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1.
Artigo em Inglês | MEDLINE | ID: mdl-34625339

RESUMO

OBJECTIVE: Early screening and intervention are crucial for the prevention and treatment of cervical cancer. TruScreen is a real-time, intelligent, pathological diagnostic technology designed for cervical cancer screening. The aim of this study was to evaluate the clinical value of TruScreen in screening for cervical lesions. STUDY DESIGN: A total of 458 women aged between 25 and 65 years were recruited to receive cervical cancer screening, including human papillomavirus (HPV) testing, cytological testing using the ThinPrep cytology test (TCT), and TruScreen from December 2018 to January 2020. The clinical performance of TruScreen, alone and in combination with HPV testing, was evaluated to detect cervical intraepithelial neoplasia grade 2 or worse (CIN2+ or CIN3+). RESULTS: For detection of CIN2+, the sensitivity and specificity of TruScreen were 83.78% and 78.86%, respectively. The specificity of TruScreen was significantly higher than those of HPV testing (50.59%, P < 0.001) and TCT (55.58%, P < 0.001). In high-risk HPV-positive women, the specificity of HPV testing combined with TruScreen was significantly higher than that of HPV testing combined with TCT (50% vs 39.9%, P = 0.004). The sensitivity of HPV testing combined with TruScreen was comparable to that of HPV testing combined with TCT (93.94% vs 87.88%, P = 0.625). Similar patterns were also observed for CIN3+ cases. CONCLUSION: TruScreen has the potential for screening high-grade cervical precancerous lesions and may replace cytological tests as a cervical cancer screening method in China to avoid subjectivity in the interpretation of cytological tests and requirements by pathologists.

2.
J Dairy Sci ; 2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34593221

RESUMO

Liver X receptor α (LXRα; NR1H3) is an important transcription factor that can facilitate milk fat synthesis by regulating the transcription of FASN in mice and goats. Nevertheless, the lipid synthesis related to LXRα and its regulation on FASN in the buffalo mammary gland remain elusive. Here, we demonstrated that the mRNA and protein expression of LXRα in buffalo mammary tissue increased in lactation compared with that in the dry-off period. Overexpression of NR1H3 enhanced the lipid droplet formation and triacylglycerol concentration in buffalo mammary epithelial cells (BuMEC), whereas the knockdown of NR1H3 resulted in a decrease in the number of lipid droplets. At the same time, NR1H3 also affected the expression of regulatory factors (INSIG1, INSIG2, SREBF1, and PPARG) related to milk fat synthesis and that of genes involved in de novo synthesis (FASN, ACACA, and SCD), and uptake and transport (LPL, CD36, and FABP3) of fatty acids as well as triacylglycerol synthesis (GPAM, APGAT6, and DGAT1). Luciferase reporter assays indicated that overexpression of NR1H3 resulted in an increase in the activity of FASN promoter, whereas the knockdown of NR1H3 had an opposite effect. When NR1H3 was overexpressed, mutations in LXRE or SRE could decrease the promoter activity of FASN. Furthermore, mutagenesis of both LXRE and SRE within the FASN promoter completely eliminated the induced activity of LXRα. Our results reveal that buffalo LXRα promotes milk fat synthesis through regulating the expression of FASN by directly interacting with FASN promoter and affecting the SREBF1 expression. This study underscores a crucial role of LXRα in regulating lipid synthesis of the buffalo mammary gland.

3.
Aging (Albany NY) ; 13(undefined)2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34610582

RESUMO

Diffuse large B-cell lymphoma (DLBCL) presents a great clinical challenge and has a poor prognosis, with immune-related genes playing a crucial role. We aimed to develop an immune-related prognostic signature for improving prognosis prediction in DLBCL. Samples from the GSE31312 dataset were randomly allocated to discovery and internal validation cohorts. Univariate Cox, random forest, LASSO regression and multivariate Cox analyses were utilized to develop a prognostic signature, which was verified in the internal validation cohort, entire validation cohort and external validation cohort (GSE10846). The tumor microenvironment was investigated using the CIBERSORT and ESTIMATE tools. Gene set enrichment analysis (GSEA) was further applied to analyze the entire GSE31312 cohort. We identified four immune-related genes (CD48, IL1RL, PSDM3, RXFP3) significantly associated with overall survival. Based on discovery and validation cohort analyses, this four-gene signature could classify patients into high- and low-risk groups, with significantly different prognoses. Activated memory CD4 T cells and activated dendritic cells were significantly decreased in the high-risk group, and these patients had lower immune scores. GSEA revealed enrichment of signaling pathways, such as T cell receptor, antigen receptor-mediated, antigen processing and presentation of peptide antigen via MHC class I, in the low-risk group. In conclusion, a robust signature based on four immune-related genes was successfully constructed for predicting prognosis in DLBCL patients.

4.
Br J Haematol ; 2021 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-34664256

RESUMO

Diffuse large B-cell lymphoma (DLBCL) is a highly heterogenous malignancy, early identification of patients for relapse remains challenging. The potential to non-invasively monitor tumour evolutionary dynamics of DLBCL needs to be further established. In the present study, 17 tumour biopsy and 38 plasma samples from 38 patients with high-intermediate/high-risk DLBCL were evaluated at baseline. Longitudinal blood samples were also collected during therapy. Circulating tumour DNA (ctDNA) was analysed using targeted sequencing based on a gene panel via a recently developed methodology, circulating single-molecule amplification and re-sequencing technology (cSMART). We found that the most frequently mutated genes were tumour protein p53 (TP53; 42·1%), histone-lysine N-methyltransferase 2D (KMT2D; 28·9%), caspase recruitment domain family member 11 (CARD11; 21·1%), cAMP response element-binding protein binding protein (CREBBP; 15·8%), ß2 -microglobulin (B2M; 15·8%), and tumour necrosis factor alpha-induced protein 3 (TNFAIP3; 15·8%). The mutation profiles between ctDNA and matched tumour tissue showed good concordance; however, more mutation sites were detected in ctDNA samples. Either TP53 or B2M mutations before treatment predicted poor prognosis. Analysis of dynamic blood samples confirmed the utility of ctDNA for the real-time assessment of treatment response and revealed that the increases in ctDNA levels and changes in KMT2D mutation status could be useful predictors of disease progression. Our present results suggest that ctDNA is a promising method for the detection of mutation spectrum and serves as a biomarker for disease monitoring and predicting clinical recurrence.

5.
Drug Des Devel Ther ; 15: 3697-3708, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34465981

RESUMO

Purpose: Puerarin (PR), a Chinese medicine rich in natural components, has been reported to display anti-fibrotic, antioxidant, anti-inflammatory and immunomodulatory properties. However, the protective mechanism of PR against unilateral ureteral obstruction (UUO)-mediated renal injury is not fully clarified. Therefore, the aim of this study was to investigate the effects of PR on UUO mice and its possible mechanisms. Methods: A total of 32 C57BL/6 mice were divided randomly into four groups (n=8): i) sham-operated group (Sham); ii) UUO group (UUO); iii) UUO + PR 50 mg/kg/day (UUO + PRL); and iv) UUO + PR 100 mg/kg/day (UUO + PRH). Continuous gavage administration for 14 days starting one week postoperatively, while the mice in Sham and UUO groups were given equal amounts of vehicle by the same means. All mice were then sacrificed and serum, 24-hour urine and tissue specimens were collected for renal function, histopathology, Western blot, immunohistochemistry. Results: Renal function and histopathology revealed that PR improved UUO-mediated renal dysfunction and partially reversed tubular injury and tubulointerstitial fibrosis. Additionally, according to the results of Western blot and immunohistochemistry, PR inhibited the expression of inflammatory factors including IL-1ß, IL-6, MCP-1 and ECM-related proteins including α-SMA, COL I and VIM. More importantly, the expression of fibrotic pathways TGF-ß1, Smad3, p-Smad3 and inflammatory pathways NF-κB p65, NF-κB p-p65, STAT3, p-STAT3 were inhibited to various extents under the PR treatment, while Smad7 was upregulated. Conclusion: These findings indicate that PR may inhibit the recruitment of inflammatory factors and extracellular matrix (ECM) deposition through the regulation of the NF-κB p65/STAT3 and TGFß1/Smads pathways, which alleviates the UUO-induced inflammatory and fibrotic response, thereby reversing renal injury.

6.
Hematol Oncol ; 2021 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-34564882

RESUMO

Secondary central nervous system (SCNS) involvement is an infrequent but universally fatal event in diffused large B-cell lymphoma. The occurrence rate of SCNS involvement is approximately 5% but comes with a poor prognosis ever after. However, existing risk models to predict the incidence and prognosis of these patients with SCNS involvement lack both efficiency and accuracy. Controversy has also been reported regarding which risk factor may best identify the population with a high CNS relapse rate. In this study, we retrospectively analyzed 831 patients with diffused large B-cell lymphoma, diagnosed between March 2008 and June 2018 in Tianjin Medical University Cancer Institute and Hospital, Beijing Cancer Hospital, and Cancer Hospital of The University of Chinese Academy of Science. Risk factors and nomogram were identified and established based on Fine and Gray's competing risk analysis. Among these patients, 55 (6.6%) of them eventually developed SCNS involvement. The 1- and 2-year incidence for SCNS involvement were 3.9% and 4.7%, respectively. The median time from de novo diagnosis to CNS relapse was 8 months, and the median overall survival of these patients was 28 months. Considering the competing mortality before SCNS involvement, Fine and Gray's competing risk model was performed to analyze the characteristics related to SCNS involvement, and identified risk factors as the multiple extranodal involvements, elevated LDH and AMC level, and the involvement of breast, adrenal gland/kidney, pulmonary and bone. Corresponding factors were integrated into the competing nomogram for SCNS involvement (c-index = 0.778). In conclusion, we present the first predictive nomogram to evaluate the risk to develop SCNS involvement in de novo DLBCL patients, which may help in both prognostic evaluation and clinical decision for this subgroup.

7.
Photodiagnosis Photodyn Ther ; 36: 102517, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34487873

RESUMO

OBJECTIVE: To evaluate the histologic response rate of high-grade squamous intraepithelial lesion (HSIL)/cervical intraepithelial neoplasia 2 (CIN2) of the cervix after photodynamic therapy (PDT) treatment in women with fertility requirements. MATERIALS AND METHODS: A retrospective study was carried out comprising 31 female patients aged 20-38 years with histologically confirmed HSIL/CIN2 with high-risk human papillomavirus (hrHPV) infection. Patients were treated with three sessions of 20% 5-aminolevulinic acid (5-ALA) PDT at intervals of 7-14 days. All patients had a follow-up including cytology, HPV testing and colposcopy-directed biopsy after PDT treatment at the 6-month and 12-month follow-up points. The main outcome measure was efficacy, defined as complete histologic remission 12 months after PDT. Secondary outcomes were the remission of HPV infection and the adverse effects of PDT treatment. RESULTS: At the 12-month follow-up, 21 out of 27 patients (77.78%) and 4 out of 27 patients (14.81%) showed histologic disappearance and histologic regression, respectively. Only 7.41% (2/27) patients persisted with HSIL/CIN2. In addition, no patients progressed to CIN3 or carcinoma. The total baseline HPV remission rate was 62.96% (17/27). The remission rate of HPV16/18 was statistically significant compared to the other hrHPV (57.14% vs. 100%, p = 0.016) in the group with HISL/CIN2 disappearance. Adverse events were mild, with increased vaginal secretion and abdominal pain being the most common complaints. There was no report of adverse events such as vaginal bleeding, colporrhagia, ulcer, or abdominal pain after PDT treatment. CONCLUSIONS: 5-ALA-PDT shows a favorable efficacy and safety profile and represents a promising alternative to observation and surgical procedures in patients with HSIL/CIN2 who have fertility requirements.

8.
Photodiagnosis Photodyn Ther ; 36: 102548, 2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34562648

RESUMO

BACKGROUND: There are insufficient studies comparing the efficacy of 5-aminolaevulinic acid (ALA) photodynamic therapy (PDT) against CO2 laser therapy in the treatment of cervical low-grade squamous intraepithelial lesion (LSIL) with high-risk human papillomavirus (HR-HPV), especially for long-term efficacy. METHODS: Patients with cervical LSIL and HR-HPV infection were divided into two treatment groups based on their own choice. All patients had a follow-up test including HPV testing, cytology and colposcopy at 4-6 months and 12 months after the treatment. RESULTS: (1) Among 277 patients, 176 patients received 5-ALA PDT and 101 patients received CO2 laser therapy. (2) 4-6 months after treatment, there was no significant difference between two groups in the complete remission (CR) rates of cervical LSIL and the clearance rate of HR-HPV infection. (3) 12 months after treatment, compared with the CO2 laser group, the CR rates of cervical LSIL in the 5-ALA PDT group was significantly higher than the CO2 laser group. There was no statistical difference in the clearance rate of HR-HPV infection between the two groups. (4) 12 months after treatment, the recurrence rate of cervical lesions and the reinfection rate of HR-HPV infection in 5-ALA PDT group were significantly lower than those in CO2 laser group. CONCLUSION: The effect of 5-ALA PDT is similar to CO2 laser at 4-6 months. The long-term efficacy of 5-ALA PDT appears better than CO2 laser. As a non-invasive treatment, 5-ALA PDT is a highly effective therapeutic procedure for cervical LSIL with HR-HPV infection.

9.
Aging (Albany NY) ; 13(17): 21102-21121, 2021 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-34508613

RESUMO

BGB-3111, a novel Bruton's tyrosine kinase (BTK) inhibitor, shows promising anti-cancer effects in chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), mantle cell lymphoma (MCL), and Waldenstrom macroglobulinemia (WM). This study aimed to investigate the anti-cancer effects of BGB-3111 combined with bortezomib (BTZ) against the BTK-expressing MCL. We found that BTK, which was overexpressed in 59.4% of patients with MCL, was mainly characterized by high Ki67 and elevated MIPI scores. BGB-3111 strongly inhibited cell proliferation, induced cell cycle arrest in the G1/G0-phase, and promoted cell apoptosis in the MCL cells expressing BTK. BGB-3111 provides better safety than another BTK inhibitor, ibrutinib as ibrutinib inhibits the inducible T-cell kinase (ITK) as an off-target effect but BGB-3111 does not inhibit ITK. Low doses of BTZ enhanced the anti-cancer effect induced by the low dose of BGB-3111 by downregulating the expression levels of PARP and Bcl-2 and increasing the expression levels of cleaved PARP and cleaved caspase-9. In addition, low doses of BGB-3111, but not of BTZ, inhibited BTK phosphorylation. However, low-doses of BTZ strengthened the anti-cancer effect induced by the low-doses of BGB-3111 via synergistically suppressing the IκBα and P65 phosphorylation. Taken together, our findings validate that BGB-3111 is a novel and effective BTK inhibitor for MCL-expressing BTK. Hence, it can be harnessed as a potential therapeutic strategy through a combinatorial treatment comprising low-dose BGB-3111 and low-dose BTZ to gain strong anti-cancer effects and better safety for MCL patients.

10.
J Cancer ; 12(20): 6126-6134, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34539885

RESUMO

Purpose: To investigate the prognostic significance of programmed cell death ligand-1 (PD-L1) and phosphorylated ERK (p-ERK) and their interactions in T-cell lymphoma (TCL). Methods: The mRNA levels of PD-L1 and ERK in TCL samples were analyzed. Formalin-fixed paraffin-embedded tissues from 69 TCL patients were collected to detect the expression of PD-L1 and p-ERK by multiplexed immunofluorescence staining. The total PD-L1 and p-ERK was measured by western blotting, and membrane PD-L1 was determined using flow cytometry. Results: PD-L1 and ERK mRNA levels were significantly upregulated in TCL. The expression rates of PD-L1 and p-ERK were 52.2% and 27.5%, respectively. PD-L1 expression correlated with stage (R=0.304, P=0.011) and IPI score (R=0.313, P=0.009), and p-ERK expression correlated with stage (R=0.330, P=0.006) and IPI score (R=0.376, P=0.002). PD-L1 expression positively correlated with p-ERK expression (R=0.355, P=0.003). Patients with co-expression of PD-L1 and p-ERK had the worst overall survival (P=0.007). In three TCL cell lines with PD-L1 expression, we demonstrated that the expression of p-ERK was upregulated after stimulation with PD-1, suggesting that ERK signaling was activated. Conclusions: The PD-1/PD-L1 axis activates intracellular ERK signaling in tumor cells and that PD-L1, p-ERK or their combination are potential biomarkers for predicting the prognosis in TCL patients.

11.
Front Oncol ; 11: 708784, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34336695

RESUMO

Purpose: Although the role of tumor-infiltrating T cells in follicular lymphoma (FL) has been reported previously, the prognostic value of peripheral blood T lymphocyte subsets has not been systematically assessed. Thus, we aim to incorporate T-cell subsets with clinical features to develop a predictive model of clinical outcome. Methods: We retrospectively screened a total of 1,008 patients, including 252 newly diagnosed de novo FL patients with available peripheral blood T lymphocyte subsets who were randomized to different sets (177 in the training set and 75 in the internal validation set). A nomogram and a novel immune-clinical prognostic index (ICPI) were established according to multivariate Cox regression analysis for progression-free survival (PFS). The concordance index (C-index), Akaike's information criterion (AIC), and likelihood ratio chi-square were employed to compare the ICPI's discriminatory capability and homogeneity to that of FLIPI, FLIPI2, and PRIMA-PI. Additional external validation was performed using a dataset (n = 157) from other four centers. Results: In the training set, multivariate analysis identified five independent prognostic factors (Stage III/IV disease, elevated lactate dehydrogenase (LDH), Hb <120g/L, CD4+ <30.7% and CD8+ >36.6%) for PFS. A novel ICPI was established according to the number of risk factors and stratify patients into 3 risk groups: high, intermediate, and low-risk with 4-5, 2-3, 0-1 risk factors respectively. The hazard ratios for patients in the high and intermediate-risk groups than those in the low-risk were 27.640 and 2.758. The ICPI could stratify patients into different risk groups both in the training set (P < 0.0001), internal validation set (P = 0.0039) and external validation set (P = 0.04). Moreover, in patients treated with RCHOP-like therapy, the ICPI was also predictive (P < 0.0001). In comparison to FLIPI, FLIPI2, and PRIMA-PI (C-index, 0.613-0.647), the ICPI offered adequate discrimination capability with C-index values of 0.679. Additionally, it exhibits good performance based on the lowest AIC and highest likelihood ratio chi-square score. Conclusions: The ICPI is a novel predictive model with improved prognostic performance for patients with de novo FL treated with R-CHOP/CHOP chemotherapy. It is capable to be used in routine practice and guides individualized precision therapy.

12.
J Nanobiotechnology ; 19(1): 181, 2021 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-34120612

RESUMO

BACKGROUND: Triple-negative breast cancer (TNBC) is a highly aggressive malignant disease with a high rate of recurrence and metastasis, few effective treatment options and poor prognosis. Here, we designed and constructed a combined photothermal immunotherapy strategy based on cancer cell membrane-coated biomimetic black phosphorus quantum dots (BBPQDs) for tumor-targeted photothermal therapy and anti-PD-L1 mediated immunotherapy. RESULTS: BBPQDs have good photothermal conversion efficiency and can efficiently target tumor cells through homologous targeting and tumor homing. Under near infrared irradiation, we found that BBPQDs kill tumors directly through photothermal effects and induce dendritic cells maturation. In vivo studies have confirmed that the combined photothermal immunotherapy strategy displays a stronger antitumor activity than anti-PD-L1 monotherapy. In addition, BBPQDs-mediated photothermal therapy in combination with anti-PD-L1 treatment inhibit tumor recurrence and metastasis by reprograming the immunosuppressive tumor microenvironment into an immune-active microenvironment, and promoting the local and systemic antitumor immune response. We further found that the combined photothermal immunotherapy strategy can produce an immune memory effect against tumor rechallenge. CONCLUSIONS: This study provides a novel therapeutic strategy for inhibiting the recurrence and metastasis of TNBC, with broad application prospects.

13.
Dev Comp Immunol ; 123: 104169, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34118280

RESUMO

Many tripartite motif (TRIM) family proteins played an important role in regulating innate immune and autophagy pathway and were important for host defenses against viral pathogens. However, the role of TRIM proteins in autophagy and innate immunity during virus infection was seldom studied in crustaceans. In this study, a novel TRIM32 homolog was identified from Penaeus monodon (named PmTRIM32). PmTRIM32 was significantly upregulated by rapamycin stimulation and WSSV infection. RNA interference experiments showed that PmTRIM32 could restrict WSSV replication and lead P. monodon more resistance to WSSV challenge. Autophagy could be induced by WSSV or rapamycin challenge and has been proved to play a positive role in restricting WSSV replication in P. monodon. The autophagy activity induced by WSSV or rapamycin challenge could be obviously inhibited by silence of PmTRIM32 in P. monodon. Further studies revealed that PmTRIM32 positively regulated the expression of nuclear transcription factor (NF-κB) and it mediated antimicrobial peptides. Moreover, Pull-down and in vitro ubiquitination assay demonstrated that PmTRIM32 could interact with WSSV envelope protein and target it for ubiquitination in vitro. Collectively, this study demonstrated that PmTRIM32 restricted WSSV replication and was involved in positively regulating autophagy and NF-κB pathway during WSSV infection in P. monodon.

14.
J Mater Chem B ; 9(28): 5664-5669, 2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34190311

RESUMO

A series of viscosity sensitive fluorescent probes 1a-e were synthesized by linking coumarin and oxazolopyridinium via dimethylene in this paper. The viscosity test of probes 1a-e indicated that the fluorescence intensity of the probes enhanced significantly with the increase of viscosity of the system (0.89-865 cP), and exhibited a nearly OFF-ON response to viscosity at 648 nm, 650 nm and 650 nm, respectively. In addition, cells still had a high survival rate after co-culturing with probes 1a-e for 12 h (94-98%). Meanwhile, the laser confocal experiment showed that the variation of the carbon chain length in the oxazolopyridinium could affect the subcellular region of the localization of the probes in cells. When the length of the carbon chain in oxazolopyridinium was between n-C7H15 and n-C12H23, probes 1b-d had the ability to target the endoplasmic reticulum in the cells. Moreover, probes 1b-d showed no significant change in fluorescence intensity after 35 min of continuous laser confocal irradiation, indicating that they had excellent anti-photobleaching properties.

15.
Front Immunol ; 12: 682562, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34046043

RESUMO

Most tripartite motif (TRIM) family proteins are critical components of the autophagy machinery and play important roles in host defense against viral pathogens in mammals. However, the roles of TRIM proteins in autophagy and viral infection have not been studied in lower invertebrates, especially crustaceans. In this study, we first identified a TRIM50-like gene from Penaeus monodon (designated PmTRIM50-like), which, after a white spot syndrome virus (WSSV) challenge, was significantly upregulated at the mRNA and protein levels in the intestine and hemocytes. Knockdown of PmTRIM50-like led to an increase in the WSSV quantity in shrimp, while its overexpression led to a decrease compared with the controls. Autophagy can be induced by WSSV or rapamycin challenge and has been shown to play a positive role in restricting WSSV replication in P. monodon. The mRNA and protein expression levels of PmTRIM50-like significantly increased with the enhancement of rapamycin-induced autophagy. The autophagy activity induced by WSSV or rapamycin challenge could be inhibited by silencing PmTRIM50-like in shrimp. Further studies showed that rapamycin failed to induce autophagy or inhibit WSSV replication after knockdown of PmTRIM50-like. Moreover, pull-down and in vitro ubiquitination assays demonstrated that PmTRIM50-like could interact with WSSV envelope proteins and target them for ubiquitination in vitro. Collectively, this study demonstrated that PmTRIM50-like is required for autophagy and is involved in restricting the proliferation of WSSV through its ubiquitination. This is the first study to report the role of a TRIM family protein in virus infection and host autophagy in crustaceans.

16.
Aquat Toxicol ; 236: 105841, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34022694

RESUMO

Estuarine environmental have been reported to undergo significant fluctuations in oxygen concentrations with hypoxic conditions and subsequent re-oxygenation events being of significant concern for resident fish populations. In this study we assessed the toxicological effects of hypoxia and re-oxygenation on the liver of hypoxia-sensitive spotted sea bass (Lateolabrax maculatus) that were exposed to hypoxia (1.17 mg/L dissolved oxygen) for 12 h and then re-oxygenated for 12 h. The activities of glutamic-pyruvic transaminase and glutamic-oxalacetic transaminase in serum significantly increased under hypoxia (p < 0.05) and continued to increase during re-oxygenation (p < 0.05), indicating that normal liver function might be disrupted by hypoxia and might become worse during re-oxygenation for 12h. Total protein, albumin, and globulin levels in serum decreased under hypoxia but began to return to normal during re-oxygenation, showing that protein synthesis in the liver decreased during hypoxia but could be restored by re-oxygenation. We also used RNA-Seq technology to identify changes in gene expression in the liver during hypoxia and re-oxygenation. Transcriptome sequencing revealed that the hypoxia-inducible factor (HIF-1) signaling pathway, apoptosis, and purine metabolism transcripts were significantly enriched under hypoxia and re-oxygenation conditions. A total of 15 and 16 apoptosis-related genes were induced by hypoxia and re-oxygenation stress, respectively. The apoptosis index increased from the normal to the hypoxic condition and was highest under re-oxygenation. Additionally, 19 and 29 genes, that are involved in purine metabolism in the liver of L. maculatus during hypoxia and re-oxygenation, respectively, were dysregulated. Unexpectedly, the serum uric acid level significantly increased during hypoxia and significantly decreased under re-oxygenation, indicating the presence of purine metabolic disorder in the liver of L. maculatus. These results illustrate that hypoxia poses a pronounced threat to hepatocyte function in L. maculatus and that liver damage is difficult to reverse with 12 h of re-oxygenation, and it may actually become worse when re-oxygenation is established.


Assuntos
Bass/fisiologia , Fígado/fisiologia , Poluentes Químicos da Água/toxicidade , Animais , Bass/metabolismo , Expressão Gênica , Hipóxia/metabolismo , Fígado/metabolismo , Oxigênio/metabolismo , Ácido Úrico/metabolismo
17.
Hematol Oncol ; 39(4): 490-497, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33908077

RESUMO

This study aimed to identify the prognostic factors in patients with Waldeyer's ring diffuse large B-cell lymphoma (WR-DLBCL), comparing the efficacy of radiotherapy (RT) for the WR-DLBCL patients in the pre-rituximab and rituximab eras. We conducted a retrospective analysis of 134 patients diagnosed with WR-DLBCL. Univariate and multivariate analyses were performed to identify the prognostic factors for WR-DLBCL. Then, we divided these patients into the rituximab plus chemotherapy group (R-chemotherapy) (n = 88) and chemotherapy group (n = 46), and the Kaplan-Meier and Cox regression model analyses were applied to investigate the treatment value of RT in both the groups. Multivariate analysis revealed international prognostic index (IPI) ≥ 3 and chemotherapy without rituximab as significant risk factors for the progression-free survival (PFS, IPI ≥ 3: p = 0.001; chemotherapy without rituximab: p = 0.002) and overall survival (OS, IPI ≥ 3, p < 0.001; chemotherapy without rituximab, p = 0.024). Rituximab combined with chemotherapy significantly improved PFS (p = 0.002) and OS (p = 0.006) in these patients. RT did not significantly contribute to the survival in the overall cohort analysis, whereas in the subgroup analysis, RT significantly improved the PFS (p = 0.025) and OS (p = 0.029) for the patients in the chemotherapy group, but not in the R-chemotherapy group. In conclusion, the WR-DLBCL patients could benefit from RT in the pre-rituximab era, whereas the addition of rituximab to chemotherapy significantly improved the survival of WR-DLBCL patients, and the clinical benefit of RT was reduced.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/radioterapia , Rituximab/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Imunológicos/farmacologia , Humanos , Linfoma Difuso de Grandes Células B/patologia , Pessoa de Meia-Idade , Fatores de Risco , Rituximab/farmacologia , Adulto Jovem
18.
Photodiagnosis Photodyn Ther ; 34: 102293, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33857599

RESUMO

BACKGROUND: High-risk HPV (hrHPV) not only increases the risk of cervical precancerous lesions and cervical cancer, but also adds psychological burden to HPV-positive women. 5-aminolevulinic acid photodynamic therapy (ALA-PDT) is a non-invasive and highly tissue-selective therapy. We aim to investigate the clinical efficacy of ALA-PDT for elimination of cervical hrHPV infection in HPV-positive women without cervical lesions. METHODS: A total of 57 hrHPV-positive women without pathologically proved cervical lesions received three treatments of ALA-PDT in total. HPV DNA testing and pap cytology were performed in all patients. Patients with positive HPV16/18 or abnormal TCT results received colposcopic biopsy during the follow-up. RESULTS: hrHPV clearance rate was 56.1 % (32/57) at 3-month follow-up and 68.1 % at 6-month follow-up. 100 % of HPV 18 and 87.5 % of HPV16 infections were cleared while the clearance rate was 48.8 % among those positive for 12 other high-risk types. Multivariate analysis showed HPV16/18 infection was associated with significantly higher clearance rate. HPV clearance rate in patients with multiple-type HPV infection was significantly lower than that in patients with single-type HPV infections. CONCLUSIONS: ALA-PDT is effective on treating hrHPV infection in patients with no cervical lesions. HPV16/18 positive cases can benefit most from ALA-PDT. Multitype-infected women need more sessions of 5- ALA-PDT to eradicate hrHPV infection.


Assuntos
Infecções por Papillomavirus , Fotoquimioterapia , Neoplasias do Colo do Útero , Ácido Aminolevulínico/uso terapêutico , Feminino , Papillomavirus Humano 16 , Papillomavirus Humano 18 , Humanos , Infecções por Papillomavirus/tratamento farmacológico , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico , Neoplasias do Colo do Útero/tratamento farmacológico
19.
Artigo em Inglês | MEDLINE | ID: mdl-33742447

RESUMO

Recent studies have shown elongase of very-long-chain fatty acids 6 (ELOVL6) is a vital protein for endogenous synthesis of saturated and monounsaturated long-chain fatty acids in some mammals. Nevertheless, its role in lipid synthesis in buffalo mammary gland is still unclear. In this work, the full-length coding sequence (CDS) of ELOVL6 was cloned and identified from buffalo mammary gland. As a result, the CDS of this gene is 795 bp, which encodes a polypeptide of 264 amino acid residues. The buffalo ELOVL6 contains an ELO domain which belongs to the ELO superfamily. Among the 10 tissues of buffalo in peak lactation detected by RT-qPCR, the expression level of ELOVL6 was the highest in the brain, followed by the spleen, and then decreased in the mammary gland, muscle, kidney, heart, liver, rumen, intestine and lung. However, only the expression in the brain and spleen was statistically different from that in other tissues (p < 0.05). Compared with that of the dry-off period, the mRNA abundance of ELOVL6 in the mammary gland was significantly increased in peak lactation. The experiments based on lentivirus transfection in buffalo mammary epithelial cells (BuMECs) displayed that the overexpression of ELOVL6 markedly promoted the expression of INSIG1, INSIG2, SREBP, PPARG, FASN, GPAM, DGAT2 and APGAT6 genes, and the knockdown of ELOVL6 significantly decreased the mRNA abundance of INSIG2, SREBP, FASN, SCD, GPAM, APGAT6 and TIP47 genes. In addition, the increase or decrease of ELOVL6 expression level also caused the corresponding change of total triglyceride content in the BuMECs. The results here suggest that the ELOVL6 can catalyse the synthesis of long-chain fatty acids in the BuMECs, and it can indirectly affect the expression of genes related to milk fat synthesis through its catalytic products to promote the lipid biosynthesis of BuMECs.

20.
Int J Nanomedicine ; 16: 2107-2121, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33737808

RESUMO

Purpose: Although anti-programmed cell death protein 1 antibody (aPD1) immunotherapy and chemotherapy has made much progress in the treatment of melanoma, the efficacy still needs to be further improved. Methods: Cancer treatment has been greatly enhanced by the use of nanotechnology. Cancer cell membrane (CCM)-camouflaged nanoparticles have shown promising potential in tumor therapy due to their excellent homologous-targeting ability, long blood circulation and immune escape. This work presents a biocompatible and tumor acidic environmental responsive CCM-camouflaged mesoporous silica nanoparticle (CMSN) that is loaded with dacarbazine (DTIC) and combined with aPD1 to achieve better antitumor efficacy. Results: In vitro cell experiments demonstrated that DTIC@CMSN exhibits a better anti-tumor killing efficiency and a stronger ability to promote the apoptosis of tumor cells than free DTIC. In vivo antitumor results demonstrated that combination therapy of DTIC@CMSN chemotherapy and aPD1 immunotherapy remarkably suppress the melanoma growth and prolong survival time due to highly selective tumor killing, activation of tumor-specific T cells, and regulation of the immunosuppressive tumor microenvironment. In addition, safety evaluation studies of DTIC@CMSN also demonstrate their increased tumor accumulation and decreased systemic toxicity. Conclusion: This study provides a promising nano-platform for the combination of chemotherapy with immunotherapy, which is potentially useful for the treatment of melanoma.


Assuntos
Antineoplásicos/farmacologia , Membrana Celular/patologia , Inibidores de Checkpoint Imunológico/farmacologia , Nanopartículas/química , Dióxido de Silício/química , Microambiente Tumoral/efeitos dos fármacos , Animais , Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Terapia Combinada , Dacarbazina/farmacologia , Dacarbazina/uso terapêutico , Humanos , Melanoma Experimental/tratamento farmacológico , Melanoma Experimental/imunologia , Melanoma Experimental/patologia , Camundongos Endogâmicos C57BL , Tamanho da Partícula , Porosidade , Eletricidade Estática
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