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1.
J Psychiatr Res ; 138: 96-102, 2021 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-33838579

RESUMEN

Effective and targeted interventions for improving quality of life (QOL) in addition to achieving 'clinical remission' are imperatives for patients with major depressive disorder (MDD). This study aimed to examine potential predictors and moderators of QOL in depression. Data were obtained from the Algorithm Guided Treatment Strategies for Major Depressive Disorder (AGTs-MDD) study, a multisite, randomized controlled trial composed of 980 depressed patients. Mixed Model Repeated Measures (MMRM) analyses were conducted to identify baseline characteristics associated with QOL overall (predictors) and their interaction effects (moderators). Severe core depressive, anxiety and pain symptoms were found to be independently associated with poor QOL over the 12-week acute phase treatment. Severe depression, severe anxiety or pain symptoms, or severe suicidal ideation predicted a larger improvement of QOL during acute phase treatment, whereas males showed less improvement. None of the putative moderators were identified except for the educational level. Patients with lower educational level showed a larger improvement of QOL in the AGT started with escitalopram (AGT-E) group and AGT started with mirtazapine (AGT-M) group compared to the treatment as usual (TAU) group. These findings may help to instruct informed decision-making for heterogeneous patients with MDD in the view of full recovery.

2.
Bioorg Chem ; 111: 104843, 2021 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-33845383

RESUMEN

Gynostemma pentaphyllum (Thunb.) Makino has a long history as food and diary supplement in China. At present, there are some products for hyperlipidemia in the market, including G. pentaphyllum tea, healthy wine and healthy food. In order to discover proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, fourteen new triterpenoid saponins named gypenoside LXXXVIII-CI (1-14) along with six known compounds (15-20) were isolated from G. pentaphyllum. Their structures were elucidated by means of various spectroscopic techniques. Eight isolates were evaluated the inhibitory effect on PCSK9 in HepG2 cells. The results showed that three dammarane-type glycosides (2, 3, 15) remarkably reduced PCSK9 expression at 10 µM concentration. These findings suggested that G. pentaphyllum was worthy of further investigation to find small molecule PCSK9 inhibitors and facilitate their utilization as functional food ingredients.

3.
Molecules ; 26(7)2021 Mar 31.
Artículo en Inglés | MEDLINE | ID: mdl-33807346

RESUMEN

Endometrial cancer is the most common malignant tumors of gynecologic neoplasms in Western society. In recent years, the incidence of endometrial cancer has increased, and it has become the third most common female gynecological cancer (after ovarian and cervical cancer) in Taiwan. Adlay (Coix lachryma-jobi L. var. Ma-yuen Stapf.) has been demonstrated to have bioactive polyphenols, flavonoids, phytosterols, and essential nutrients for health benefits, including anticancer effects in humans. However, little is known about the effect of adlay seeds on endometrial cancer. Our study aimed to investigate the potential growth inhibitory effects of several adlay seed fractions, including ethyl acetate (ATE-EA) and its bioactive constituents, separately on endometrial cancer cells-HEC-1A (phosphatase and tensin homolog-positive) and RL95-2 (phosphatase and tensin homolog-negative)-and identify related active ingredients. In addition, the potential active fractions and the phytochemical compounds were elucidated. The results demonstrate superior activity of ATE-EA with significant in vitro cell proliferation inhibitory capacity, particularly its C.D.E.F-subfraction. Moreover, HPLC- and GC/FID-based quantification of ATE-EA subfractions showed that phenolic compounds (caffeic acid, protocatechuic acid, and p-hydroxybenzaldehyde), flavonoids, steroids, and fatty acid compounds exert anti-proliferative effects in the cell model. Finally, it was shown that cell growth and cell cycle arrest most significantly occurred in the in G1 or G2/M phase under ATE-EA treatment. Collectively, our results demonstrate an antiproliferative effect of ATE-EA on endometrial cancer cells that suggest a positive health outcome for women from consumption of these compounds.

4.
Mar Drugs ; 19(3)2021 Mar 22.
Artículo en Inglés | MEDLINE | ID: mdl-33809909

RESUMEN

The prognosis of liver cancer was inferior among tumors. New medicine treatments are urgently needed. In this study, a novel exopolysaccharide EPS364 was purified from Vibrio alginolyticus 364, which was isolated from a deep-sea cold seep of the South China Sea. Further research showed that EPS364 consisted of mannose, glucosamine, gluconic acid, galactosamine and arabinose with a molar ratio of 5:9:3.4:0.5:0.8. The relative molecular weight of EPS364 was 14.8 kDa. Our results further revealed that EPS364 was a ß-linked and phosphorylated polysaccharide. Notably, EPS364 exhibited a significant antitumor activity, with inducing apoptosis, dissipation of the mitochondrial membrane potential (MMP) and generation of reactive oxygen species (ROS) in Huh7.5 liver cancer cells. Proteomic and quantitative real-time PCR analyses indicated that EPS364 inhibited cancer cell growth and adhesion via targeting the FGF19-FGFR4 signaling pathway. These findings suggest that EPS364 is a promising antitumor agent for pharmacotherapy.

5.
Med Sci Monit ; 27: e930176, 2021 Apr 13.
Artículo en Inglés | MEDLINE | ID: mdl-33846282

RESUMEN

BACKGROUND Intrahepatic cholestasis of pregnancy (ICP) is a condition specific to pregnancy, leading to increased fetal morbidity and mortality. Nitric oxide synthase (iNOS) may be a factor regulating the vasodilation of blood vessels, which are relevant to ischemic-hypoxic conditions. We aimed to explore the potential relationship between iNOS and ICP. MATERIAL AND METHODS A prospective, case-control study was conducted including 77 pregnant women with ICP and 80 healthy pregnant women as controls. Enzyme-linked immunosorbent assays were used to investigate maternal plasma iNOS levels. The placenta mRNA levels and cell-specific localization of iNOS were determined by quantitative polymerase chain reaction, western blotting, and immunohistochemical analysis. A multivariate linear regression model was used to identify the independent factors of serum total biliary acids (TAB) in ICP. RESULTS Compared with controls, the expression of iNOS was significantly lower in maternal serum and placentas with ICP (P<0.001). Maternal plasm iNOS levels were negatively correlated with TAB (r=-0.450, P<0.001), cholyglycine (r=-0.367, P<0.001), alanine aminotransferase (r=-.359, P<0.001), and aspartate aminotransferase (r=-0.329, P<0.001). iNOS level was an indicator for ICP by multivariate linear regression analysis (ß=-0.505, P<0.001). The ROC curve indicated the optimal cut-off level for iNOS was 2865.43 pg/mL (sensitivity, 85.71%; specificity, 63.75%). The ROC curve area for iNOS was 0.793 (95% CI 0.722-0.864). CONCLUSIONS iNOS plays an important role in poor fetoplacental vascular perfusion and adverse pregnancy outcomes. iNOS can provide complementary information in predicting the extent and severity of ICP.

6.
Neurochem Res ; 2021 Apr 13.
Artículo en Inglés | MEDLINE | ID: mdl-33847855

RESUMEN

The mechanisms underlying postoperative pain differ from the inflammatory or neuropathic pain. Previous studies have demonstrated that intrathecal α-amino-3-hydroxy-5-methy-4-isoxazole propionate (AMPA) -kainate (KA) receptor antagonist inhibits the guarding pain behavior and mechanical hyperalgesia, indicating a critical role of spinal KA receptors in postoperative pain hypersensitivity. However, how the functional regulations of spinal KA receptor subunits are involved in the postoperative pain hypersensitivity remains elusive. Therefore, in the current study, we investigated the synaptic delivery of spinal KA receptor subunits and the interaction between KA receptor subunits and glutamate receptor-interacting protein (GRIP) during the postoperative pain. Our data indicated that plantar incision induced the synaptic delivery of GluK2, but not GluK1 or GluK3 in ipsilateral spinal cord dorsal horns. The co-immunoprecipitation showed an increased GluK2 -GRIP interaction in ipsilateral dorsal horn neurons at 6 h post-incision. Interestingly, Intrathecal pretreatment of GRIP siRNA increased the paw withdrawal thresholds to mechanical stimuli and decreased the cumulative pain scores in the paws ipsilateral to the incision at 6 h post-incision. Additionally, Intrathecal pretreatment of GRIP siRNA reduced the synaptic abundance of GluK2 in ipsilateral spinal dorsal horn at 6 h after plantar incision. In general, our data have demonstrated that the GluK2- GRIP interaction-mediated synaptic abundance of GluK2 in dorsal horn neurons plays an important role in the postoperative pain hypersensitivity. Disrupting the GluK2- GRIP interaction may provide a new approach for relieving postoperative pain.

7.
Sleep Med ; 81: 375-381, 2021 Mar 13.
Artículo en Inglés | MEDLINE | ID: mdl-33813234

RESUMEN

BACKGROUND: The co-occurrence of insomnia and hypersomnia symptoms in patients with major depressive disorder (MDD) is associated with suicidal ideation and functional impairment. The relationship between sleep disturbances and clinical features and outcomes may not be adequately studied. In this study, we measured the functional impairments and clinical features of co-occurring insomnia and hypersomnia symptoms in Chinese patients with MDD. METHODS: A post-hoc analysis was performed on data from the National Survey on Symptomatology of Depression (NSSD), which assessed the MDD patients in 32 hospitals by a clinician-rating questionnaire. The clinical features and outcomes were compared among the following four groups: insomnia symptom only, hypersomnia symptom only, both insomnia and hypersomnia symptoms, no sleep disturbance, respectively. RESULTS: Totally, 234 (7.15%) of 3275 participants with MDD co-occurred insomnia and hypersomnia symptoms. They had more depressive symptoms (27.41 ± 9.123), higher rate of suicide ideation (39.7%), more severe impairment in physical (58.1%), economic (32.9%), work (55.1%), and relationship with families (29.5%). Patients with both sleep disturbances were more likely to excessive worry about sleep, have suicidal ideation, the distress of social disharmony, more somatic symptoms, lack of energy, hyperphagia, loss of mood reactivity, and diurnal change, whereas less likely to have anxious mood. LIMITATIONS: Sleep disorders were not diagnosed by current standard diagnostic criteria. CONCLUSIONS: Patients co-occurring with both sleep disturbances are associated with a higher rate of suicide risk and poorer social function. Our study could provide implications for suicidal risk evaluation and the development of therapeutic strategies for depression.

8.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(2): 643-647, 2021 Apr.
Artículo en Chino | MEDLINE | ID: mdl-33812445

RESUMEN

Sickle cell disease (SCD) is a single gene genetic disease, which seriously threatens the life span and quality of patients. On the basis of the pathogenesis of SCD and the alternative therapy based on fetal hemoglobin F (HbF), the research progress of transcription factors involved in the regulation of HbF gene expression, such as BCL11A, ZBTB7A, KLF-1, c-MYB and SOX6, as well as the application of CRISPR / Cas9, TALEN, zinc finger nuclease and other gene editing technologies in this field has been made, providing a solid theoretical basis for the exploration of new treatment schemes for ß- like hemoglobin diseases, such as sickle cell disease and ß- thalassemia.


Asunto(s)
Anemia de Células Falciformes , Hemoglobina Fetal , Anemia de Células Falciformes/genética , Anemia de Células Falciformes/terapia , Línea Celular Tumoral , Proteínas de Unión al ADN , Hemoglobina Fetal/genética , Terapia Genética , Humanos , Proteínas Represoras/genética , Factores de Transcripción
9.
Int J Clin Pract ; : e14192, 2021 Mar 31.
Artículo en Inglés | MEDLINE | ID: mdl-33792114

RESUMEN

AIMS: To compare patient mortality and technique survival between patients undergoing assisted peritoneal dialysis (aPD) and self-care peritoneal dialysis (sPD). METHODS: Patients who underwent peritoneal dialysis (PD) at the dialysis center of Second Affiliated Hospital of Soochow University from January 1st, 2012 to Dec 31th, 2016, were included and followed to December 31th, 2019. Subjects were divided into aPD and sPD groups according to whether the patient could independently complete the PD procedure. Differences in mortality and technique failure rates were compared using competing risk analysis. RESULTS: A total of 384 patients were included in this study, with 274 patients in the sPD group and 110 patients in the aPD group. The multivariate competing risk regression analysis revealed that age (HR 1.03,95%CI 1.01-1.05, p<0.001), aPD(HR 1.84,95%CI 1.10-3.08, p=0.02), diabetes(HR 1.51,95%CI 1.00-2.30, p=0.05), residual renal function(HR 0.89, 95%CI 0.82-0.97, p=0.005) and serum albumin level(HR 0.92,95%CI 0.89-0.96, p<0.001) were the independent risk factors for mortality. Besides, technique failure in aPD patients was lower than in the sPD group (HR=0.85, 95% CI 0.68-0.97, p =0.03). CONCLUSION: These results found that aPD patients had higher mortality rates but lower technique failure rates than sPD patients. Higher mortality in aPD is probably related to the negative selection of the more comorbid patients.

10.
Artículo en Inglés | MEDLINE | ID: mdl-33809086

RESUMEN

Hypoxia remains a flight-safety issue in terms of aviation medicine. Hypoxia-awareness training has been used to help aircrew members recognize personal hypoxia symptoms. There is still no study, as yet, to establish the association of within-subject data between inflight hypoxia events and the altitude chamber. The main purpose of our study was to use paired subjects' data on inflight hypoxia symptoms compared with those experienced during training. A questionnaire was developed to obtain information on military aircrew members in 2018. Among 341 subjects, 46 (13.49%) suffered from inflight hypoxia. The majority of the subjects detected ongoing inflight hypoxia on the basis of their previous experience with personal hypoxia symptoms or sensations in previous chamber flights. Of the top five hypoxia symptoms, the data revealed that hot flashes, poor concentration, and impaired cognitive function appeared both during the inflight events and during the hypoxia-awareness training. The occurrence rate of hypoxia symptoms was found to not be significantly different between the in-flight events and the past chamber flights through an analysis of within-subject data. Because the individual memory had faded away over time, fresher hypoxia awareness training is still mandatory and valuable to recall personal hypoxia experience for military aircrew members.

11.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 38(4): 380-382, 2021 Apr 10.
Artículo en Chino | MEDLINE | ID: mdl-33834471

RESUMEN

OBJECTIVE: To analyze a patient with infertility and a fragile site found at 16q22 by using cytogenetic methods. METHODS: Peripheral blood sample was taken from the patient and subjected to chromosomal karyotyping and single nucleotide polymorphism microarray (SNP-array) analysis. RESULTS: The patient was found to be a mosaicism for a fragile site at 16q22, which has a variable morphology and cannot be induced by folic acid treatment. No abnormality was found by SNP-array analysis. CONCLUSION: A rare fragile site, which can be induced without folic acid treatment, has been identified at 16q22. The strategy of assisted reproduction for such individuals is yet to be explored.

12.
Oncoimmunology ; 10(1): 1896643, 2021 Mar 18.
Artículo en Inglés | MEDLINE | ID: mdl-33796403

RESUMEN

Prostaglandin E2 (PGE2), an arachidonic acid pathway metabolite produced by cyclooxygenase (COX)-1/2, has been shown to impair anti-tumor immunity through engagement with one or more E-type prostanoid receptors (EP1-4). Specific targeting of EP receptors, as opposed to COX-1/2 inhibition, has been proposed to achieve preferential antagonism of PGE2-mediated immune suppression. Here we describe the anti-tumor activity of MF-766, a potent and highly selective small-molecule inhibitor of the EP4 receptor. EP4 inhibition by MF-766 synergistically improved the efficacy of anti-programmed cell death protein 1 (PD-1) therapy in CT26 and EMT6 syngeneic tumor mouse models. Multiparameter flow cytometry analysis revealed that treatment with MF-766 promoted the infiltration of CD8+ T cells, natural killer (NK) cells and conventional dendritic cells (cDCs), induced M1-like macrophage reprogramming, and reduced granulocytic myeloid-derived suppressor cells (MDSC) in the tumor microenvironment (TME). In vitro experiments demonstrated that MF-766 restored PGE2-mediated inhibition of lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF)-α production in THP-1 cells and human blood, and PGE2-mediated inhibition of interleukin (IL)-2-induced interferon (IFN)-γ production in human NK cells. MF-766 reversed the inhibition of IFN-γ in CD8+ T-cells by PGE2 and impaired suppression of CD8+ T-cells induced by myeloid-derived suppressor cells (MDSC)/PGE2. In translational studies using primary human tumors, MF-766 enhanced anti-CD3-stimulated IFN-γ, IL-2, and TNF-α production in primary histoculture and synergized with pembrolizumab in a PGE2 high TME. Our studies demonstrate that the combination of EP4 blockade with anti-PD-1 therapy enhances antitumor activity by differentially modulating myeloid cell, NK cell, cDC and T-cell infiltration profiles.

13.
J Clin Gastroenterol ; 55(5): 393-399, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33828065

RESUMEN

Hepatitis B virus reactivation (HBVr) can occur spontaneously, but more often occurs when a patient is in an immunocompromised state or on immunosuppressive therapy. HBVr can lead to clinical hepatitis, acute liver failure, and even death. HBVr is preventable with screening of at-risk patients and initiation of prophylactic antiviral therapy for appropriate candidates. Screening for hepatitis B virus is recommended for all patients who plan to initiate immunosuppressive therapy. An individual's serological profile, underlying disease, and planned type of immunosuppression contribute to their risk of HBVr. This review serves to summarize the major society guidelines regarding screening, management of, and monitoring for HBVr in individuals on anticancer therapy and immunosuppressive therapy.

14.
Artículo en Inglés | MEDLINE | ID: mdl-33837020

RESUMEN

Land-use types with different disturbance gradients show many variations in soil properties, but the effects of different land-use types on soil nitrifying communities and their ecological implications remain poorly understood. Using 13CO2-DNA-based stable isotope probing (DNA-SIP), we examined the relative importance and active community composition of ammonia-oxidizing archaea (AOA) and bacteria (AOB), and nitrite-oxidizing bacteria (NOB) in soils under three land-use types, forest, cropland, and greenhouse vegetable soil, representing three interference gradients. Soil net nitrification rate was in the order forest soil > cropland soil > greenhouse vegetable soil. DNA-SIP showed that active AOA outcompeted AOB in the forest soil, whereas AOB outperformed AOA in the cropland and greenhouse vegetable soils. Cropland soil was richer in NOB than in AOA and AOB. Phylogenetic analysis revealed that ammonia oxidation in the forest soil was predominantly catalyzed by the AOA Nitrosocosmicus franklandus cluster within the group 1.1b lineage. The 13C-labeled AOB were overwhelmingly dominated by Nitrosospira cluster 3 in the cropland soil. The active AOB Nitrosococcus watsonii lineage was observed in the greenhouse vegetable soil, and it played an important role in nitrification. Active NOB communities were closely affiliated with Nitrospira in the forest and cropland soils, and with Nitrolancea and Nitrococcus in the greenhouse vegetable soil. Canonical correlation analysis showed that soil pH and organic matter content significantly affected the active nitrifier community composition. These results suggest that land-use types with different disturbance gradients alter the distribution of active nitrifier communities by affecting soil physicochemical properties.IMPORTANCENitrification plays an important role in the soil N cycle, and land-use management has a profound effect on soil nitrifiers. It is unclear how different gradients of land use affect active ammonia-oxidizing archaea and bacteria and nitrite-oxidizing bacteria. Our research is significant because we determined the response of nitrifiers to human disturbance, which will greatly improve our understanding of the niche of nitrifiers and the differences in their physiology.

15.
Chemistry ; 2021 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-33844332

RESUMEN

Zn-air battery is a perspective power source for grid-storage. But, after they are discharged at 1.1 to 1.2 V, large overpotential is required for their charging, usually 2.5 V. This is due to sluggish the oxygen evolution reaction (OER); Incorporating organic pollutants into the cathode electrolyte is a feasible strategy for lowering the required charging potential. On the other hand, in discharge process related oxygen reduction reaction, hydrophobic electrocatalyst is more popular than hydrophilic one. Here, a hydrophobic bi-functional polyoxometalate electrocatalyst is synthesized by precise structural design. It shows excellent activities in both bisphenol A degradation and oxygen reduction reactions. In bisphenol A containing electrolyte, to achieve 100 mA·cm -2 , its potential is only 1.32 V, which is 0.34 V lower than oxygen evolution reaction. In oxygen reduction reaction, this electrocatalyst follows four-electron mechanism. In both bisphenol A degradation and oxygen reduction reactions, it shows excellent stability. With this electrocatalyst as cathode material and bisphenol A containing KOH as electrolyte, Zn-air battery is assembled. When "charge" at 85 mA·cm -2 , it only requires 1.98 V. Peak power density of this Zn-air battery reaches 120.5 mW·cm -2 . More importantly, in "charge" process, bisphenol A is degraded, which achieves energy saving and pollutants removal simultaneously in one Zn-air battery.

16.
Pharmaceuticals (Basel) ; 14(3)2021 Mar 08.
Artículo en Inglés | MEDLINE | ID: mdl-33800276

RESUMEN

The purpose of our study was to investigate whether genetic variations in lncRNA H19 were associated with susceptibility to childhood leukemia. Two hundred and sixty-six childhood leukemia patients and 266 healthy controls were enrolled in Taiwan, and two single nucleotide polymorphisms (SNPs), rs2839698 and rs217727, in H19 were genotyped and analyzed. There was a significant difference in the genotypic distribution of rs2839698 between patients and healthy controls (p = 0.0277). Compared to the wild-type CC genotype, the heterozygous variant CT and homozygous variant TT genotypes were associated with significantly increased risks of childhood leukemia with an adjusted odd ratio (OR) of 1.46 (95% confidence interval (CI), 1.08-2.14, p = 0.0429) and 1.94 (95%CI, 1.15-3.31, p = 0.0169), respectively (pfor tread = 0.0277). The difference in allelic frequencies between childhood leukemia patients and controls was also significant (T versus C, adjusted OR = 1.53, 95%CI, 1.13-1.79, p = 0.0077). There were no significant differences in the genotypic and allelic distributions of rs217727 between cases and controls. Interestingly, the average level of H19 rs2839698 was statistically significantly higher for patients with CT and TT genotypes than from those with the CC genotype (p < 0.0001). Our results indicate that H19 SNP rs2839698, but not rs217727, may serve as a novel susceptibility marker for childhood leukemia.

17.
Zhongguo Fei Ai Za Zhi ; 24(3): 182-187, 2021 Mar 20.
Artículo en Chino | MEDLINE | ID: mdl-33819968

RESUMEN

BACKGROUND: The aim of this study is to investigate the changes of peripheral blood lymphocyte subsets before and after treatment with pembrolizumab for non-small cell lung cancer and its clinical significance. METHODS: A total of 32 patients with non-small cell lung cancer who received pembrolizumab treatment in The Affiliated Hospital of Qingdao University and Weifang People's Hospital of Shandong Province from January 2015 to December 2020 were selected as the observation group, and 30 healthy people during the same period were selected as the control group. Before treatment and in cycles 1, 2 and 4 after treatment, fluid cytometry was used to detect changes in the levels of lymphocyte subsets in the peripheral blood of patients. RESULTS: The CD3⁺, CD4⁺, CD4⁺/CD8⁺ indexes of patients with non-small cell lung cancer before the treatment were significantly lower than those in the control group (P<0.05), and the CD8⁺ level was significantly increased (P<0.05); After 1 cycle of pembrolizumab treatment, there was no significant difference in the changes of lymphocyte subsets compared with before immunotherapy; After 2 cycles of the treatment, the CD3⁺, CD4⁺, CD4⁺/CD8⁺ values were higher than before the treatment (P>0.05), and the CD8⁺ index was slightly lower than before the treatment (P<0.05); After the fourth cycle of treatment, the CD3⁺, CD4⁺, CD4⁺/CD8⁺ values were significantly improved compared to before the treatment (P<0.05), and the CD8⁺ index was significantly lower than before the treatment (P<0.05); In the treatment process of patients with stable disease (SD)/partial response (PR), the CD3⁺, CD4⁺, CD4⁺/CD8⁺ values of the fourth cycles were higher than before the treatment (P<0.05), and the CD8⁺ index was lower than before the treatment (P<0.05); During the treatment of progressive disease (PD) patients, the changes of lymphocyte subsets in the fourth cycles were not significantly different from those before the treatment (P>0.05). At the same time, this article shows through analysis that the expression of programmed cell death ligand 1 (PD-L1) and pathological types have no obvious influence on the effect of immunotherapy. Multi-factor analysis shows that it is more meaningful to observe the changes of CD3⁺, CD4⁺ and CD8⁺ at the same time to predict the effect of immunotherapy. CONCLUSIONS: Pembrolizumab can regulate the changes of T lymphocyte subsets in patients with non-small cell lung cancer, improve the immune status of the patients, and there is no obvious adverse reaction. At the same time, monitoring the changes of lymphocyte subsets during treatment can predict the effect of immunotherapy.

18.
Cell Death Dis ; 12(4): 336, 2021 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-33795653

RESUMEN

The tumor necrosis factor (TNF) receptor superfamily member 11a (TNFRSF11a, also known as RANK) was demonstrated to play an important role in tumor metastasis. However, the specific function of RANK in colorectal cancer (CRC) metastasis and the underlying mechanism are unknown. In this study, we found that RANK expression was markedly upregulated in CRC tissues compared with that in matched noncancerous tissues. Increased RANK expression correlated positively with metastasis, higher TNM stage, and worse prognosis in patients with CRC. Overexpression of RANK promoted CRC cell metastasis in vitro and in vivo, while knockdown of RANK decreased cell migration and invasion. Mechanistically, RANK overexpression significantly upregulated the expression of tartrate-resistant acid phosphatase 5 (TRAP/ACP5) in CRC cells. Silencing of ACP5 in RANK-overexpressing CRC cells attenuated RANK-induced migration and invasion, whereas overexpression of ACP5 increased the migration and invasion of RANK-silencing cells. The ACP5 expression was transcriptionally regulated by calcineurin/nuclear factor of activated T cells c1 (NFATC1) axis. The inhibition of calcineurin/NFATC1 significantly decreased ACP5 expression, and attenuated RANK-induced cell migration and invasion. Furthermore, RANK induced phospholipase C-gamma (PLCγ)-mediated inositol-1,4,5-trisphosphate receptor (IP3R) axis and stromal interaction molecule 1 (STIM1) to evoke calcium (Ca2+) oscillation. The RANK-mediated intracellular Ca2+ mobilization stimulated calcineurin to dephosphorylate NFATC1 and induce NFATC1 nuclear translocation. Both blockage of PLCγ-IP3R axis and STIM1 rescued RANK-induced NFATC1 nuclear translocation, ACP5 expression, and cell metastasis. Our study revealed the functional expression of RANK in human CRC cells and demonstrated that RANK induced the Ca2+-calcineurin/NFATC1-ACP5 axis in the regulation of CRC metastasis, that might be amenable to therapeutic targeting.

19.
Mar Pollut Bull ; 167: 112220, 2021 Apr 07.
Artículo en Inglés | MEDLINE | ID: mdl-33836332

RESUMEN

Cadmium (Cd) and lead (Pb) are two hazardous pollutants that threaten shrimp farming. The intestine is an important organ for digestion and immunity. We separately exposed Pacific white shrimp Litopenaeus vannamei to 500 µg/L Cd or 500 µg/L Pb seawater for 7 days, and 45 shrimp from each group were used to evaluate the changes of intestinal histopathological, oxidative stress, and microbiota composition. After Cd and Pb exposure, shrimp intestine appeared significant mucosal damage and oxidative stress, and the microbiota variation were induced. Specifically, the abundance of the phyla Bacteroidetes and Actinobacteria were induced, that of Proteobacteria and Firmicutes were deduced. The abundances of putative beneficial bacteria (Lactobacillus, Weissella, Demequina, Formosa and Ruegeria) and potentially pathogenic bacteria (Vibrio and Photobacterium) were fluctuated. Furthermore, the nutrient metabolic function of intestinal microbes was significantly altered. We concluded that Cd and Pb exposure had negative effects on the intestinal health of shrimp.

20.
Food Res Int ; 140: 110009, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33648241

RESUMEN

Starch, which is a carbohydrate polymer with a semicrystalline granular structure, has been the subject of academic research for decades due to its renewable and biodegradable property as well as various applications in food, pharmaceutical and other industries. Nano-starch (NS) is a novel type of starch material with unique physiochemical properties due to its small size. However, the nano-size nature of NS determines its tendency to agglomeration as a natural process to approach a thermodynamically steady state, and the single hydroxyl functional group is also not favorable to its applications in hydrophobic environments. Thus, modified-NS with improved dispersion property, hydrophobicity, and stability is emerging as a new research direction. However, information about modified-NS is sporadic in literature, and a systematic review from its preparation, application, the problem and challenge as well as related health concerns is carried out to further the understanding of modified-NS. It is expected that the theoretical basis and new insight into the development of modified-NS will be improved.

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