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1.
Surg Today ; 2021 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-33846839

RESUMO

PURPOSES: A previous study reported that the ventricular septum is more fragile in geriatric patients, and thus myectomy may expose geriatric patients to a higher risk of serious complications. This single-center study evaluates the impacts of the advanced age on the results following myectomy for symptomatic hypertrophic obstructive cardiomyopathy (HOCM). METHODS: All eligible patients were divided into an elderly group (septuagenarians, n = 35) and a control group (patients under 70 years, n = 197). The patients were followed up for a median of 10 months. Thereafter, the perioperative and follow-up results were compared. RESULTS: Thirteen patients (8.6% for the elderly group and 5.1% for the control group, p = 0.422) underwent immediate repeat surgery. Surgical mortality did not differ between groups (0 vs. 0.5%, p > 0.05). There was no significant difference in the incidence of complete atrioventricular block between groups (5.7 vs. 3.0%, p = 0.346). No follow-up deaths occurred in either group. The maximum gradients at the latest follow-up were significantly lower than the preoperative values in either group. Additionally, grouping (septuagenarians vs. patients under 70 years of age) was not an independent risk factor for surgical complications and results via multivariable logistic regression. CONCLUSIONS: Septuagenarians with HOCM may obtain favorable results following septal myectomy, the same as did HOCM patients under 70 years of age.

3.
J Hematol Oncol ; 14(1): 54, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33794982

RESUMO

N6-methyladenosine (m6A) modification is the most prevalent modification in eukaryotic RNAs while accumulating studies suggest that m6A aberrant expression plays an important role in cancer. HNRNPA2B1 is a m6A reader which binds to nascent RNA and thus affects a perplexing array of RNA metabolism exquisitely. Despite unveiled facets that HNRNPA2B1 is deregulated in several tumors and facilitates tumor growth, a clear role of HNRNPA2B1 in multiple myeloma (MM) remains elusive. Herein, we analyzed the function and the regulatory mechanism of HNRNPA2B1 in MM. We found that HNRNPA2B1 was elevated in MM patients and negatively correlated with favorable prognosis. The depletion of HNRNPA2B1 in MM cells inhibited cell proliferation and induced apoptosis. On the contrary, the overexpression of HNRNPA2B1 promoted cell proliferation in vitro and in vivo. Mechanistic studies revealed that HNRNPA2B1 recognized the m6A sites of ILF3 and enhanced the stability of ILF3 mRNA transcripts, while AKT3 downregulation by siRNA abrogated the cellular proliferation induced by HNRNPA2B1 overexpression. Additionally, the expression of HNRNPA2B1, ILF3 and AKT3 was positively associated with each other in MM tissues tested by immunohistochemistry. In summary, our study highlights that HNRNPA2B1 potentially acts as a therapeutic target of MM through regulating AKT3 expression mediated by ILF3-dependent pattern.

4.
Clin Genet ; 2021 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-33834495

RESUMO

RAPGEF1 is a guanine nucleotide exchange factor responsible for transmitting extracellular signals to the Ras family of GTPase located at the inside of membrane. Here, we report for the first time a homozygous mutation of RAPGEF1 in a consanguineous family with two siblings affected by neuropsychiatric disorder. To confirm the correlation of the mutation and the phenotype, we utilized in silico analysis and established a zebrafish model. Survival rate was reduced in the rapgef1a-knockdown model, and the zebrafish showed global morphological abnormalities, particularly of brain and blood vessels. Co-application of human RAPGEF1 wildtype mRNA effectively rescued the abnormal phenotype, while that of RAPGEF1 mRNA carrying the human mutation did not. This work is the first report of a human Mendelian disease associated with RAPGEF1 and the first report of a zebrafish model built for this gene. The phenotype of zebrafish model provides further evidence that defective RAPGEF1 may lead to global developmental delay in human patients.

5.
BMC Surg ; 21(1): 175, 2021 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-33789634

RESUMO

BACKGROUND: Thyroid fine needle aspiration (FNA) is the procedure of choice in the management of thyroid nodules. Acute thyroid swelling after FNA is a rare complication and is reported in a finite number of literatures. To the best of our knowledge, only seven reported cases exist in literatures. This study describes an addition case with an acute thyroid swelling after FNA, as well as puts forward a new hypothesis of this phenomenon. CASE PRESENTATION: The case is presented of a 30-year-old female with an acute thyroid swelling after FNA, with funicular hypoechoic lesions in thyroid gland. The size of thyroid was 1.5-fold enlarged in the unilateral thyroid gland. No complains of pain or other discomforts with her and no signs of hemorrhage were found along the passage of the fine needle. The episode was recovered spontaneously. CONCLUSIONS: An acute thyroid swelling is a rare complication of FNA. A hypothesis of anaphylactic reaction was suggested in our study. Physicians should pay more attention of this phenomenon and more information is needed to support our hypothesis.


Assuntos
Biópsia por Agulha Fina , Edema , Doenças da Glândula Tireoide , Adulto , Biópsia por Agulha Fina/efeitos adversos , Edema/diagnóstico , Edema/etiologia , Feminino , Humanos , Doenças da Glândula Tireoide/diagnóstico , Doenças da Glândula Tireoide/etiologia
6.
Int Heart J ; 62(2): 329-336, 2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33731518

RESUMO

The reasons of residual left ventricular outflow tract (LVOT) obstruction following alcohol septal ablation (ASA) remain unclear, and outcomes of myectomy following failed ASA remain underreported.Thirteen symptomatic patients (10 women, a median age of 60.0 years) who underwent septal myectomy following failed ASA were reviewed. The patients were followed up for a median of 6 months. The clinical characteristics and outcomes of these patients were analyzed and were compared with those of 178 patients who underwent isolated myectomy without previous ASA at our institution during the same period.In the first ASA procedure, the median number of septal perforator arteries injected was 1.0 with the median value of peak creatine kinase following ablation of 978.5 U/L.Uncontrollable extent and location of infarcted myocardium caused by ablation and mitral subvalvular anomalies were found in four (30.8%) and seven (53.8%) patients, respectively. No operative or follow-up deaths occurred. The median maximum LVOT gradients fell from preoperative 112.0 to 8.5 mmHg at follow-up (P < 0.001). Compared with controls, patients with failed ASA had a higher proportion of mitral subvalvular anomalies (53.8% versus 13.5%, P = 0.001) and developed a higher incidence of complete atrioventricular block following myectomy (15.4% versus 1.7%, P = 0.038).Low institutional or operator experience with ablation, uncontrollable extent and location of infarcted myocardium caused by ablation, and mitral subvalvular anomalies may be reasons for failed ASA. Surgical myectomy for the treatment of residual LVOT obstruction after unsuccessful ASA may be associated with favorable results.


Assuntos
Técnicas de Ablação/efeitos adversos , Procedimentos Cirúrgicos Cardíacos/métodos , Etanol/farmacologia , Septos Cardíacos/cirurgia , Obstrução do Fluxo Ventricular Externo/terapia , Adulto , Idoso , Feminino , Seguimentos , Frequência Cardíaca/fisiologia , Septos Cardíacos/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Falha de Tratamento , Obstrução do Fluxo Ventricular Externo/diagnóstico , Obstrução do Fluxo Ventricular Externo/fisiopatologia
7.
Poult Sci ; 100(5): 101037, 2021 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-33752074

RESUMO

Ochratoxin A (OTA) is a widespread mycotoxin, that has strong thermal stability, and is difficult to remove from feed. OTA is nephrotoxic, hepatotoxic, teratogenic, immunotoxic, and enterotoxic to several species of animals. The gut is the first defense barrier against various types of mycotoxins present in feed that enter the body, and it is closely connected to other tissues through enterohepatic circulation. Compared with mammals, poultry is more sensitive to OTA and has a lower absorption rate. Therefore, the gut is an important target tissue for OTA in poultry. This review comprehensively discusses the role of OTA in gut health and the gut microbiota of poultry, focusing on the effect of OTA on digestive and absorptive processes, intestinal barrier integrity, intestinal histomorphology, gut immunity, and gut microbiota. According to the studies described to date, OTA can affect gut dysbiosis, including increasing gut permeability, immunity, and bacterial translocation, and can eventually lead to gut and other organ injury. Although there are many studies investigating the effects of OTA on the gut health of poultry, further studies are needed to better characterize the underlying mechanisms of action and develop preventative or therapeutic interventions for mycotoxicosis in poultry.

8.
PLoS One ; 16(3): e0248348, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33690649

RESUMO

Pseudoviruses are useful surrogates for highly pathogenic viruses because of their safety, genetic stability, and scalability for screening assays. Many different pseudovirus platforms exist, each with different advantages and limitations. Here we report our efforts to optimize and characterize an HIV-based lentiviral pseudovirus assay for screening neutralizing antibodies for SARS-CoV-2 using a stable 293T cell line expressing human angiotensin converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2). We assessed different target cells, established conditions that generate readouts over at least a two-log range, and confirmed consistent neutralization titers over a range of pseudovirus input. Using reference sera and plasma panels, we evaluated assay precision and showed that our neutralization titers correlate well with results reported in other assays. Overall, our lentiviral assay is relatively simple, scalable, and suitable for a variety of SARS-CoV-2 entry and neutralization screening assays.


Assuntos
/metabolismo , Lentivirus/metabolismo , Testes de Neutralização/métodos , /genética , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Avaliação Pré-Clínica de Medicamentos/métodos , Células HEK293 , Humanos , /patogenicidade , Glicoproteína da Espícula de Coronavírus/genética
9.
Ren Fail ; 43(1): 606-616, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33781160

RESUMO

BACKGROUND: The present meta-analysis of propensity score-matching studies aimed to compare the long-term survival outcomes and adverse events associated with coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) in patients with chronic kidney disease (CKD). METHODS: Electronic databases were searched for studies comparing CABG and PCI in patients with CKD. The search period extended to 13 February 2021. The primary outcome was all-cause mortality, and the secondary endpoints included myocardial infarction, revascularization, and stroke. Odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (CIs) were used to express the pooled effect. Study quality was assessed using the Newcastle-Ottawa scale. The analyses were performed using RevMan 5.3. RESULTS: Thirteen studies involving 18,005 patients were included in the meta-analysis. Long-term mortality risk was significantly lower in the CABG group than in the PCI group (HR: 0.76, 95% CI: 0.70-0.83, p < .001), and similar results were observed in the subgroup analysis of patients undergoing dialysis and for different estimated glomerular filtration rate ranges. The incidence rates of myocardial infarction (OR: 0.25, 95% CI: 0.12-0.54, p < .001) and revascularization (OR: 0.17, 95% CI: 0.08-0.35, p < .001) were lower in the CABG group than in the PCI group, although there were no significant differences in the incidence of stroke between the two groups (OR: 1.24; 95% CI: 0.89-1.73, p > .05). Subgroup analysis among patients on dialysis yielded similar results. CONCLUSIONS: Our propensity score matching analysis revealed that, based on long-term follow-up outcomes, CABG remains superior to PCI in patients with CKD.

10.
BMC Womens Health ; 21(1): 99, 2021 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-33676505

RESUMO

BACKGROUND: The present study aims to use two different kinds of filling materials, oxidized regenerated cellulose and gelatin sponge, to repair defects of breast-conserving surgery due to breast cancer, and compare the clinical efficacy, cosmetic effect and complication rate among groups. METHODS: A total of 125 patients, who had breast -conserving surgery due to breast cancer, were enrolled into the present study. Postoperative efficacy was assessed by a doctor and patient, according to the Harvard/NSABP/RTOG Breast Cosmetic Grading Scale. RESULTS: Among these patients, 41 patients received conventional breast-conserving surgery, and 84 patients received breast-conserving surgery plus filling implantation (41 patients in the oxidized regenerated cellulose group and 43 patients in the gelatin sponge group). All patients had small to medium sized breasts (cup size A and B). The average weight of tumor tissues was 56.61 ± 11.57 g in the conventional breast-conserving surgery group, 58.41 ± 8.53 g in the oxidized regenerated cellulose group, and 58.77 ± 9.90 g in the gelatin sponge group. The difference in pathological factors, average operation time, length of stay and local infection rate was not statistically significant among the three groups. 18 patients in the oxidized regenerated cellulose group and 15 patients in the gelatin sponge group were evaluated to have a good cosmetic effect by the surgeon and patient, while 12 patients in the conventional breast-conserving surgery group were evaluated to be have good cosmetic effect by the surgeon and patient. The cosmetic effects in the oxidized regenerated cellulose group and gelatin sponge group were comparable, and these were superior to those in the conventional breast-conserving surgery group. CONCLUSION: The use of oxidized regenerated cellulose and gelatin sponge is a feasible approach for defect repair after breast-conserving surgery.

11.
J Cardiothorac Surg ; 16(1): 25, 2021 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-33731165

RESUMO

BACKGROUND: Although septal myectomy is a standard strategy for managing patients with hypertrophic obstructive cardiomyopathy (HOCM) and drug-refractory symptoms, so far, only a few experienced myectomy centers exist globally. Mainly, this can be explained by the many technical challenges presented by myectomy. From our clinical experience, applying the mini-invasive surgical instruments during myectomy potentially reduces the technical difficulty. This study reports the preliminary experience regarding transaortic septal myectomy using mini-invasive surgical instruments for managing patients with HOCM and drug-refractory symptoms; also, we evaluate the early results following myectomy. METHODS: Between March 2016 and March 2019, consecutive HOCM patients who underwent isolated transaortic septal myectomy using the mini-invasive surgical instruments were enrolled in this analysis. Intraoperative, in-hospital and follow-up results were analyzed. RESULTS: We included 168 eligible patients (83 males, mean 56.8 ± 12.3 years). The midventricular obstruction was recorded in 7 (4.2%) patients. All patients underwent transaortic septal myectomy with a mean aortic cross-clamping time of 36.0 ± 8.1 min. During myectomy, 9 (5.4%) patients received repeat aortic cross-clamping. Surgical mortality was 0.6%. Notably, 5 (3.0%) patients developed complete atrioventricular block, they needed permanent pacemaker implantation. The median follow-up time was 6 months; however, no follow-up deaths occurred with a significant improvement in New York Heart Association functional status. We reported a sharp decrease in the maximum gradients from the preoperative value (11.6 ± 7.4 mmHg vs. 94.4 ± 22.6 mmHg, p < 0.001). The median degree of mitral regurgitation fell to 1.0 (vs. 3.0 preoperatively, p < 0.001) with a significant reduction in the proportion of moderate or more regurgitation (1.2% vs. 57.7%, p < 0.001). CONCLUSIONS: Mini-invasive surgical instruments may be beneficial in reducing the technical challenges of transaortic septal myectomy procedure. Of note, transaortic septal myectomy using the mini-invasive surgical instruments may present with favorable results.

12.
ACS Nano ; 15(3): 4608-4616, 2021 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-33625839

RESUMO

The transport of nanoparticles in semiflexible networks, which form diverse principal structural components throughout living systems, is important in biology and biomedical applications. By combining large-scale molecular simulations as well as theoretical analysis, we demonstrate here that nanoparticles in polymer networks with semiflexible strands possess enhanced heterogeneous diffusion characterized by more evident hopping dynamics. Particularly, the hopping energy barrier approximates to linear dependence on confinement parameters in the regime of moderate rigidity, in contrast to the quadratic dependence of both its soft and hard counterparts. This nonmonotonic feature can be attributed to the competition between the conformation entropy and the bending energy regulated by the chain rigidity, captured by developing an analytical model of a hopping energy barrier. Moreover, these theoretical results agree reasonably well with previous experiments. The findings bear significance in unraveling the fundamental physics of substance transport confined in network-topological environments and would provide an explanation for the dynamics diversity of nanoparticles within various networks, biological or synthetic.

13.
J Int Med Res ; 49(2): 300060520982828, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33530808

RESUMO

Large bowel perforation is an acute abdominal emergency requiring rapid diagnosis for proper treatment. The high mortality rate associated with large bowel perforation underlines the importance of an accurate and timely diagnosis. Computed tomography is useful for diagnosis of ingested foreign bodies, and endoscopic repair using clips can be an effective treatment of colon perforations. We herein describe a 78-year-old man with sigmoid colon perforation caused by accidental swallowing of a jujube pit. The jujube pit had become stuck in the wall of the sigmoid colon and was successfully removed by colonoscopy, avoiding an aggressive surgery. As a result of developments in endoscopic techniques, endoscopic closure has become a feasible option for the management of intestinal perforation.

14.
J Colloid Interface Sci ; 590: 424-435, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33561592

RESUMO

The development of easily recyclable non-noble metal plasmonic photocatalysts with high performance is highly desired for the removal of Cr(VI). Herein, the in-situ growth of plasmonic-bismuth (Bi) combined with magnetic ferroferric (Fe3O4) nanoparticles on biochar (BC) was realized by a facile high temperature calcination. BC/Bi/Fe3O4 exhibits broad photoabsorption from 200 to 2000 nm. The weaker photoluminescence (PL) spectrum or stronger photocurrent density confirmed its higher separation efficiency of photogenerated carriers than that of BC or Bi/Fe3O4. Under visible light irradiation, BC/Bi/Fe3O4 exhibits excellent adsorption-photocatalytic performance for Cr(VI) (95%) in 180 min. With BC/Bi/Fe3O4 as a working electrode, the higher removal efficiency (97%) was achieved than that using BC/Bi (65%), BC/Fe3O4 (79%) or Bi/Fe3O4 (66%) after 160 min under visible light irradiation, rooting from wide spectral absorption and efficient separation of photogenerated carriers. BC/Bi/Fe3O4 can be easily recycled by magnetism with good stability. This work not only provides ideas for the preparation of surface plasma resonance (SPR) semiconductor photocatalyst for removing heavy metal, but also realizes the resource utilization of agricultural and forestry waste.

15.
BMC Pediatr ; 21(1): 62, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33522911

RESUMO

BACKGROUND: To explore the association between cesarean section (CS) and risk of autism spectrum disorder (ASD), and evaluate the possible factors influencing this association. METHODS: In total, 950 patients diagnosed with ASD and 764 healthy controls were recruited in this study. Socio-demographic characteristics and prenatal, perinatal, and neonatal characteristics were compared between the two groups. Univariate and multivariable conditional logistic regression analyses were applied to adjust for confounders. Further stratified analyses based on sex and miscarriage history were similarly performed to explore the factors influencing the association between CS and ASD. RESULTS: CS was evidently associated with an elevated risk of ASD (adjusted odds ratio [aOR] = 1.606, 95% confidence interval (CI) = 1.311-1.969). Unlike regional anesthesia (RA), only CS performed under general anesthesia (GA) consistently elevated the risk of ASD (aOR = 1.887, 95% CI = 1.273-2.798) in females and males in further stratified analysis. The risk of children suffering from ASD following emergency CS was apparently increased in males (aOR = 2.390, 95% CI = 1.392-5.207), whereas a higher risk of ASD was observed among voluntary CS and indicated CS subgroups (aOR = 2.167, 95% CI = 1.094-4.291; aOR = 2.919, 95% CI = 1.789-4.765, respectively) in females. Moreover, the interaction term of CS and past miscarriage history (ß = - 0.68, Wald χ2 = 7.5, df = 1, p = 0.006)) was similarly defined as influencing ASD. CONCLUSIONS: The exposure of children to GA during CS may explain the possible/emerging association between CS and ASD. In addition, sex and miscarriage history could equally be factors influencing the association between CS and ASD.

16.
BMC Psychiatry ; 21(1): 70, 2021 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-33535976

RESUMO

BACKGROUND: This study aimed to investigate the influence of CYP2D6 polymorphisms on risperidone plasma concentrations in patients with schizophrenia. Based on pharmacogenomics, we examined whether plasma concentration of risperidone is associated with clinical response and adverse side-effects. METHODS: We recruited patients with chronic schizophrenia who were then treated with risperidone. The CYP2D6 genotypes were determined using targeted sequencing. All high-frequency mutation sites of the nine exons of the gene were assayed in the present study. Plasma concentrations of risperidone and 9-hydroxyrisperidone (9-OH-RIS) were measured using high-performance liquid chromatography (HPLC). Psychiatric symptoms were monitored using The Positive and Negative Syndrome Scale (PANSS), Brief Psychiatric Rating Scale (BPRS), and Clinical Global Impression (CGI). Adverse effects were evaluated using the Barnes Akathisia Scale (BAS) and Extrapyramidal Symptom Rating Scale (ESRS). Follow-up visits were scheduled at weeks 2,4, and 8 after treatment initiation. RESULTS: Among the 76 patients, 100 C > T (rs1065852), 1038 C > T (rs1081003), 1662 G > C (rs1058164), 2851 C > T (rs16947), and 4181G > C (rs1135840) variants were detected. The most common allele was CYP2D6*10 (81.6%), whereas CYP2D6*2 (9.2%) and CYP2D6*5 (17.1%) were relatively rare. Plasma levels of risperidone and the risperidone/9-OH risperidone ratio (R/9-OH) were significantly increased in individuals with CYP2D6*10 (P < 0.05). The change in PANSS score, weight, high-density lipoprotein (HDL) level, prolactin (PRL) level, and ESRS were significantly different from baseline, between the different genotypes (P < 0.01). Moreover, individuals with CYP2D6*10 homozygous (TT) mutations were associated with higher risperidone concentration and R/9-OH ratio than those with heterozygous mutations (CT) (P < 0.01). A change from baseline in BPRS scores was observed only during week 8 and was different between heterozygous and homozygous mutations. As for the C2851T polymorphism, the incidence of adverse metabolic effects was significantly different between the C/C and C/T genotypes (P < 0.01). Regarding the G4181C polymorphisms, the changes from baseline in GLU and TG, were different between the C/C and C/G genotypes (P < 0.01). CONCLUSIONS: The genotype of CYP2D6 significantly influences the plasma concentration of risperidone and may subsequently influence the adverse side-effects following risperidone treatment, while also exerting a slight influence on clinical outcomes.

17.
Int J Biol Macromol ; 177: 422-429, 2021 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-33631260

RESUMO

We isolated and purified a pectin from Portulaca oleracea L. (P. oleracea), and analysed its structure by high-performance size exclusion chromatography (HPSEC), high-performance liquid chromatography (HPLC), gas chromatograph-mass spectrometer (GC-MS), fourier transform infrared spectroscopy (FT-IR), and 1H, 13C nuclear magnetic resonance spectroscopy (NMR). The data indicated that this pectin (designated as POPW-HG) was a linear non-esterified homogalacturonan, which is unique in plants; its molecular weight was around 41.2 kDa. Meanwhile, POPW-HG as an adjuvant was evaluated in the mice immunized with OVA subcutaneously. OVA-specific antibody titres from the sera of immunized mice were tested by ELISA. It showed that POPW-HG significantly enhanced OVA-specific antibody titres (IgG, IgG1, and IgG2b) (p < 0.05) in a dose-dependent manner in the OVA-immunized mice, preliminarily indicating POPW-HG could increase an antibody response, Th1 and Th2 immune response. In addition, the ratio of IgG1/IgG2b suggested POPW-HG induced a Th2-biased response in the OVA-immunized mice. The results demonstrated POPW-HG could be a potential adjuvant candidate in vaccines.

18.
Trials ; 22(1): 159, 2021 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-33622382

RESUMO

BACKGROUND: Atypical antipsychotic medications, which are effective for the treatment of schizophrenia and bipolar disorder, are associated with features of metabolic syndrome, such as weight gain, hyperglycemia, dyslipidemia, and insulin resistance. Although there are a few studies on the effects of dietary fiber or probiotics on weight loss in obese people, no published trials have reported the efficacy of dietary fiber and probiotics on reducing atypical antipsychotic-induced weight gain. METHODS: For this 12-week randomized, double-blind, placebo-controlled study, 100 patients with a weight gain of more than 10% after taking atypical antipsychotic medications were recruited. Participants were randomized to four groups as follows: probiotics (840 mg twice daily (bid)) plus dietary fiber (30 g bid), probiotics (840 mg bid) plus placebo, placebo plus dietary fiber (30 g bid), or placebo group. The primary outcome was the change in body weight. Secondary outcomes included changes in metabolic syndrome parameters, appetite score, biomarkers associated with a change in weight, and gut microbiota composition and function. DISCUSSION: To date, this is the first randomized, placebo-controlled, double-blinded trial investigating the efficacy of dietary fiber and probiotics alone and in combination to reduce metabolic side effects induced by atypical antipsychotic medications. If effective, it is possible to conclude that dietary fiber and probiotics can reduce atypical antipsychotic-induced metabolic side effects. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT03379597 . Registered on 19 November 2017.

19.
Signal Transduct Target Ther ; 6(1): 78, 2021 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-33623018

RESUMO

The abnormal regulation of alternative splicing is usually accompanied by the occurrence and development of tumors, which would produce multiple different isoforms and diversify protein expression. The aim of the present study was to conduct a systematic review in order to describe the regulatory mechanisms of alternative splicing, as well as its functions in tumor cells, from proliferation and apoptosis to invasion and metastasis, and from angiogenesis to metabolism. The abnormal splicing events contributed to tumor progression as oncogenic drivers and/or bystander factors. The alterations in splicing factors detected in tumors and other mis-splicing events (i.e., long non-coding and circular RNAs) in tumorigenesis were also included. The findings of recent therapeutic approaches targeting splicing catalysis and splicing regulatory proteins to modulate pathogenically spliced events (including tumor-specific neo-antigens for cancer immunotherapy) were introduced. The emerging RNA-based strategies for the treatment of cancer with abnormally alternative splicing isoforms were also discussed. However, further studies are still required to address the association between alternative splicing and cancer in more detail.

20.
Cell Death Dis ; 12(2): 206, 2021 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-33627630

RESUMO

Steroid 5α-reductase type I (SRD5A1) is a validated oncogene in many sex hormone-related cancers, but its role in multiple myeloma (MM) remains unknown. Based on gene expression profiling (GEP) of sequential MM samples during the disease course, we found that the aberrant expression of SRD5A1 was correlated with progression and poor prognosis in MM patients. In this study, the oncogenic roles of SRD5A1 were validated in human MM cell lines (ARP1 and H929) and the xenograft MM model as well as the 5TMM mouse model. MTT and flow cytometry were used to assess MM cell proliferation, cell cycle, and apoptosis post inducible knockdown SRD5A1 by lentivirus-mediated short-hairpin RNA (shRNA). Transcriptomic sequencing, immunofluorescence, and western blot were used to investigate the effects of SRD5A1 suppression on cell apoptosis and autophagy. Mechanistically, SRD5A1 downregulation simultaneously regulated both the Bcl-2 family protein-mediated apoptosis and the autophagic process via PI3K/Akt/mTOR signaling pathway in MM cells. Meanwhile, the autophagy inhibitor (3-methyladenine) and SRD5A1 inhibitor (Dutasteride) were utilized to evaluate their anti-myeloma effect. Thus, our results demonstrated that SRD5A1 downregulation simultaneously regulated both the apoptosis and the autophagic process in MM cells. The dual autophagy-apoptosis regulatory SRD5A1 may serve as a biomarker and potential target for MM progression and prognosis.

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