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1.
BMC Palliat Care ; 20(1): 152, 2021 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-34627225

RESUMO

BACKGROUND: Among the few existing needs assessment tools for family carers, the 14-item Carer Support Needs Assessment Tool (CSNAT) is the only brief and holistic needs screening tool designed for everyday use in palliative care practices. The aim of this study was to evaluate the reliability, validity, and acceptability of the traditional Chinese version of the CSNAT in palliative care settings in Hong Kong. METHODS: This adopted a cross-sectional and correlation design with repeated measures. The participants were 125 family carers of palliative cancer patients and 10 healthcare providers (HCPs) that were recruited from two local hospitals. The evaluation of psychometric properties included the following: (1) content validity through HCPs including frontline physicians, nurses, social workers, and clinical psychologists; (2) construct validity between the CSNAT items and those of the validated tools that measured caregiver burden, social support, and caregiving self-efficacy; and (3) one-week test-retest reliability in a sub-sample of 81 caregivers. The acceptability of the tool was assessed by the carers using several closed-ended questions. RESULTS: The content validity index of the CSNAT at the scale level was 0.98. Each item of the CSNAT was significantly and moderately correlated with caregiver burden (Spearman's r = 0.24 to 0.50) and caregiving self-efficacy (r = - 0.21 to - 0.52), but not for social support. All CSNAT items had fair to moderate test-retest reliability (weighted kappa = 0.21 to 0.48), with the exception of two items "managing your relatives' symptoms, including giving medicines" and "having time for yourself in the day". Regarding the acceptability of the CSNAT, almost all HCPs were willing to use the CSNAT for carer assessment and support. 89.6% of the carers demonstrated a comprehensibility of the CSNAT tool and 92.9% felt comfortable answering the questions. Around 90% of the carers agreed to use the tool for screening, discussing needs, and making referrals. CONCLUSION: The traditional Chinese version of the CSNAT is a tool with high validity and acceptability and adequate reliability that measures family carers' support needs, which should be considered for wide application in local palliative care practices.

2.
J Hematol Oncol ; 14(1): 161, 2021 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-34627333

RESUMO

BACKGROUND: BCMA-specific chimeric antigen receptor-T cells (CAR-Ts) have exhibited remarkable efficacy in refractory or relapsed multiple myeloma (RRMM); however, primary resistance and relapse exist with single-target immunotherapy. Bispecific CARs are proposed to mitigate these limitations. METHODS: We constructed a humanized bispecific BM38 CAR targeting BCMA and CD38 and tested the antimyeloma activity of BM38 CAR-Ts in vitro and in vivo. Twenty-three patients with RRMM received infusions of BM38 CAR-Ts in a phase I trial. RESULTS: BM38 CAR-Ts showed stronger in vitro cytotoxicity to heterogeneous MM cells than did T cells expressing an individual BCMA or CD38 CAR. BM38 CAR-Ts also exhibited potent antimyeloma activity in xenograft mouse models. In the phase I trial, cytokine release syndrome occurred in 20 patients (87%) and was mostly grade 1-2 (65%). Neurotoxicity was not observed. Hematologic toxicities were common, including neutropenia in 96% of the patients, leukopenia in 87%, anemia in 43% and thrombocytopenia in 61%. At a median follow-up of 9.0 months (range 0.5 to 18.5), 20 patients (87%) attained a clinical response and minimal residual disease-negativity (≤ 10-4 nucleated cells), with 12 (52%) achieving a stringent complete response. Extramedullary plasmacytoma was eliminated completely in 56% and partially in 33% and of 9 patients. The median progression-free survival was 17.2 months. Two relapsed patients maintained BCMA and CD38 expression on MM cells. Notably, BM38 CAR-Ts cells were detectable in 77.8% of evaluable patients at 9 months and 62.2% at 12 months. CONCLUSION: Bispecific BM38 CAR-Ts were feasible, safe and significantly effective in patient with RRMM. TRIAL REGISTRATION: Chictr.org.cn ChiCTR1800018143.

3.
Medicine (Baltimore) ; 100(40): e27371, 2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34622838

RESUMO

BACKGROUND: Anemia in patients with chronic kidney disease (CKD) presents significant impacts on patients, the health-care system, and financial resources. Therefore, this study aimed to identify the risk factors of anemia among CKD patients. METHODS: This meta-analysis was conducted in accordance with the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols statement guidelines. Studies were identified through systematic searches in September 2021 with no restrictions on date and time, and publication status using the following bibliographic databases: Embase, Medline, PubMed, Web of Science, Science Direct, and the Cochrane Library. The search was conducted using the following terms and phrases: "anemia", "risk factors", "associated factors", "chronic kidney injury", "chronic kidney disease", and "chronic renal insufficiency". The quality of each included study was assessed according to the Newcastle-Ottawa scale. Meta-analysis was performed using STATATM version 14 statistical software for WindowsTM. RESULTS: The results of this systematic review and meta-analysis will be published in a peer-reviewed journal. CONCLUSION: This meta-analysis may help policymakers and program managers design evidence-based interventions on preventing the occurrence of anemia with CKD patient populations.


Assuntos
Anemia/etiologia , Insuficiência Renal Crônica/complicações , Humanos , Metanálise como Assunto , Fatores de Risco , Revisões Sistemáticas como Assunto
4.
Int Immunopharmacol ; 101(Pt B): 108259, 2021 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-34666303

RESUMO

Depression is a prevalent mental disorder. However, its pathophysiological mechanism has still remained elusive, and a limited number of effective treatments have been presented. Recent studies have shown that neuroinflammation and microglial activation are involved in the pathogenesis of depression. Histone deacetylase 3 (HDAC3) has neurotoxic effects on several neuropathological conditions. The inhibition of HDAC3 has been reported to induce anti-inflammatory and antioxidant effects. RGFP966 is a highly selective inhibitor of HDAC3. This study aimed to investigate the antidepressant effect of RGFP966 on lipopolysaccharide (LPS)-induced depressive-like behaviors in mice and to explore its possible mechanism. Adult male C57BL/6J mice were utilized in this study. The LPS and RGFP966 were injected intraperitoneally daily for 5 days. The behavior tests were performed to elucidate the depression-like behaviors. Western blot, ELISA and immunofluorescence staining were used to study the HDAC3/TLR4/NLRP3 pathway-related proteins. The results of behavioral tests showed that RGFP966 could improve the LPS-induced depressive-like behaviors in mice. The results of Western blotting showed that RGFP966 treatment downregulated the expression levels of toll-like receptor 4 (TLR4), nucleotide-binding oligomerization domain-like receptor pyrin domain-containing-3 (NLRP3), caspase-1, and interleukin-1ß (IL-1ß) (P < 0.05). Furthermore, the results of immunofluorescence staining showed that RGFP966 treatment inhibited microglial activation in the hippocampus of mice (P < 0.01). These findings suggested that RGFP966 could effectively ameliorate LPS-induced depressive-like behaviors in mice by inhibiting neuroinflammation and microglial activation. The anti-inflammatory mechanism of RGFP966 might be related to the inhibition of the HDAC3/TLR4/NLRP3 signaling pathway. Therefore, inhibition of HDAC3 using RGFP966 could serve as a potential treatment strategy for depression.

5.
Mar Pollut Bull ; 173(Pt A): 113019, 2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34627031

RESUMO

The grain size and heavy metals (Cu, Pb, Zn, Cr, Cd, and Hg) in 42 seafloor and eight river sediments from the Kompong Som Bay of Cambodia were analyzed to identify sediment characteristics and environmental quality. The high-value areas for all the metals were mainly distributed in the northern and central parts of the bay, occupied by fine-grained sediments. There was slightly to moderately severe enrichment of Pb, Cd, and Hg in the southern and western coastal areas of Sihanoukville. Although the current ecological environment risk was relatively low, the coastal areas of Sihanoukville had low to moderate pollution of Pb, Cd, and Hg, which were closely related to pollutant emissions from the industrial production from power plants and oil refineries. It is recommended to establish a normalized monitoring mechanism and control the discharge of coastal pollutants to ensure the sustainable development of the coastal environment.

6.
Nat Prod Res ; : 1-6, 2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34498954

RESUMO

A new cyclopentenone derivative, 4-hydroxyhypocrenone A, and a new naturally-occurring wickerol derivative, 8-acetoxywickerol A, as well as two known compounds, hypocrenone A and wickerol B, were purified from Trichoderma atroviride A-YMD-9-4, an endophytic fungus isolated from the marine red alga Gracilaria verrucosa. The structures and relative configurations of two new isolates were established by a combination of 1 D/2D NMR, IR, and mass spectroscopic methods, and the absolute configuration of 1 was assigned on the basis of ECD data analyzed by quantum chemical calculations. Compounds 1 and 2 exhibited weak inhibition of one or two marine phytoplankton species.

7.
Drug Deliv ; 28(1): 1849-1860, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34515617

RESUMO

Melanoma is one of the most common malignant tumors. The anti-PD-1 antibody is used for the treatment of metastatic melanoma. Treatment success is only 35-40% and a range of immune-related adverse reactions can occur. Combination of anti-PD1 antibody therapy with other oncology therapies has been attempted. Herein, we assessed whether chlorogenic acid liposomes modified with sialic acid (CA-SAL) combined with anti-PD1 antibody treatment was efficacious as immunotherapy for melanoma. CA-SAL liposomes were prepared and characterized. In a mouse model of B16F10 tumor, mice were treated with an anti-PD1 antibody, CA-SAL, or combination of CA-SAL + anti-PD1 antibody, and compared with no treatment controls. The tumor inhibition rate, tumor-associated macrophages (TAMs) phenotype, T-cell activity, and safety were investigated. We observed a significant decrease in the proportion of M2-TAMs and CD4+Fop3+ T cells, while there was a significant increase in the proportion of M1-TAMs and CD8+ T cells, and in the activity of T cells, and thus in the tumor inhibition rate. No significant toxicity was observed in major organs. CA-SAL and anti-PD1 Ab combination therapy presented synergistic anti-tumor activity, which enhanced the efficacy of the PD-1 checkpoint blocker in a mouse model of melanoma. In summary, combination immunotherapy of CA-SAL and anti-PD1 Ab has broad prospects in improving the therapeutic effect of melanoma, and may provide a new strategy for clinical treatment.

9.
Br J Radiol ; : 20210348, 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34520235

RESUMO

OBJECTIVE: This study aimed to establish a mammography-based radiomics model for predicting the risk of estrogen receptor (ER)-positive, lymph node (LN)-negative invasive breast cancer recurrence based on Oncotype DX and validated it by using multicenter data. METHODS: A total of 304 potentially eligible patients with pre-operative mammography images and available Oncotype DX score were retrospectively enrolled from two hospitals. The patients were grouped as training set (168 patients), internal test set (72 patients), and external test set (64 patients). Radiomics features were extracted from the mammography images of each patient. Spearman correlation analysis, analysis of variance, and least absolute shrinkage and selection operator regression were performed to reduce the redundant features in the training set, and the least absolute shrinkage and selection operator algorithm was used to construct the radiomics signature based on selected features. Multivariate logistic regression was utilized to construct classification models that included radiomics signature and clinical risk factors to predict low vs intermediate and high recurrence risk of ER-positive, LN-negative invasive breast cancer in the training set. The models were evaluated with the receiver operating characteristic curve in the training set. The internal and external test sets were used to confirm the discriminatory power of the models. The clinical usefulness was evaluated by using decision curve analysis. RESULTS: The radiomics signature consisting of three radiomics features achieved favorable prediction performance. The multivariate logistic regression model including radiomics signature and clinical risk factors (tumor grade and HER 2) showed good performance with areas under the curve of 0.92 (95% confidence interval [CI] 0.86 to 0.97), 0.88 (95% CI 0.75 to 1.00), and 0.84 (95% CI 0.69 to 0.99) in the training, internal and external test sets, respectively. The DCA indicated that when the threshold probability is ranges from 0.1 to 1.0, the radiomics model adds more net benefit than the "treat all" or "treat none" scheme in internal and external test sets. CONCLUSION: As a non-invasive pre-operative prediction tool, the mammography-based radiomics model incorporating radiomics and clinical factors show favorable predictive performance for predicting the risk of ER-positive, LN-negative invasive breast cancer recurrence based on Oncotype DX. ADVANCES IN KNOWLEDGE: The mammography-based radiomics model incorporating radiomics and clinical factors shows favorable predictive performance for predicting the risk of ER-positive, LN-negative invasive breast cancer recurrence.

10.
J Nurs Meas ; 2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34518437

RESUMO

BACKGROUND AND PURPOSE: Fear of cancer recurrence (FCR) is a frequent psychological adverse effect among cancer survivors. This study aimed to test the psychometric properties of the Traditional Chinese version of the 12-item Fear of Progression Questionnaire-Short Form (FoP-Q-SF). METHODS: An online survey was conducted with 311 cancer survivors in Hong Kong. The factor structure, known-group validity, and internal consistency reliability were examined. RESULTS: The values measuring validity is good, with acceptable goodness-of-fit indexes (RMSEA = 0.073, SRMR = 0.042, CFI = 0.954), moderate to large correlations with unmet needs (0.339.0.816), being female, younger, had completed treatment ≤ 2 years, and had undergone chemotherapy/radiotherapy scored significantly higher on the FoP-Q-SF. The Cronbach's alpha of the scale was .922. CONCLUSIONS: High validity and reliability indicate the scale's value in assessing FCR in Hong Kong cancer survivors.

11.
Hum Reprod ; 2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34590680

RESUMO

STUDY QUESTION: Is CDC26 a key factor in human oocyte aging? SUMMARY ANSWER: The lack of CDC26 disrupts the oocytes maturation process, leading to oocyte aging, but these defects could be partially rescued by overexpression of the CDC26 protein. WHAT IS KNOWN ALREADY: Age-related oocyte aging is the main cause of female fertility decline. In mammalian oocytes, aberrant meiosis can cause chromosomal abnormalities that might lead to infertility and developmental disorders. CDC26 participates in the meiosis process. STUDY DESIGN, SIZE, DURATION: Differential gene expression in young and old women oocytes were screened by single-cell RNA-seq technology, and the functions of differentially genes were verified on mouse oocytes. Finally, transfection technology was used to evaluate the effect of a differentially expressed gene in rescuing human oocyte from aging. PARTICIPANTS/MATERIALS, SETTING, METHODS: Discarded human oocytes were collected for single-cell RNA-seq, q-PCR and immunocytochemical analyses to screen for and identify differential gene expression. Female KM mice oocytes were collected for IVM of oocytes, q-PCR and immunocytochemical analyses to delineate the relationships between oocyte aging and differential gene expression. Additionally, recombinant lentiviral vectors encoding CDC26 were transfected into the germinal vesicle oocytes of older women, to investigate the effects of the CDC26 gene expression on oocyte development. MAIN RESULTS AND THE ROLE OF CHANCE: Many genes were found to be differentially expressed in the oocytes of young versus old patients via RNA-seq technology. CDC26 mRNA and protein levels in aged oocytes were severely decreased, when compared with the levels observed in young oocytes. Moreover, aged oocytes lacking CDC26 were more prone to aneuploidy. These defects in aged oocytes could be partially rescued by overexpression of the CDC26 protein. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: Our study delineated key steps in the oocyte aging process by identifying the key role of CDC26 in the progression of oocyte maturation. Future studies are required to address whether other signaling pathways play a role in regulating oocyte maturation via CDC26 and which genes are the direct molecular targets of CDC26. WIDER IMPLICATIONS OF THE FINDINGS: Our results using in vitro systems for both mouse and human oocyte maturation provide a proof of principle that CDC26 may represent a novel therapeutic approach against maternal aging-related spindle and chromosomal abnormalities. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by grants from the National Natural Science Foundation of China (81571442 and 81170571), the outstanding Talent Project of Shanghai Municipal Commission of Health (XBR2011067) and Clinical Research and Cultivation Project in Shanghai Municipal Hospitals (SHDC12019X32). The authors declare no conflict of interest.

12.
BMJ Open ; 11(9): e048611, 2021 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-34551944

RESUMO

OBJECTIVE: To develop a virtual reality simulation training programme, and further verify the effect of the programme on improving the response capacity of emergency reserve nurses confronting public health emergencies. DESIGN: A prospective quasiexperimental design with a control group. PARTICIPANTS: A total of 120 nurses were recruited and randomly divided into the control group and the intervention group. INTERVENTION: Participants underwent a 3-month training. The control group received the conventional training of emergency response (eg, theoretical lectures, technical skills and psychological training), while the intervention group underwent the virtual reality simulation training in combination with skills training. The COVID-19 cases were incorporated into the intervention group training, and the psychological training was identical to both groups. At the end of the training, each group conducted emergency drills twice. Before and after the intervention, the two groups were assessed for the knowledge and technical skills regarding responses to fulminate respiratory infectious diseases, as well as the capacity of emergency care. Furthermore, their pandemic preparedness was assessed with a disaster preparedness questionnaire. RESULTS: After the intervention, the scores of the relevant knowledge, the capacity of emergency care and disaster preparedness in the intervention group significantly increased (p<0.01). The score of technical skills in the control group increased more significantly than that of the intervention group (p<0.01). No significant difference was identified in the scores of postdisaster management in two groups (p>0.05). CONCLUSION: The virtual reality simulation training in combination with technical skills training can improve the response capacity of emergency reserve nurses as compared with the conventional training. The findings of the study provide some evidence for the emergency training of reserve nurses in better response to public health emergencies and suggest this methodology is worthy of further research and popularisation.


Assuntos
COVID-19 , Enfermeiras de Saúde Pública , Treinamento por Simulação , Realidade Virtual , China , Competência Clínica , Emergências , Humanos , Estudos Prospectivos , Saúde Pública , SARS-CoV-2
13.
Nutrients ; 13(9)2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34579068

RESUMO

Treatment for non-alcoholic fatty liver disease (NAFLD) currently consists of lifestyle modifications such as a low-fat diet, weight loss, and exercise. The gut microbiota forms part of the gut-liver axis and serves as a potential target for NAFLD treatment. We investigated the effect of probiotics on hepatic steatosis, fibrosis, and biochemical blood tests in patients with NAFLD. At the small intestinal mucosal level, we examined the effect of probiotics on the expression of CD4+ and CD8+ T lymphocytes, as well as the tight junction protein zona occluden-1 (ZO-1). This was a randomized, double-blind, placebo-controlled trial involving ultrasound-diagnosed NAFLD patients (n = 39) who were supplemented with either a probiotics sachet (MCP® BCMC® strains) or a placebo for a total of 6 months. Multi-strain probiotics (MCP® BCMC® strains) containing six different Lactobacillus and Bifidobacterium species at a concentration of 30 billion CFU were used. There were no significant changes at the end of the study in terms of hepatic steatosis (probiotics: -21.70 ± 42.6 dB/m, p = 0.052 vs. placebo: -10.72 ± 46.6 dB/m, p = 0.29) and fibrosis levels (probiotics: -0.25 ± 1.77 kPa, p = 0.55 vs. placebo: -0.62 ± 2.37 kPa, p = 0.23) as measured by transient elastography. Likewise, no significant changes were found for both groups for the following parameters: LiverFAST analysis (steatosis, fibrosis and inflammation scores), alanine aminotransferase, total cholesterol, triglycerides, and fasting glucose. In the immunohistochemistry (IHC) analysis, no significant expression changes were seen for CD4+ T lymphocytes in either group (probiotics: -0.33 ± 1.67, p = 0.35 vs. placebo: 0.35 ± 3.25, p = 0.63). However, significant reductions in the expression of CD8+ T lymphocytes (-7.0 ± 13.73, p = 0.04) and ZO-1 (Z-score = -2.86, p = 0.04) were found in the placebo group, but no significant changes in the probiotics group. In this pilot study, the use of probiotics did not result in any significant clinical improvement in NAFLD patients. However, at the microenvironment level (i.e., the small intestinal mucosa), probiotics seemed to be able to stabilize the mucosal immune function and to protect NAFLD patients against increased intestinal permeability. Therefore, probiotics might have a complementary role in treating NAFLD. Further studies with larger sample sizes, a longer duration, and different probiotic strains are needed to evaluate the real benefit of probiotics in NAFLD.

14.
Br J Haematol ; 2021 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-34528239

RESUMO

We performed a double-blind, double-dummy controlled study to compare the efficacy between recombinant human thrombopoietin (rhTPO) and eltrombopag in rapidly increasing the platelet counts in Chinese patients with immune thrombocytopenia (ITP). A total of 96 patients diagnosed with ITP for ≥6 months who had baseline platelet counts of <30 × 109 /l were randomly assigned (1:1 ratio) to receive eltrombopag 25 mg/day or rhTPO 300 u/kg for 2 weeks. Compared with the eltrombopag group, a significantly higher proportion of patients in the rhTPO group achieved platelet counts of ≥50 × 109 /l [75·00% (36/48) vs. 43·75% (21/48), P = 0·003] or complete response (64·58% vs. 25·00%) on day 15. Moreover, a higher proportion of patients in the rhTPO group either had platelet counts that rapidly increased to twice that of baseline and with platelet counts of ≥30 × 109 /l, or reached ≥50 × 109 /l at least once when analysed on day 9, 12, and 15. However, upon discontinuation of the treatment, the platelet counts reduced to the baseline within 1 week in the rhTPO group, but on the fourth week in the eltrombopag group. Adverse events were similar in patients given rhTPO and eltrombopag. To conclude, rhTPO is superior to eltrombopag at 25 mg/day in rapidly increasing platelet counts in patients with ITP (ClinicalTrials.gov Identifier: NCT03771378).

15.
Artigo em Inglês | MEDLINE | ID: mdl-34444520

RESUMO

Temperature change is an important meteorological indicator reflecting weather stability. This study aimed to examine the effects of ambient temperature change on non-accidental mortality using diurnal temperature change (DTR) and temperature change between neighboring days (TCN) from two perspectives, intra-day and inter-day temperature change, and further, to explore seasonal variations of mortality, identify the susceptible population and investigate the interaction between temperature change and apparent temperature (AT). We collected daily data on cause-specific mortality, air pollutants and meteorological indicators in Shenzhen, China, from 1 January 2013 to 29 December 2017. A Quasi-Poisson generalized linear regression combined with distributed lag non-linear models (DLNMs) were conducted to estimate the effects of season on temperature change-related mortality. In addition, a non-parametric bivariate response surface model was used to explore the interaction between temperature change and AT. The cumulative effect of DTR was a U-shaped curve for non-accidental mortality, whereas the curve for TCN was nearly monotonic. The overall relative risks (RRs) of non-accidental, cardiovascular and respiratory mortality were 1.407 (95% CI: 1.233-1.606), 1.470 (95% CI: 1.220-1.771) and 1.741 (95% CI: 1.157-2.620) from exposure to extreme large DTR (99th) in cold seasons. However, no statistically significant effects were observed in warm seasons. As for TCN, the effects were higher in cold seasons than warm seasons, with the largest RR of 1.611 (95% CI: 1.384-1.876). The elderly and females were more sensitive, and low apparent temperature had a higher effect on temperature change-related non-accidental mortality. Temperature change was positively correlated with an increased risk of non-accidental mortality in Shenzhen. Both female and elderly people are more vulnerable to the potential adverse effects, especially in cold seasons. Low AT may enhance the effects of temperature change.


Assuntos
Poluentes Atmosféricos , Idoso , Poluentes Atmosféricos/análise , China/epidemiologia , Temperatura Baixa , Feminino , Temperatura Alta , Humanos , Mortalidade , Estações do Ano , Temperatura
16.
Indian J Pathol Microbiol ; 64(3): 579-583, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34341278

RESUMO

Plasmablastic lymphoma (PBL) is a rare aggressive subtype of mature large B cell lymphoma involving almost exclusively the extranodal regions particularly the oral cavity, frequently described in immunocompromised patients. PBL is characterized histologically by diffuse proliferation of large neoplastic cells resembling B immunoblasts or plasmablasts. The diagnosis of PBL can be difficult due to its ambiguous histopathological features mimicking most large cell lymphomas and lacking a distinctive immunophenotypic pattern. They typically lack expression of CD20 and CD79a but may express plasma cell marker, CD138. Aberrant immunoexpression of CD3, a T-cell marker in PBL in the absence of other B-cell markers is exceptionally rare, may potentially lead to incorrect interpretation. Herein, we report a case series of CD3-positive PBL of oral cavity in two individuals, which were initially misdiagnosed as high-grade T-cell lymphomas including extranodal NK/T-cell lymphoma, nasal type. Useful distinguishing clinical settings, histomorphological features, immunohistochemistry and molecular expression profiles of PBL are discussed.

17.
Bioorg Chem ; 115: 105223, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34339977

RESUMO

Ten new bisabolane derivatives, trichobisabolins Q-Z (1-10), one new cadinane derivative, cadin-4-en-11-ol (11), and three new cyclonerane derivatives, cycloner-3-en-7,11-diol (12), isoepicyclonerodiol oxide (13), and norepicyclonerodiol oxide (14), were isolated from the endophytic fungal strain RR-dl-6-11 of Trichoderma asperelloides that was obtained from a marine alga. Their structures along with relative configurations were established mainly by NMR and IR as well as MS techniques, and the absolute configurations of 10 and 11 were assigned by ECD and X-ray diffraction data, respectively. Sesquiterpenes from the fungus T. asperelloides are reported for the first time. It is interesting that half of the bisabolane derivatives are demethylated. Compound 12 represents the first the occurrence of cyclopentenyl-bearing cycloneranes, and 14 seems a cyclopentyl-degrading cyclonerane derivative. Several isolates feature potent inhibition of marine phytoplankton species.

18.
Nat Cell Biol ; 23(8): 894-904, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34354233

RESUMO

The shieldin complex functions as the downstream effector of 53BP1-RIF1 to promote DNA double-strand break end-joining by restricting end resection. The SHLD2 subunit binds to single-stranded DNA ends and blocks end resection through OB-fold domains. Besides blocking end resection, it is unclear how the shieldin complex processes SHLD2-bound single-stranded DNA and promotes non-homologous end-joining. Here, we identify a downstream effector of the shieldin complex, ASTE1, as a structure-specific DNA endonuclease that specifically cleaves single-stranded DNA and 3' overhang DNA. ASTE1 localizes to DNA damage sites in a shieldin-dependent manner. Loss of ASTE1 impairs non-homologous end-joining, leads to hyper-resection and causes defective immunoglobulin class switch recombination. ASTE1 deficiency also causes resistance to poly(ADP-ribose) polymerase inhibitors in BRCA1-deficient cells owing to restoration of homologous recombination. These findings suggest that ASTE1-mediated 3' single-stranded DNA end cleavage contributes to the control of DSB repair choice by 53BP1, RIF1 and shieldin.


Assuntos
Reparo do DNA por Junção de Extremidades , Desoxirribonuclease I/fisiologia , Proteínas/fisiologia , Animais , Proteínas de Ciclo Celular/fisiologia , DNA/metabolismo , Proteínas de Ligação a DNA/fisiologia , Feminino , Instabilidade Genômica , Células HEK293 , Humanos , Switching de Imunoglobulina/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Recombinantes de Fusão
19.
Stem Cell Reports ; 16(9): 2099-2106, 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34388365

RESUMO

Uterine leiomyoma (LM) is the most common tumor in women. Via its receptor (PGR) expressed in differentiated LM cells, progesterone stimulates paracrine signaling that induces proliferation of PGR-deficient LM stem cells (LSCs). Antiprogestins shrink LM but tumors regrow after treatment cessation possibly due to persisting LSCs. Using sorted primary LM cell populations, we found that the PGR gene locus and its target cistrome are hypermethylated in LSCs, inhibiting the expression of genes critical for progesterone-induced LSC differentiation. PGR knockdown shifted the transcriptome of total LM cells toward LSCs and increased global DNA methylation by regulating TET methylcytosine dioxygenases. DNA methylation inhibitor 5'-Aza activated PGR signaling, stimulated LSC differentiation, and synergized with antiprogestin to reduce tumor size in vivo. Taken together, targeting the feedback loop between DNA methylation and progesterone signaling may accelerate the depletion of LSCs through rapid differentiation and sensitize LM to antiprogestin therapy, thus preventing tumor regrowth.

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