Ocimum gratissimum Aqueous Extract Induces Apoptotic Signalling in Lung Adenocarcinoma Cell A549

Ocimum gratissimum (OG) is widely used as a traditional herb for its antibacterial activity in Taiwan. Recently, antitumor effect of OG on breast cancer cell is also reported; however, the effects of OG on human pulmonary adenocarcinoma cell A549 remain unclear. Therefore, we aimed to investigate whether aqueous OG extract (OGE) affects viability of A549 cells and the signals induced by OGE in A549 cells. Cell viability assays revealed that OGE significantly and dose-dependently decreased the viability of A549 cell but not that of BEAS-2B cell. Morphological examination and DAPI staining indicated that OGE induced cell shrinkage and DNA condensation for A549 cells. Further investigation showed that OGE enhanced activation of caspase-3, caspase-9 and caspase-8 and increased protein level of Apaf-1 and Bak, but diminished the level of Bcl-2. Additionally, OGE inhibited the phosphorylation of extracellular signal-regulated kinase (ERK) yet enhanced the phosphorylation of c-Jun N-terminal kinase (JNK) and p38 MAP kinase (p38). In conclusion, our findings indicate that OGE suppressed the cell viability of A549 cells, which may result from the activation of apoptotic signaling and the inhibition of anti-apoptotic signaling, suggesting that OGE might be beneficial to lung carcinoma treatment

Temporal and Spatial Variations in spatial variations in symbiont communities of catch bowl coral Isopora palifera (Scleractinia: Acroporidae) on reefs in Kenting National Park, Taiwan

Acclimatization through Symbiodinium shuffling is one of potential mechanisms in reef-building corals to survive environmental stress. In our previous study, the catch bowl coral Isopora palifera in Tantzei Bay (TZB), Nanwan, Kenting National Park (KNP), southern Taiwan was demonstrated to shuffle thermal-tolerant Symbiodinium D1a and thermal-sensitive Symbiodinium C3 in response to seasonal variations in sea surface temperatures (SSTs) in 2000 and 2001. In this study, we reexamined the temporal dynamics of the Symbiodinium community of I. palifera in TZB in 2006-2009. In addition, spatial variations in Symbiodinium communities in I. palifera were also examined at 6 other sites of Nanwan, KNP in 2009, including a site located at a nuclear power plant outlet (NPP-OL) in southern Taiwan with a yearly mean SST 0.6-1.5 degrees C higher compared to the other sites. Phylotyping and DNA sequence analyses of Symbiodinium ribosomal 28S and ITS2 markers showed that I. palifera colonies at TZB continued to show seasonal shuffling, but shifted to thermal-sensitive type C3 dominant in 2006-2009. This differed from the symbiont community originally dominated by the thermal-tolerant Symbiodinium D1a in 2000 and 2001 after the 1998 mass-bleaching event. Significant differences in spatial variations of the symbiont community in Nanwan were detected with I. palifera colonies at the NPP-OL dominated by Symbiodinium D1a. Our study results suggest that I. palifera can acclimatize to SST anomalies by shuffling to thermal-tolerant Symbiodinium D1a and can revert to thermal-sensitive C3 when the stress disappears, but will maintain the thermally tolerant Symbiodinium D1a as the dominant symbiont if the heat stress continues

A randomized controlled trial of a homeâ based training programme to decrease depression in family caregivers of persons with dementia

AimsThe aim of this study was to explore distinct trajectories of caregiversâ depressive symptoms and the effects of a training programme on these trajectories over 18 months after the programme.BackgroundOverall effects of caregiverâ training programmes on family caregiversâ depressive symptoms have been reported, but few studies explored distinct courses of changes in caregiversâ depressive symptoms and followed up intervention effects on these distinct courses.DesignRandomized clinical trial.MethodsFamily caregivers (n = 116) were randomly assigned into experimental (n = 57) and control (n = 59) groups. The experimental group received the training programme with telephone consultation and the control group received written educational materials and social telephone followâ ups. Caregiversâ depressive symptoms were assessed from June 2009 â March 2012 by selfâ completed questionnaires before, at 2 weeks and 3, 6, 12 and 18 months after the intervention. Groups of individual trajectories were distinguished using groupâ based trajectory modelling.ResultsCaregiversâ depressive symptoms fell into three stable trajectories: nonâ depressed, mildly blue and depressed. After controlling for covariates, caregivers who received the caregiverâ training programme were less likely than those who did not experience persistent depressive symptoms (b = â 1·92, odds ratio = 0·15, P < 0·05).ConclusionDepressive symptoms of family caregivers of persons with dementia were relatively stable and followed three distinct courses: nonâ depressed, mildly blue and depressed. Therefore, caregiversâ depressive symptoms should be assessed as early as possible. Caregivers in the experimental group had a lower probability of persistent depressive symptoms than caregivers in the control group. Therefore, this training programme can be used by healthcare providers for persons with dementia and their caregivers. Trial registration number: NCT02667951.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/136266/1/jan13157.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136266/2/jan13157_am.pd

Impact of cognitive behavior therapy on osteoarthritis-associated pain, insomnia, depression, fatigue, and physical function in patients with knee/hip osteoarthritis: A systematic review and meta-analysis of randomized controlled trials

BackgroundThis meta-analysis aimed at evaluating the efficacy of cognitive behavior therapy (CBT) against osteoarthritis-associated symptoms in patients with knee/hip osteoarthritis.MethodsMedline, PubMed, Cochrane Library, and EMBASE databases were searched from inception to July 2022 to identify randomized controlled trials (RCTs) comparing the efficacy of CBT with other treatment approaches in adults with confirmed knee/hip osteoarthritis. The pain intensity (primary outcome) and the secondary outcomes including insomnia severity, sleep efficiency, physical function as well as the severity of depression and fatigue were assessed at two time points (i.e., immediately after treatment and during the follow-up period). The effect size is expressed as standardized mean difference (SMD) with SMDs of &lt; 0.2, 0.2–0.5, and 0.5–0.8, and &gt; 0.8 representing negligible, small, medium, and large effect sizes, respectively.ResultsFifteen RCTs were included for analysis. Immediately after CBT intervention, meta-analysis showed similar treatment effect in pain severity [SMD = –0.46, 95% confidence interval (CI): –0.95 to 0.04, 11 studies, 1557 participants] and other symptoms including depression (SMD = –0.26, 95% CI: –0.58 to 0.06, five studies, 735 participants), fatigue (SMD = –2.44, 95% CI:–6.53 to 1.65, two RCTs, 511 participants), and physical function (SMD = –0.11, 95% CI:–0.25 to 0.02, five RCTs, 720 participants) between CBT and control groups, while there was an improvement in insomnia severity (SMD = –0.65, 95% CI: –1.06 to –0.24, four RCTs, 639 participants, medium treatment effect) and sleep efficiency (SMD = 0.32, 95% CI: 0.04 to 0.59, three RCTs, 352 patients, small treatment effect). During follow-up, CBT improved pain severity (SMD = –0.52, 95% CI: –1.03 to –0.01, eight studies, 1447 participants, medium treatment effect), insomnia (SMD = –0.43, 95% CI: –0.85 to –0.01, three RCTs, 571 participants, small treatment effect), and depression (SMD = –0.39, 95% CI: –0.59 to –0.18, four RCTs, 791 participants, small treatment effect). Nevertheless, sleep efficiency, fatigue, and physical function were not improved in the follow-up period.ConclusionOur results may suggest the durability of CBT-associated treatment benefits, supporting its role as a potential promising alternative or complementary intervention for patients with knee/hip osteoarthritis, especially against pain and insomnia. Future large-scale investigations are warranted to verify our findings.Systematic review registration[https://www.crd.york.ac.uk/prospero/], identifier [CRD42022331165]

A Dose Escalation Study of Trientine Plus Carboplatin and Pegylated Liposomal Doxorubicin in Women With a First Relapse of Epithelial Ovarian, Tubal, and Peritoneal Cancer Within 12 Months After Platinum-Based Chemotherapy

Background: Epithelial ovarian cancer (EOC) is the leading cause of gynecological cancer-related deaths worldwide. Preclinical studies found that copper-lowering agents could re-sensitize platinum-resistant cancer cells by enhancing the human copper transporter 1 (hCtr1)-mediated uptake of platinum. In the clinic, re-sensitization of platinum-resistance in relapsed EOC has been discovered by the application of trientine plus platinum (NCT01178112). However, no pharmacokinetic data of trientine has been reported in cancer patients.Purpose: Our study aimed to explore the safety and activity of trientine combined with carboplatin and pegylated liposomal doxorubicin (PLD) in patients with EOC, tubal, and peritoneal cancer who experienced disease progression during platinum-based chemotherapy or showed relapse &lt;12 months after completing first-line chemotherapy. Also, we aimed to demonstrate pharmacokinetic parameters and to discover potential biomarkers in our EOC patients.Methods: In this dose escalation study, 18 Asian patients in six dosing cohorts received fixed doses of carboplatin (AUC 4) and PLD (LipoDox®, TTY Biopharm Co. Ltd., Taipei, Taiwan) (40 mg/m2, day 1 per 4-week cycle), and escalated daily trientine doses (range: 300–1800 mg; initiated 7 days before the 1st combination cycle) according to a 3 + 3 design.Results: No dose-limiting toxicity or treatment-related death was observed. Four patients (22.2%) developed grade 3 drug-related adverse events (AEs), whereas no grade 4 AEs were encountered. Anemia and grade 2 dizziness were the most common hematological toxicity and neurotoxicity, respectively. In a pharmacokinetics comparison with healthy volunteers in the literature, our patients achieved greater absorption after oral trientinem, and more rapid elimination of triethylenetetramine dihydrochloride at high doses. The clinical benefit rate was 33.3 and 50.0% in the platinum-resistant and the partially platinum-sensitive group, respectively. A high baseline serum iron level and low serum copper level might help differentiate subgroups of patients with different clinical responses. Nevertheless, no associations of the clinical response with the levels of serum hCtr1, ceruloplasmin, or copper were observed.Conclusion: Combination therapy with carboplatin, trientine, and PLD was well-tolerated and safe. Our results encourage the development of a future phase II trial.Clinical trial registration:ClinicalTrials.gov # NCT03480750

Serologic Status for Pandemic (H1N1) 2009 Virus, Taiwan

We studied preexisting immunity to pandemic (H1N1) 2009 virus in persons in Taiwan. A total of 18 (36%) of 50 elderly adults in Taiwan born before 1935 had protective antibodies against currently circulating pandemic (H1N1) 2009 virus. Seasonal influenza vaccines induced antibodies that did not protect against pandemic (H1N1) 2009 virus

Development of Interstitial Lung Disease Among Patients With Atrial Fibrillation Receiving Oral Anticoagulants in Taiwan.

ImportanceThere are emerging concerns from case reports and pharmacovigilance analyses of a possible risk of interstitial lung disease (ILD) associated with the use of factor Xa (FXa) inhibitors.ObjectiveTo evaluate the risk of incident ILD associated with the use of oral anticoagulants (OACs) in patients with nonvalvular atrial fibrillation (NVAF).Design, setting, and participantsThis nationwide retrospective cohort study used data from the Taiwan National Health Insurance Research Database. Patients with NVAF without preexisting lung disease who received OACs from June 1, 2012, to December 31, 2017, were included. Propensity score stabilized weighting (PSSW) was used to balance covariates across the medication groups (FXa inhibitors, dabigatran, and warfarin, with warfarin as the reference). Patients were followed up from the drug index date until the onset of ILD, death, or end of the study (December 31, 2019), whichever occurred first. Data were analyzed from September 11, 2021, to August 3, 2022.ExposuresPatients with NVAF were treated with FXa inhibitors, dabigatran, or warfarin.Main outcomes and measuresNew-onset idiopathic ILD.ResultsAmong the 106 044 patients (mean [SD] age, 73.4 [11.9] years; 59 995 men [56.6%]) included in the study, 64 555 (60.9%) received FXa inhibitors (apixban [n = 15 386], edoxaban [n = 12 413], and rivaroxaban [n = 36 756]), 22 501 (21.2%) received dabigatran, and 18 988 (17.9%) received warfarin at baseline. The FXa inhibitors were associated with a higher risk of incident ILD (0.29 vs 0.17 per 100 patient-years; hazard ratio, 1.54 [95% CI, 1.22-1.94]; P Conclusions and relevanceResults of this study suggest that FXa inhibitors were associated with lung injury among patients with NVAF who were treated with OACs. Physicians should be vigilant in monitoring for any potential adverse lung outcomes associated with the use of these drugs

The risk of incident atrial fibrillation in patients with type 2 diabetes treated with sodium glucose cotransporter-2 inhibitors, glucagon-like peptide-1 receptor agonists, and dipeptidyl peptidase-4 inhibitors: a nationwide cohort study.

BackgroundAlthough a few meta-analyses were conducted to compare the risk of incident atrial fibrillation (AF) between sodium-glucose cotransporter-2 inhibitor (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP-1RA), and other anti-hyperglycemic agents using indirect or direct comparison, the above analyses showed conflicting results with each other. We aimed to evaluate the risk of new-onset AF associated with the use of SGLT2i, GLP-1RA, and dipeptidyl peptidase-4 inhibitor (DPP4i) among a large longitudinal cohort of diabetic patients.MethodsIn this nationwide retrospective cohort study based on the Taiwan National Health Insurance Research Database, a total of 344,893, 44,370, and 393,100 consecutive patients with type 2 diabetes without preexisting AF receiving GLP-1RA, SGLT2i, and DPP4i, respectively, were enrolled from May 1, 2016, to December 31, 2019. We used 1:1 propensity score matching (PSM) to balance covariates across paired study groups. Patients were followed from the drug index date until the occurrence of AF, death, discontinuation of the index drug, or the end of the study period (December 31, 2020), whichever occurred first.ResultsAfter PSM, there were 245,442, 43,682, and 39,190 paired cohorts of SGLT2i-DPP4i, SGLT2i-GLP-1RA, and GLP-1RA-DPP4i, respectively. SGLT2i treatment was associated with lower risk of new-onset AF in participants with type 2 diabetes compared with either DPP4i [hazard ratio (HR):0.90; 95% confidential interval (CI) 0.84-0.96; P = 0.0028] or GLP-1RA [HR 0.74; 95% CI 0.63-0.88; P = 0.0007] treatment after PSM. There was no difference in the risk of incident AF between GLP-1RA and DPP4i users [HR 1.01; 95% CI 0.86-1.19; P = 0.8980]. The above findings persisted among several important subgroups. Dapagliflozin was specifically associated with a lower risk of new-onset AF compared with DPP4i (P interaction = 0.02).ConclusionsCompared with DPP4i, SGLT2i but not GLP-1RA was associated with a lower risk of incident AF in patients with type 2 diabetes