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1.
Chin J Nat Med ; 19(5): 364-375, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33941341

RESUMO

Huang-Qin Decoction (HQD) is a classic prescription for diarrhea in Chinese medicine treatment. Recent studies have demonstrated that HQD and its modified formulation PHY906 could ameliorate irinotecan (CPT-11) induced gastrointestinal (GI) toxicity and enhance its anticancer therapeutic efficacy. Nevertheless, which constituents in HQD are effective is still unclear so far. The study aims to screen out the key bioactive components combination from HQD that could enhance the anticancer effect of CPT-11. First, the potential bioactive constituents were obtained through system pharmacology strategy. Then the bioactivity of each constituent was investigated synthetically from the aspects of NCM460 cell migration, TNF-α release of THP-1-derived macrophage and MTT assay in HCT116 cell. The contribution of each constituent in HQD was evaluated using the bioactive index Ei, which taken the content and bioactivity into comprehensive consideration. And then, the most contributing constituents were selected out to form a key-component combination. At last, the bioefficacy of the key-component combination was validated in vitro and in vivo. As a result, a key-component combination (HB4) consisting of four compounds baicalin, baicalein, glycyrrhizic acid and wogonin was screened out. In vitro assessment indicated that HB4 could enhance the effect of CPT-11 on inhibiting cell proliferation and inducing apoptosis in HCT116. Furthermore, the in vivo study confirmed that HB4 and HQD have similar pharmacological activity and could both enhance the antitumor effect of CPT-11 in HCT116 xenograft model. Meanwhile, HB4 could also reduce the CPT-11 induced GI toxicity.

2.
Med Sci Monit ; 27: e929911, 2021 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-33935279

RESUMO

BACKGROUND We performed the present study to better elucidate the correlation of reduced folate carrier-1 (RFC1) A80G (rs1051266) polymorphism with the risk of congenital heart disease (CHD). MATERIAL AND METHODS According to the designed search strategy, a systematic literature search was performed through the PubMed, Cochrane Library, Web of Science, EMBASE, CNKI, VIP, and Wan Fang databases to collect published case-control studies on the correlation between RFC1 A80G polymorphism and CHD. All relevant studies up to October 1, 2019 were identified. The odds ratio (OR) and 95% confidence interval (CI) of the genotype distribution were used as the effect indicators. RESULTS A total of 6 eligible studies was finally included in our meta-analysis, including 724 children with CHD, 760 healthy children, 258 mothers of the children with CHD, and 334 mothers of healthy control children. The meta-analysis revealed that for fetal analysis, only in the heterozygous model (GA vs GG, OR=1.36, 95% CI [1.06, 1.75], P=0.02) was RFC1 A80G polymorphism associated with risk of CHD. In maternal analysis, 3 genetic models of RFC1 A80G polymorphism increased the risk of CHD: the allelic model (A vs G, OR=1.36, 95% CI [1.07, 1.71], P=0.01), the homozygote model (AA vs GG, OR=2.99, 95%CI [1.06, 8.41], P=0.04), and the dominance model (GA+AA vs GG, OR=1.53, 95%CI [1.08, 2.16], P=0.02). CONCLUSIONS The maternal RFC1 A80G polymorphism has a strong correlation with CHD. Compared with the G allele, the A allele increases the risk of CHD by 0.36-fold.

3.
Brain Connect ; 2021 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-33947271

RESUMO

Aim The aim of this study was to investigate basic task-fMRI or resting-state fMRI (rs-fMRI) results on Sprague Dawley (SD) rats and Wistar rats under three anesthetic regimes. Introduction SD rats and Wistar rats are the two most commonly used rat strains in medical research and neuroimaging studies. It still lacks a direct comparison of basic task-fMRI and rs-fMRI results between the Wistar rats and SD rats under different anesthetic regimes. Methods Two rat strains and different time points were adopted to investigate task-fMRI activation and rs-fMRI functional connectivity results under three kinds of anesthetic regimes (2~2.5% Isoflurane only, Dexmedetomidine bolus combined with a continuous infusion, and Dexmedetomidine bolus combined with 0.3%-0.5% isoflurane). The electrical forepaw stimulation method and seed-based functional connectivity results were used to compare the task-fMRI brain activation and rs-fMRI functional connectivity patterns between the two rat strains. Results The results showed that Wistar rats had more robust brain activation in task fMRI experiments while exhibiting a less specific inter-hemispheric functional connectivity than that of SD rats under the two dexmedetomidine anesthetic regimes. Moreover, even low-level isoflurane could significantly affect task-fMRI and rs-fMRI results in both rat strains. Conclusions SD and Wistar rats showed different brain activation and inter-hemispheric functional connectivity pattern under the two dexmedetomidine anesthetic regimes. These results may serve as reference information for small animal fMRI studies.

4.
PLoS One ; 16(5): e0250685, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33939740

RESUMO

BACKGROUND: Chinese herbal footbaths are an external therapy of traditional Chinese medicine that has been widely used to treat dysmenorrhea. This review aims to systematically evaluate its efficacy and safety for the treatment of dysmenorrhea. METHODS: Databases of PubMed, EMBASE, Cochrane Library, CIHAHL, Web of Science, Chinese National Knowledge Infrastructure(CNKI), Chinese Scientific Journals Database (VIP), Wanfang Database, China Biomedical Literature Database(CBM), and Chinese Biomedical Literature Service System (SinoMed) will be searched from the inception to September 30, 2020. The eligible randomized controlled trials (RCTs) will be identified and included. The primary outcomes include pain intensity measured by validated scales of visual analog scale, numeric rating scale, and response rate of symptom reduction. The secondary outcomes are scores on validated pain questionnaires, quality of life measured by SF-36 or other validated scales, and adverse events. Study selection, data extraction, and assessment of bias risk will be conducted by two reviewers independently. RevMan software (V.5.3.5) will be utilized to perform data synthesis. Subgroup and sensitivity analysis will be performed when necessary. The strength of the evidence will be evaluated with the Grading of Recommendations Assessment, Development and Evaluation System. RESULTS: A high-quality synthesis of current evidence of Chinese herbal footbaths for patients with dysmenorrhea will be provided in this study. CONCLUSION: This systematic review will provide evidence of whether Chinese herbal footbaths are an effective and safe intervention for the treatment of dysmenorrhea. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020188256.

5.
New Phytol ; 2021 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-33914920

RESUMO

․Lichens play crucial roles in sustaining the functioning of terrestrial ecosystems; however, the diversity and ecological factors associated with lichenized soil fungi remain poorly understood. ․To address this knowledge gap, we used a global field survey including information on fungal sequences of topsoils from 235 terrestrial ecosystems. ․We identified 880 lichenized fungal phylotypes across nine biomes ranging from deserts to tropical forests. The diversity and proportion of lichenized soil fungi peaked in shrublands and dry grasslands. Aridity index, plant cover and soil pH were the most important factors associated with the distribution of lichenized soil fungi. Further, we identified Endocarpon, Verrucaria and Rinodina as some of the most dominant lichenized genera across the globe, and they had similar environmental preferences to the lichenized fungal community. In addition, precipitation seasonality and mean diurnal temperature range were also important in predicting the proportion of these dominant genera. Using this information, we were able to create the first global maps of the richness and the proportion of dominant genera of lichenized fungi. ․This work provides new insight into the global distribution and ecological preferences of lichenized soil fungi, and supports their dominance in drylands across the globe.

6.
Eur J Hum Genet ; 2021 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-33867526

RESUMO

Critically ill coronavirus disease 2019 (COVID-19) is characterized by severe cytokine storms, a hyperinflammatory condition intimately related to the development of fatal outcomes. Why some individuals seem particularly vulnerable to severe cytokine storms is still unknown. Primary immunodeficiency (PID)-related genes are inherited factors that dysregulate host inflammatory responses to infection, especially hemophagocytic lymphohistiocytosis (HLH)-related genes, established as contributors to the development of excessive cytokine storms. We analyzed the association between PID gene variants with severe cytokine storms in COVID-19. We conducted whole-exome sequencing in 233 hospitalized COVID-19 patients and identified four PID gene (UNC13D, AP3B1, RNF168, DHX58) variants were significantly enriched in COVID-19 patients experiencing severe cytokine storms. The total percentage of COVID-19 patients with variants in UNC13D or AP3B1, two typical HLH genes, was dramatically higher in high-level cytokine group than in low-level group (33.3 vs. 5.7%, P < 0.001). Germline variants in UNC13D and AP3B1 were associated with the development of severe cytokine storms, fatal outcomes in COVID-19. These findings advance the understanding of individual susceptibility to severe cytokine storms and help optimize the current management of COVID-19.

7.
Medicine (Baltimore) ; 100(15): e25509, 2021 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-33847668

RESUMO

BACKGROUND: Fasting and caloric restriction have a potential means of anti-inflammatory, as they can decrease the level of systemic inflammation. Although encouraging results have been obtained in animal experiments, there is no consensus on whether these results are applicable to human. The objective of this systematic review and meta-analysis is to analyze the influence of fasting and caloric restriction on inflammation levels in humans. METHODS: The systematic review and meta-analysis will be conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. The following eight databases will be searched:(The retrieval time is from the establishment of each database to December 2020): PubMed, the Cochrane Library, Embase, Web of Science, China National Knowledge infrastructure (CNKI), China Biology Medicine (CBM), Wan Fang Data, the Chinese Science and Technology Periodical Database (VIP). Relevant data will be performed by Revman 5.3 software provided (Cochrane Collaboration) and Stata 14.0 statistical software. RESULTS: The results of this systematic review and meta-analysis will be published in a peer-reviewed journal. CONCLUSIONS: This systematic review will provide evidence to judge the effectiveness of fasting and calorie restriction in human subjects, so as to provide a sound basis for future research and lifestyle promotion. INPLASY REGISTRATION NUMBER: INPLASY202130026.


Assuntos
Restrição Calórica/métodos , Dieta/métodos , Ingestão de Alimentos/fisiologia , Jejum/fisiologia , Inflamação/dietoterapia , Adulto , Feminino , Humanos , Masculino , Metanálise como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Revisões Sistemáticas como Assunto , Adulto Jovem
8.
Anim Sci J ; 92(1): e13551, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33847030

RESUMO

The objective of this study was to investigate whether feeding selenium (Se)-replete cows a Se-yeast supplement in late pregnancy affects nutrient metabolism and inflammatory response during the periparturient period. Twenty cows were randomly assigned to two groups with 10 cows each. Cows in one group received Se-yeast at 0.3 mg Se/kg DM during the last 4 weeks before calving in addition to fed a TMR containing supplemented sodium selenite at 0.3 mg Se/kg DM (Se-yeast), while cows in another group were only fed a TMR containing supplemented sodium selenite at 0.3 mg Se/kg DM (Control). Blood samples were collected and analyzed for nonesterified fatty acids (NEFA), ß-hydroxybutyrate (BHBA), glucose, insulin, tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, IL-6, serum amyloid A (SAA), haptoglobin (Hp), and albumin. In control cows, plasma NEFA, IL-1ß, IL-6, SAA, and Hp levels increased after calving, but glucose, insulin, and albumin levels decreased after parturition. Se-yeast supplemental cows had lower postpartum concentrations of NEFA, TNF-α, IL-1ß, IL-6, SAA, and Hp, and higher postpartum levels of glucose, insulin, and albumin compared with control cows. The results indicate that feeding Se-replete cows a Se-yeast supplement in late pregnancy improves nutrient metabolism and attenuates the inflammatory response after calving.

9.
Biomaterials ; 273: 120792, 2021 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-33872856

RESUMO

The race is on for therapeutic agents that stop cancer. An effective vaccine offers a safe and promising approach for cancer immunotherapy. However, substantial barriers to immunotherapy in cancer vaccines include the low immunogenicity of cancer antigens and the immunosuppression commonly present in solid tumors, resulting in significant challenges for developing a clinically effective cancer vaccine. Here, the state of the art of synergistic therapy, which includes the photothermal effect combined with immunotherapy, was investigated to target tumors. For the first time, indocyanine green (ICG, referred to as I), imiquimod (R837, referred to as R) and a foreign cytotoxic T lymphocyte antigen peptide (CTL-Ap, referred to as Ap) with the sequence of SIINFEKL from ovalbumin (OVA) were encapsulated by acetalated dextran (AcDEX) to form nanoparticles (NPs) averaging 92 nm in diameter as an immunogen. Administration of the resulting multifunctional vaccine I-R-Ap-AcDEX NPs enhanced antitumor cytotoxic T lymphocyte (CTL) immunotherapy. On the one hand, subcutaneous immunization of the NPs allows foreign Ap to enter the major histocompatibility complex class I (MHC-I) cross-presentation pathway of antigen-presenting cells, thereby presenting Ap and eliciting high levels of Ap-specific CTLs. On the other hand, intratumor/intravenous injections of the NPs allow foreign Ap to enter tumor cells and present Ap through the MHC-I cross-presentation pathway. Ap-specific CTLs can kill Ap-presented tumor cells. Furthermore, the NPs generated near-infrared laser triggered the photothermal killing of tumor cells. To our knowledge, this is the first report of AcDEX NPs in antitumor photothermal therapy. Strikingly, systemic administration of the I-R-Ap-AcDEX NPs combined with near-infrared laser irradiation allowed for complete protection to mice from the tumors when applied to two non-OVA tumor models. This quite impressive result displays the great promise of synergistic therapy by the vaccine I-R-Ap-AcDEX NPs, an approach that harnesses the photothermal effect to boost antitumor immunotherapy.

10.
Epilepsy Res ; 174: 106641, 2021 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-33878595

RESUMO

OBJECTIVE: Epilepsy is a common complication in glioma patients after undergoing brain tumor surgery combined with chemotherapy and/or radiotherapy. Whether antiepileptic drug prophylaxis could be used in these patients remains an open question. The purpose of this study was to produce a model for predicting the risk of epilepsy occurrence in such patients. METHODS: The clinicopathologic data of glioma patients after tumor treatment were reviewed in this study. Univariate and multivariate logistic regression analyses were carried out to analyze the correlation between the clinicopathologic data and the risk of epilepsy occurrence. A nomogram was built according to the multivariate logistic regression model results. RESULTS: A total of 219 patients with gliomas were reviewed. Univariate analyses revealed that age, WHO glioma classification, CD34, EGFR, Ki67, MGMT, P53 and VIM were significantly associated with the risk of epilepsy occurrence. Multivariate analyses revealed that age, WHO glioma classification, CD34, EGFR, MGMT, and VIM were predictors of risk of epilepsy occurrence. A nomogram of the risk of epilepsy occurrence was built based on statistically significant variables from the multivariate logistic regression analysis. The c-index of the nomogram was 0.755 (95 % confidence interval (CI), 0.742-0.769). SIGNIFICANCE: This nomogram model provides reliable information about the risk of epilepsy occurrence for oncologists and neurological physicians.

11.
Artigo em Inglês | MEDLINE | ID: mdl-33895906

RESUMO

Six aerobic Gram-negative bacteria were isolated from seawater in Guangdong Province, P.R. China. Cells were observed to be Gram-negative, aerobic, non-motile and non-spore forming. Growth of the designated type strain 19X3-30T occurred at a temperature range of 14-37 °C (optimum, 28 °C), a pH range of 6.0-8.0 (optimum, pH 7) and up to 7.5% NaCl (optimum, 1.5%; w/v), and was enhanced by CO2 and L-cysteine supplementation. The major polar lipids identified in strain 19X3-30T were diphosphatidylglycerol, phosphatidylethanolamine and phosphatidylglycerol. The principal cellular fatty acids profile showed the presence of anteiso-C15:0, anteiso-C17:0 and C18:0 (> 8% of total fatty acids), and the respiratory quinone was ubiquinone 8 (UQ-8). According to the analysis of 16S rRNA gene sequences, these strains represented a novel species within the family Fastidiosibacteraceae, sharing maximum similarities with Cysteiniphilum litorale DSM 101832T (96.6%) and Cysteiniphilum halobium DSM 103992T (95.3%). Phylogenetic dendrograms based on 16S rRNA gene and protein marker genes from the genomic sequences both indicated that the strains formed a monophyletic lineage closely linked to the genus Cysteiniphilum, which was also supported by the UPGMA dendrogram based on the MALDI-TOF MS profile. The genomic DNA G + C contents of six strains ranged from 38.0% to 38.1%. Based on different taxonomic genomic metrics, phylogeny and phenotypic features, we propose that the strains warrant the assignment to a novel species, for which the name Cysteiniphilum marinum sp. nov. is proposed. The type strain is 19X3-30T (= KCTC 82154T = CGMCC 1.18585T).

12.
Micron ; 145: 103060, 2021 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-33799086

RESUMO

Quantification of immuno-gold labeling can provide valuable information on the quantity and localization of a target within a region of interest (ROI). Background subtraction usually requires preparation of material with a deliberately reduced amount of target component often by gene knockout/knockdown. This paper reports a modified method without the need for gene knockout/knockdown, by using a region outside the ROI as a background and non-immune serum to verify the reliability of the data. An optimized parameter for use in image processing was also developed to improve semi-automatic segmentation of gold particles, by using the standard deviation of pixel intensity together with default parameters (size and intensity) to improve specificity. The modified methods were used to quantify the gold labeling of various components within chloroplasts and their 3 sub-organelle compartments (thylakoid, stroma and starch). Rubisco, actin, myosin, ß-tubulin, Endoplasmic reticulum-retention signal HDEL, Sterol methyltransferase 1, and double stranded RNA were all effectively and consistently quantified at the level of the different sub-chloroplast compartments. The approach should be applicable more widely for high resolution labelling of samples in which a background requiring gene knockout/knockdown is not a realistic option.

13.
Anal Chem ; 93(17): 6599-6603, 2021 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-33871967

RESUMO

Due to the widespread use of dinotefuran around the world, its impact on food and environmental safety has aroused great concern, and the establishment of a rapid and convenient approach for dinotefuran detection is necessary but challenging. Herein, we synthesized a unique three-dimensional framework {[(CH3)2NH2]2[Cd3(BCP)2]·10H2O·3.5DMF}n (1). Single-crystal X-ray analysis indicates that 1 possesses a 4,8-connected anion framework that corresponds to alb topology, with a one-dimensional rectangular channel along the c-axis with the size of 4 Å × 10 Å. Compound 1 displays satisfactory solvent and thermal stability. Luminescent investigations reveal that 1 can selectively detect dinotefuran by fluorescence quenching among other pesticides, displaying excellent anti-interference performance with common ions in water. Importantly, the limit of detection is as low as 2.09 ppm, which is far below the residual concentration of the U.S. food standard. A fluorescence quenching mechanism study shows that there exists competitive energy absorption and static quenching processes. To our knowledge, 1 is the first MOF-based fluorescence probe for dinotefuran detection.

14.
Aging (Albany NY) ; 13(7): 10158-10174, 2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33819184

RESUMO

This study examined whether hypoxia-induced microRNA (miRNA) upregulation was related to the inhibition of chondriosome aliphatic acid oxidation in myocardial cells under anoxia. We showed that anoxia induced high expression of hypoxia-inducible factor-1-alpha, muscle carnitine palmitoyltransferase I, and vascular endothelial growth factor in cardiomyocytes. Meanwhile, miR-27 and miR-195 were also upregulated in hypoxia-induced cardiomyocytes. Furthermore, hypoxia induction led to reductions in the adenosine triphosphate (ATP) consumption rate and oxidative metabolism as well as an increase in cardiomyocyte glycolysis. Metabolic reprogramming was reduced by hypoxia, as evidenced by the downregulation of sirtuin 1, forkhead box protein O1, sterol regulatory element-binding protein 1c, ATP citrate lyase, acetyl-coenzyme A carboxylase 2, adiponutrin, adipose triglyceride lipase, and glucose transporter type 4, while miR-27 and miR-195 inhibition partially recovered the expression of these transcription factors. In addition, hypoxia induction reduced cell viability and survival by triggering apoptosis; however, miR-27 and miR-195 inhibition partially increased cell viability. Moreover, miR-27 and miR-195 targeted the 3'untranslated regions of two key lipid-associated metabolic players, peroxisome proliferator-activated receptor gamma and fatty acid synthase. In conclusion, miR-27 and miR-195 are related to hypoxia-mediated ATP levels, glycolysis, oxidation, cell survival, and a cascade of transcription factors that control metabolism in cardiomyocytes.

15.
Anal Chim Acta ; 1157: 338396, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33832593

RESUMO

Exosomal microRNAs (miRNAs) derived from different cells are proposed to be important noninvasive biomarkers for the diagnosis of cardiovascular disease. Recently, sensitive and reliable sensing of exosomal miRNAs has been garnered significant attention. Herein, a novel electrochemical biosensor based on a step polymerization catalytic hairpin assembly (SP-CHA) circuit is designed for exosomal miR-181 detection. Exosomal miR-181 as a trigger, induced SP-CHA process and generated a large number of T shaped concatemers with different length on the electrode surface. These ultra-concatemers could provide a much enhanced signal-to-noise ratio with the linear range from 10 fM to 100 nM and the detection limit of 7.94 fM. Furthermore, this assay was successfully applied to the detection of exosomal miR-181 in serum samples of normal healthy controls and patients with coronary heart disease (CHD) and the results were consistent with those analysis collected from qRT-PCR. The assembly demonstrated great performance in differentiating CHD patients from healthy controls (AUC:0.9867). Collectively, this sensing system possessed high stability and sensitivity with ease of operation and cost efficiency, leading to great potential for exosomal miRNAs detection in cardiovascular disease.

16.
Nat Chem ; 2021 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-33833447

RESUMO

Singlet fission (SF) can potentially boost the efficiency of solar energy conversion by converting a singlet exciton (S1) into two free triplets (T1 + T1) through an intermediate state of a correlated triplet pair (TT). Although efficient TT generation has been recently realized in many intramolecular SF materials, their potential applications have been hindered by the poor efficiency of TT dissociation. Here we demonstrate that this can be overcome by employing a spatially separated 1(T…T) state with weak intertriplet coupling in tetracene oligomers with three or more chromophores. By using transient magneto-optical spectroscopic methods, we show that free-triplet generation can be markedly enhanced through the SF pathway that involves the spatially separated 1(T…T) state rather than the pathway mediated by the spatially adjacent TT state, leading to a marked improvement in free-triplet generation with an efficiency increase from 21% for the dimer to 85% (124%) for the trimer (tetramer).

17.
Bioorg Med Chem Lett ; 43: 128045, 2021 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-33865968

RESUMO

Inhibiting myocardial fibrosis can help prevent cardiovascular diseases, including heart failure. Magnolol (Mag), a natural component of Magnoliae officinalis, has been reported to inhibit fibrosis. However, the mechanism of Mag activity and its effects on myocardial fibrosis remain unclear. Here, we investigated the involvement of ALDH2, an endogenous protective agent against myocardial fibrosis, in the Mag-mediated inhibition of cardiac fibroblast proliferation and collagen synthesis. We found that Mag significantly inhibited cardiac fibroblast proliferation and collagen synthesis, based on the results of MTT, EdU and western blot assays. Moreover, molecular docking, molecular dynamics simulation and surface plasmon resonance (SPR) assays showed that Mag could bind directly and stably to ALDH2. Further analysis of the mechanism of these effects indicated that treatment with Mag dose-dependently enhanced ALDH2 activity without altering protein expression. Mag could enhance the activity of recombinant human ALDH2 proteins with a half-maximal effective concentration of 5.79 × 10-5 M. In addition, ALDH2 activation via Alda-1 inhibited cardiac fibroblast proliferation and collagen synthesis, while ALDH2 inhibition via daidzin partially blocked the suppressive effects of Mag. In summary, Mag may act as a natural ALDH2 agonist and inhibit cardiac fibroblast proliferation and collagen synthesis.

18.
BMC Musculoskelet Disord ; 22(1): 305, 2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33771135

RESUMO

BACKGROUND: Arthroscopic repair is recommended for young patients with full-thickness rotator cuff tears (RCTs), but the healing rates have raised concerns. The Southern California Orthopedic Institute (SCOI) row method has been developed based on greater than 3 decades of experience with excellent clinical outcomes; however, studies with a focus on the younger patient population are limited in number. The current study assessed the short-term clinical outcome and the initial tendon-to-bone healing in a young cohort after repair of a full-thickness RCT using the SCOI row method. METHODS: A retrospective cohort study was performed. Patients < 55 years of age who had a full-thickness RCT and underwent an arthroscopic repair using the SCOI row method were reviewed. Clinical outcomes were assessed at baseline, and 3 and 6 months post-operatively. The visual analog scale (VAS), University of California at Los Angeles (UCLA) scale, and Constant-Murley score were completed to assess pain and function. Active range of motion was also examined, including abduction and flexion of the involved shoulder. A preoperative MRI was obtained to assess the condition of the torn tendon, while 3- and 6-month postoperative MRIs were obtained to assess tendon-to-bone healing. Repeated measurement ANOVA and chi-square tests were used as indicated. RESULTS: Eighty-nine patients (57 males and 32 females) with a mean age of 44.1 ± 8.6 years who met the criteria were included in the study. Compared with baseline, clinical outcomes were significantly improved 3 and 6 months postoperatively based on improvement in the VAS, UCLA score, and Constant-Murley score, as well as range of motion. Greater improvement was also noted at the 6-month postoperative assessment compared to the 3-month postoperative assessment. Three- and six-month postoperative MRIs demonstrated intact repairs in all shoulders and footprint regeneration, which supported satisfactory tendon-to-bone healing. The mean thickness of regeneration tissue was 7.35 ± 0.76 and 7.75 ± 0.79 mm as measured from the 3- and 6-month MRI (P = 0.002). The total satisfactory rate was 93.3 %. CONCLUSIONS: Arthroscopic primary rotator cuff repair of a full-thickness RCT using the SCOI row method in patients < 55 years of age yields favorable clinical outcomes and early footprint regeneration.

19.
Clin Transl Med ; 11(3): e346, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33784005

RESUMO

BACKGROUND: Relapsed/refractory (R/R) multiple myeloma (MM) patients and primary plasma cell leukemia (PCL) have an unfavorable prognosis and no effective treatment. This study was designed to assess the safety and preliminary efficacy of a novel anti-B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T cell in R/R MM and PCL. METHODS: Between February 22, 2017, and June 25, 2018, 28 R/R and two R/R primary PCL patients received a median dose of 11.2 × 106 CAR+ cells/kg. The subjects were refractory to a proteasome inhibitor and/or an immunomodulatory agent. Fludarabine and cyclophosphamide were given as lymphodepletion chemotherapy. RESULTS: Results for these 30 consecutive patients who received an anti-BCMA CAR T cell infusion are reported. The patients had received a median of four prior lines of therapy. A total of 44 different types of adverse events were recorded, and hematologic toxic effects were the most common events of any grade during treatment. Hematologic toxic effects were also the most common events of grade 3 or higher. A total of 29 patients (96.7%) had cytokine release syndrome, which was of grade 1 or 2 in 24 patients (80%) and grade 3 in five patients (16.7%). Neurologic toxic effects only occurred in one patient (3.3%) and were of grade 1. The objective response rate was 90%, and the complete response rate was 43.3%. With a median follow-up of 12.6 months, the median progression-free survival (PFS) and overall survival were 5.2 months and 14.0 months. One of the two primary PCL achieved a complete response with a PFS of 307 days. The other patients achieved a very good partial response with a PFS of 117 days. CONCLUSIONS: Anti-BCMA CAR T cell treatment is safe and highly active in R/R multiple myeloma.

20.
J Mol Diagn ; 2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33781963

RESUMO

We compared chromosomal mosaicism, detected by next-generation sequencing (NGS), during preimplantation genetic testing (PGT) with that detected by single-nucleotide polymorphism (SNP) array-based PGT to assess the pregnancy outcomes associated with both platforms in a retrospective cohort study of patients undergoing in vitro fertilization in a single university-based assisted reproduction center. In total, 6427 blastocysts biopsied from 1513 patients who underwent 2833 oocyte retrievals from January 2017 to February 2019 were identified. The incidence of mosaicism was significantly higher in the NGS-based PGT group than in the SNP array-based PGT group. Furthermore, some aneuploid specimens were affected by mosaicism. The total mosaicism detection rate with NGS-based PGT (23.3%) was significantly higher than that with SNP array-based PGT (7.7%). Mosaicism rates did not vary significantly when stratified by maternal age or PGT type. The SNP array cohort showed a significantly higher spontaneous abortion rate than the NGS cohort (10.07% versus 6.33%; P = 0.0403). The ongoing pregnancy/live birth rate was higher in the NGS cohort (44.1%) than in the SNP array cohort (42.28%). Our results confirm that NGS-based PGT can detect mosaicism more frequently than SNP array-based PGT in trophectoderm specimens; therefore, we expect that clinical application of NGS for PGT can improve pregnancy outcomes compared with that of SNP array-based PGT. More detailed blastocyst detection and classification is necessary to prioritize embryo transfers.

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