are not spared from COVID-19. But implementing preventive measures and strategies can be made to control the spread.
OBJECTIVE
This study was conducted to describe the epidemiologic situation and the healthcare capacity of the locality, determine the responses and strategies implemented in the control of COVID-19, and explain the activities performed in relation to the epidemiologic situation in Tarangnan, Samar - a low-income class municipality in the Philippines.
METHODS
A mixed qualitative-quantitative design was employed in this study. Descriptive documentary research design through review of records from March to October 2020 was utilized. For the qualitative context, a case study design was employed whereby focus group discussions and key informant interviews using open-ended questions were performed.
RESULTS
A total of 66 individuals were recorded as having COVID-19 in the municipality from March to October 2020. The first recorded confirmed cases of COVID-19 in Eastern Visayas were two adults in Tarangnan, Samar, in March 2020. Since then, additional confirmed cases have been recorded every month, but confirmed COVID-19 dramatically reduced from August to October 2020. Qualitative analysis revealed stringent COVID-19 preventive measures reflected in the confirmed case numbers. The tailwinds of the COVID-19 response include: the SARS pandemic precedent, coordination and communication, outpouring of support from other government and non-government partners, and innovative community-based approaches. The headwinds of COVID-19 response were challenges in imposing minimum health and safety precautions, stigmatization, and discrimination.
CONCLUSION
Even if challenges have arisen in implementing measures against the spread of the disease, good outcomes have been achieved through persistent good practice, positive modifications, and community-based innovations.
PubMed: 38966153
DOI: 10.47895/amp.vi0.6169 -
Acta Medica Philippina 2024The primary aim of this study was to determine quantitatively the extent of coverage of the Hong Kong Laboratory Accreditation Scheme (HOKLAS 015) requirements by...
OBJECTIVES
The primary aim of this study was to determine quantitatively the extent of coverage of the Hong Kong Laboratory Accreditation Scheme (HOKLAS 015) requirements by guidance checklists (HOKLAS 016-02 and HOKLAS 021).
METHODS
The level of conformance requirement coverage of HOKLAS 015 by HOKLAS 016-02 and HOKLAS 021 was calculated by an evaluation checklist based on conformance requirements in HOKLAS 015. A distribution analysis of conformance requirements relating to the International Standard ISO 15189:2012 process-based quality management system model was also performed to elicit further coverage information.
RESULTS
HOKLAS 016-02 was found to provide coverage of 76% while HOKLAS 021 was found to provide coverage of 11%. HOKLAS 015 was also found to have a distribution coverage of 78% relating to the International Standard ISO 15189:2012 process-based quality management system model.
CONCLUSION
The results of this analysis should be of value to medical laboratories wishing to maintain the internal auditability required by HOKLAS 015 by gaining an awareness of the extent of coverage provided by HOKLAS 016-02 and HOKLAS 021.
PubMed: 38966151
DOI: 10.47895/amp.vi0.6196 -
Frontiers in Plant Science 2024Abscisic acid (ABA) can negatively regulate seed germination, but the mechanisms of ABA-mediated metabolism modulation are not well understood. Moreover, it remains...
INTRODUCTION
Abscisic acid (ABA) can negatively regulate seed germination, but the mechanisms of ABA-mediated metabolism modulation are not well understood. Moreover, it remains unclear whether metabolic pathways vary with the different tissue parts of the embryo, such as the radicle, hypocotyl and cotyledon.
METHODS
In this report, we performed the first comprehensive metabolome analysis of the radicle and hypocotyl + cotyledon in Pinus koraiensis seeds in response to ABA treatment during germination.
RESULTS AND DISCUSSION
Metabolome profiling showed that following ABA treatment, 67 significantly differentially accumulated metabolites in the embryo were closely associated with pyrimidine metabolism, phenylalanine metabolism, cysteine and methionine metabolism, galactose metabolism, terpenoid backbone biosynthesis, and glutathione metabolism. Meanwhile, 62 metabolites in the hypocotyl + cotyledon were primarily involved in glycerophospholipid metabolism and glycolysis/gluconeogenesis. We can conclude that ABA may inhibit Korean pine seed germination primarily by disrupting the biosynthesis of certain plant hormones mediated by cysteine and methionine metabolism and terpenoid backbone biosynthesis, as well as reducing the reactive oxygen species scavenging ability regulated by glutathione metabolism and shikimate pathway in radicle. ABA may strongly disrupt the structure and function of cellular membranes due to alterations in glycerophospholipid metabolism, and weaken glycolysis/gluconeogenesis in the hypocotyl + cotyledon, both of which are major contributors to ABA-mediated inhibition of seed germination. These results highlight that the spatial modulation of metabolic pathways in Pinus koraiensis seeds underlies the germination response to ABA.
PubMed: 38966139
DOI: 10.3389/fpls.2024.1417632 -
International Journal of Dentistry 2024This study aimed to perform a histological evaluation of teeth diagnosed with internal root resorption.
OBJECTIVE
This study aimed to perform a histological evaluation of teeth diagnosed with internal root resorption.
MATERIALS AND METHODS
A descriptive study involved the examination of 50 human teeth extracted due to an unfavorable prognosis for retention in the oral cavity. Teeth were preserved in 10% buffered formalin and subsequently subjected to the decalcification process. Masson-Goldner staining was applied for comprehensive histological assessment.
RESULTS
In all the 50 teeth examined, resorption gaps within the dentin tissue were identified, accompanied by the presence of reparative cells in the vicinity of these cavities. Marked structural loss and dentin fragmentation were evident, with regions exhibiting fissures and an absence of dentinal tubules.
CONCLUSIONS
The histological evaluation of 50 teeth diagnosed with internal dental resorption revealed significant structural alterations, including resorption lacunae, the presence of multinucleated osteoclast-like cells, and reparative connective tissue. These findings highlight the complex and multifaceted nature of internal dental resorption. These histological insights provide a deeper understanding of the pathological processes involved in internal dental resorption and underscore the necessity for early detection and intervention to mitigate tooth loss and preserve dental health.
PubMed: 38966138
DOI: 10.1155/2024/1454079