Ganoderma lucidum Extracts Inhibited Leukemia WEHI-3 Cells in BALB/c Mice and Promoted an Immune Response in Vivo

[[abstract]]Ganoderma lucidum (G. lucidum) is a medicinal mushroom having biological effects such as immuno-modulation and anti-tumor actions. In China and many other Asian countries, G. lucidum is used as a folk remedy to promote health and longevity. Although many studies have shown that G. lucidum modulates the immune system, including, for example, antigen-presenting cells, natural killer (NK) cells, and the T and B lymphocytes, the effects of G. lucidum on the WEHI-3 leukemic BALB/c mice are unclear. We attempted to determine whether G. lucidum would promote immune responses in BALB/c mice injected with WEHI-3 leukemia cells. The effects of G. lucidum on the survival rate of WEHI-3 leukemia cells injected into BALB/c mice were examined. It increased the percentages of CD3 and CD19, but decreased, the percentages of Mac-3 and CD11b markers, suggesting that differentiation of the precursor of T and B cells was promoted but macrophages were inhibited. It decreased the weight of spleens as compared with control mice. It also promoted phagocytosis by macrophage from peripheral blood mononuclear cell (PBMC) and it also promoted natural killer cell activity. It decreased the percentage of leukemia cells in the spleens of mice before they were injected with WEHI-3 cells. Apparently, G. lucidum affects murine leukemia WEHI-3 cells in vivo

Gandoderma lucidum Extract Promotes Immune Responses in Normal BALB/c Mice In Vivo

[[abstract]]Enhanced fruit and vegetable consumption is closely related to reduced cancer incidence as shown in epidemiological studies. Ganoderma lucidum, one of the most well-known traditional Chinese medicines, has been demonstrated to have pharmacological activities and antitumor effects, in Asian populations. However, the promotion of immune responses in normal BALB/c mice is unclear. In the present study, we investigated the immune responses of BALB/c mice after treatment with G. lucidum extract in vivo. The results demonstrated that G. lucidum extract was able to promote the proliferation of splenocytes under Concanavalin A or lipopolysaccharide stimulation. Compared with the control group, phagocytosis of macrophage was significantly enhanced by intraperitoneal administration of G. lucidum extract at both 3 and 6 mg/kg. Compared with the control group, natural killer cell activity was significantly enhanced by intraperitoneal administration of G. lucidum extract (6 mg/kg). Results of cytometric bead array and flow cytometry indicated that the expressions of interleukin-6 and interferon-gamma also increased (p<0.001) by treatment with G. lucidum extract (3 and 6 mg/kg). In conclusion, the findings of this study implied that G. lucidum extract was able to effectively promote immune responses in BALB/c mice

Physicochemical characteristics and toxicity of surface-modified zinc oxide nanoparticles to freshwater and marine microalgae

published_or_final_versio

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

Direct Oral Anticoagulants in Atrial Fibrillation Patients With Concomitant Hyperthyroidism

Objective Patients with hyperthyroidism were excluded from randomized clinical trials of direct oral anticoagulants(DOACs) for stroke prevention in patients with non-valvular atrial fibrillation (NVAF). Methods We performed a nationwide retrospective cohort study using data from the Taiwan National Health Insurance Research Database. We enrolled 3,213 and 1,181 NVAF patients with hyperthyroidism taking DOACs and warfarin, respectively, from June 1, 2012 to December 31, 2017. We also enrolled 53,591 and 16,564 NVAF patients without hyperthyroidism taking DOACs and warfarin, respectively. We used propensity score-based stabilized weights (PSSWs) to balance covariates across the study groups. We also used 1:4 matching on both taking DOACs, with (n=3,213) and without hyperthyroidism (n=12,852); and both taking warfarin, with (n=1,181) and without hyperthyroidism (n=4,724). Results After PSSW, DOAC had a comparable risk of ischemic stroke/systemic embolism (IS/SE) and a lower risk of major bleeding (hazard ratio (HR):0.65; [95% confidential interval (CI):0.44-0.96]; P=0.0295) than warfarin among patients with hyperthyroidism. There were comparable risks of IS/SE and major bleeding between those patients with and without hyperthyroidism. However, patients taking warfarin with hyperthyroidism had a lower risk of IS/SE than those without hyperthyroidism (HR:0.61; [95%CI:0.43-0.86]; P=0.0050). Conclusion Among NVAF Asian patients with concomitant hyperthyroidism, DOACs may be an effective and safer alternative to warfarin. Thromboprophylaxis with DOACs may be considered for such patients, and it is important to validate this finding in further prospective study.Supplemental materials (figures and tables) for the article of "Direct Oral Anticoagulants in Atrial Fibrillation Patients with Concomitant Hyperthyroidism" Funding provided by: Chang Gung Memorial HospitalCrossref Funder Registry ID: http://dx.doi.org/10.13039/100012553Award Number: CMRPG3G1371-3Funding provided by: Chang Gung Memorial HospitalCrossref Funder Registry ID: http://dx.doi.org/10.13039/100012553Award Number: CMRPG3F0991-3Funding provided by: Chang Gung Memorial HospitalCrossref Funder Registry ID: http://dx.doi.org/10.13039/100012553Award Number: CMRPD1K0031Funding provided by: Chang Gung Memorial HospitalCrossref Funder Registry ID: http://dx.doi.org/10.13039/100012553Award Number: CMRPG3K0021We performed a nationwide retrospective cohort study using data from the Taiwan National Health Insurance Research Database. We enrolled 3,213 and 1,181 NVAF patients with hyperthyroidism taking DOACs and warfarin, respectively, from June 1, 2012 to December 31, 2017

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

A Method for Structure–Activity Analysis of Quorum-Sensing Signaling Peptides from Naturally Transformable Streptococci

Many species of streptococci secrete and use a competence-stimulating peptide (CSP) to initiate quorum sensing for induction of genetic competence, bacteriocin production, and other activities. These signaling molecules are small, unmodified peptides that induce powerful strain-specific activity at nano-molar concentrations. This feature has provided an excellent opportunity to explore their structure–function relationships. However, CSP variants have also been identified in many species, and each specifically activates its cognate receptor. How such minor changes dramatically affect the specificity of these peptides remains unclear. Structure–activity analysis of these peptides may provide clues for understanding the specificity of signaling peptide–receptor interactions. Here, we use the Streptococcus mutans CSP as an example to describe methods of analyzing its structure–activity relationship. The methods described here may provide a platform for studying quorum-sensing signaling peptides of other naturally transformable streptococci